GSEA research notes.md

There are no explicitly immune related pathways highly ranked in GSEA at 1WPC. However, they show up prominently at 4WPC.

Can this be related to the fact that the heart is not an 'immune organ'? What is the case in the liver, head-kidney, and spleen?

However, in EOMES, more general GO terms like negative regulation of response to external stimulus, positive regulation of response to external stimulus, and regulation of response to external stimulus are present, with relatively large gene sets, generally upregulated. Is this evidence of an early antiviral response?

Responses to external stimuli show up in the DNA vaccine, EOMES, and GATA3, but not in IV-HD? Evidence of viral infection recognition?

Heart

1WPC

DNA vaccine

Running GSEA results through ReactomePA, I get a set of downregulated pathways for DNA vaccine:

Description	NES
Interferon alpha/beta signaling	-2.511935
Potassium Channels	-2.462609
p130Cas linkage to MAPK signaling for integrins	-2.066685
Formation of Fibrin Clot (Clotting Cascade)	-2.022246
ATF4 activates genes in response to endoplasmic reticulum stress	-1.990491
TNFR1-induced NF-kappa-B signaling pathway	-1.947870
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-1.925654
PERK regulates gene expression	-1.912257
Inactivation of CSF3 (G-CSF) signaling	-1.868618
Membrane binding and targetting of GAG proteins	-1.867574
Synthesis And Processing Of GAG, GAGPOL Polyproteins	-1.867574
Nicotinamide salvaging	-1.867505
Nicotinate metabolism	-1.866540
Assembly Of The HIV Virion	-1.859421
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	-1.812187
GRB2:SOS provides linkage to MAPK signaling for Integrins	-1.793079
IKK complex recruitment mediated by RIP1	-1.783806
Interleukin-6 family signaling	-1.776561
Regulation of NF-kappa B signaling	-1.772008
Chaperone Mediated Autophagy	-1.762597
TAK1-dependent IKK and NF-kappa-B activation	-1.753485
Nucleotide catabolism	-1.750191
Response of EIF2AK1 (HRI) to heme deficiency	-1.730220
Complement cascade	-1.727122
Nucleotide salvage	-1.724230
Negative regulators of DDX58/IFIH1 signaling	-1.719055
TICAM1, RIP1-mediated IKK complex recruitment	-1.697703
Regulated Necrosis	-1.686290
Signaling by CSF3 (G-CSF)	-1.671001
Negative regulation of FLT3	-1.659995
Negative regulation of MAPK pathway	-1.631777
Regulation of TNFR1 signaling	-1.594833
rRNA modification in the nucleus and cytosol	-1.574979
DDX58/IFIH1-mediated induction of interferon-alpha/beta	-1.552165
ER-Phagosome pathway	-1.521858
Interleukin-4 and Interleukin-13 signaling	-1.463792

Relevant pathways for immune response and inflammation, cell stress and homeostasis, and viral infection and response:

Immune Response and Inflammation

1. Interferon Alpha/Beta Signaling:
   • Critical for antiviral defense, activating immune cells, and upregulating antigen presentation.
2. TNFR1-induced NF-kappa-B Signaling Pathway:
   • Involved in inflammation, immune response, and cell survival.
3. Activation of IRF3, IRF7 Mediated by TBK1, IKKε (IKBKE):
   • Plays a role in antiviral responses by activating interferon-stimulated genes.
4. Regulation of NF-kappa B Signaling:
   • Central in controlling immune responses, inflammation, and cell survival.
5. Interleukin-6 Family Signaling:
   • Important for immune responses, inflammation, and hematopoiesis.
6. Interleukin-4 and Interleukin-13 Signaling:
   • Involved in the regulation of immune responses, particularly in allergic reactions.
7. Complement Cascade:
   • Part of the innate immune system, enhancing the ability to clear microbes and damaged cells.

Cell Stress and Homeostasis

1. ATF4 Activates Genes in Response to Endoplasmic Reticulum Stress:
   • Manages stress responses within the endoplasmic reticulum, crucial for cell survival under stress.
2. PERK Regulates Gene Expression:
   • Involved in the unfolded protein response, helping cells cope with endoplasmic reticulum stress.
3. Chaperone Mediated Autophagy:
   • Selective degradation of damaged or misfolded proteins, crucial for cellular homeostasis.
4. Response of EIF2AK1 (HRI) to Heme Deficiency:
   • Regulates protein synthesis in response to heme availability, affecting red blood cell production.

Viral Infection and Response

1. Assembly of the HIV Virion:
   • Pathway detailing the steps in the assembly of HIV, a key process in the viral life cycle.
2. Membrane Binding and Targeting of GAG Proteins:
   • Involved in the assembly and budding of retroviruses like HIV.
3. Synthesis and Processing of GAG, GAGPOL Polyproteins:
   • Crucial for the production of viral proteins necessary for viral replication and assembly.

Summary

These pathways reflect a wide range of cellular functions, including immune responses, stress responses, metabolic processes, cell signaling, viral infection mechanisms, and apoptosis. This combination suggests a coordinated effort to maintain cellular homeostasis, respond to external and internal stressors, and regulate immune and inflammatory responses. Understanding these pathways can provide insights into various physiological conditions and potential therapeutic targets for diseases such as infections, cancer, immune disorders, and metabolic syndromes.

EOMES

Running GSEA results through ReactomePA, I get a set of downregulated pathways:

Description	NES
Potassium Channels	-2.584500
Inwardly rectifying K+ channels	-2.124522
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-2.007038
Nicotinamide salvaging	-1.994544
Neuronal System	-1.967783
Nicotinate metabolism	-1.955000
GABA B receptor activation	-1.936191
Activation of GABAB receptors	-1.936191
Response of EIF2AK1 (HRI) to heme deficiency	-1.902384
ATF4 activates genes in response to endoplasmic reticulum stress	-1.870037
GABA receptor activation	-1.861655
mRNA decay by 3' to 5' exoribonuclease	-1.853049
Response of Mtb to phagocytosis	-1.784642
Mitochondrial tRNA aminoacylation	-1.739713

This combination of pathways suggests an integration of diverse cellular functions:

• Neuronal Function and Neurotransmission: Pathways involving potassium channels, GABA receptor activation, and the neuronal system highlight critical mechanisms in maintaining neuronal excitability and neurotransmission.
• Metabolic Processes: Nicotinamide salvaging and nicotinate metabolism are crucial for NAD+ production, affecting cellular energy metabolism.
• Immune Response and Stress: Pathways involving IRF3/IRF7 activation, ATF4 in ER stress, and response to phagocytosis are indicative of cellular responses to stress and infection.
• RNA Processing and Mitochondrial Function: mRNA decay mechanisms and mitochondrial tRNA aminoacylation point to the importance of RNA regulation and mitochondrial protein synthesis.

Overall, this combination of pathways illustrates a complex network of interactions that are vital for cellular homeostasis, neuronal function, metabolic processes, and immune responses. Understanding these pathways provides insights into how cells respond to various physiological and pathological conditions.

GATA3

Description	NES
Keratinization	-2.378933
Formation of the cornified envelope	-2.378933
Interferon alpha/beta signaling	-2.337436
Potassium Channels	-2.330262
Nicotinate metabolism	-2.132847
Nicotinamide salvaging	-2.116462
Evasion by RSV of host interferon responses	-2.077602
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-1.972133
TRAF3-dependent IRF activation pathway	-1.945352
Translation of Structural Proteins	-1.886217
Inactivation of CSF3 (G-CSF) signaling	-1.866082
Maturation of nucleoprotein	-1.817987
TRAF6 mediated IRF7 activation	-1.786926
Negative regulators of DDX58/IFIH1 signaling	-1.749586
RIPK1-mediated regulated necrosis	-1.740030
Regulation of necroptotic cell death	-1.740030
Maturation of nucleoprotein	-1.727373
Synthesis of PE	-1.713567
Assembly Of The HIV Virion	-1.680388
Interleukin-6 family signaling	-1.679486
Chondroitin sulfate biosynthesis	-1.662545
Membrane binding and targetting of GAG proteins	-1.653289
Synthesis And Processing Of GAG, GAGPOL Polyproteins	-1.653289
Signaling by CSF3 (G-CSF)	-1.652082

IV-HD

Description	NES
Interferon alpha/beta signaling	-2.493979
Keratinization	-2.373031
Formation of the cornified envelope	-2.373031
RHO GTPase cycle	1.357184
M Phase	1.377808
Signaling by GPCR	1.404715
G2/M Checkpoints	1.419820
Cellular Senescence	1.423657
DNA Double-Strand Break Repair	1.442063
GPCR downstream signalling	1.462783
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.463620
Signaling by Rho GTPases	1.487763
RHOJ GTPase cycle	1.514199
trans-Golgi Network Vesicle Budding	1.520059
COPI-dependent Golgi-to-ER retrograde traffic	1.535652
RAC1 GTPase cycle	1.540232
Assembly of collagen fibrils and other multimeric structures	1.547597
G2/M DNA damage checkpoint	1.553502
Fcgamma receptor (FCGR) dependent phagocytosis	1.557622
RHO GTPase Effectors	1.561024
Kinesins	1.563174
Collagen formation	1.587237
FCGR3A-mediated IL10 synthesis	1.591024
SUMOylation of DNA damage response and repair proteins	1.593563
SUMOylation of DNA methylation proteins	1.599738
Diseases of mitotic cell cycle	1.602410
Transcription of E2F targets under negative control by DREAM complex	1.606372
RHOC GTPase cycle	1.607240
Sensory Perception	1.611937
Synthesis of bile acids and bile salts	1.613874
E2F mediated regulation of DNA replication	1.615655
Aquaporin-mediated transport	1.620156
Resolution of D-loop Structures through Holliday Junction Intermediates	1.621492
RND2 GTPase cycle	1.621869
Presynaptic phase of homologous DNA pairing and strand exchange	1.627912
G alpha (i) signalling events	1.630012
Arachidonic acid metabolism	1.630762
Leishmania infection	1.631708
Parasitic Infection Pathways	1.631708
VEGFR2 mediated cell proliferation	1.633267
RHOQ GTPase cycle	1.635536
SUMOylation	1.639222
Vasopressin regulates renal water homeostasis via Aquaporins	1.642338
Ca-dependent events	1.644998
RND3 GTPase cycle	1.648496
SUMO E3 ligases SUMOylate target proteins	1.652404
RHOU GTPase cycle	1.653308
Removal of the Flap Intermediate	1.653557
Aberrant regulation of mitotic cell cycle due to RB1 defects	1.655203
Defective pyroptosis	1.659783
Processive synthesis on the lagging strand	1.664029
G1/S Transition	1.666620
Cell Cycle	1.670658
PCNA-Dependent Long Patch Base Excision Repair	1.672704
PLC beta mediated events	1.673461
Resolution of D-Loop Structures	1.682975
Ion homeostasis	1.684722
Mitotic Prometaphase	1.687451
Chromosome Maintenance	1.688812
Cell Cycle Checkpoints	1.690703
Calmodulin induced events	1.693557
CaM pathway	1.693557
HDR through Homologous Recombination (HRR)	1.694333
EML4 and NUDC in mitotic spindle formation	1.696535
Telomere Maintenance	1.697580
HDR through Single Strand Annealing (SSA)	1.699025
RHO GTPases Activate Formins	1.699854
Homology Directed Repair	1.706192
Impaired BRCA2 binding to RAD51	1.708318
Mitotic G1 phase and G1/S transition	1.711530
Cholesterol biosynthesis	1.711996
DNA Replication	1.712553
Opioid Signalling	1.714581
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1.717834
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1.719656
Homologous DNA Pairing and Strand Exchange	1.734755
G0 and Early G1	1.738882
Synthesis of DNA	1.742812
Diseases of DNA repair	1.744355
Anti-inflammatory response favouring Leishmania parasite infection	1.753147
Leishmania parasite growth and survival	1.753147
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1.755019
G-protein mediated events	1.757053
Mitotic Spindle Checkpoint	1.764308
Extension of Telomeres	1.765192
Regulation of insulin secretion	1.772276
Cell Cycle, Mitotic	1.781071
Polymerase switching	1.784076
Leading Strand Synthesis	1.784076
Resolution of Abasic Sites (AP sites)	1.790265
Amplification of signal from the kinetochores	1.792241
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1.792241
Diseases of DNA Double-Strand Break Repair	1.795437
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1.795437
G1/S-Specific Transcription	1.797571
Base Excision Repair	1.809282
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1.813502
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1.813502
Resolution of Sister Chromatid Cohesion	1.820693
S Phase	1.820888
Lagging Strand Synthesis	1.831390
Activation of the pre-replicative complex	1.833038
DAG and IP3 signaling	1.833079
CDC42 GTPase cycle	1.841011
Activation of ATR in response to replication stress	1.869308
Unwinding of DNA	1.886716
Polymerase switching on the C-strand of the telomere	1.888445
Telomere C-strand (Lagging Strand) Synthesis	1.891149
DNA strand elongation	2.134875

The pathways cover a wide range of biological processes, including cell cycle regulation ("M Phase", "G2/M Checkpoints", "G1/S Transition"), DNA repair ("DNA Double-Strand Break Repair", "Base Excision Repair"), signaling pathways ("Signaling by GPCR", "Interferon alpha/beta signaling"), and metabolism ("Synthesis of bile acids and bile salts", "Arachidonic acid metabolism").

IV-LD

The only Reactome pathway is 'Neuronal System'.

4WPC

DNA vaccine

Running GSEA with the whole gene list, without pre-selecting by p-value, yields the following downregulated pathways on ReactomePA.

Description	NES
Interferon alpha/beta signaling	-2.245783
Signaling by CSF1 (M-CSF) in myeloid cells	-2.183906
GPVI-mediated activation cascade	-2.156946
Interleukin-3, Interleukin-5 and GM-CSF signaling	-2.118311
ROS and RNS production in phagocytes	-2.073070
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-2.063355
RHO GTPases Activate NADPH Oxidases	-1.964348
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-1.956229
Inactivation of CSF3 (G-CSF) signaling	-1.950036
Regulation of signaling by CBL	-1.915487
Cytosolic tRNA aminoacylation	-1.915362
Signaling by CSF3 (G-CSF)	-1.897145
FCERI mediated MAPK activation	-1.881534
Parasite infection	-1.788290
Leishmania phagocytosis	-1.788290
FCGR3A-mediated phagocytosis	-1.788290
Generation of second messenger molecules	-1.780454
Antigen processing-Cross presentation	-1.775111
Signaling by the B Cell Receptor (BCR)	-1.749496
Costimulation by the CD28 family	-1.702488
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	-1.690269
Hh mutants are degraded by ERAD	-1.689402
Hh mutants abrogate ligand secretion	-1.689402
DAP12 interactions	-1.671403
DAP12 signaling	-1.671403
FCERI mediated NF-kB activation	-1.665623
Defective CFTR causes cystic fibrosis	-1.665085
Regulation of actin dynamics for phagocytic cup formation	-1.648707
SCF-beta-TrCP mediated degradation of Emi1	-1.615164
Fcgamma receptor (FCGR) dependent phagocytosis	-1.603441
Hedgehog ligand biogenesis	-1.602925
TCR signaling	-1.595014
Degradation of GLI2 by the proteasome	-1.585871
Activation of NF-kappaB in B cells	-1.577746
Fc epsilon receptor (FCERI) signaling	-1.544485
Interleukin-1 family signaling	-1.528250
Signaling by Interleukins	-1.498810
Cytokine Signaling in Immune system	-1.396404
Adaptive Immune System	-1.241338

Overall, these pathways highlight key processes in the immune response, cell signaling, and regulation, emphasizing their roles in maintaining immune system function and responding to pathogens. Negative NES values indicate downregulation, suggesting a potential suppression of these pathways under certain conditions.

On the opposite side of the spectrum, the upregulated pathways:

Description	NES
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.166720
Aerobic respiration and respiratory electron transport	2.127555
Respiratory electron transport	2.114959
Post-translational protein phosphorylation	2.086596
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	2.085496
Formation of Fibrin Clot (Clotting Cascade)	2.065645
Intrinsic Pathway of Fibrin Clot Formation	2.043202
Complex I biogenesis	1.923962
Heme signaling	1.898826
Mitochondrial biogenesis	1.863493
Branched-chain amino acid catabolism	1.830416
Muscle contraction	1.819388
Potassium Channels	1.815271
Platelet degranulation	1.802439
Cristae formation	1.799254
Voltage gated Potassium channels	1.788866
Mitochondrial protein degradation	1.783941
Response to elevated platelet cytosolic Ca2+	1.782834
Formation of ATP by chemiosmotic coupling	1.775668
Citric acid cycle (TCA cycle)	1.772693
Nuclear Receptor transcription pathway	1.759821
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1.731914
GABA receptor activation	1.727551
Striated Muscle Contraction	1.712729
Transcriptional activation of mitochondrial biogenesis	1.683622
FOXO-mediated transcription	1.682785
Collagen chain trimerization	1.670550
Metabolism of nitric oxide: NOS3 activation and regulation	1.669765
Gluconeogenesis	1.665098
Opioid Signalling	1.652053
Sensory Perception	1.651697
Collagen biosynthesis and modifying enzymes	1.622587
Neuronal System	1.596390
Cardiac conduction	1.584142
Organelle biogenesis and maintenance	1.496958
Hemostasis	1.421507

Overall, these pathways collectively impact:

• Cellular energy production and metabolism.
• Cell signaling and regulatory mechanisms.
• Blood clotting and cardiovascular health.
• Muscle function and movement.
• Structural maintenance and tissue integrity.
• Protein synthesis, modification, and degradation.
• Growth, development, and response to environmental stimuli.

If one starts from a list of genes pre-selected by p-value (p < 0.05), and runs GSEA against a genome wide annotation for human (not ReactomePA, org.Hs.eg.db), the overall result is the same, with immune-related pathways downregulated and energy production upregulated.

Description	NES
aerobic respiration	3.157926
oxidative phosphorylation	2.937657
proton motive force-driven mitochondrial ATP synthesis	2.624725
dicarboxylic acid metabolic process	2.361743
mitochondrial respiratory chain complex assembly	2.300209
muscle system process	2.252134
regulation of muscle system process	2.094244
rhythmic process	2.085570
nucleoside triphosphate biosynthetic process	1.995967
ribonucleoside triphosphate biosynthetic process	1.995967
amino acid catabolic process	1.936152
nucleoside triphosphate metabolic process	1.881641
ribonucleoside triphosphate metabolic process	1.881641
ATP metabolic process	1.810749
small molecule catabolic process	1.722197
purine-containing compound metabolic process	1.656750
cellular response to oxygen-containing compound	1.647138
small molecule metabolic process	1.549061
multicellular organismal process	-1.425700
cell communication	-1.510842
signaling	-1.521286
positive regulation of biological process	-1.575174
negative regulation of macromolecule biosynthetic process	-1.634718
negative regulation of biosynthetic process	-1.663773
negative regulation of cellular biosynthetic process	-1.663773
import into cell	-1.684992
lymphocyte apoptotic process	-1.774158
regulation of leukocyte mediated cytotoxicity	-1.787597
positive regulation of cell migration	-1.792857
positive regulation of locomotion	-1.792857
positive regulation of cell motility	-1.792857
locomotion	-1.801708
positive regulation of cell development	-1.812092
regulation of protein phosphorylation	-1.822433
negative regulation of T cell activation	-1.848189
collagen metabolic process	-1.854287
leukocyte homeostasis	-1.856544
response to cytokine	-1.858390
regulation of cell killing	-1.860695
regulated exocytosis	-1.866868
positive regulation of catalytic activity	-1.872830
regulation of chemotaxis	-1.875409
negative regulation of protein transport	-1.894241
negative regulation of establishment of protein localization	-1.894241
peptidyl-tyrosine modification	-1.894578
import across plasma membrane	-1.895777
regulation of leukocyte migration	-1.897036
response to external stimulus	-1.933134
positive regulation of phosphorylation	-1.949875
phagocytosis, engulfment	-1.953162
membrane invagination	-2.007528
plasma membrane invagination	-2.007528
regulation of binding	-2.009462
leukocyte mediated cytotoxicity	-2.029608
epithelial to mesenchymal transition	-2.038571
cytokine-mediated signaling pathway	-2.057145
steroid biosynthetic process	-2.079742
skeletal system development	-2.103461
production of molecular mediator of immune response	-2.113634
regulation of production of molecular mediator of immune response	-2.113634
T cell mediated immunity	-2.115681
positive regulation of response to stimulus	-2.123837
positive regulation of multicellular organismal process	-2.132066
regulation of ERK1 and ERK2 cascade	-2.137176
regulation of innate immune response	-2.137273
cell killing	-2.172378
leukocyte activation involved in immune response	-2.183926
biological process involved in interspecies interaction between organisms	-2.186225
regulation of lymphocyte differentiation	-2.199522
phagocytosis	-2.208789
regulation of defense response	-2.223763
chemotaxis	-2.247164
taxis	-2.247164
response to biotic stimulus	-2.281739
leukocyte migration	-2.302119
cell chemotaxis	-2.305048
positive regulation of T cell activation	-2.309675
regulation of cell adhesion	-2.366362
leukocyte cell-cell adhesion	-2.372385
cytokine production	-2.409554
regulation of cytokine production	-2.409554
regulation of mononuclear cell proliferation	-2.450445
defense response to other organism	-2.457111
lymphocyte proliferation	-2.480956
mononuclear cell differentiation	-2.565588
leukocyte proliferation	-2.596309
inflammatory response	-2.599778
immune system process	-2.732992
cell activation	-2.764861
lymphocyte activation	-2.795845
regulation of immune system process	-2.824275
positive regulation of immune system process	-2.826171
regulation of leukocyte activation	-2.841657
T cell activation	-2.872483
regulation of immune response	-2.915157
leukocyte activation	-2.962128
immune response	-3.085458

EOMES

Description	NES	setSize	Count
Aerobic respiration and respiratory electron transport	1.949627	164	106
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.895979	98	68
Formation of definitive endoderm	1.894218	10	4
Respiratory electron transport	1.884847	83	57
Complex I biogenesis	1.784491	44	32
Mitochondrial biogenesis	1.754441	79	41
Muscle contraction	1.745952	117	60
NCAM1 interactions	1.719882	16	7
Adaptive Immune System	-1.363424	491	125
Cell Cycle	-1.394166	496	155
Cytokine Signaling in Immune system	-1.425435	424	143
Neutrophil degranulation	-1.470707	298	84
Cell Cycle Checkpoints	-1.518823	211	107
Cholesterol biosynthesis	-1.777279	20	9
ABC transporter disorders	-1.902475	62	33
Antigen processing-Cross presentation	-1.915112	75	32
Diseases of Immune System	-1.920536	15	6
Diseases associated with the TLR signaling cascade	-1.920536	15	6
Inwardly rectifying K+ channels	-1.944344	14	4
Chromosome Maintenance	-1.961067	77	29
RHO GTPases Activate NADPH Oxidases	-1.973060	19	7
Regulation of Complement cascade	-2.085535	17	7
Interferon alpha/beta signaling	-2.096606	34	18
Potassium Channels	-2.124389	34	6

Key regulated pathways

Upregulated

• Aerobic respiration and respiratory electron transport:
  • This pathway is highly upregulated. It involves processes crucial for energy production via aerobic respiration, indicating an increase in metabolic activity.
• Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins
  • This pathway is also significantly upregulated. It points to active ATP synthesis and possible thermogenesis through uncoupling proteins, suggesting heightened mitochondrial activity.
• Respiratory electron transport
  • Similar to the first pathway, this one focuses on electron transport, further emphasizing the increased mitochondrial function and energy production.
• Complex I biogenesis
  • Upregulation of this pathway indicates an increase in the formation of Complex I of the mitochondrial electron transport chain, supporting enhanced respiration and ATP production.
• Mitochondrial biogenesis
  • Increased biogenesis of mitochondria, which correlates with the upregulation of respiratory pathways and overall cellular energy production.

Downregulated

• Adaptive immune system

  • Downregulation suggests a suppressed adaptive immune response, potentially indicating an immune evasion mechanism or reduced immune activity.

• Cell cycle

  • Suggests a reduction in cell proliferation activities, possibly indicating a shift from cell division to other cellular activities.

• Cytokine signaling in immune system

  • Downregulation here indicates reduced cytoking-mediated signaling, which could be part of broader suppression of immune responses.

• Neutrophil degranulation

  • Indicative of reduced neutrophil activity, which play a key role in innate immunity.

• Antigen processing-cross presentation

  • Reduced antigen presentation capability, further suggesting immune suppression.

• Diseases of Immune System and Diseases associated with the TLR signaling cascade

• RHO GTPases activate NADPH oxidases

  • Reduced activity in oxidative stress responses mediated by RHO GTPases.

• Regulation of Complement cascade

  • Deregulation of complement regulation could impair immune complex clearance and inflammatory response.

• Interferon alpha/beta signaling

  • Reduced interferon signaling, affecting antiviral responses and immune modulation.

Overall Interpretation

• Upregulation: The upregulated pathways largely involve mitochondrial activity, energy production, and muscle contraction. This suggests a state of increased metabolic activity and energy demand.
• Downregulation: The downregulated pathways are predominantly associated with immune responses, cell cycle processes, and certain biosynthetic pathways like cholesterol synthesis. This indicates a suppression of immune activity and cell proliferation, possibly in favor of energy conservation or other cellular priorities.

These changes might reflect a specific physiological or pathological state where the organism is prioritizing energy production and mitochondrial function over immune responses and cell division. This could be relevant in contexts such as metabolic adaptation, stress responses, or certain disease states.

GATA3

Description	NES	setSize	Count
Aerobic respiration and respiratory electron transport	2.204298	164	104
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.082230	98	77
Collagen chain trimerization	2.024129	18	5
Respiratory electron transport	2.002613	83	65
Collagen biosynthesis and modifying enzymes	1.906599	35	6
Formation of definitive endoderm	1.899582	10	1
Muscle contraction	1.857070	115	39
Complex I biogenesis	1.837222	44	36
Mitochondrial biogenesis	1.795692	79	37
Pyruvate metabolism	1.793286	40	19
Regulation of pyruvate metabolism	1.775754	29	12
Cristae formation	1.757520	24	18
Eukaryotic Translation Elongation	1.738635	73	53
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1.738402	17	11
Citric acid cycle (TCA cycle)	1.737412	30	17
Peptide chain elongation	1.730130	71	52
Formation of ATP by chemiosmotic coupling	1.729062	12	10
Mitochondrial protein degradation	1.712164	80	49
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1.710878	17	9
Striated Muscle Contraction	1.701422	25	9
FOXO-mediated transcription	1.697493	46	21
TP53 Regulates Transcription of Cell Death Genes	1.663520	27	6
Formation of a pool of free 40S subunits	1.651648	83	56
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1.648478	75	52
Aberrant regulation of mitotic cell cycle due to RB1 defects	1.647869	30	15
Viral mRNA Translation	1.634192	70	50
Platelet Adhesion to exposed collagen	1.631415	10	4
Nonsense-Mediated Decay (NMD)	1.617930	92	60
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1.617930	92	60
Eukaryotic Translation Initiation	1.597933	98	61
Cap-dependent Translation Initiation	1.597933	98	61
L13a-mediated translational silencing of Ceruloplasmin expression	1.577314	91	58
GTP hydrolysis and joining of the 60S ribosomal subunit	1.565948	92	58
Cardiac conduction	1.557649	65	24
SRP-dependent cotranslational protein targeting to membrane	1.556804	89	55
Selenocysteine synthesis	1.554998	75	54
Eukaryotic Translation Termination	1.527636	74	52
Organelle biogenesis and maintenance	1.518678	218	61
Factors involved in megakaryocyte development and platelet production	1.497255	102	20
Adaptive Immune System	-1.272833	486	96
GPCR downstream signalling	-1.338223	244	44
Hemostasis	-1.343668	375	75
Signaling by GPCR	-1.375192	271	47
Signaling by Interleukins	-1.383535	264	84
Metabolism of steroids	-1.431832	95	26
Interferon Signaling	-1.444722	147	41
Signaling by the B Cell Receptor (BCR)	-1.469307	92	34
SARS-CoV-2 activates/modulates innate and adaptive immune responses	-1.469872	74	18
Cytokine Signaling in Immune system	-1.474240	417	120
G alpha (q) signalling events	-1.511764	89	16
Interleukin-1 family signaling	-1.515449	104	34
Neutrophil degranulation	-1.522535	296	83
Disorders of transmembrane transporters	-1.565124	120	35
Plasma lipoprotein assembly, remodeling, and clearance	-1.577641	43	12
TCR signaling	-1.592106	83	31
Toll Like Receptor 4 (TLR4) Cascade	-1.601942	93	22
GPCR ligand binding	-1.628377	112	26
ABC transporter disorders	-1.679921	62	21
Toll-like Receptor Cascades	-1.706463	109	27
Class A/1 (Rhodopsin-like receptors)	-1.706959	80	21
tRNA Aminoacylation	-1.714003	40	14
ER-Phagosome pathway	-1.738654	63	24
Post-translational protein phosphorylation	-1.754338	61	18
Signaling by FGFR1 in disease	-1.762609	24	15
Plasma lipoprotein remodeling	-1.773702	18	6
Binding and Uptake of Ligands by Scavenger Receptors	-1.788881	24	6
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-1.794771	69	23
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-1.820756	26	13
FCERI mediated MAPK activation	-1.833991	25	11
Platelet activation, signaling and aggregation	-1.844287	179	39
Scavenging by Class A Receptors	-1.849698	13	3
Signaling by CSF1 (M-CSF) in myeloid cells	-1.864712	26	13
Response to elevated platelet cytosolic Ca2+	-1.989799	90	23
Cytosolic tRNA aminoacylation	-2.003514	23	12
Antigen processing-Cross presentation	-2.005494	75	33
Platelet degranulation	-2.005702	86	22
GPVI-mediated activation cascade	-2.009896	26	11
ROS and RNS production in phagocytes	-2.063678	22	11
Peptide ligand-binding receptors	-2.074588	39	11
RHO GTPases Activate NADPH Oxidases	-2.092266	19	8
Diseases of Immune System	-2.198914	14	8
Diseases associated with the TLR signaling cascade	-2.198914	14	8
Complement cascade	-2.263055	20	10
Regulation of Complement cascade	-2.307570	16	7
Interferon alpha/beta signaling	-2.342834	33	17

IV-HD

Description	NES	setSize	Count
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.373994	98	68
Aerobic respiration and respiratory electron transport	2.360927	164	104
Respiratory electron transport	2.283299	83	56
Muscle contraction	2.067722	112	49
Collagen chain trimerization	2.041581	18	9
Collagen biosynthesis and modifying enzymes	2.029762	35	11
Complex I biogenesis	2.018103	44	31
Mitochondrial biogenesis	1.996827	77	51
Mitochondrial protein degradation	1.921150	79	44
Cristae formation	1.903527	24	19
Formation of ATP by chemiosmotic coupling	1.872484	12	11
Cardiac conduction	1.842621	62	25
Nuclear Receptor transcription pathway	1.828501	34	16
Citric acid cycle (TCA cycle)	1.817385	30	18
Striated Muscle Contraction	1.809174	25	12
Glyoxylate metabolism and glycine degradation	1.784874	14	9
Signaling by Retinoic Acid	1.776750	26	15
Branched-chain amino acid catabolism	1.775862	19	18
Pyruvate metabolism	1.740393	40	20
Maturation of TCA enzymes and regulation of TCA cycle	1.733603	17	11
Signaling by BMP	1.728433	20	9
Collagen formation	1.722355	50	14
Lysine catabolism	1.688240	12	7
Defective B3GALTL causes PpS	1.687668	18	11
FOXO-mediated transcription	1.684639	46	22
Processing of SMDT1	1.680166	16	3
Regulation of pyruvate dehydrogenase (PDH) complex	1.679770	13	10
Transcriptional activation of mitochondrial biogenesis	1.673736	46	21
Mitochondrial protein import	1.656725	50	35
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1.654292	17	9
Myogenesis	1.650532	21	16
Triglyceride metabolism	1.639665	19	11
Assembly of collagen fibrils and other multimeric structures	1.632868	32	11
Ion homeostasis	1.628526	33	13
O-glycosylation of TSR domain-containing proteins	1.618838	19	11
Regulation of pyruvate metabolism	1.605760	29	15
ADORA2B mediated anti-inflammatory cytokines production	1.593179	25	12
Diseases associated with O-glycosylation of proteins	1.590013	28	15
Peroxisomal lipid metabolism	1.588763	21	13
Regulation of TP53 Activity through Association with Co-factors	1.588492	10	7
Receptor-type tyrosine-protein phosphatases	1.577917	14	5
Factors involved in megakaryocyte development and platelet production	1.575224	102	28
Extra-nuclear estrogen signaling	1.564253	47	29
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1.558617	16	13
Phase 0 - rapid depolarisation	1.554122	14	9
Metabolism of nitric oxide: NOS3 activation and regulation	1.544521	11	7
Transcriptional Regulation by MECP2	1.539376	40	15
Collagen degradation	1.534987	33	10
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1.532652	34	11
Transmission across Chemical Synapses	1.530830	125	44
G alpha (s) signalling events	1.528299	55	16
Energy dependent regulation of mTOR by LKB1-AMPK	1.527262	24	17
Heme biosynthesis	1.506504	12	6
Protein localization	1.496549	126	70
Signaling by Nuclear Receptors	1.485743	165	60
ESR-mediated signaling	1.403965	123	50
Adaptive Immune System	-1.266639	476	118
Mitotic Metaphase and Anaphase	-1.312167	184	61
Cytokine Signaling in Immune system	-1.345557	406	130
SARS-CoV-2-host interactions	-1.351659	136	40
Platelet activation, signaling and aggregation	-1.392250	177	46
Downstream signaling events of B Cell Receptor (BCR)	-1.398520	67	25
Interferon Signaling	-1.409395	145	52
APC/C:Cdc20 mediated degradation of Securin	-1.434706	58	24
TNFR2 non-canonical NF-kB pathway	-1.436748	57	24
Neutrophil degranulation	-1.441234	293	111
Regulation of PTEN stability and activity	-1.447049	60	23
Respiratory Syncytial Virus Infection Pathway	-1.447476	75	21
Dual incision in TC-NER	-1.450489	53	25
Fcgamma receptor (FCGR) dependent phagocytosis	-1.464650	73	21
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	-1.471462	64	27
Presynaptic phase of homologous DNA pairing and strand exchange	-1.482260	29	21
Fc epsilon receptor (FCERI) signaling	-1.483509	105	39
Interleukin-1 family signaling	-1.489433	102	40
SARS-CoV-2 modulates host translation machinery	-1.494387	39	24
Regulation of RAS by GAPs	-1.498015	56	22
CLEC7A (Dectin-1) signaling	-1.503632	78	29
Platelet degranulation	-1.510700	84	26
Toll Like Receptor 4 (TLR4) Cascade	-1.512454	90	22
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	-1.513434	63	26
Dectin-1 mediated noncanonical NF-kB signaling	-1.518192	52	22
RSV-host interactions	-1.521409	57	15
Switching of origins to a post-replicative state	-1.529257	79	32
Chromosome Maintenance	-1.539670	74	25
FCERI mediated Ca+2 mobilization	-1.540980	24	10
TNF signaling	-1.541100	45	12
Interferon gamma signaling	-1.542065	38	9
DNA Replication Pre-Initiation	-1.545875	89	35
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	-1.547625	64	27
Cytosolic tRNA aminoacylation	-1.547764	23	12
Signaling by FGFR1 in disease	-1.552353	23	13
Ubiquitin-dependent degradation of Cyclin D	-1.557170	46	20
Costimulation by the CD28 family	-1.562173	42	14
Regulation of ornithine decarboxylase (ODC)	-1.576657	46	21
UCH proteinases	-1.576768	74	26
Response of Mtb to phagocytosis	-1.577899	16	3
APC/C:Cdc20 mediated degradation of mitotic proteins	-1.580759	65	28
Disorders of transmembrane transporters	-1.581266	117	44
HDR through Single Strand Annealing (SSA)	-1.585122	29	19
Binding and Uptake of Ligands by Scavenger Receptors	-1.591402	24	6
Cell Cycle Checkpoints	-1.591653	209	77
AUF1 (hnRNP D0) binds and destabilizes mRNA	-1.598520	47	20
Regulation of signaling by CBL	-1.598687	20	8
MAP2K and MAPK activation	-1.605994	29	9
Ovarian tumor domain proteases	-1.610943	28	9
Signaling by FGFR3	-1.611010	23	5
Signaling by FGFR4	-1.611010	23	5
Dual Incision in GG-NER	-1.615932	33	17
Processing of DNA double-strand break ends	-1.616790	50	16
Downstream TCR signaling	-1.616901	67	26
Regulation of actin dynamics for phagocytic cup formation	-1.617697	50	16
Regulation of Apoptosis	-1.619726	46	20
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	-1.620192	66	29
Stabilization of p53	-1.626019	48	20
FCERI mediated NF-kB activation	-1.628735	64	24
Removal of the Flap Intermediate	-1.633338	13	12
Regulation of APC/C activators between G1/S and early anaphase	-1.634746	70	30
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	-1.634863	31	16
G2/M DNA damage checkpoint	-1.636487	49	26
Activation of NF-kappaB in B cells	-1.641091	56	24
Fanconi Anemia Pathway	-1.646247	32	17
Glycosphingolipid metabolism	-1.648253	35	18
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	-1.652383	45	20
p53-Independent DNA Damage Response	-1.652383	45	20
p53-Independent G1/S DNA damage checkpoint	-1.652383	45	20
Host Interactions of HIV factors	-1.661886	105	40
Signaling by high-kinase activity BRAF mutants	-1.663672	26	9
SARS-CoV-2 activates/modulates innate and adaptive immune responses	-1.664612	74	25
APC/C-mediated degradation of cell cycle proteins	-1.666051	76	33
Regulation of mitotic cell cycle	-1.666051	76	33
FCERI mediated MAPK activation	-1.666453	25	9
Lagging Strand Synthesis	-1.667606	18	15
Processive synthesis on the lagging strand	-1.670080	14	13
DNA Replication	-1.670569	113	44
NRIF signals cell death from the nucleus	-1.670941	11	4
Termination of translesion DNA synthesis	-1.672201	25	19
NIK-->noncanonical NF-kB signaling	-1.672782	51	22
Cross-presentation of soluble exogenous antigens (endosomes)	-1.673384	42	20
Degradation of AXIN	-1.676835	48	20
Toll-like Receptor Cascades	-1.678746	106	30
TCR signaling	-1.692458	83	34
Class A/1 (Rhodopsin-like receptors)	-1.702797	73	26
Parasite infection	-1.718058	51	17
Leishmania phagocytosis	-1.718058	51	17
FCGR3A-mediated phagocytosis	-1.718058	51	17
MAP3K8 (TPL2)-dependent MAPK1/3 activation	-1.718704	14	4
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	-1.727324	48	22
Regulation of activated PAK-2p34 by proteasome mediated degradation	-1.728387	44	20
Unwinding of DNA	-1.729156	11	10
Synthesis of DNA	-1.729487	104	42
Negative regulators of DDX58/IFIH1 signaling	-1.732429	25	9
Degradation of DVL	-1.733938	50	21
Negative regulation of FGFR3 signaling	-1.734380	14	3
Negative regulation of FGFR4 signaling	-1.734380	14	3
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	-1.737255	46	20
Autodegradation of the E3 ubiquitin ligase COP1	-1.739149	46	20
p130Cas linkage to MAPK signaling for integrins	-1.749088	12	5
Impaired BRCA2 binding to RAD51	-1.749773	26	20
Degradation of GLI1 by the proteasome	-1.757204	50	22
Plasma lipoprotein remodeling	-1.764388	17	9
Suppression of phagosomal maturation	-1.764965	10	3
Signaling by FGFR3 in disease	-1.768984	10	4
Alpha-protein kinase 1 signaling pathway	-1.773696	10	3
GLI3 is processed to GLI3R by the proteasome	-1.776562	51	22
Diseases associated with glycosylation precursor biosynthesis	-1.777302	13	11
STING mediated induction of host immune responses	-1.785335	10	5
Signaling by the B Cell Receptor (BCR)	-1.790076	92	40
Defective CFTR causes cystic fibrosis	-1.790669	52	23
Vif-mediated degradation of APOBEC3G	-1.794264	47	21
Vpu mediated degradation of CD4	-1.795407	45	21
Evasion by RSV of host interferon responses	-1.795968	17	8
GRB2:SOS provides linkage to MAPK signaling for Integrins	-1.801383	12	5
Activation of ATR in response to replication stress	-1.801752	32	22
Regulation of RUNX3 expression and activity	-1.806489	47	22
Degradation of GLI2 by the proteasome	-1.812854	50	22
Amyloid fiber formation	-1.813502	35	14
Translesion Synthesis by POLH	-1.818860	16	12
TRAF3-dependent IRF activation pathway	-1.831612	10	7
Integrin signaling	-1.840796	24	5
RHO GTPases Activate NADPH Oxidases	-1.851174	18	6
GPVI-mediated activation cascade	-1.851624	26	13
Peptide ligand-binding receptors	-1.858229	34	14
Diseases of Immune System	-1.860082	12	7
Diseases associated with the TLR signaling cascade	-1.860082	12	7
DAP12 interactions	-1.861983	18	8
DAP12 signaling	-1.861983	18	8
Hedgehog ligand biogenesis	-1.873010	51	24
Formation of Fibrin Clot (Clotting Cascade)	-1.876662	17	8
ER-Phagosome pathway	-1.879640	61	25
Activation of Matrix Metalloproteinases	-1.882756	12	8
Hh mutants are degraded by ERAD	-1.883445	48	23
Hh mutants abrogate ligand secretion	-1.883445	48	23
SCF-beta-TrCP mediated degradation of Emi1	-1.888642	48	23
Orc1 removal from chromatin	-1.895336	62	29
G2/M Checkpoints	-1.908061	112	60
Inactivation of CSF3 (G-CSF) signaling	-1.909885	20	12
ABC transporter disorders	-1.934190	62	28
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-1.935602	26	13
Signaling by CSF3 (G-CSF)	-1.948166	25	12
Interleukin-3, Interleukin-5 and GM-CSF signaling	-1.948460	33	15
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-1.975521	10	5
Signaling by CSF1 (M-CSF) in myeloid cells	-2.003615	26	9
DNA strand elongation	-2.010772	29	24
Activation of the pre-replicative complex	-2.033192	27	22
Glycosphingolipid catabolism	-2.090416	26	16
Antigen processing-Cross presentation	-2.098850	73	33
Potassium Channels	-2.126779	28	4
Regulation of Complement cascade	-2.143450	16	10
Complement cascade	-2.147672	19	11
Cholesterol biosynthesis	-2.205904	20	12
ROS and RNS production in phagocytes	-2.257629	22	11
Interferon alpha/beta signaling	-2.287254	33	22

IV-LD

Description	NES	setSize	Count
Interferon alpha/beta signaling	-2.558410	33	19
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-2.256919	26	14
Signaling by CSF1 (M-CSF) in myeloid cells	-2.247666	25	9
Signaling by CSF3 (G-CSF)	-2.180512	25	8
Evasion by RSV of host interferon responses	-2.177209	17	9
Cytosolic tRNA aminoacylation	-2.161461	22	14
Regulation of RUNX3 expression and activity	-2.148208	47	29
Hh mutants are degraded by ERAD	-2.132418	48	31
Hh mutants abrogate ligand secretion	-2.132418	48	31
Glycosphingolipid catabolism	-2.129369	20	14
ROS and RNS production in phagocytes	-2.114074	21	15
GPVI-mediated activation cascade	-2.104005	26	13
FCERI mediated Ca+2 mobilization	-2.089354	23	9
Inactivation of CSF3 (G-CSF) signaling	-2.080420	20	8
Signaling by the B Cell Receptor (BCR)	-2.078370	92	47
Antigen processing-Cross presentation	-2.055188	73	40
Hedgehog ligand biogenesis	-2.049071	51	32
Vif-mediated degradation of APOBEC3G	-2.047086	47	28
TCR signaling	-2.021049	81	42
RHO GTPases Activate NADPH Oxidases	-2.020000	17	7
Defective CFTR causes cystic fibrosis	-2.005344	52	31
Interleukin-3, Interleukin-5 and GM-CSF signaling	-1.991710	33	12
SARS-CoV-2 activates/modulates innate and adaptive immune responses	-1.988786	71	23
Vpu mediated degradation of CD4	-1.988303	45	27
TRAF6 mediated IRF7 activation	-1.984811	12	6
Activation of NF-kappaB in B cells	-1.980958	56	35
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	-1.966287	46	25
Diseases associated with glycosylation precursor biosynthesis	-1.953961	13	10
Regulation of signaling by CBL	-1.938136	20	9
Degradation of GLI2 by the proteasome	-1.932326	50	27
FCERI mediated MAPK activation	-1.931653	25	10
Degradation of AXIN	-1.920396	48	28
DAP12 interactions	-1.906521	18	8
DAP12 signaling	-1.906521	18	8
TRAF3-dependent IRF activation pathway	-1.905810	10	6
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	-1.905041	48	27
Autodegradation of the E3 ubiquitin ligase COP1	-1.896513	46	27
Stabilization of p53	-1.885473	48	27
Regulation of activated PAK-2p34 by proteasome mediated degradation	-1.882216	44	26
Generation of second messenger molecules	-1.880302	14	7
NRIF signals cell death from the nucleus	-1.871491	10	5
FCERI mediated NF-kB activation	-1.865545	63	34
DDX58/IFIH1-mediated induction of interferon-alpha/beta	-1.859041	45	18
Cross-presentation of soluble exogenous antigens (endosomes)	-1.850929	42	25
Parasite infection	-1.845931	49	15
Leishmania phagocytosis	-1.845931	49	15
FCGR3A-mediated phagocytosis	-1.845931	49	15
SCF-beta-TrCP mediated degradation of Emi1	-1.845172	47	27
SARS-CoV-1 modulates host translation machinery	-1.837814	30	16
AUF1 (hnRNP D0) binds and destabilizes mRNA	-1.835794	47	28
Formation of the ternary complex, and subsequently, the 43S complex	-1.832124	45	27
Regulation of Apoptosis	-1.827798	46	26
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	-1.827420	45	26
p53-Independent DNA Damage Response	-1.827420	45	26
p53-Independent G1/S DNA damage checkpoint	-1.827420	45	26
Fc epsilon receptor (FCERI) signaling	-1.826947	103	46
Interferon gamma signaling	-1.826233	37	16
Negative regulators of DDX58/IFIH1 signaling	-1.824630	24	10
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	-1.813470	10	6
Degradation of GLI1 by the proteasome	-1.801153	50	27
Regulation of KIT signaling	-1.794670	13	6
Orc1 removal from chromatin	-1.793490	62	29
ER-Phagosome pathway	-1.793228	61	32
Cholesterol biosynthesis	-1.789364	18	10
SARS-CoV-2 modulates host translation machinery	-1.775869	39	21
Interferon Signaling	-1.771713	140	49
Negative regulation of NOTCH4 signaling	-1.766764	47	25
Cytokine Signaling in Immune system	-1.759874	387	120
Degradation of DVL	-1.759245	49	27
Interleukin-1 signaling	-1.739892	81	41
TNFR2 non-canonical NF-kB pathway	-1.730040	56	31
NIK-->noncanonical NF-kB signaling	-1.728636	51	28
Fcgamma receptor (FCGR) dependent phagocytosis	-1.726647	71	19
GLI3 is processed to GLI3R by the proteasome	-1.722373	51	27
Ovarian tumor domain proteases	-1.708164	25	10
Selenocysteine synthesis	-1.702643	74	47
Response of EIF2AK4 (GCN2) to amino acid deficiency	-1.702423	82	52
Downstream TCR signaling	-1.702062	66	35
Regulation of NF-kappa B signaling	-1.701554	13	9
tRNA Aminoacylation	-1.698055	37	12
SARS-CoV-2-host interactions	-1.694829	133	49
Cytosolic sulfonation of small molecules	-1.693484	12	7
Toll-like Receptor Cascades	-1.685631	96	31
Translation of Structural Proteins	-1.683454	21	12
Viral mRNA Translation	-1.681921	70	45
Interleukin-1 family signaling	-1.677088	95	45
Regulation of actin dynamics for phagocytic cup formation	-1.676820	48	17
Signaling by Interleukins	-1.667910	242	76
Membrane binding and targetting of GAG proteins	-1.667162	11	7
Synthesis And Processing Of GAG, GAGPOL Polyproteins	-1.667162	11	7
IKK complex recruitment mediated by RIP1	-1.663769	13	5
Host Interactions of HIV factors	-1.646932	102	43
Formation of a pool of free 40S subunits	-1.645196	83	51
Downstream signaling events of B Cell Receptor (BCR)	-1.642879	67	36
Regulation of RAS by GAPs	-1.633428	56	30
TICAM1, RIP1-mediated IKK complex recruitment	-1.625165	12	5
Chondroitin sulfate biosynthesis	-1.619294	10	5
SRP-dependent cotranslational protein targeting to membrane	-1.618303	89	56
Regulation of ornithine decarboxylase (ODC)	-1.617211	46	26
ABC transporter disorders	-1.605174	59	33
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	-1.603848	19	9
Eukaryotic Translation Termination	-1.602546	73	46
Ubiquitin-dependent degradation of Cyclin D	-1.602206	46	26
Eukaryotic Translation Elongation	-1.594347	73	47
Ribosomal scanning and start codon recognition	-1.589249	51	29
Nucleotide salvage	-1.588633	20	7
C-type lectin receptors (CLRs)	-1.586923	88	39
Late SARS-CoV-2 Infection Events	-1.583797	48	24
NOD1/2 Signaling Pathway	-1.579994	25	9
Translation initiation complex formation	-1.579983	50	29
RAC2 GTPase cycle	-1.577927	75	17
Neutrophil degranulation	-1.574600	281	81
Eukaryotic Translation Initiation	-1.567530	98	60
Cap-dependent Translation Initiation	-1.567530	98	60
Nuclear events stimulated by ALK signaling in cancer	-1.563483	26	6
Peptide chain elongation	-1.557095	71	45
IRE1alpha activates chaperones	-1.554711	39	22
Dectin-1 mediated noncanonical NF-kB signaling	-1.552256	52	28
L13a-mediated translational silencing of Ceruloplasmin expression	-1.549401	91	56
RSV-host interactions	-1.547365	55	17
GTP hydrolysis and joining of the 60S ribosomal subunit	-1.544596	92	56
Influenza Viral RNA Transcription and Replication	-1.538636	109	67
Plasma lipoprotein assembly, remodeling, and clearance	-1.531178	39	11
Regulation of expression of SLITs and ROBOs	-1.520219	134	83
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	-1.518961	75	47
Selenoamino acid metabolism	-1.513412	95	44
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	-1.512898	51	29
Metabolism of polyamines	-1.510906	53	28
Signaling by SCF-KIT	-1.510103	34	11
Influenza Infection	-1.501986	123	72
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	-1.490813	30	12
XBP1(S) activates chaperone genes	-1.489123	38	21
RAC1 GTPase cycle	-1.488345	143	33
RHO GTPases Activate WASPs and WAVEs	-1.488342	30	8
Signaling by ERBB4	-1.477576	31	9
Toll Like Receptor 4 (TLR4) Cascade	-1.476812	82	24
CLEC7A (Dectin-1) signaling	-1.470010	76	36
p75 NTR receptor-mediated signalling	-1.452464	59	16
SARS-CoV-2 Infection	-1.448607	197	69
Somitogenesis	-1.447189	44	24
G2/M Checkpoints	-1.446871	109	43
rRNA modification in the nucleus and cytosol	-1.437797	55	30
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	-1.437746	59	29
Respiratory Syncytial Virus Infection Pathway	-1.418738	73	22
rRNA processing	-1.417312	166	96
rRNA processing in the nucleus and cytosol	-1.399510	158	91
Ion channel transport	-1.390974	87	21
Major pathway of rRNA processing in the nucleolus and cytosol	-1.389697	148	87
Degradation of beta-catenin by the destruction complex	-1.389099	68	32
Adaptive Immune System	-1.352343	455	97
Disorders of transmembrane transporters	-1.348539	109	46
Asparagine N-linked glycosylation	-1.258391	190	79
Response to elevated platelet cytosolic Ca2+	1.397186	79	14
Protein localization	1.428193	122	56
Platelet degranulation	1.436491	75	14
Transmission across Chemical Synapses	1.486063	103	34
Extra-nuclear estrogen signaling	1.519005	44	22
Diseases associated with O-glycosylation of proteins	1.548805	24	11
Regulation of pyruvate dehydrogenase (PDH) complex	1.554923	12	7
MTOR signalling	1.560298	36	19
Retinoid metabolism and transport	1.571927	17	8
Organelle biogenesis and maintenance	1.579733	180	65
Signaling by Activin	1.584837	11	5
Maturation of TCA enzymes and regulation of TCA cycle	1.589006	17	10
Glyoxylate metabolism and glycine degradation	1.592081	13	7
Metabolism of nitric oxide: NOS3 activation and regulation	1.603027	10	10
Formation of Fibrin Clot (Clotting Cascade)	1.620177	12	4
FOXO-mediated transcription of cell cycle genes	1.629367	12	7
Striated Muscle Contraction	1.631289	22	6
Ion homeostasis	1.634688	28	15
Regulation of TP53 Activity through Association with Co-factors	1.636267	10	7
Signaling by Retinoic Acid	1.649813	23	13
Sensory Perception	1.652458	68	26
Cardiogenesis	1.667700	20	9
Regulation of Complement cascade	1.676912	12	5
Defective B3GALTL causes PpS	1.685302	15	9
Protein-protein interactions at synapses	1.685851	39	15
Signaling by BMP	1.701077	19	7
Nuclear Receptor transcription pathway	1.705083	30	14
Heme signaling	1.711499	37	18
Neuronal System	1.716657	147	52
Mitochondrial protein degradation	1.735200	78	38
Lysine catabolism	1.741260	12	6
Aberrant regulation of mitotic cell cycle due to RB1 defects	1.742286	28	13
Diseases of mitotic cell cycle	1.744056	30	14
O-glycosylation of TSR domain-containing proteins	1.744456	16	10
Energy dependent regulation of mTOR by LKB1-AMPK	1.744984	24	15
Citric acid cycle (TCA cycle)	1.746457	30	18
Complex I biogenesis	1.785015	44	32
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1.791713	15	9
Cardiac conduction	1.797730	54	22
Cristae formation	1.835000	24	17
Transcriptional activation of mitochondrial biogenesis	1.852857	42	28
Formation of ATP by chemiosmotic coupling	1.871819	12	11
Muscle contraction	1.889581	99	42
Respiratory electron transport	1.950513	83	58
FOXO-mediated transcription	1.970064	44	22
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.018368	98	70
Aerobic respiration and respiratory electron transport	2.033819	160	106
Mitochondrial biogenesis	2.128263	73	46

10WPC

DNA vaccine

ReactomePA results

Description	NES	setSize	Count
Plasma lipoprotein clearance	-2.134091	14	3
Plasma lipoprotein assembly, remodeling, and clearance	-2.014837	18	3
E3 ubiquitin ligases ubiquitinate target proteins	-2.003184	11	5
Protein ubiquitination	-1.963409	14	6
Complex I biogenesis	-1.898460	35	15
Prefoldin mediated transfer of substrate to CCT/TriC	-1.826903	15	7
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	-1.826903	15	7
Aerobic respiration and respiratory electron transport	-1.781939	112	41
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	-1.750500	76	37
Macroautophagy	-1.684341	44	8
Respiratory electron transport	-1.652091	64	30
Signaling by Receptor Tyrosine Kinases	1.579934	118	30
Metabolism of water-soluble vitamins and cofactors	1.735677	17	10
Non-integrin membrane-ECM interactions	1.769223	20	6
RHOQ GTPase cycle	1.769246	15	7
SLC transporter disorders	1.786018	10	5
MET promotes cell motility	1.789446	11	5
ECM proteoglycans	1.796718	25	9
RHOG GTPase cycle	1.849696	22	11
Signaling by PDGF	1.851149	12	7
Assembly of collagen fibrils and other multimeric structures	1.862744	16	10
MET activates PTK2 signaling	1.864245	10	5
RHOJ GTPase cycle	1.981134	13	7
Cell surface interactions at the vascular wall	1.988497	31	14
RAC3 GTPase cycle	2.011709	18	11
RAC2 GTPase cycle	2.035045	21	12
Syndecan interactions	2.045470	13	7

Overall Interpretation

• Downregulation: The downregulated pathways are primarily involved in lipid metabolism, protein ubiquitination, mitochondrial function, and autophagy. This suggests a suppression of energy production, lipid clearance, protein turnover, and cellular recycling processes.
• Upregulation: The upregulated pathways involve cell signaling, particularly through receptor tyrosine kinases, GTPase cycles, extracellular matrix interactions, and vitamin metabolism. This indicates enhanced cellular communication, structural dynamics, and metabolic activities.

The combination of these changes suggests a cellular state where there's a shift away from energy production and basic metabolic processes towards more complex signaling and structural functions. This could be indicative of a response to external stimuli, tissue repair, or a shift towards a more specialized cellular function.

EOMES

Description	NES	setSize	Count
Post-translational protein phosphorylation	1.858368	72	23
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1.851716	82	27
Formation of Fibrin Clot (Clotting Cascade)	1.833651	22	11
Common Pathway of Fibrin Clot Formation	1.810430	11	8
Regulation of Complement cascade	1.739036	23	11
Platelet degranulation	1.703373	96	23
Intrinsic Pathway of Fibrin Clot Formation	1.684758	13	5
Response to elevated platelet cytosolic Ca2+	1.672309	100	23
Plasma lipoprotein remodeling	1.652534	22	10
Gluconeogenesis	1.650880	20	9
Nuclear Receptor transcription pathway	1.639433	41	18
Surfactant metabolism	1.633069	14	8
Complement cascade	1.620782	29	11
Platelet activation, signaling and aggregation	1.435253	200	62
G alpha (i) signalling events	1.394216	151	51
GPCR ligand binding	1.376630	197	66
Hemostasis	1.341971	429	168
Signaling by GPCR	1.293262	385	118
Chromosome Maintenance	-1.362768	83	28
Dual incision in TC-NER	-1.480243	54	19
Gap-filling DNA repair synthesis and ligation in TC-NER	-1.494346	54	20
Homology Directed Repair	-1.523449	92	24
DNA strand elongation	-1.716627	30	12
Activation of ATR in response to replication stress	-1.716692	35	14
Cytoprotection by HMOX1	-1.881835	47	2
Triglyceride metabolism	-2.211085	25	4
Triglyceride catabolism	-2.249671	15	4
Metabolism of porphyrins	-2.452706	21	2

Overall Interpretation

• Upregulated Pathways: The upregulated pathways in Atlantic salmon heart tissue are predominantly related to blood clotting (hemostasis), platelet activation, immune response (complement cascade), and various signaling pathways (GPCR signaling, insulin-like growth factor transport). This suggests an enhanced readiness for hemostasis, immune defense, and cellular communication, which are critical for maintaining cardiovascular function and responding to physiological stress or injury.
• Downregulated Pathways: The downregulated pathways are mainly involved in DNA repair and maintenance (chromosome maintenance, nucleotide excision repair, homologous recombination), cytoprotection (HMOX1), and lipid metabolism (triglyceride metabolism and catabolism). This indicates a reduced capacity for DNA repair, potentially leading to genomic instability, and decreased lipid metabolism, which may affect energy balance and cellular health.

This combination of upregulated and downregulated pathways provides a snapshot of the metabolic and regulatory state of the heart tissue, highlighting areas of increased activity in response to physiological demands and potential vulnerabilities in DNA repair and lipid metabolism.

GATA3

Description	NES	setSize	Count
ECM proteoglycans	2.104700	25	11
Syndecan interactions	2.099630	13	7
Signaling by NTRK1 (TRKA)	2.083449	36	12
Signaling by NTRKs	2.026909	38	12
Nuclear Events (kinase and transcription factor activation)	2.017561	21	8
Non-integrin membrane-ECM interactions	1.996021	20	7
RHOJ GTPase cycle	1.900899	13	6
RHOQ GTPase cycle	1.847776	15	6
Signaling by PDGF	1.813468	12	8
Elastic fibre formation	1.782823	10	8
NGF-stimulated transcription	1.776159	11	6
RAC3 GTPase cycle	1.744556	18	8
MAPK targets/ Nuclear events mediated by MAP kinases	1.735685	12	3
Striated Muscle Contraction	1.731935	13	6
MET activates PTK2 signaling	1.729049	10	4
Assembly of collagen fibrils and other multimeric structures	1.724211	16	10
NCAM signaling for neurite out-growth	1.723873	12	9
MET promotes cell motility	1.618208	11	4
Signaling by GPCR	1.613790	57	27
Cell surface interactions at the vascular wall	1.613695	31	11
Signaling by Receptor Tyrosine Kinases	1.608698	118	32
Integrin cell surface interactions	1.588736	24	12
GPCR downstream signalling	1.511815	53	25
Signal Transduction	1.212872	467	115
Metabolism of RNA	-1.309920	246	68
Immune System	-1.401149	383	125
Infectious disease	-1.410132	308	113
Aerobic respiration and respiratory electron transport	-1.442175	112	48
Signaling by Hedgehog	-1.451002	53	23
Viral Infection Pathways	-1.453647	261	96
TCR signaling	-1.470209	46	20
RHO GTPase Effectors	-1.470920	71	27
C-type lectin receptors (CLRs)	-1.483550	44	19
Assembly of the pre-replicative complex	-1.486404	39	20
Macroautophagy	-1.489676	44	17
S Phase	-1.503583	50	25
FCERI mediated NF-kB activation	-1.510886	39	19
Hedgehog ligand biogenesis	-1.524564	40	20
Innate Immune System	-1.524781	232	79
Cell Cycle	-1.526362	140	53
MITF-M-dependent gene expression	-1.529256	22	8
MITF-M-regulated melanocyte development	-1.541983	29	11
Cytosolic tRNA aminoacylation	-1.553471	11	5
Protein folding	-1.556639	22	11
ABC transporter disorders	-1.556750	41	19
Translation	-1.559095	163	73
Switching of origins to a post-replicative state	-1.562362	38	20
Resolution of Sister Chromatid Cohesion	-1.567546	27	13
Cell Cycle, Mitotic	-1.569749	117	46
mRNA Splicing - Minor Pathway	-1.570548	21	11
Aggrephagy	-1.579937	12	7
Chaperonin-mediated protein folding	-1.585963	21	11
DNA Replication	-1.601078	45	25
Neutrophil degranulation	-1.603845	123	51
Protein ubiquitination	-1.610171	14	8
The role of GTSE1 in G2/M progression after G2 checkpoint	-1.613267	42	20
Cilium Assembly	-1.617508	26	12
Synthesis of DNA	-1.636671	42	24
Cell Cycle Checkpoints	-1.641058	68	31
ABC-family proteins mediated transport	-1.650507	46	24
Mitotic G2-G2/M phases	-1.655254	62	28
G2/M Transition	-1.655254	62	28
M Phase	-1.657101	94	39
RNA Polymerase II Pre-transcription Events	-1.659920	18	8
Interferon alpha/beta signaling	-1.663718	19	8
tRNA Aminoacylation	-1.681849	13	6
Mitotic Metaphase and Anaphase	-1.689240	73	32
Mitotic Anaphase	-1.689240	73	32
Formation of tubulin folding intermediates by CCT/TriC	-1.711465	10	7
Separation of Sister Chromatids	-1.730907	61	30
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	-1.757196	76	31
Host Interactions of HIV factors	-1.793768	50	27
Amyloid fiber formation	-1.794465	15	5
Respiratory electron transport	-1.805950	64	29
HIV Infection	-1.887990	75	37
Prefoldin mediated transfer of substrate to CCT/TriC	-1.911113	15	10
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	-1.911113	15	10
Mitochondrial translation initiation	-1.946643	39	23
Mitochondrial translation termination	-1.946643	39	23
Plasma lipoprotein clearance	-1.955145	14	5
Mitochondrial translation	-1.978389	40	24
Mitochondrial translation elongation	-1.978389	40	24
Complex I biogenesis	-2.008212	35	19

Conclusion

The pathways in Atlantic salmon heart tissue exhibit significant upregulation in signaling pathways related to cell adhesion, growth, and cytoskeletal dynamics, which are essential for maintaining cardiac function and responding to stress or damage. Simultaneously, there is downregulation in pathways associated with the immune response, DNA repair, and mitochondrial function, which may impact the heart’s ability to cope with oxidative stress and maintain cellular homeostasis. This combination of pathway activities suggests a complex regulatory environment in the heart tissue, balancing between structural integrity, signaling, and energy metabolism.

IV-HD

Description	NES	setSize	Count
FOXO-mediated transcription	2.027766	40	21
Nuclear Receptor transcription pathway	1.902506	23	14
Response of EIF2AK1 (HRI) to heme deficiency	1.816329	12	7
PI3K/AKT Signaling in Cancer	1.816199	44	19
Gluconeogenesis	1.786022	13	5
IRS-related events triggered by IGF1R	1.764965	19	10
SUMOylation of intracellular receptors	1.715626	11	7
Myogenesis	1.709299	17	10
Signaling by ALK	1.705864	20	14
IGF1R signaling cascade	1.704783	20	10
TNFR1-induced proapoptotic signaling	1.702236	13	6
DAG and IP3 signaling	1.678151	20	15
Signaling by NTRK1 (TRKA)	1.676073	67	26
Signaling by NTRKs	1.663244	75	27
Transcriptional activation of mitochondrial biogenesis	1.653007	36	13
Striated Muscle Contraction	1.630470	20	6
NGF-stimulated transcription	1.622448	20	10
Insulin receptor signalling cascade	1.609549	20	10
Sensory processing of sound by outer hair cells of the cochlea	1.602291	17	6
Constitutive Signaling by AKT1 E17K in Cancer	1.601176	18	9
Transport of bile salts and organic acids, metal ions and amine compounds	1.595090	20	9
IRS-mediated signalling	1.594991	16	8
Sema4D in semaphorin signaling	1.587064	19	11
Transcriptional regulation of brown and beige adipocyte differentiation	1.586154	18	7
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1.586154	18	7
NCAM1 interactions	1.585243	11	4
Circadian Clock	1.584840	49	22
PI3K Cascade	1.584450	14	7
Constitutive Signaling by Aberrant PI3K in Cancer	1.583423	25	10
HSF1-dependent transactivation	1.577341	18	13
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1.576598	39	14
Negative regulation of the PI3K/AKT network	1.558053	43	15
Mitochondrial biogenesis	1.532060	67	20
Chromatin modifying enzymes	1.464375	145	53
Chromatin organization	1.464375	145	53
Adaptive Immune System	-1.279300	380	90
Class I MHC mediated antigen processing & presentation	-1.310807	230	56
Late Phase of HIV Life Cycle	-1.455370	102	22
Toll-like Receptor Cascades	-1.466204	79	21
Parasite infection	-1.471162	45	17
Leishmania phagocytosis	-1.471162	45	17
FCGR3A-mediated phagocytosis	-1.471162	45	17
Nucleotide Excision Repair	-1.472963	73	19
G2/M Checkpoints	-1.474537	91	28
HIV Infection	-1.475500	172	50
HCMV Early Events	-1.495223	45	16
Orc1 removal from chromatin	-1.498078	59	22
APC/C-mediated degradation of cell cycle proteins	-1.503137	64	17
Regulation of mitotic cell cycle	-1.503137	64	17
APC/C:Cdc20 mediated degradation of mitotic proteins	-1.513624	56	16
Disorders of transmembrane transporters	-1.519665	96	36
Diseases of metabolism	-1.526189	99	28
Toll Like Receptor 4 (TLR4) Cascade	-1.537714	67	12
Regulation of TP53 Activity through Phosphorylation	-1.543226	56	14
tRNA processing in the nucleus	-1.546369	36	18
Rev-mediated nuclear export of HIV RNA	-1.547519	24	14
Global Genome Nucleotide Excision Repair (GG-NER)	-1.552979	52	15
Diseases of DNA repair	-1.556339	24	8
RHO GTPases Activate Formins	-1.558956	69	24
RHO GTPase Effectors	-1.559479	153	33
Interactions of Rev with host cellular proteins	-1.561168	26	14
Neutrophil degranulation	-1.565604	253	69
Metabolism of nucleotides	-1.572199	64	24
Innate Immune System	-1.574096	500	126
RHO GTPases Activate WASPs and WAVEs	-1.584989	28	14
M Phase	-1.589299	209	45
The role of GTSE1 in G2/M progression after G2 checkpoint	-1.593841	55	16
Antiviral mechanism by IFN-stimulated genes	-1.596708	85	27
Nuclear import of Rev protein	-1.597922	25	12
Inactivation of CSF3 (G-CSF) signaling	-1.598513	17	5
Postmitotic nuclear pore complex (NPC) reformation	-1.606989	21	7
Gene Silencing by RNA	-1.616104	48	20
Regulation of APC/C activators between G1/S and early anaphase	-1.617718	60	17
Interferon Signaling	-1.621163	119	28
Antigen processing-Cross presentation	-1.622320	69	23
Export of Viral Ribonucleoproteins from Nucleus	-1.635787	23	14
NEP/NS2 Interacts with the Cellular Export Machinery	-1.635787	23	14
ZBP1(DAI) mediated induction of type I IFNs	-1.637511	10	7
TICAM1, RIP1-mediated IKK complex recruitment	-1.638459	11	8
IKK complex recruitment mediated by RIP1	-1.638459	11	8
RAS processing	-1.642218	11	6
Late endosomal microautophagy	-1.659282	22	7
Translesion synthesis by REV1	-1.666679	13	7
Translesion synthesis by POLK	-1.666679	13	7
Translesion synthesis by POLI	-1.666679	13	7
DNA Replication Pre-Initiation	-1.671594	74	25
snRNP Assembly	-1.675309	36	20
Metabolism of non-coding RNA	-1.675309	36	20
HIV Life Cycle	-1.675813	108	26
APC-Cdc20 mediated degradation of Nek2A	-1.682318	13	6
Evasion by RSV of host interferon responses	-1.685048	15	6
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	-1.685854	57	17
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	-1.686556	55	18
Mitotic Metaphase and Anaphase	-1.691937	145	41
Mitotic Anaphase	-1.691937	145	41
DNA Repair	-1.694000	154	50
Vpr-mediated nuclear import of PICs	-1.699164	22	12
Removal of the Flap Intermediate from the C-strand	-1.699755	10	5
Transport of Mature mRNA Derived from an Intronless Transcript	-1.699973	29	15
Intraflagellar transport	-1.700724	15	7
Mitotic G1 phase and G1/S transition	-1.703992	104	37
Cell Cycle Checkpoints	-1.706984	156	47
SUMOylation of SUMOylation proteins	-1.711252	24	12
Mitotic Spindle Checkpoint	-1.711715	58	20
S Phase	-1.712102	114	40
Cell Cycle	-1.717875	357	83
Mitotic Prometaphase	-1.728689	96	31
Transport of Mature mRNAs Derived from Intronless Transcripts	-1.739550	30	16
NS1 Mediated Effects on Host Pathways	-1.739940	27	13
G0 and Early G1	-1.740154	19	8
Regulation of Glucokinase by Glucokinase Regulatory Protein	-1.744939	21	12
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	-1.744939	21	12
Separation of Sister Chromatids	-1.747329	112	34
DNA Double-Strand Break Repair	-1.747986	70	21
Activation of the pre-replicative complex	-1.752334	20	12
Transport of Ribonucleoproteins into the Host Nucleus	-1.760923	22	12
ISG15 antiviral mechanism	-1.763340	49	22
Assembly Of The HIV Virion	-1.764618	12	4
Mitotic Prophase	-1.767757	60	25
Interactions of Vpr with host cellular proteins	-1.768833	23	13
Transport of the SLBP independent Mature mRNA	-1.770231	24	13
Nuclear Pore Complex (NPC) Disassembly	-1.774378	27	14
Detoxification of Reactive Oxygen Species	-1.777591	20	11
Interferon alpha/beta signaling	-1.787480	30	8
Mismatch Repair	-1.790752	10	6
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	-1.790752	10	6
Processive synthesis on the C-strand of the telomere	-1.793722	11	6
Amplification of signal from the kinetochores	-1.798714	51	19
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	-1.798714	51	19
SARS-CoV-2 activates/modulates innate and adaptive immune responses	-1.806068	60	19
SUMOylation of ubiquitinylation proteins	-1.809136	25	13
Membrane binding and targetting of GAG proteins	-1.810276	10	4
Synthesis And Processing Of GAG, GAGPOL Polyproteins	-1.810276	10	4
Cell Cycle, Mitotic	-1.817094	296	75
Viral Messenger RNA Synthesis	-1.839346	34	16
Transport of the SLBP Dependant Mature mRNA	-1.845530	25	14
Removal of the Flap Intermediate	-1.846852	10	8
SUMOylation of DNA replication proteins	-1.849425	32	13
Condensation of Prophase Chromosomes	-1.855634	12	6
G1/S Transition	-1.856244	96	35
Resolution of Sister Chromatid Cohesion	-1.867741	65	25
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	-1.873296	49	19
Homology Directed Repair	-1.878242	54	20
Activation of ATR in response to replication stress	-1.890795	22	11
Nuclear Envelope Breakdown	-1.891515	40	19
Aggrephagy	-1.898108	19	6
Processing of DNA double-strand break ends	-1.900354	34	16
Complement cascade	-1.901982	11	5
Fanconi Anemia Pathway	-1.906671	14	7
EML4 and NUDC in mitotic spindle formation	-1.908350	59	23
Processive synthesis on the lagging strand	-1.915336	11	9
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	-1.926414	24	11
Transcriptional regulation by small RNAs	-1.926959	37	18
Regulation of Complement cascade	-1.938878	10	5
Synthesis of DNA	-1.944058	85	34
Dual incision in TC-NER	-1.944684	44	20
DNA Replication	-1.948402	91	35
Gap-filling DNA repair synthesis and ligation in TC-NER	-1.963493	46	21
G1/S-Specific Transcription	-1.966459	17	9
DNA Damage Bypass	-1.967414	31	17
Translesion Synthesis by POLH	-1.979068	14	9
Polymerase switching on the C-strand of the telomere	-1.988556	12	10
HDR through Homologous Recombination (HRR)	-1.994096	30	12
Dual Incision in GG-NER	-2.018387	24	11
Base Excision Repair	-2.024403	27	12
Resolution of Abasic Sites (AP sites)	-2.040838	24	11
Polymerase switching	-2.050733	10	9
Leading Strand Synthesis	-2.050733	10	9
Interconversion of nucleotide di- and triphosphates	-2.063412	18	7
Cytosolic sensors of pathogen-associated DNA	-2.095129	33	8
DNA strand elongation	-2.108992	22	15
Telomere C-strand (Lagging Strand) Synthesis	-2.159225	18	13
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	-2.160075	19	14
Recognition of DNA damage by PCNA-containing replication complex	-2.172609	21	14
Termination of translesion DNA synthesis	-2.187390	20	11
PCNA-Dependent Long Patch Base Excision Repair	-2.196541	15	11
Lagging Strand Synthesis	-2.208056	15	12
Gap-filling DNA repair synthesis and ligation in GG-NER	-2.257043	17	10
Telomere Maintenance	-2.307736	45	24
Extension of Telomeres	-2.308929	29	19
Chromosome Maintenance	-2.314235	53	27

Conclusion

The combination of upregulated and downregulated pathways in Atlantic salmon heart tissue indicates a complex regulatory environment focused on maintaining cardiac function. Upregulation of pathways involved in stress response, metabolism, and muscle maintenance suggests an adaptive response to ensure energy supply and muscle integrity. In contrast, downregulation of immune responses and cell cycle activities indicates a shift away from proliferation and inflammation towards stability and homeostasis. Understanding these dynamics can provide deeper insights into how salmon hearts adapt to various environmental stresses and maintain function.

IV-LD

Description	NES	setSize	Count
Complex I biogenesis	-2.377325	44	31
Respiratory electron transport	-2.261479	83	53
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	-2.195094	98	60
Aerobic respiration and respiratory electron transport	-1.986631	162	95
Recognition of DNA damage by PCNA-containing replication complex	-1.964693	25	13
Vesicle-mediated transport	1.306716	455	124
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.477766	497	214
Signaling by GPCR	1.483679	228	75
Signaling by Rho GTPases	1.484225	485	212
Hemostasis	1.497283	338	135
Platelet activation, signaling and aggregation	1.506632	164	69
GPCR downstream signalling	1.535800	208	74
Transcriptional regulation of granulopoiesis	1.580512	25	8
Chromatin modifying enzymes	1.596529	170	83
Chromatin organization	1.596529	170	83
Death Receptor Signaling	1.633401	100	40
PPARA activates gene expression	1.656990	92	32
RHOQ GTPase cycle	1.666565	50	34
Regulation of lipid metabolism by PPARalpha	1.671811	94	33
Kinesins	1.680260	28	11
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1.697851	54	15
RHO GTPase cycle	1.703439	345	175
RAC1 GTPase cycle	1.723827	144	80
RHOB GTPase cycle	1.750238	57	35
Heme signaling	1.759474	37	14
RHOC GTPase cycle	1.761050	61	37
NRAGE signals death through JNK	1.769988	38	22
Post-translational protein phosphorylation	1.779441	49	12
G alpha (12/13) signalling events	1.841983	47	26
RHOA GTPase cycle	1.895649	117	71
Binding and Uptake of Ligands by Scavenger Receptors	1.925324	23	6
Factors involved in megakaryocyte development and platelet production	1.941952	94	39
Regulation of Complement cascade	1.959766	12	4
CDC42 GTPase cycle	1.971144	119	69

Summary

The combination of these pathways suggests that in Atlantic salmon heart tissue:

• Positive Enrichment: There is a significant enrichment in pathways related to signal transduction (GPCR and Rho GTPases), vesicle transport, chromatin organization, lipid metabolism, and platelet production. These processes are essential for cell communication, structural integrity, energy metabolism, and cardiovascular function.
• Negative Enrichment: There is a downregulation of pathways involved in mitochondrial respiration and DNA damage recognition. This may indicate a reduced emphasis on oxidative phosphorylation and a potential adaptation in energy metabolism specific to the heart tissue in salmon, possibly reflecting unique metabolic demands or environmental adaptations.

10WPI

DNA vaccine

Description	NES	setSize	Count
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	-1.875194	17	8
Peroxisomal lipid metabolism	-1.861756	10	8
Metabolism of porphyrins	-1.849627	15	8
Retrograde transport at the Trans-Golgi-Network	-1.680493	25	7
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	-1.660422	14	5
Synthesis of substrates in N-glycan biosythesis	-1.648169	12	5
Transcriptional Regulation by MECP2	-1.644640	26	9
Iron uptake and transport	-1.481796	28	10
Intra-Golgi traffic	-1.463751	19	5
Amino acids regulate mTORC1	-1.460133	26	9
NR1H2 and NR1H3-mediated signaling	-1.398787	20	8
Rab regulation of trafficking	-1.398765	53	12
Cytoprotection by HMOX1	-1.380078	29	9
Fatty acid metabolism	-1.377250	68	19
Innate Immune System	1.201911	406	102
Adaptive Immune System	1.275866	298	117
Developmental Biology	1.288259	489	178
Translation	1.326355	216	73
Organelle biogenesis and maintenance	1.327841	117	40
Signaling by WNT	1.341702	135	59
Generic Transcription Pathway	1.341753	416	117
RNA Polymerase II Transcription	1.354023	489	136
Axon guidance	1.363787	272	98
Nervous system development	1.366108	279	100
Interleukin-1 family signaling	1.369676	69	33
PTEN Regulation	1.375740	91	46
HIV Infection	1.379078	141	58
C-type lectin receptors (CLRs)	1.380200	70	32
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1.402031	54	27
PPARA activates gene expression	1.405988	58	16
Regulation of lipid metabolism by PPARalpha	1.405988	58	16
Muscle contraction	1.406642	67	20
CLEC7A (Dectin-1) signaling	1.408456	64	37
Dectin-1 mediated noncanonical NF-kB signaling	1.409906	51	25
RAF/MAP kinase cascade	1.413687	122	36
Asparagine N-linked glycosylation	1.414279	117	38
Cross-presentation of soluble exogenous antigens (endosomes)	1.416515	40	22
Transcriptional regulation by RUNX1	1.417350	103	48
Maternal to zygotic transition (MZT)	1.418396	29	11
Diseases of signal transduction by growth factor receptors and second messengers	1.419982	252	67
Signaling by Receptor Tyrosine Kinases	1.420946	224	64
Cell-Cell communication	1.421635	50	18
NIK-->noncanonical NF-kB signaling	1.426048	50	25
FCERI mediated NF-kB activation	1.429243	53	32
Somitogenesis	1.433963	41	21
HCMV Early Events	1.438138	34	22
Ovarian tumor domain proteases	1.441190	17	7
Activation of NF-kappaB in B cells	1.441425	52	25
Deubiquitination	1.441902	131	66
Signaling by BRAF and RAF1 fusions	1.441959	30	8
Infectious disease	1.444793	495	189
Signaling by moderate kinase activity BRAF mutants	1.446979	24	7
Signaling by RAS mutants	1.446979	24	7
Paradoxical activation of RAF signaling by kinase inactive BRAF	1.446979	24	7
Signaling downstream of RAS mutants	1.446979	24	7
Regulation of RUNX3 expression and activity	1.452362	45	25
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1.456245	23	11
Cell junction organization	1.458881	36	14
Striated Muscle Contraction	1.459084	15	5
Viral Infection Pathways	1.461613	413	167
Transcriptional and post-translational regulation of MITF-M expression and activity	1.461784	17	8
Degradation of beta-catenin by the destruction complex	1.462974	63	34
Late SARS-CoV-2 Infection Events	1.464714	32	17
Signaling by FGFR1	1.464931	21	8
XBP1(S) activates chaperone genes	1.466037	29	11
Cytosolic sensors of pathogen-associated DNA	1.466218	27	9
tRNA processing	1.466390	30	21
Downstream TCR signaling	1.467353	57	36
TNFR2 non-canonical NF-kB pathway	1.468366	52	27
Metabolism of RNA	1.469617	440	200
Transcriptional regulation of brown and beige adipocyte differentiation	1.473896	11	7
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1.473896	11	7
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1.475095	19	6
Downregulation of ERBB2 signaling	1.475369	12	4
Signaling by Interleukins	1.479267	177	79
Downregulation of TGF-beta receptor signaling	1.479837	16	7
TCR signaling	1.482881	66	39
Respiratory Syncytial Virus Infection Pathway	1.483024	51	17
RHOV GTPase cycle	1.486042	17	14
Regulation of signaling by CBL	1.487300	13	8
MAPK1/MAPK3 signaling	1.488863	124	37
tRNA processing in the nucleus	1.489286	20	14
DNA Damage Recognition in GG-NER	1.489538	24	6
Extra-nuclear estrogen signaling	1.489627	33	10
Defective CFTR causes cystic fibrosis	1.491180	50	27
p53-Dependent G1 DNA Damage Response	1.493831	50	29
p53-Dependent G1/S DNA damage checkpoint	1.493831	50	29
G1/S DNA Damage Checkpoints	1.493831	50	29
Transcriptional regulation by RUNX2	1.494496	76	36
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1.494784	46	25
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1.496392	23	12
DNA Double Strand Break Response	1.496392	23	12
RSV-host interactions	1.498827	35	14
Degradation of GLI1 by the proteasome	1.499899	48	26
Disorders of transmembrane transporters	1.500319	80	41
Transcriptional Regulation by TP53	1.501665	181	55
Oncogenic MAPK signaling	1.501734	40	10
Antigen processing-Cross presentation	1.504948	61	29
Diseases of glycosylation	1.505632	36	11
Regulation of RAS by GAPs	1.507103	50	26
RHO GTPases Activate ROCKs	1.510670	13	6
Negative regulation of MAPK pathway	1.512410	22	8
Activation of BH3-only proteins	1.512440	15	9
Degradation of DVL	1.515973	46	25
Regulation of TP53 Activity	1.516938	82	32
MAPK family signaling cascades	1.519287	146	41
SCF(Skp2)-mediated degradation of p27/p21	1.520072	47	27
MHC class II antigen presentation	1.520683	56	21
EPH-Ephrin signaling	1.522294	40	15
Golgi-to-ER retrograde transport	1.522548	65	31
IRE1alpha activates chaperones	1.522732	30	12
Regulation of RUNX2 expression and activity	1.523176	51	27
Autodegradation of Cdh1 by Cdh1:APC/C	1.523870	46	25
Cyclin E associated events during G1/S transition	1.527174	56	30
Ub-specific processing proteases	1.529103	101	57
Nuclear events stimulated by ALK signaling in cancer	1.529185	18	4
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.532654	320	96
RAF-independent MAPK1/3 activation	1.533953	10	4
Regulation of TP53 Activity through Phosphorylation	1.535663	42	21
Regulation of TP53 Degradation	1.536500	23	7
Regulation of TP53 Expression and Degradation	1.536500	23	7
Unfolded Protein Response (UPR)	1.538254	52	18
Downstream signaling events of B Cell Receptor (BCR)	1.539050	58	33
Signaling by FGFR	1.539195	41	19
Vif-mediated degradation of APOBEC3G	1.539460	45	25
Vpu mediated degradation of CD4	1.540976	44	25
Hedgehog 'on' state	1.543479	51	28
HDR through Single Strand Annealing (SSA)	1.544441	10	7
Signaling by Rho GTPases	1.544952	312	95
ABC transporter disorders	1.547030	56	29
APC/C:Cdc20 mediated degradation of Securin	1.548144	48	26
Fc epsilon receptor (FCERI) signaling	1.549192	77	45
Regulation of PTEN stability and activity	1.550553	53	31
Cell-extracellular matrix interactions	1.551846	10	5
Signaling by the B Cell Receptor (BCR)	1.555098	70	43
Cyclin A:Cdk2-associated events at S phase entry	1.555133	57	31
Regulation of Apoptosis	1.555829	45	28
mRNA Splicing	1.556819	156	68
Semaphorin interactions	1.556961	35	13
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	1.557155	43	25
p53-Independent DNA Damage Response	1.557155	43	25
p53-Independent G1/S DNA damage checkpoint	1.557155	43	25
Apoptotic cleavage of cellular proteins	1.557588	19	7
CDK-mediated phosphorylation and removal of Cdc6	1.562933	49	27
Stabilization of p53	1.563927	47	27
Signaling by MET	1.564324	39	11
ABC-family proteins mediated transport	1.564600	63	32
Defective pyroptosis	1.567603	13	6
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	1.567627	46	25
Meiotic recombination	1.570290	12	7
mRNA Splicing - Major Pathway	1.570960	155	68
Degradation of AXIN	1.571070	46	26
Negative regulation of NOTCH4 signaling	1.573798	46	25
UCH proteinases	1.579481	60	32
Integrin cell surface interactions	1.580383	37	13
Sema4D in semaphorin signaling	1.580631	19	8
Scavenging by Class A Receptors	1.580917	11	4
Hh mutants are degraded by ERAD	1.586187	48	27
Hh mutants abrogate ligand secretion	1.586187	48	27
ER-Phagosome pathway	1.586237	56	29
Regulation of activated PAK-2p34 by proteasome mediated degradation	1.586941	44	26
SARS-CoV-1 Infection	1.587453	86	27
Nuclear Pore Complex (NPC) Disassembly	1.589285	17	9
AUF1 (hnRNP D0) binds and destabilizes mRNA	1.589295	46	26
Regulation of mRNA stability by proteins that bind AU-rich elements	1.589529	63	33
Autodegradation of the E3 ubiquitin ligase COP1	1.592145	46	27
Degradation of GLI2 by the proteasome	1.594191	49	28
GLI3 is processed to GLI3R by the proteasome	1.594191	49	28
Host Interactions of HIV factors	1.596458	81	44
Potential therapeutics for SARS	1.597710	54	29
Formation of Incision Complex in GG-NER	1.599244	22	9
Amyloid fiber formation	1.602731	26	5
MAPK6/MAPK4 signaling	1.607457	66	34
Mitochondrial calcium ion transport	1.610278	19	8
Homologous DNA Pairing and Strand Exchange	1.614107	10	9
Presynaptic phase of homologous DNA pairing and strand exchange	1.614107	10	9
Diseases of DNA Double-Strand Break Repair	1.614107	10	9
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1.614107	10	9
SCF-beta-TrCP mediated degradation of Emi1	1.615640	47	27
Sema4D induced cell migration and growth-cone collapse	1.619142	15	7
Hedgehog 'off' state	1.624340	61	34
Nuclear Envelope (NE) Reassembly	1.625253	35	12
RHO GTPases activate PKNs	1.626478	24	10
Plasma lipoprotein clearance	1.626860	19	7
SARS-CoV Infections	1.627337	203	82
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1.627489	50	28
SUMOylation	1.627917	71	34
Depolymerization of the Nuclear Lamina	1.628143	10	4
Hedgehog ligand biogenesis	1.629750	50	28
Interleukin-12 signaling	1.631015	27	14
Cilium Assembly	1.633841	57	26
Nuclear Envelope Breakdown	1.637358	27	12
Interconversion of nucleotide di- and triphosphates	1.639861	15	5
SUMO E3 ligases SUMOylate target proteins	1.643844	70	34
Beta-catenin independent WNT signaling	1.643980	78	40
SARS-CoV-2-host interactions	1.646402	89	26
Cytokine Signaling in Immune system	1.646422	272	105
Asymmetric localization of PCP proteins	1.647368	48	29
HSF1 activation	1.647702	10	8
Programmed Cell Death	1.649376	117	61
Collagen degradation	1.651167	24	11
Translation of Structural Proteins	1.651474	29	17
Transport of Mature mRNA derived from an Intron-Containing Transcript	1.657034	45	28
Base Excision Repair	1.658025	22	12
Resolution of Abasic Sites (AP sites)	1.659551	20	11
SARS-CoV-2 Infection	1.661052	136	44
Collagen chain trimerization	1.662029	12	9
Ubiquitin-dependent degradation of Cyclin D	1.662795	46	28
SARS-CoV-1 activates/modulates innate immune responses	1.664464	19	11
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1.666022	44	11
Signaling by Hedgehog	1.670115	72	38
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1.670966	29	13
Regulation of HSF1-mediated heat shock response	1.671310	36	22
Interleukin-12 family signaling	1.671664	29	15
Diseases of programmed cell death	1.672776	29	17
RHO GTPases activate IQGAPs	1.675864	10	7
MET promotes cell motility	1.678117	22	8
Post-translational protein phosphorylation	1.681680	41	10
RMTs methylate histone arginines	1.682722	20	9
Processing of SMDT1	1.685182	13	6
Hemostasis	1.686948	229	72
Evasion by RSV of host interferon responses	1.687224	12	7
Interferon alpha/beta signaling	1.687884	23	10
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1.688558	37	19
VEGFR2 mediated vascular permeability	1.690740	15	6
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1.691042	12	8
Apoptotic execution phase	1.693896	23	10
ISG15 antiviral mechanism	1.694347	38	25
HDR through Homologous Recombination (HRR)	1.694722	18	9
Bacterial Infection Pathways	1.695498	36	10
RHO GTPases activate PAKs	1.695609	13	7
Negative regulators of DDX58/IFIH1 signaling	1.696613	18	11
Transport of Mature Transcript to Cytoplasm	1.697061	51	30
Processing of Capped Intron-Containing Pre-mRNA	1.697898	193	91
COPI-dependent Golgi-to-ER retrograde traffic	1.699115	42	21
Degradation of the extracellular matrix	1.699132	45	23
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1.705549	11	5
Signaling by PDGF	1.706033	29	12
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1.710573	51	29
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1.710573	51	29
Cytosolic tRNA aminoacylation	1.711575	17	10
Apoptosis	1.716386	96	53
Anchoring of the basal body to the plasma membrane	1.718040	33	18
PCNA-Dependent Long Patch Base Excision Repair	1.721329	13	8
PCP/CE pathway	1.722499	62	36
Cellular response to heat stress	1.727544	52	29
mRNA 3'-end processing	1.732851	43	29
RNA Polymerase II Transcription Termination	1.733893	47	32
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1.736483	45	14
Dual incision in TC-NER	1.739729	34	14
Diseases associated with glycosaminoglycan metabolism	1.742922	13	6
Meiotic synapsis	1.744094	13	10
Regulation of APC/C activators between G1/S and early anaphase	1.747809	55	31
Aggrephagy	1.748793	18	14
APC/C:Cdc20 mediated degradation of mitotic proteins	1.750323	52	30
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1.750323	52	30
tRNA Aminoacylation	1.751536	24	14
Recruitment of mitotic centrosome proteins and complexes	1.752162	27	16
Centrosome maturation	1.752162	27	16
Binding and Uptake of Ligands by Scavenger Receptors	1.756294	16	8
Assembly of the pre-replicative complex	1.763883	58	32
Loss of Nlp from mitotic centrosomes	1.765790	26	16
Loss of proteins required for interphase microtubule organization from the centrosome	1.765790	26	16
AURKA Activation by TPX2	1.765790	26	16
Switching of origins to a post-replicative state	1.766310	60	33
Processing of DNA double-strand break ends	1.766419	20	12
APC/C-mediated degradation of cell cycle proteins	1.775820	57	32
Regulation of mitotic cell cycle	1.775820	57	32
Homology Directed Repair	1.781699	34	16
Recognition of DNA damage by PCNA-containing replication complex	1.786301	17	8
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1.786342	16	10
Mitotic Prophase	1.787350	44	17
Interferon Signaling	1.790467	93	43
SARS-CoV-1-host interactions	1.791140	62	21
Kinesins	1.791811	19	10
Orc1 removal from chromatin	1.792007	55	32
Infection with Mycobacterium tuberculosis	1.796039	13	3
Recruitment of NuMA to mitotic centrosomes	1.802060	27	17
Dual Incision in GG-NER	1.803412	19	9
MET activates PTK2 signaling	1.813860	14	7
SUMOylation of DNA replication proteins	1.814669	22	13
The role of GTSE1 in G2/M progression after G2 checkpoint	1.815821	52	33
Translesion synthesis by REV1	1.817679	10	8
Translesion synthesis by POLK	1.817679	10	8
Translesion synthesis by POLI	1.817679	10	8
Translesion Synthesis by POLH	1.822036	12	9
Initiation of Nuclear Envelope (NE) Reformation	1.822563	10	5
Syndecan interactions	1.823063	15	9
APC/C:Cdc20 mediated degradation of Cyclin B	1.829894	10	4
G0 and Early G1	1.830428	12	5
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1.836886	31	15
Regulation of PLK1 Activity at G2/M Transition	1.841462	36	17
Platelet activation, signaling and aggregation	1.852929	109	37
Gap-filling DNA repair synthesis and ligation in TC-NER	1.862584	36	14
M Phase	1.866915	169	91
Removal of the Flap Intermediate	1.867534	10	7
DNA Damage Bypass	1.869623	25	11
Condensation of Prophase Chromosomes	1.870740	10	6
Prefoldin mediated transfer of substrate to CCT/TriC	1.874904	16	12
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1.874904	16	12
Smooth Muscle Contraction	1.875071	19	10
Nucleotide Excision Repair	1.878546	60	20
Mitotic G2-G2/M phases	1.878659	91	53
G2/M Transition	1.878659	91	53
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1.878682	20	11
DNA Double-Strand Break Repair	1.881783	47	22
Termination of translesion DNA synthesis	1.885894	17	10
Fanconi Anemia Pathway	1.887161	10	8
Mitotic Metaphase and Anaphase	1.890600	120	45
Mitotic Anaphase	1.890600	120	45
Formation of tubulin folding intermediates by CCT/TriC	1.893730	10	10
Signaling by ALK in cancer	1.910403	58	22
Signaling by ALK fusions and activated point mutants	1.910403	58	22
PKR-mediated signaling	1.911955	28	17
Gap-filling DNA repair synthesis and ligation in GG-NER	1.914112	15	10
Global Genome Nucleotide Excision Repair (GG-NER)	1.918114	43	16
Non-integrin membrane-ECM interactions	1.923018	26	13
Meiosis	1.924771	24	16
Telomere C-strand (Lagging Strand) Synthesis	1.926484	14	9
DNA Replication Pre-Initiation	1.931193	66	29
Antiviral mechanism by IFN-stimulated genes	1.948182	66	36
Processive synthesis on the lagging strand	1.956764	11	8
Reproduction	1.958722	26	17
Mitotic Spindle Checkpoint	1.967847	43	15
Lagging Strand Synthesis	1.968093	13	9
DNA Repair	1.969906	106	42
Separation of Sister Chromatids	1.972554	94	58
Assembly of collagen fibrils and other multimeric structures	1.976660	25	14
Amplification of signal from the kinetochores	1.979575	39	15
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1.979575	39	15
E2F mediated regulation of DNA replication	1.983529	11	6
G2/M DNA damage checkpoint	1.989389	22	16
RHO GTPases Activate Formins	1.999289	53	24
Collagen biosynthesis and modifying enzymes	2.010105	21	15
DNA Replication	2.019335	79	35
Collagen formation	2.021605	34	19
EML4 and NUDC in mitotic spindle formation	2.023676	46	21
S Phase	2.023840	93	41
Synthesis of DNA	2.028324	74	34
RHO GTPase Effectors	2.030571	125	51
Platelet degranulation	2.042536	57	28
Telomere Maintenance	2.050957	37	19
Extension of Telomeres	2.054685	22	16
Mitotic Prometaphase	2.062503	75	50
Cell Cycle, Mitotic	2.065679	231	89
Response to elevated platelet cytosolic Ca2+	2.069555	61	29
Cell Cycle	2.079722	276	106
Activation of ATR in response to replication stress	2.083787	14	9
G2/M Checkpoints	2.098970	74	43
Extracellular matrix organization	2.111018	111	59
Mitotic G1 phase and G1/S transition	2.113026	87	27
G1/S Transition	2.141832	81	39
Resolution of Sister Chromatid Cohesion	2.143426	50	24
Chromosome Maintenance	2.156192	42	22
Cell Cycle Checkpoints	2.172180	122	56
ECM proteoglycans	2.270187	31	20
DNA strand elongation	2.289468	18	14
Activation of the pre-replicative complex	2.292947	16	11

Pathways with Significant NES

Negative NES (Under-represented Pathways):

1. NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux:
   • NES: -1.875194
   • Set Size: 17
   • Count: 8
2. Peroxisomal lipid metabolism:
   • NES: -1.861756
   • Set Size: 10
   • Count: 8
3. Metabolism of porphyrins:
   • NES: -1.849627
   • Set Size: 15
   • Count: 8

These pathways have significant negative NES, indicating they are under-represented in the dataset compared to other pathways.

Positive NES (Over-represented Pathways):

1. Innate Immune System:
   • NES: 1.201911
   • Set Size: 406
   • Count: 102
2. Adaptive Immune System:
   • NES: 1.275866
   • Set Size: 298
   • Count: 117
3. Developmental Biology:
   • NES: 1.288259
   • Set Size: 489
   • Count: 178

These pathways have significant positive NES, indicating they are over-represented in the dataset.

Key Observations

1. Immune System Pathways:
   • Both innate and adaptive immune system pathways are highly represented, reflecting their crucial role in response mechanisms.
2. Developmental Biology:
   • This pathway shows high representation, highlighting its importance in various biological processes and potentially indicating a focus on developmental studies.
3. Under-represented Pathways:
   • Pathways related to lipid metabolism, cholesterol transport, and efflux are under-represented, suggesting less focus or a negative impact in these areas.

Interpretation and Usage

• NES Interpretation:
  • Positive NES indicates over-representation, suggesting these pathways are more active or prevalent in the given condition or dataset.
  • Negative NES indicates under-representation, suggesting these pathways are less active or prevalent.
• Set Size and Count:
  • Set Size refers to the total number of genes or components in the pathway.
  • Count refers to the number of genes or components from the dataset that fall into the pathway.

Negative NES (Under-represented Pathways):

1. NR1H3 & NR1H2 Regulation of Gene Expression Linked to Cholesterol Transport and Efflux:
   • NES: -1.875194
   • Set Size: 17
   • Count: 8
   • Reason for Focus: This pathway is significantly under-represented, suggesting that genes involved in cholesterol transport and efflux are less active in the dataset. Given the critical role of cholesterol metabolism in cellular processes and disease, this under-representation could point to important biological insights or potential dysregulation in the condition studied.
2. Peroxisomal Lipid Metabolism:
   • NES: -1.861756
   • Set Size: 10
   • Count: 8
   • Reason for Focus: Peroxisomes play a vital role in lipid metabolism, including the breakdown of very long-chain fatty acids. An under-representation of this pathway might indicate metabolic disruptions or alterations in lipid processing, which can have significant implications for metabolic health and diseases.
3. Metabolism of Porphyrins:
   • NES: -1.849627
   • Set Size: 15
   • Count: 8
   • Reason for Focus: Porphyrins are essential components of hemoglobin, and disruptions in their metabolism can lead to disorders such as porphyrias. The under-representation of this pathway could suggest potential issues in hemoglobin synthesis or related metabolic processes, which are critical for understanding various hematological conditions.

Positive NES (Over-represented Pathways):

1. Innate Immune System:
   • NES: 1.201911
   • Set Size: 406
   • Count: 102
   • Reason for Focus: The innate immune system is the body's first line of defense against pathogens. Its over-representation indicates an elevated immune response, which could be associated with inflammation, infection, or other immune-related conditions.
2. Adaptive Immune System:
   • NES: 1.275866
   • Set Size: 298
   • Count: 117
   • Reason for Focus: The adaptive immune system is responsible for targeted and long-lasting immune responses. Over-representation here suggests an active immune response possibly due to chronic inflammation, autoimmune conditions, or response to infection.
3. Developmental Biology:
   • NES: 1.288259
   • Set Size: 489
   • Count: 178
   • Reason for Focus: Developmental biology pathways are crucial for the formation and differentiation of tissues and organs. Over-representation in these pathways could indicate active developmental processes, regeneration, or even pathological conditions like cancer, where developmental pathways can be aberrantly activated.

Summary

These pathways were selected based on their extreme NES values, which highlight significant deviations from the norm in the dataset. By focusing on both under-represented and over-represented pathways, we can gain insights into potential metabolic disruptions, immune responses, and developmental changes that may be pertinent to the biological condition under investigation. These insights are valuable for forming hypotheses about underlying mechanisms and potential therapeutic targets.

EOMES

These are the differentially regulated pathways from ReactomePA.

Description	NES	setSize	Count
Potassium Channels	1.603122	69	14
Neuronal System	1.456785	313	131
Muscle contraction	1.437219	150	62
Transmission across Chemical Synapses	1.419551	208	89

The plot below shows only upregulated pathways, since none of the enriched pathways was downregulated. These we obtained by running gseGO against the org.Hs.eg.db.

Summary of Findings

The pathways with positive NES values in the Atlantic salmon heart tissue, obtained through ReactomePA and human orthologs conversion, emphasize several key biological processes:

• Electrophysiology and Ion Transport (Potassium Channels): Essential for maintaining cardiac rhythm and function.
• Neuronal Regulation (Neuronal System): Suggests significant neural control and integration in cardiac function.
• Cardiac Muscle Activity (Muscle Contraction): Reflects the fundamental role of muscle contraction in heart mechanics.
• Neuro-Cardiac Interaction (Transmission Across Chemical Synapses): Indicates significant synaptic communication affecting cardiac physiology.

These pathways collectively highlight the intricate regulation and active processes within the salmon heart, underscoring the importance of both muscular and neural components in maintaining cardiac health and performance. This information can be crucial for understanding cardiac physiology in salmon, with potential implications for aquaculture and conservation efforts.

Spleen

10WPI

DNA vaccine

ReactomePA differentially regulated pathways.

Description	NES	setSize	Count
Regulation of Complement cascade	-2.241270	15	11
Amyloid fiber formation	-2.117998	27	5
Complement cascade	-1.984553	19	11
Striated Muscle Contraction	-1.884199	14	5
Neurotransmitter release cycle	-1.783909	14	6
Peroxisomal protein import	-1.779507	27	11
GPCR ligand binding	-1.777843	68	14
Post-translational modification: synthesis of GPI-anchored proteins	-1.766703	17	12
Metabolic disorders of biological oxidation enzymes	-1.735140	10	6
Insulin processing	-1.633392	15	3
Diseases of metabolism	-1.561942	94	35
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	-1.507741	36	18
Peptide hormone metabolism	-1.503343	31	6
Platelet degranulation	-1.494170	72	14
Class A/1 (Rhodopsin-like receptors)	-1.486493	51	10
Biological oxidations	-1.477513	62	23
Response to elevated platelet cytosolic Ca2+	-1.466929	76	17
Axon guidance	1.359716	303	124
Nervous system development	1.370982	309	58
Mitotic Metaphase and Anaphase	1.400823	160	73
Mitotic Anaphase	1.400823	160	73
Cellular Senescence	1.413021	86	34
Mitotic G2-G2/M phases	1.426075	121	59
G2/M Transition	1.426075	121	59
Cell Cycle Checkpoints	1.428235	176	77
Cytokine Signaling in Immune system	1.438643	359	113
G1/S Transition	1.448713	102	52
Death Receptor Signaling	1.457112	84	26
Mitotic Prometaphase	1.479377	120	48
Signaling by NTRK1 (TRKA)	1.481876	65	31
TCF dependent signaling in response to WNT	1.485156	115	33
Ub-specific processing proteases	1.487941	115	59
Signaling by VEGF	1.488078	77	20
Adipogenesis	1.504584	66	24
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1.506024	65	22
Signaling by the B Cell Receptor (BCR)	1.509223	87	47
SARS-CoV-2-host interactions	1.511130	121	32
Apoptosis	1.513401	112	53
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1.513965	43	16
Activation of HOX genes during differentiation	1.513965	43	16
Interferon Signaling	1.517474	126	40
Mitotic Prophase	1.517506	61	21
Hedgehog 'off' state	1.519717	69	38
Fc epsilon receptor (FCERI) signaling	1.524962	99	50
RHO GTPase Effectors	1.526557	166	73
Signaling by ALK in cancer	1.528765	64	21
Signaling by ALK fusions and activated point mutants	1.528765	64	21
CLEC7A (Dectin-1) signaling	1.529449	75	40
MAPK1/MAPK3 signaling	1.529760	143	39
S Phase	1.532588	126	66
Costimulation by the CD28 family	1.533874	39	15
G alpha (12/13) signalling events	1.533885	38	17
Respiratory Syncytial Virus Infection Pathway	1.537826	67	25
RAC1 GTPase cycle	1.539850	126	52
RAF/MAP kinase cascade	1.540032	140	39
Estrogen-dependent gene expression	1.541615	67	28
M Phase	1.542473	234	104
Signaling by Nuclear Receptors	1.543015	126	48
Anchoring of the basal body to the plasma membrane	1.546421	48	19
Signaling by NOTCH1	1.548265	43	16
MAPK family signaling cascades	1.549645	167	79
Regulation of MITF-M-dependent genes involved in apoptosis	1.552282	11	7
Adherens junctions interactions	1.553615	25	9
Cell Cycle, Mitotic	1.555357	330	111
Deubiquitination	1.558352	161	50
RHOJ GTPase cycle	1.564518	40	19
Cell Cycle	1.566349	398	135
C-type lectin receptors (CLRs)	1.566550	86	45
RAC3 GTPase cycle	1.568830	61	25
Constitutive Signaling by EGFRvIII	1.569113	11	4
Signaling by EGFRvIII in Cancer	1.569113	11	4
Transcriptional regulation by RUNX3	1.569290	67	35
ESR-mediated signaling	1.573844	99	38
Signaling by WNT	1.574110	166	82
VEGFA-VEGFR2 Pathway	1.575299	70	19
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1.576634	13	4
Signaling by EGFR in Cancer	1.576634	13	4
Signaling by Ligand-Responsive EGFR Variants in Cancer	1.576634	13	4
Interferon gamma signaling	1.577620	35	17
Oxidative Stress Induced Senescence	1.579621	44	21
RIPK1-mediated regulated necrosis	1.582296	21	6
Regulation of necroptotic cell death	1.582296	21	6
SARS-CoV-2 Infection	1.583791	178	50
Degradation of beta-catenin by the destruction complex	1.598609	65	38
Interferon alpha/beta signaling	1.606583	30	13
Beta-catenin independent WNT signaling	1.607205	90	50
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1.610306	11	7
RHO GTPase cycle	1.612038	291	115
Transcriptional regulation by RUNX1	1.615748	133	40
Platelet calcium homeostasis	1.621076	12	5
Diseases of signal transduction by growth factor receptors and second messengers	1.625372	284	98
Potential therapeutics for SARS	1.626597	68	35
SARS-CoV Infections	1.632015	259	81
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.634491	422	164
Programmed Cell Death	1.635565	132	51
RHOC GTPase cycle	1.636843	55	26
Opioid Signalling	1.637278	38	20
NOTCH1 Intracellular Domain Regulates Transcription	1.638939	29	12
RHOF GTPase cycle	1.641598	30	16
Signaling by Rho GTPases	1.645400	413	161
Condensation of Prophase Chromosomes	1.649244	14	7
RND2 GTPase cycle	1.659249	31	17
Maternal to zygotic transition (MZT)	1.660534	33	18
RAF activation	1.662111	26	12
HSF1-dependent transactivation	1.663105	15	8
RHOBTB GTPase Cycle	1.663225	25	9
RAC2 GTPase cycle	1.667253	66	33
Regulation of RUNX1 Expression and Activity	1.669452	13	9
HDMs demethylate histones	1.672443	16	9
RHOA GTPase cycle	1.673734	101	47
Sema4D induced cell migration and growth-cone collapse	1.681423	13	6
Mitotic Telophase/Cytokinesis	1.683839	10	7
Regulation of MECP2 expression and activity	1.687468	20	12
Signalling to ERKs	1.688122	22	13
RND1 GTPase cycle	1.688583	28	15
Evasion by RSV of host interferon responses	1.695392	13	5
Ca2+ pathway	1.696858	26	16
Initiation of Nuclear Envelope (NE) Reformation	1.707072	13	7
Interleukin-3, Interleukin-5 and GM-CSF signaling	1.710003	31	8
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1.711621	32	14
RSV-host interactions	1.712072	51	23
CDC42 GTPase cycle	1.712230	102	44
Trafficking of AMPA receptors	1.714581	15	5
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1.714581	15	5
Translation of Structural Proteins	1.717780	18	8
RHOB GTPase cycle	1.718858	49	26
Chromatin modifying enzymes	1.734738	152	58
Chromatin organization	1.734738	152	58
Signaling by WNT in cancer	1.737845	17	11
Apoptotic cleavage of cellular proteins	1.751430	23	14
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1.754826	39	11
RHO GTPases activate PAKs	1.755418	15	6
Maturation of nucleoprotein	1.755831	13	5
Effects of PIP2 hydrolysis	1.757041	16	5
Apoptotic execution phase	1.758126	30	15
Negative regulators of DDX58/IFIH1 signaling	1.759331	20	6
Platelet homeostasis	1.762752	32	19
RHOBTB2 GTPase cycle	1.768215	16	7
E2F mediated regulation of DNA replication	1.774100	16	8
Meiotic synapsis	1.776616	18	9
RHO GTPases activate CIT	1.801145	13	6
SARS-CoV-1 Infection	1.802731	95	27
NR1H2 and NR1H3-mediated signaling	1.813403	22	14
RND3 GTPase cycle	1.814530	31	18
RHOD GTPase cycle	1.822609	39	21
Regulation of signaling by CBL	1.829728	19	7
Beta-catenin phosphorylation cascade	1.843554	11	8
Signaling by AXIN mutants	1.843554	11	8
Signaling by CTNNB1 phospho-site mutants	1.843554	11	8
Signaling by APC mutants	1.843554	11	8
Signaling by AMER1 mutants	1.843554	11	8
Signaling by GSK3beta mutants	1.843554	11	8
CTNNB1 S33 mutants aren't phosphorylated	1.843554	11	8
CTNNB1 S37 mutants aren't phosphorylated	1.843554	11	8
CTNNB1 S45 mutants aren't phosphorylated	1.843554	11	8
CTNNB1 T41 mutants aren't phosphorylated	1.843554	11	8
APC truncation mutants have impaired AXIN binding	1.843554	11	8
AXIN missense mutants destabilize the destruction complex	1.843554	11	8
Truncations of AMER1 destabilize the destruction complex	1.843554	11	8
PKMTs methylate histone lysines	1.847820	30	15
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1.848806	20	13
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1.872158	17	11
Negative regulation of MAPK pathway	1.885807	26	13
TRAF6 mediated IRF7 activation	1.982506	11	6

EOMES

Description	NES	setSize	Count
Signaling by ALK	1.649581	26	10
Voltage gated Potassium channels	1.566912	29	14
TNFR1-induced NF-kappa-B signaling pathway	1.552213	28	13
Sensory processing of sound	1.545197	57	29
Signaling by ERBB4	1.533551	47	22
Sensory processing of sound by inner hair cells of the cochlea	1.530252	53	26
Neurexins and neuroligins	1.515727	47	15
Neuronal System	1.427153	299	104
Transmission across Chemical Synapses	1.360267	195	74
Signaling by Receptor Tyrosine Kinases	1.215053	432	192
Response to elevated platelet cytosolic Ca2+	-1.818670	100	14
Platelet degranulation	-1.853988	96	14
Post-translational protein phosphorylation	-1.883851	76	13
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-1.922559	86	15
Synthesis of glycosylphosphatidylinositol (GPI)	-1.976571	16	7
Initial triggering of complement	-1.987510	13	5
Pyrimidine catabolism	-2.036910	11	5
Diseases of hemostasis	-2.163460	12	6
Common Pathway of Fibrin Clot Formation	-2.331327	11	7
Intrinsic Pathway of Fibrin Clot Formation	-2.350957	13	8
Formation of Fibrin Clot (Clotting Cascade)	-2.661372	22	10
Regulation of Complement cascade	-2.773996	24	13
Complement cascade	-2.832269	31	14

GATA3

Description	NES	setSize	Count
CD209 (DC-SIGN) signaling	1.695850	17	6
Signaling by Hippo	1.656248	16	10
ECM proteoglycans	1.614106	47	26
MITF-M-dependent gene expression	1.606173	64	31
RHOH GTPase cycle	1.595730	30	13
MITF-M-regulated melanocyte development	1.533134	88	38
RHOB GTPase cycle	1.532649	61	35
L1CAM interactions	1.510738	68	35
RHOA GTPase cycle	1.457084	125	60
RHO GTPase cycle	1.441012	363	155
Chromatin modifying enzymes	1.433822	175	75
Chromatin organization	1.433822	175	75
RAC1 GTPase cycle	1.418491	150	68
Nervous system development	1.393143	393	132
Axon guidance	1.375631	377	123
Signaling by Receptor Tyrosine Kinases	1.355121	374	164
Metabolism of nucleotides	-1.619210	76	19
Diseases of carbohydrate metabolism	-2.005272	26	5
Post-translational protein phosphorylation	-2.012732	60	10
Cholesterol biosynthesis	-2.041372	24	9
Tryptophan catabolism	-2.055674	10	3
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-2.057657	69	13
Response to elevated platelet cytosolic Ca2+	-2.143473	90	14
Platelet degranulation	-2.204138	86	14
Intrinsic Pathway of Fibrin Clot Formation	-2.463928	12	6
Common Pathway of Fibrin Clot Formation	-2.465193	10	8
Regulation of Complement cascade	-2.562415	21	9
Complement cascade	-2.603283	26	9
Formation of Fibrin Clot (Clotting Cascade)	-2.750159	21	11

IV-HD

nMDS plots? Can I use them?

Description	NES	setSize	Count
CD209 (DC-SIGN) signaling	1.695850	17	6
Signaling by Hippo	1.656248	16	10
ECM proteoglycans	1.614106	47	26
MITF-M-dependent gene expression	1.606173	64	31
RHOH GTPase cycle	1.595730	30	13
MITF-M-regulated melanocyte development	1.533134	88	38
RHOB GTPase cycle	1.532649	61	35
L1CAM interactions	1.510738	68	35
RHOA GTPase cycle	1.457084	125	60
RHO GTPase cycle	1.441012	363	155
Chromatin modifying enzymes	1.433822	175	75
Chromatin organization	1.433822	175	75
RAC1 GTPase cycle	1.418491	150	68
Nervous system development	1.393143	393	132
Axon guidance	1.375631	377	123
Signaling by Receptor Tyrosine Kinases	1.355121	374	164
Metabolism of nucleotides	-1.619210	76	19
Diseases of carbohydrate metabolism	-2.005272	26	5
Post-translational protein phosphorylation	-2.012732	60	10
Cholesterol biosynthesis	-2.041372	24	9
Tryptophan catabolism	-2.055674	10	3
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-2.057657	69	13
Response to elevated platelet cytosolic Ca2+	-2.143473	90	14
Platelet degranulation	-2.204138	86	14
Intrinsic Pathway of Fibrin Clot Formation	-2.463928	12	6
Common Pathway of Fibrin Clot Formation	-2.465193	10	8
Regulation of Complement cascade	-2.562415	21	9
Complement cascade	-2.603283	26	9
Formation of Fibrin Clot (Clotting Cascade)	-2.750159	21	11

IV-LD

Description	NES	setSize	Count
Striated Muscle Contraction	-2.560859	14	2
Complement cascade	-2.413080	18	8
Platelet degranulation	-2.101032	70	9
Response to elevated platelet cytosolic Ca2+	-2.082864	74	9
SARS-CoV Infections	1.450543	255	88
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.545675	402	183
Signaling by Rho GTPases	1.549295	393	181
RHO GTPase cycle	1.621215	278	96
CDC42 GTPase cycle	1.632554	97	43
RHOBTB2 GTPase cycle	1.753969	16	7
RHOB GTPase cycle	1.757849	48	30
RHOA GTPase cycle	1.784755	94	50
RHOBTB1 GTPase cycle	1.813043	16	8
RND3 GTPase cycle	1.857320	30	16
RHOBTB GTPase Cycle	1.877992	25	12

4WPC

DNA vaccine

Description	NES	setSize	Count
Metabolism of porphyrins	2.068871	16	9
L1CAM interactions	1.995875	56	21
Heme biosynthesis	1.961682	11	6
Mitochondrial iron-sulfur cluster biogenesis	1.877300	11	2
The phototransduction cascade	1.875759	11	2
Inactivation, recovery and regulation of the phototransduction cascade	1.875759	11	2
Regulated Necrosis	1.839602	37	16
Iron uptake and transport	1.771661	35	10
Programmed Cell Death	1.726049	138	37
Apoptosis	1.607348	116	27
Axon guidance	1.457884	318	80
Metabolism of lipids	-1.412703	395	100
Diseases of metabolism	-1.645383	108	42
Diseases of glycosylation	-1.701822	59	25
Metabolism of steroids	-1.725580	69	23
Common Pathway of Fibrin Clot Formation	-1.871216	10	7
Formation of Fibrin Clot (Clotting Cascade)	-1.932278	17	10
Complement cascade	-1.984173	20	5
Regulation of Complement cascade	-2.004786	16	8
Response to elevated platelet cytosolic Ca2+	-2.028299	80	17
Insulin processing	-2.043490	16	6
Platelet degranulation	-2.059360	76	17
Post-translational protein phosphorylation	-2.217165	53	13
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-2.225907	60	23

EOMES

Description	NES	setSize	Count
Metabolism of porphyrins	2.148982	16	8
Heme biosynthesis	2.022551	11	6
Keratinization	1.996972	17	4
Formation of the cornified envelope	1.996972	17	4
CD209 (DC-SIGN) signaling	1.912676	14	5
Generation of second messenger molecules	1.906672	16	6
Intrinsic Pathway for Apoptosis	1.894452	31	12
Cobalamin (Cbl, vitamin B12) transport and metabolism	1.838560	10	2
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1.802697	17	12
The phototransduction cascade	1.802022	11	4
Inactivation, recovery and regulation of the phototransduction cascade	1.802022	11	4
Muscle contraction	1.779787	72	31
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1.779769	75	47
L1CAM interactions	1.758115	56	17
Formation of a pool of free 40S subunits	1.724827	83	50
GTP hydrolysis and joining of the 60S ribosomal subunit	1.715622	92	53
FCERI mediated Ca+2 mobilization	1.709010	24	11
Eukaryotic Translation Initiation	1.708851	98	56
Cap-dependent Translation Initiation	1.708851	98	56
Striated Muscle Contraction	1.706148	14	7
L13a-mediated translational silencing of Ceruloplasmin expression	1.695828	91	52
Eukaryotic Translation Termination	1.687454	73	45
Eukaryotic Translation Elongation	1.685674	72	53
Peptide chain elongation	1.683744	70	44
rRNA processing in the nucleus and cytosol	1.679949	157	103
Visual phototransduction	1.678981	29	5
Estrogen-dependent gene expression	1.660740	70	28
Response of EIF2AK4 (GCN2) to amino acid deficiency	1.658338	81	50
FOXO-mediated transcription	1.652512	36	19
Major pathway of rRNA processing in the nucleolus and cytosol	1.651185	147	95
Selenoamino acid metabolism	1.649109	92	46
Death Receptor Signaling	1.646330	95	38
NR1H2 and NR1H3-mediated signaling	1.639777	25	6
Selenocysteine synthesis	1.636396	73	45
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1.633773	25	11
Nonsense-Mediated Decay (NMD)	1.632377	89	51
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1.632377	89	51
rRNA processing	1.631788	165	106
ESR-mediated signaling	1.589157	104	41
Signaling by Nuclear Receptors	1.503294	136	44
Axon guidance	1.357830	318	70
Asparagine N-linked glycosylation	-1.350545	190	87
DNA Double-Strand Break Repair	-1.415577	90	30
RHO GTPases Activate Formins	-1.433743	88	22
Diseases of metabolism	-1.474885	108	42
Cell Cycle, Mitotic	-1.478818	359	80
Homology Directed Repair	-1.486808	71	26
G2/M Checkpoints	-1.497634	105	35
M Phase	-1.511043	255	58
DNA strand elongation	-1.522111	28	11
Cell Cycle	-1.534260	434	98
Unfolded Protein Response (UPR)	-1.541637	70	27
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-1.553914	60	22
APC/C:Cdc20 mediated degradation of mitotic proteins	-1.554022	63	27
COPI-dependent Golgi-to-ER retrograde traffic	-1.594287	59	21
APC/C-mediated degradation of cell cycle proteins	-1.594544	73	32
Regulation of mitotic cell cycle	-1.594544	73	32
Separation of Sister Chromatids	-1.600186	137	32
Diseases of glycosylation	-1.609731	59	20
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	-1.631899	64	28
Telomere C-strand (Lagging Strand) Synthesis	-1.634018	24	12
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	-1.639731	66	25
Mitotic Anaphase	-1.644432	171	41
Synthesis of very long-chain fatty acyl-CoAs	-1.670293	14	7
Mitotic Metaphase and Anaphase	-1.679851	172	42
Nuclear Pore Complex (NPC) Disassembly	-1.699523	29	11
Resolution of D-Loop Structures	-1.710262	19	8
Diseases of DNA repair	-1.761204	32	16
Mitotic Prometaphase	-1.763232	132	39
Golgi Cisternae Pericentriolar Stack Reorganization	-1.766836	10	9
Resolution of Sister Chromatid Cohesion	-1.777846	85	26
Impaired BRCA2 binding to RAD51	-1.781533	23	10
Cyclin A/B1/B2 associated events during G2/M transition	-1.783024	16	8
Phosphorylation of the APC/C	-1.787385	15	6
Resolution of D-loop Structures through Holliday Junction Intermediates	-1.790687	18	8
HDR through Homologous Recombination (HRR)	-1.793318	42	17
XBP1(S) activates chaperone genes	-1.798648	37	12
Glycosaminoglycan metabolism	-1.799723	58	17
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	-1.801198	11	4
Presynaptic phase of homologous DNA pairing and strand exchange	-1.803251	25	11
G2/M DNA damage checkpoint	-1.818246	42	15
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	-1.822299	15	8
Diseases of DNA Double-Strand Break Repair	-1.828098	26	13
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	-1.828098	26	13
Regulation of Complement cascade	-1.840737	16	9
EML4 and NUDC in mitotic spindle formation	-1.851267	77	24
Complement cascade	-1.858660	20	11
IRE1alpha activates chaperones	-1.859516	38	13
Homologous DNA Pairing and Strand Exchange	-1.870689	27	14
HDR through Single Strand Annealing (SSA)	-1.894345	26	12
Diseases associated with glycosaminoglycan metabolism	-1.925171	16	4
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	-1.931827	14	8
Defective homologous recombination repair (HRR) due to PALB2 loss of function	-1.931827	14	8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	-1.931827	14	8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	-1.931827	14	8
Impaired BRCA2 binding to PALB2	-1.931827	14	8
Cell Cycle Checkpoints	-1.995867	192	49
Mitotic Spindle Checkpoint	-2.074298	80	25
Amplification of signal from the kinetochores	-2.078635	68	22
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	-2.078635	68	22

GATA3

Description	NES	setSize	Count
Metabolism of porphyrins	2.202361	16	9
Heme biosynthesis	2.074192	11	7
Unfolded Protein Response (UPR)	-1.716388	70	26
Glycosaminoglycan metabolism	-1.740617	57	23
Post-translational protein phosphorylation	-1.781209	50	19
Sensory processing of sound	-1.877618	25	5
Plasma lipoprotein remodeling	-1.948396	16	5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-1.950295	57	18
XBP1(S) activates chaperone genes	-2.023765	37	11
IRE1alpha activates chaperones	-2.034111	38	13

IV-HD

Description	NES	setSize	Count
Metabolism of porphyrins	2.025030	17	9
Heme biosynthesis	1.956092	11	6
CD209 (DC-SIGN) signaling	1.905132	16	4
Keratinization	1.866491	20	5
Formation of the cornified envelope	1.866491	20	5
rRNA modification in the nucleus and cytosol	1.790658	55	34
rRNA processing in the nucleus and cytosol	1.698858	160	84
Major pathway of rRNA processing in the nucleolus and cytosol	1.655784	150	77
rRNA processing	1.612426	169	86
Platelet activation, signaling and aggregation	-1.792341	169	34
XBP1(S) activates chaperone genes	-1.853295	39	16
Sensory processing of sound by inner hair cells of the cochlea	-1.864196	25	8
IRE1alpha activates chaperones	-1.908621	40	17
Cholesterol biosynthesis	-1.928222	19	13
Post-translational protein phosphorylation	-2.089087	56	11
Intrinsic Pathway of Fibrin Clot Formation	-2.117373	11	5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-2.172118	63	13
Response to elevated platelet cytosolic Ca2+	-2.179590	85	25
Common Pathway of Fibrin Clot Formation	-2.191657	10	8
Platelet degranulation	-2.214696	81	25
Regulation of Complement cascade	-2.402575	19	8
Formation of Fibrin Clot (Clotting Cascade)	-2.411237	19	10
Complement cascade	-2.440427	23	9

IV-LD

Description	NES	setSize	Count
Striated Muscle Contraction	2.125201	18	7
Muscle contraction	2.011388	87	24
Heme biosynthesis	1.951132	11	7
Metabolism of porphyrins	1.946705	17	9
Transcription of E2F targets under negative control by DREAM complex	1.837145	16	9
G0 and Early G1	1.825592	23	13
TP53 Regulates Transcription of Cell Death Genes	1.822671	25	9
Aberrant regulation of mitotic cell cycle due to RB1 defects	1.819579	28	13
Formation of tubulin folding intermediates by CCT/TriC	1.800396	13	8
snRNP Assembly	1.797102	42	19
Metabolism of non-coding RNA	1.797102	42	19
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1.791607	27	12
HCMV Early Events	1.775093	50	19
Prefoldin mediated transfer of substrate to CCT/TriC	1.771623	19	12
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1.771623	19	12
Transport of the SLBP Dependant Mature mRNA	1.763561	27	14
Transport of the SLBP independent Mature mRNA	1.760120	26	14
Diseases of mitotic cell cycle	1.756363	30	10
tRNA processing in the nucleus	1.745351	45	19
Polymerase switching	1.737348	12	6
Leading Strand Synthesis	1.737348	12	6
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	1.727841	14	9
SUMOylation of SUMOylation proteins	1.706052	27	13
Extension of Telomeres	1.699124	41	18
S Phase	1.697397	142	49
tRNA processing	1.694374	85	38
Synthesis of DNA	1.684453	105	54
Switching of origins to a post-replicative state	1.661922	80	42
CDK-mediated phosphorylation and removal of Cdc6	1.641596	63	31
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1.628545	64	32
Mitochondrial protein degradation	1.616809	80	33
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1.599286	63	35
Respiratory electron transport	1.566409	82	31
Factors involved in megakaryocyte development and platelet production	1.549917	95	28
G1/S Transition	1.540709	112	57
Separation of Sister Chromatids	1.508940	144	44
Mitotic G1 phase and G1/S transition	1.505042	123	42
Aerobic respiration and respiratory electron transport	1.459795	157	57
Metabolism of lipids	-1.545778	490	129
Metabolism of vitamins and cofactors	-1.624853	131	36
Diseases of hemostasis	-1.672322	11	5
Response to elevated platelet cytosolic Ca2+	-1.708887	88	21
ABC transporters in lipid homeostasis	-1.723269	10	4
Post-translational protein phosphorylation	-1.725481	56	12
Retinoid metabolism and transport	-1.731038	22	8
Platelet degranulation	-1.741427	84	21
Diseases of Immune System	-1.772153	14	4
Diseases associated with the TLR signaling cascade	-1.772153	14	4
IRS-related events triggered by IGF1R	-1.773082	25	9
Sensory processing of sound by outer hair cells of the cochlea	-1.775328	22	10
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	-1.786118	26	9
IGF1R signaling cascade	-1.786118	26	9
Metabolism of fat-soluble vitamins	-1.795160	26	10
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	-1.801806	63	14
Intrinsic Pathway of Fibrin Clot Formation	-1.845032	12	6
Common Pathway of Fibrin Clot Formation	-1.897044	10	6
Formation of Fibrin Clot (Clotting Cascade)	-2.077895	20	10
Regulation of Complement cascade	-2.146441	21	10
Complement cascade	-2.181194	25	11

Need to do spleen 6WPC, liver (10WPI and 4WPC), and head-kidney (10WPI and 4WPC).

Scripts in use are vaccine_contrasts.R, deseq_modelling_lymphoid.R, and gsea_new_and_definitive_4wpc.R.

Liver

10/06/2024

Created sampleTables and DGE objects for liver and head-kidney.

Wrote vaccine constrasts and extracted results tables for 10wpi and 4wpc.

There were 53 pathways for which P-values were not calculated properly due to unbalanced (positive and negative) gene-level statistic values. For such pathways pval, padj, NES, log2err are set to NA.

This kept happening, so I added an nPermSimple = 100000 flag to gseGO and nPermSimple = 100000 to gsePathway.

10WPI

DNA vaccine

Signaling by interleukins shows upregulated.

Description	NES	setSize	Count
rRNA modification in the nucleus and cytosol	-2.772010	54	39
rRNA processing	-2.453593	160	65
rRNA processing in the nucleus and cytosol	-2.407239	154	61
Major pathway of rRNA processing in the nucleolus and cytosol	-2.239763	145	53
tRNA processing	-2.218107	64	29
tRNA modification in the nucleus and cytosol	-2.091645	21	15
PERK regulates gene expression	-2.048805	24	11
ATF4 activates genes in response to endoplasmic reticulum stress	-1.987790	19	12
Formation of tubulin folding intermediates by CCT/TriC	-1.887469	10	4
Transcriptional regulation by small RNAs	-1.805579	40	20
RNA Polymerase I Promoter Escape	-1.793334	23	15
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	-1.781392	23	13
RNA Pol II CTD phosphorylation and interaction with CE	-1.781392	23	13
mRNA Capping	-1.750957	25	14
Unfolded Protein Response (UPR)	-1.743634	70	28
TAK1-dependent IKK and NF-kappa-B activation	-1.741067	18	7
Gene Silencing by RNA	-1.733720	52	24
snRNP Assembly	-1.727473	36	18
Metabolism of non-coding RNA	-1.727473	36	18
KSRP (KHSRP) binds and destabilizes mRNA	-1.727124	11	8
Formation of TC-NER Pre-Incision Complex	-1.720563	41	22
HIV Life Cycle	-1.711677	107	47
Late Phase of HIV Life Cycle	-1.710021	101	45
mRNA decay by 3' to 5' exoribonuclease	-1.707305	13	9
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	-1.669651	30	9
tRNA processing in the nucleus	-1.667210	38	16
RNA Polymerase III Chain Elongation	-1.663220	12	7
Viral Messenger RNA Synthesis	-1.653304	34	17
Inflammasomes	-1.653136	12	4
SUMOylation of RNA binding proteins	-1.653020	29	15
Mitochondrial translation elongation	-1.648479	70	33
Nuclear import of Rev protein	-1.645935	24	13
RNA polymerase II transcribes snRNA genes	-1.624966	58	27
Mitochondrial translation	-1.612842	75	34
Interleukin-4 and Interleukin-13 signaling	-1.607890	39	19
Formation of the Early Elongation Complex	-1.596029	28	14
Formation of the HIV-1 Early Elongation Complex	-1.596029	28	14
tRNA Aminoacylation	-1.587923	33	18
Mitochondrial translation initiation	-1.573332	70	32
Mitochondrial translation termination	-1.563183	69	31
HCMV Late Events	-1.551581	40	19
HIV Infection	-1.361084	170	60
Processing of Capped Intron-Containing Pre-mRNA	-1.346116	222	69
Cell Cycle	1.314339	363	127
Diseases of signal transduction by growth factor receptors and second messengers	1.316558	266	77
Axon guidance	1.344675	289	118
SARS-CoV Infections	1.349494	247	74
Signaling by Receptor Tyrosine Kinases	1.349672	257	71
Nervous system development	1.390382	298	122
Cell Cycle, Mitotic	1.405877	306	110
Signaling by Nuclear Receptors	1.426774	132	33
Hemostasis	1.432707	270	101
MAPK family signaling cascades	1.442332	159	41
Signaling by WNT	1.476225	150	54
Transmission across Chemical Synapses	1.478456	70	24
Mitotic Metaphase and Anaphase	1.501343	146	58
Mitotic Anaphase	1.501343	146	58
Cell Cycle Checkpoints	1.507114	156	61
GTP hydrolysis and joining of the 60S ribosomal subunit	1.514329	91	47
L13a-mediated translational silencing of Ceruloplasmin expression	1.517851	90	44
Signaling by GPCR	1.521175	154	54
GPCR downstream signalling	1.529661	147	52
Beta-catenin independent WNT signaling	1.541891	80	33
Muscle contraction	1.559529	51	15
Response of EIF2AK4 (GCN2) to amino acid deficiency	1.562418	80	42
Formation of a pool of free 40S subunits	1.583754	82	41
Integration of energy metabolism	1.584293	38	14
RHOG GTPase cycle	1.586506	51	16
Platelet activation, signaling and aggregation	1.590911	125	39
RAC2 GTPase cycle	1.594233	59	19
RND1 GTPase cycle	1.594742	27	9
Parasite infection	1.607800	42	22
Leishmania phagocytosis	1.607800	42	22
FCGR3A-mediated phagocytosis	1.607800	42	22
ECM proteoglycans	1.610333	30	10
Neurotransmitter receptors and postsynaptic signal transmission	1.624353	53	20
Nonsense-Mediated Decay (NMD)	1.626122	87	48
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1.626122	87	48
Semaphorin interactions	1.627524	35	15
GPVI-mediated activation cascade	1.628625	20	9
PLC beta mediated events	1.629346	16	7
RAF activation	1.631989	21	10
Myogenesis	1.640567	13	7
Eukaryotic Translation Termination	1.642670	72	40
Separation of Sister Chromatids	1.648325	115	48
MAP2K and MAPK activation	1.650966	23	11
Meiotic synapsis	1.654659	16	7
Oncogenic MAPK signaling	1.662560	44	18
Potential therapeutics for SARS	1.665109	63	27
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1.671597	26	12
CDC42 GTPase cycle	1.674033	86	22
Sensory Perception	1.690622	60	28
Collagen biosynthesis and modifying enzymes	1.693640	23	7
Degradation of cysteine and homocysteine	1.694713	10	4
RHO GTPase cycle	1.708945	264	84
TRAF6 mediated IRF7 activation	1.709489	11	6
NR1H2 and NR1H3-mediated signaling	1.711277	26	7
Viral mRNA Translation	1.717562	69	38
Mitotic Prometaphase	1.720485	107	42
Extracellular matrix organization	1.730960	117	37
SRP-dependent cotranslational protein targeting to membrane	1.731785	88	48
Signaling by high-kinase activity BRAF mutants	1.732551	20	11
Notch-HLH transcription pathway	1.733203	18	9
Interleukin-12 signaling	1.735706	32	14
Cholesterol biosynthesis	1.735860	23	14
Mitotic Spindle Checkpoint	1.748624	62	28
RHO GTPases Activate Formins	1.748758	68	32
EPHB-mediated forward signaling	1.754624	23	13
G alpha (12/13) signalling events	1.760218	36	20
Interleukin-12 family signaling	1.761629	35	15
G-protein beta:gamma signalling	1.770287	14	8
EML4 and NUDC in mitotic spindle formation	1.788346	61	29
L1CAM interactions	1.793282	53	18
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1.799826	74	43
RHOD GTPase cycle	1.802760	39	19
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1.818813	382	120
RHOA GTPase cycle	1.821890	87	26
Peptide chain elongation	1.824288	69	38
Signaling by Rho GTPases	1.832108	372	117
Selenocysteine synthesis	1.833169	72	39
RHOC GTPase cycle	1.847258	50	17
RND3 GTPase cycle	1.859686	30	15
Signaling by RAF1 mutants	1.860056	23	13
Eukaryotic Translation Elongation	1.861776	71	40
Amplification of signal from the kinetochores	1.872992	54	26
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1.872992	54	26
Cardiac conduction	1.921692	26	8
Signaling by moderate kinase activity BRAF mutants	1.930290	25	14
Signaling by RAS mutants	1.930290	25	14
Paradoxical activation of RAF signaling by kinase inactive BRAF	1.930290	25	14
Signaling downstream of RAS mutants	1.930290	25	14
RHO GTPase Effectors	1.934879	146	72
RHOQ GTPase cycle	1.973296	38	14
Resolution of Sister Chromatid Cohesion	1.978613	69	36
RHOB GTPase cycle	2.086523	42	16

EOMES

Signaling by interleukins shows upregulated.

Description	NES	setSize	Count
rRNA modification in the nucleus and cytosol	-2.629134	57	38
Mitochondrial translation	-2.510041	82	52
Mitochondrial translation elongation	-2.498719	76	49
Mitochondrial translation termination	-2.465083	76	48
Mitochondrial translation initiation	-2.452399	76	47
Cobalamin (Cbl, vitamin B12) transport and metabolism	-2.190745	15	4
Activation of Matrix Metalloproteinases	-2.169753	15	2
Mitochondrial tRNA aminoacylation	-2.086415	20	14
tRNA Aminoacylation	-2.004145	40	28
rRNA processing	-1.981503	174	60
rRNA processing in the mitochondrion	-1.974662	10	8
Removal of the Flap Intermediate	-1.917535	13	8
Processive synthesis on the lagging strand	-1.902146	14	8
Kidney development	-1.896871	19	7
Extension of Telomeres	-1.887146	45	20
rRNA processing in the nucleus and cytosol	-1.882236	164	54
Translation	-1.855510	250	87
Chromosome Maintenance	-1.846192	80	32
Formation of ATP by chemiosmotic coupling	-1.827672	12	10
tRNA processing	-1.795627	89	35
RNA Polymerase III Chain Elongation	-1.783728	16	10
Telomere Maintenance	-1.765739	62	30
Major pathway of rRNA processing in the nucleolus and cytosol	-1.724958	154	46
E2F mediated regulation of DNA replication	-1.701744	16	8
DNA strand elongation	-1.700657	30	17
Mitochondrial protein import	-1.698303	54	24
Cytosolic tRNA aminoacylation	-1.680270	23	13
Cristae formation	-1.672193	24	14
Hemostasis	1.246532	399	152
Signaling by Interleukins	1.278670	277	102
Diseases of signal transduction by growth factor receptors and second messengers	1.299682	349	123
MAPK family signaling cascades	1.305292	225	78
Nervous system development	1.321692	403	130
Axon guidance	1.324522	388	91
Intracellular signaling by second messengers	1.348471	230	72
MAPK1/MAPK3 signaling	1.354531	193	68
RAF/MAP kinase cascade	1.362480	190	67
Signaling by Nuclear Receptors	1.368205	181	61
ESR-mediated signaling	1.369432	129	43
Signaling by Receptor Tyrosine Kinases	1.370449	383	184
Chromatin modifying enzymes	1.398007	174	77
Chromatin organization	1.398007	174	77
MITF-M-regulated melanocyte development	1.419168	85	34
Sensory Perception	1.426483	112	56
Epigenetic regulation of gene expression	1.428471	116	37
Adipogenesis	1.431171	88	26
RHO GTPase cycle	1.437374	374	144
Signaling by NTRKs	1.447580	99	42
Platelet activation, signaling and aggregation	1.450350	186	81
Cell-Cell communication	1.457617	96	50
Activation of NMDA receptors and postsynaptic events	1.462013	55	22
Leishmania infection	1.466123	117	48
Parasitic Infection Pathways	1.466123	117	48
Sphingolipid metabolism	1.469900	77	23
RAC1 GTPase cycle	1.470595	157	80
Signaling by TGF-beta Receptor Complex	1.474899	77	25
Sensory processing of sound by inner hair cells of the cochlea	1.475068	45	27
Sensory processing of sound	1.475908	48	28
Death Receptor Signaling	1.479910	118	42
Inositol phosphate metabolism	1.484833	40	20
Regulation of insulin secretion	1.497956	44	17
RHOC GTPase cycle	1.503305	64	27
Signaling by TGFB family members	1.509704	97	32
NRAGE signals death through JNK	1.510095	45	21
Signaling by NTRK1 (TRKA)	1.515012	85	37
CDC42 GTPase cycle	1.520473	130	73
Ca2+ pathway	1.523515	42	25
Platelet Aggregation (Plug Formation)	1.524694	32	18
Constitutive Signaling by Aberrant PI3K in Cancer	1.526696	42	22
Pre-NOTCH Transcription and Translation	1.527756	30	12
G alpha (s) signalling events	1.529277	69	36
TGF-beta receptor signaling activates SMADs	1.532312	38	15
Potential therapeutics for SARS	1.537806	77	42
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1.538548	33	16
Nephrin family interactions	1.539485	19	9
NOTCH1 Intracellular Domain Regulates Transcription	1.542501	38	13
Sema4D induced cell migration and growth-cone collapse	1.543528	17	6
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1.544392	25	8
Transcriptional regulation by RUNX3	1.544888	79	24
Collagen degradation	1.545320	35	18
Post NMDA receptor activation events	1.552244	46	19
Neurotransmitter release cycle	1.552616	31	15
MAP2K and MAPK activation	1.556544	28	16
Signaling by GPCR	1.556555	302	133
MET promotes cell motility	1.557673	27	17
PI3K events in ERBB2 signaling	1.560929	11	6
HDMs demethylate histones	1.562580	17	8
NR1H2 and NR1H3-mediated signaling	1.567284	36	17
Regulation of CDH11 Expression and Function	1.570134	21	13
Adrenaline,noradrenaline inhibits insulin secretion	1.571358	14	6
G alpha (q) signalling events	1.575934	100	41
Adenylate cyclase inhibitory pathway	1.576767	11	6
G alpha (12/13) signalling events	1.579723	55	25
Oncogenic MAPK signaling	1.583526	60	28
Formation of WDR5-containing histone-modifying complexes	1.584590	35	17
MITF-M-dependent gene expression	1.585433	63	27
Synthesis of IP3 and IP4 in the cytosol	1.587776	21	12
L1CAM interactions	1.590207	72	39
Uptake and actions of bacterial toxins	1.590709	18	9
Interleukin-4 and Interleukin-13 signaling	1.593440	58	27
SUMOylation of intracellular receptors	1.595570	25	14
Elastic fibre formation	1.597056	35	13
Regulation of beta-cell development	1.600646	24	10
G alpha (i) signalling events	1.602068	115	51
GPVI-mediated activation cascade	1.608847	27	13
Polo-like kinase mediated events	1.609342	14	6
RHOA GTPase cycle	1.615091	127	51
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1.617192	21	12
Non-integrin membrane-ECM interactions	1.622412	42	17
Interferon gamma signaling	1.626992	40	24
FOXO-mediated transcription of cell cycle genes	1.638358	13	8
Sphingolipid catabolism	1.638525	10	5
GPCR downstream signalling	1.639542	275	125
Signaling by NODAL	1.641624	11	8
Neurotransmitter receptors and postsynaptic signal transmission	1.642256	107	52
Signaling by high-kinase activity BRAF mutants	1.643647	25	16
Integrin signaling	1.645587	24	17
ECM proteoglycans	1.645736	46	22
Bacterial Infection Pathways	1.646065	50	18
HSF1-dependent transactivation	1.648852	17	8
Anti-inflammatory response favouring Leishmania parasite infection	1.655132	49	21
Leishmania parasite growth and survival	1.655132	49	21
Interaction between L1 and Ankyrins	1.657753	13	7
Integration of energy metabolism	1.660360	71	29
RHOQ GTPase cycle	1.660770	50	27
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1.665302	28	14
Aquaporin-mediated transport	1.665910	29	14
RHO GTPases activate CIT	1.666394	15	8
G alpha (z) signalling events	1.667774	29	16
FCGR3A-mediated IL10 synthesis	1.671625	29	13
Long-term potentiation	1.675547	10	7
Molecules associated with elastic fibres	1.678294	28	13
Signaling by BMP	1.682198	22	10
ADORA2B mediated anti-inflammatory cytokines production	1.682606	24	13
RUNX3 regulates NOTCH signaling	1.688974	11	7
RHOJ GTPase cycle	1.690497	47	26
Neuronal System	1.697738	206	98
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1.704705	13	7
Voltage gated Potassium channels	1.706622	13	9
NCAM signaling for neurite out-growth	1.708120	40	17
Notch-HLH transcription pathway	1.712344	22	9
PKA activation in glucagon signalling	1.717508	13	9
Signaling by RAF1 mutants	1.722014	29	17
Transmission across Chemical Synapses	1.727897	144	68
Glucagon signaling in metabolic regulation	1.729771	20	12
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1.731729	12	5
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1.741200	11	7
PKA-mediated phosphorylation of CREB	1.744077	16	8
Myogenesis	1.750783	20	13
GPER1 signaling	1.764746	27	15
Signaling by moderate kinase activity BRAF mutants	1.768421	32	19
Signaling by RAS mutants	1.768421	32	19
Paradoxical activation of RAF signaling by kinase inactive BRAF	1.768421	32	19
Signaling downstream of RAS mutants	1.768421	32	19
Vasopressin regulates renal water homeostasis via Aquaporins	1.769831	24	13
PKA activation	1.771608	14	8
Phase 0 - rapid depolarisation	1.777203	12	7
G-protein mediated events	1.881901	39	24
Opioid Signalling	1.900240	55	30
DAG and IP3 signaling	1.907237	30	18
PLC beta mediated events	1.910717	36	23
Calmodulin induced events	1.970152	24	16
CaM pathway	1.970152	24	16
Ca-dependent events	2.019479	26	18

GATA3

Description	NES	setSize	Count
rRNA processing in the mitochondrion	-2.379128	10	9
Metabolism of Angiotensinogen to Angiotensins	-2.372706	10	3
rRNA modification in the nucleus and cytosol	-2.293831	57	34
Mitochondrial tRNA aminoacylation	-2.253875	20	9
Mitochondrial translation	-1.936104	82	41
Mitochondrial translation initiation	-1.887474	76	38
Mitochondrial translation elongation	-1.875701	76	39
Mitochondrial translation termination	-1.836147	76	38
rRNA processing	-1.637892	174	62
rRNA processing in the nucleus and cytosol	-1.436040	164	55
Signaling by Receptor Tyrosine Kinases	1.237291	397	172
RHO GTPase cycle	1.256677	382	199
GPCR downstream signalling	1.330100	309	135
Extracellular matrix organization	1.330252	196	93
Transmission across Chemical Synapses	1.330932	159	75
Signaling by GPCR	1.346442	339	135
RAC1 GTPase cycle	1.362416	159	104
Neurotransmitter receptors and postsynaptic signal transmission	1.406526	116	62
PLC beta mediated events	1.549178	36	29
ECM proteoglycans	1.578233	50	18
Non-integrin membrane-ECM interactions	1.581483	44	17
Myogenesis	1.661284	23	13

IV-HD

IV-LD

4WPC

DNA vaccine

Description	NES	setSize	Count
SRP-dependent cotranslational protein targeting to membrane	2.746160	88	49
Viral mRNA Translation	2.562936	69	43
Eukaryotic Translation Elongation	2.560727	71	44
Peptide chain elongation	2.526258	69	42
Selenocysteine synthesis	2.465764	73	44
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.459142	74	43
Formation of a pool of free 40S subunits	2.438645	82	43
L13a-mediated translational silencing of Ceruloplasmin expression	2.412538	90	52
GTP hydrolysis and joining of the 60S ribosomal subunit	2.389440	91	52
Eukaryotic Translation Initiation	2.260711	97	47
Cap-dependent Translation Initiation	2.260711	97	47
Eukaryotic Translation Termination	2.230120	73	39
Response of EIF2AK4 (GCN2) to amino acid deficiency	2.215357	80	42
Formation of the ternary complex, and subsequently, the 43S complex	2.175515	44	23
SARS-CoV-1 modulates host translation machinery	2.158552	29	15
Nonsense-Mediated Decay (NMD)	2.128311	89	43
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2.128311	89	43
Formation of ATP by chemiosmotic coupling	2.069048	12	7
Ribosomal scanning and start codon recognition	2.001157	50	23
Translation initiation complex formation	1.997164	49	23
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1.985995	50	23
SARS-CoV-2 modulates host translation machinery	1.942443	38	16
Selenoamino acid metabolism	1.923872	93	45
Mitochondrial Fatty Acid Beta-Oxidation	1.897481	27	10
Cellular response to starvation	1.895605	117	51
Defects in vitamin and cofactor metabolism	1.882877	17	11
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.826944	96	45
Regulation of expression of SLITs and ROBOs	1.720593	132	49
Fatty acid metabolism	1.692700	108	36
Respiratory electron transport	1.650109	80	36
Signaling by ROBO receptors	1.603262	161	54
Translation	1.598214	237	84
Aerobic respiration and respiratory electron transport	1.559828	151	61
Metabolism of amino acids and derivatives	1.373951	264	70
Cytokine Signaling in Immune system	-1.333362	352	103
RHO GTPase cycle	-1.341345	305	81
Signaling by Interleukins	-1.450596	224	63
Hemostasis	-1.510786	305	103
RAC1 GTPase cycle	-1.542343	128	36
Platelet activation, signaling and aggregation	-1.544752	145	46
SLC-mediated transmembrane transport	-1.547072	104	36
Chromosome Maintenance	-1.593103	66	29
VEGFA-VEGFR2 Pathway	-1.608699	70	26
RAC3 GTPase cycle	-1.653358	64	20
Mitochondrial tRNA aminoacylation	-1.655229	16	11
Transport of inorganic cations/anions and amino acids/oligopeptides	-1.657739	45	15
RHO GTPases Activate NADPH Oxidases	-1.741948	17	8
Cyclin D associated events in G1	-1.765330	28	14
G1 Phase	-1.765330	28	14
Cell surface interactions at the vascular wall	-1.768807	66	22
RAF-independent MAPK1/3 activation	-1.791937	14	6
Amino acid transport across the plasma membrane	-1.807066	18	8
Interleukin-4 and Interleukin-13 signaling	-1.848273	43	24

EOMES

There is a marked difference between the number of enriched GO terms and enriched pathways from ReactomePA.

While 257 GO terms were enriched with gseGO, 400 pathways were tagged in ReactomePA.

In this case, I arranged them in ascending NES, as the downregulated pathways were more interesting.

Description	NES	setSize	Count
Interleukin-4 and Interleukin-13 signaling	-2.262873	38	22
GPER1 signaling	-2.096039	15	7
Fcgamma receptor (FCGR) dependent phagocytosis	-2.089789	52	19
FCGR3A-mediated IL10 synthesis	-2.083127	16	9
Integrin signaling	-2.057657	19	9
G alpha (s) signalling events	-2.040387	24	10
Platelet Aggregation (Plug Formation)	-2.038182	22	11
RHO GTPase Effectors	-2.018924	135	49
Cell surface interactions at the vascular wall	-2.016042	53	20
GPVI-mediated activation cascade	-1.987619	19	8
Hemostasis	-1.979233	261	87
Interferon gamma signaling	-1.945199	29	18
Integrin cell surface interactions	-1.937112	36	15
Leishmania infection	-1.929806	79	32
Parasitic Infection Pathways	-1.929806	79	32
Signaling by CSF1 (M-CSF) in myeloid cells	-1.928144	18	10
Signal transduction by L1	-1.918460	15	8
Anti-inflammatory response favouring Leishmania parasite infection	-1.912667	29	17
Leishmania parasite growth and survival	-1.912667	29	17
Parasite infection	-1.911090	39	13
Leishmania phagocytosis	-1.911090	39	13
FCGR3A-mediated phagocytosis	-1.911090	39	13
RHO GTPases Activate Formins	-1.883883	61	24
RAC1 GTPase cycle	-1.871119	102	38
GPCR downstream signalling	-1.864692	128	54
Signaling by GPCR	-1.854200	134	57
Semaphorin interactions	-1.840478	35	17
RAC2 GTPase cycle	-1.835605	54	20
EML4 and NUDC in mitotic spindle formation	-1.834083	56	23
FLT3 Signaling	-1.832020	22	11
Processive synthesis on the C-strand of the telomere	-1.823964	12	7
Regulation of actin dynamics for phagocytic cup formation	-1.822127	39	12
MAPK targets/ Nuclear events mediated by MAP kinases	-1.804437	19	12
Metabolism of nitric oxide: NOS3 activation and regulation	-1.803939	11	4
Platelet activation, signaling and aggregation	-1.802865	121	37
Extra-nuclear estrogen signaling	-1.801008	29	8
VEGFA-VEGFR2 Pathway	-1.793506	57	28
DNA strand elongation	-1.792021	24	15
Collagen degradation	-1.783196	28	9
Amplification of signal from the kinetochores	-1.782581	49	19
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	-1.782581	49	19
Interleukin-3, Interleukin-5 and GM-CSF signaling	-1.781255	26	13
Mitotic Prometaphase	-1.780742	96	43
RAC3 GTPase cycle	-1.776373	53	18
Signaling by VEGF	-1.771072	61	30
Toll Like Receptor 7/8 (TLR7/8) Cascade	-1.770673	46	25
MyD88 dependent cascade initiated on endosome	-1.770673	46	25
G1/S-Specific Transcription	-1.764554	14	9
Toll Like Receptor 9 (TLR9) Cascade	-1.764530	49	26
Muscle contraction	-1.761417	48	20
Extracellular matrix organization	-1.760416	108	32
Signaling by Interleukins	-1.759556	197	71
Cytokine Signaling in Immune system	-1.757916	308	105
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-1.756051	16	9
EPHA-mediated growth cone collapse	-1.753683	10	8
MAP kinase activation	-1.752945	36	19
Processive synthesis on the lagging strand	-1.749877	12	8
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	-1.744003	19	11
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	-1.736590	45	24
Mitotic Spindle Checkpoint	-1.735430	57	21
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	-1.728680	19	9
Cell-extracellular matrix interactions	-1.727461	10	5
MyD88-independent TLR4 cascade	-1.725437	54	26
TRIF (TICAM1)-mediated TLR4 signaling	-1.725437	54	26
Lagging Strand Synthesis	-1.721041	16	11
Telomere C-strand (Lagging Strand) Synthesis	-1.719281	19	11
G-protein beta:gamma signalling	-1.709217	12	5
Fanconi Anemia Pathway	-1.699367	17	11
FLT3 signaling in disease	-1.698379	17	8
G alpha (12/13) signalling events	-1.691303	32	20
Toll Like Receptor 10 (TLR10) Cascade	-1.687917	45	23
Toll Like Receptor 5 (TLR5) Cascade	-1.687917	45	23
MyD88 cascade initiated on plasma membrane	-1.687917	45	23
RHO GTPases Activate NADPH Oxidases	-1.686677	12	7
Removal of the Flap Intermediate from the C-strand	-1.684042	11	6
Regulation of CDH11 Expression and Function	-1.682777	14	8
Regulation of Homotypic Cell-Cell Adhesion	-1.682777	14	8
Regulation of Expression and Function of Type II Classical Cadherins	-1.682777	14	8
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	-1.681754	23	12
Toll Like Receptor 4 (TLR4) Cascade	-1.681057	64	29
Smooth Muscle Contraction	-1.679834	20	10
ERK/MAPK targets	-1.679352	13	8
Toll Like Receptor 3 (TLR3) Cascade	-1.676690	52	25
Resolution of Sister Chromatid Cohesion	-1.674593	63	24
Signaling by TGFB family members	-1.672626	63	23
Sema4D induced cell migration and growth-cone collapse	-1.670284	11	7
Signaling by RAF1 mutants	-1.668716	22	8
Signaling by high-kinase activity BRAF mutants	-1.668466	19	8
Nuclear Envelope Breakdown	-1.667025	39	11
Regulation of signaling by CBL	-1.666557	15	9
DAP12 interactions	-1.664445	14	5
DAP12 signaling	-1.664445	14	5
Removal of the Flap Intermediate	-1.664370	11	8
Signaling by TGF-beta Receptor Complex	-1.663848	53	21
Uptake and actions of bacterial toxins	-1.659376	12	2
Signaling by ERBB2	-1.658931	24	15
Interleukin-17 signaling	-1.646827	37	19
ECM proteoglycans	-1.645292	29	9
Signaling by moderate kinase activity BRAF mutants	-1.635207	24	8
Signaling by RAS mutants	-1.635207	24	8
Paradoxical activation of RAF signaling by kinase inactive BRAF	-1.635207	24	8
Signaling downstream of RAS mutants	-1.635207	24	8
Depolymerization of the Nuclear Lamina	-1.629480	12	5
Activation of ATR in response to replication stress	-1.626161	23	17
Signaling by Rho GTPases	-1.625659	346	101
Syndecan interactions	-1.622241	17	7
Elastic fibre formation	-1.617773	17	9
Role of phospholipids in phagocytosis	-1.613648	10	5
FCERI mediated MAPK activation	-1.610961	18	12
Cell Cycle, Mitotic	-1.604524	282	106
Activation of Matrix Metalloproteinases	-1.604274	12	4
FCERI mediated Ca+2 mobilization	-1.601557	13	9
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	-1.597643	13	6
Signaling by EGFR in Cancer	-1.597643	13	6
Signaling by Ligand-Responsive EGFR Variants in Cancer	-1.597643	13	6
Basigin interactions	-1.588490	13	5
Potential therapeutics for SARS	-1.587549	60	20
Termination of translesion DNA synthesis	-1.586378	18	10
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	-1.582732	354	101
Signaling by FGFR1	-1.581086	17	8
HDR through Homologous Recombination (HRR)	-1.579300	27	13
ADORA2B mediated anti-inflammatory cytokines production	-1.578305	12	6
Notch-HLH transcription pathway	-1.577985	17	7
Miscellaneous transport and binding events	-1.573612	12	6
Interleukin-2 family signaling	-1.572867	16	7
Signaling by Receptor Tyrosine Kinases	-1.571384	243	89
Cell junction organization	-1.568458	43	17
Gap-filling DNA repair synthesis and ligation in GG-NER	-1.566696	16	9
MAP2K and MAPK activation	-1.565525	22	8
G0 and Early G1	-1.564954	15	10
Mitotic Prophase	-1.562224	56	13
DDX58/IFIH1-mediated induction of interferon-alpha/beta	-1.560684	36	13
Signaling by CSF3 (G-CSF)	-1.556781	20	8
Translesion Synthesis by POLH	-1.555846	14	8
L1CAM interactions	-1.555558	50	17
Signaling by FGFR3	-1.551163	13	7
Signaling by FGFR4	-1.551163	13	7
Death Receptor Signaling	-1.548836	77	30
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	-1.545719	48	24
Toll Like Receptor TLR1:TLR2 Cascade	-1.545719	48	24
Toll Like Receptor TLR6:TLR2 Cascade	-1.545719	48	24
Toll Like Receptor 2 (TLR2) Cascade	-1.545719	48	24
DARPP-32 events	-1.545263	13	5
TNFR1-induced NF-kappa-B signaling pathway	-1.544483	16	8
Constitutive Signaling by EGFRvIII	-1.543304	11	5
Signaling by EGFRvIII in Cancer	-1.543304	11	5
G-protein mediated events	-1.542183	17	11
Cell-Cell communication	-1.540384	57	20
Signaling by NTRK2 (TRKB)	-1.537126	11	7
Downregulation of ERBB2 signaling	-1.536510	12	7
Amino acid transport across the plasma membrane	-1.536036	15	6
Signaling by FGFR	-1.533343	39	16
RHOB GTPase cycle	-1.529351	40	22
NRAGE signals death through JNK	-1.527677	27	17
Signaling by FLT3 fusion proteins	-1.527151	12	8
Chromosome Maintenance	-1.526339	55	19
Extension of Telomeres	-1.525929	31	19
VEGFR2 mediated vascular permeability	-1.525305	18	12
Resolution of Abasic Sites (AP sites)	-1.520702	23	11
Signaling by ALK in cancer	-1.514907	61	26
Signaling by ALK fusions and activated point mutants	-1.514907	61	26
Homology Directed Repair	-1.507547	47	19
Nuclear events stimulated by ALK signaling in cancer	-1.506139	20	11
Inactivation of CSF3 (G-CSF) signaling	-1.506066	16	7
Degradation of the extracellular matrix	-1.505435	54	13
Platelet degranulation	-1.503440	65	14
Cell Cycle	-1.495341	334	121
p75 NTR receptor-mediated signalling	-1.492332	47	24
Toll-like Receptor Cascades	-1.490329	76	31
Assembly of collagen fibrils and other multimeric structures	-1.488964	22	7
Interferon alpha/beta signaling	-1.487745	26	14
Response to elevated platelet cytosolic Ca2+	-1.486235	69	14
Deactivation of the beta-catenin transactivating complex	-1.485505	19	9
DNA Damage Bypass	-1.485166	29	13
Factors involved in megakaryocyte development and platelet production	-1.484846	71	22
Opioid Signalling	-1.479913	28	15
Signaling by SCF-KIT	-1.476386	25	11
DNA Repair	-1.465392	150	40
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	-1.464608	29	10
Negative regulation of the PI3K/AKT network	-1.464134	39	23
Signaling by BRAF and RAF1 fusions	-1.461940	32	9
AURKA Activation by TPX2	-1.459428	35	10
Cell death signalling via NRAGE, NRIF and NADE	-1.457175	38	20
TGF-beta receptor signaling activates SMADs	-1.456626	25	12
RHO GTPase cycle	-1.450703	245	64
Pre-NOTCH Transcription and Translation	-1.448507	22	15
Base Excision Repair	-1.445906	27	11
Interferon Signaling	-1.445318	110	39
Negative regulation of MAPK pathway	-1.444211	22	13
NOTCH1 Intracellular Domain Regulates Transcription	-1.439979	27	10
SUMOylation of DNA damage response and repair proteins	-1.439858	43	9
Non-integrin membrane-ECM interactions	-1.438765	27	11
Rab regulation of trafficking	-1.436890	67	17
Signaling by FGFR2	-1.436754	35	14
G alpha (q) signalling events	-1.435915	48	21
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	-1.424922	37	22
Signaling by MET	-1.414098	39	20
SARS-CoV-2 activates/modulates innate and adaptive immune responses	-1.406048	60	12
DNA Double-Strand Break Repair	-1.399285	63	22
Generic Transcription Pathway	-1.396730	473	164
CDC42 GTPase cycle	-1.393908	80	33
Diseases of signal transduction by growth factor receptors and second messengers	-1.391798	256	71
M Phase	-1.377932	201	66
SUMO E3 ligases SUMOylate target proteins	-1.372799	92	23
Cilium Assembly	-1.357340	71	15
ESR-mediated signaling	-1.340824	91	38
SUMOylation	-1.336488	95	23
Adaptive Immune System	-1.335264	341	112
Mitotic G1 phase and G1/S transition	-1.324119	96	40
Transcriptional Regulation by TP53	-1.301197	208	78
Innate Immune System	-1.296696	480	125
Diseases of metabolism	1.316776	115	44
Respiratory electron transport	1.353684	74	34
Aerobic respiration and respiratory electron transport	1.380650	140	52
Mitochondrial protein degradation	1.384518	73	28
Autodegradation of the E3 ubiquitin ligase COP1	1.412268	43	24
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1.419517	62	31
Stabilization of p53	1.443104	44	25
Nonsense-Mediated Decay (NMD)	1.459617	86	45
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1.459617	86	45
Metabolism of lipids	1.463174	381	95
Signaling by ROBO receptors	1.470582	150	76
Golgi-to-ER retrograde transport	1.476496	79	39
SARS-CoV-1 modulates host translation machinery	1.485222	29	15
ABC transporter disorders	1.489243	59	30
COPI-dependent Golgi-to-ER retrograde traffic	1.490854	52	17
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.495957	90	41
Protein localization	1.498337	106	33
Disorders of transmembrane transporters	1.502778	104	48
Cellular response to starvation	1.505566	112	54
Hh mutants are degraded by ERAD	1.510001	46	25
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1.511547	39	18
Complement cascade	1.512167	26	5
Plasma lipoprotein assembly, remodeling, and clearance	1.524190	43	18
rRNA processing in the nucleus and cytosol	1.534583	151	75
rRNA processing	1.535307	157	61
Defective CFTR causes cystic fibrosis	1.541313	50	27
Fatty acid metabolism	1.545336	92	18
ABC-family proteins mediated transport	1.549515	66	32
Post-translational protein phosphorylation	1.554096	54	27
COPII-mediated vesicle transport	1.562566	38	16
Lysine catabolism	1.565716	12	7
Regulation of Glucokinase by Glucokinase Regulatory Protein	1.567169	22	2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1.567169	22	2
Cytochrome P450 - arranged by substrate type	1.575572	21	12
Metabolism of vitamins and cofactors	1.578185	103	37
Hh mutants abrogate ligand secretion	1.578914	47	26
Major pathway of rRNA processing in the nucleolus and cytosol	1.581543	142	72
Intra-Golgi and retrograde Golgi-to-ER traffic	1.592137	124	57
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1.603380	49	27
Translation initiation complex formation	1.618414	48	27
Maturation of spike protein	1.626331	19	7
Glutathione conjugation	1.627009	13	6
Retrograde transport at the Trans-Golgi-Network	1.627279	35	14
Hedgehog ligand biogenesis	1.632777	49	28
Sensory Perception	1.633976	57	17
Ribosomal scanning and start codon recognition	1.645786	49	28
Visual phototransduction	1.679929	34	12
Regulation of expression of SLITs and ROBOs	1.681093	128	71
Fatty acyl-CoA biosynthesis	1.689937	23	7
Response of EIF2AK4 (GCN2) to amino acid deficiency	1.703857	78	46
Phase II - Conjugation of compounds	1.721793	38	14
Metabolism of water-soluble vitamins and cofactors	1.722364	63	28
Formation of ATP by chemiosmotic coupling	1.740552	12	11
Mitochondrial translation	1.757240	71	33
Metabolism of amino acids and derivatives	1.792006	246	120
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1.796156	73	42
Transport to the Golgi and subsequent modification	1.823875	101	44
Mitochondrial translation elongation	1.828171	67	33
Mitochondrial translation initiation	1.830089	66	19
Mitochondrial translation termination	1.839537	66	19
Nucleotide biosynthesis	1.841813	13	7
Cytosolic tRNA aminoacylation	1.842301	21	11
Phase I - Functionalization of compounds	1.842301	34	19
Asparagine N-linked glycosylation	1.864055	172	74
Biological oxidations	1.886675	77	32
Eukaryotic Translation Initiation	1.913272	95	57
Cap-dependent Translation Initiation	1.913272	95	57
Formation of the ternary complex, and subsequently, the 43S complex	1.917351	43	21
Selenoamino acid metabolism	1.919174	90	49
Defects in vitamin and cofactor metabolism	1.919440	14	11
Eukaryotic Translation Elongation	1.920686	70	42
Cristae formation	1.928859	24	13
COPI-mediated anterograde transport	1.929901	60	31
Peptide chain elongation	1.931277	68	40
Eukaryotic Translation Termination	1.957626	71	47
The canonical retinoid cycle in rods (twilight vision)	1.978377	10	8
L13a-mediated translational silencing of Ceruloplasmin expression	2.003959	88	53
ER to Golgi Anterograde Transport	2.008324	88	42
GTP hydrolysis and joining of the 60S ribosomal subunit	2.015188	89	54
Selenocysteine synthesis	2.036777	70	41
Purine ribonucleoside monophosphate biosynthesis	2.048663	10	7
Viral mRNA Translation	2.074703	68	41
Formation of a pool of free 40S subunits	2.149929	80	49
Translation	2.201753	223	121
Regulation of cholesterol biosynthesis by SREBP (SREBF)	2.294680	45	17
Metabolism of steroids	2.298662	86	32
SRP-dependent cotranslational protein targeting to membrane	2.401320	87	58
Activation of gene expression by SREBF (SREBP)	2.409997	35	17
Cholesterol biosynthesis	2.573984	23	18

GATA3

Description	NES	setSize	Count
Transport of inorganic cations/anions and amino acids/oligopeptides	-1.929944	44	16
RHO GTPases Activate NADPH Oxidases	-1.885335	15	8
Cell surface interactions at the vascular wall	-1.877235	65	30
Amino acid transport across the plasma membrane	-1.855301	18	10
Platelet Aggregation (Plug Formation)	-1.799747	25	12
Interleukin-4 and Interleukin-13 signaling	-1.785542	42	25
Signaling by FGFR1	-1.783707	24	11
Binding and Uptake of Ligands by Scavenger Receptors	-1.728694	23	5
Negative regulation of FGFR1 signaling	-1.724222	13	5
Basigin interactions	-1.718560	15	7
Signaling by GPCR	-1.712427	167	56
GPCR downstream signalling	-1.708012	157	48
Integrin signaling	-1.704380	21	10
Signaling by CSF1 (M-CSF) in myeloid cells	-1.702810	21	11
RAC1 GTPase cycle	-1.702467	120	46
Cyclin D associated events in G1	-1.698183	27	12
G1 Phase	-1.698183	27	12
Signaling by FLT3 fusion proteins	-1.687607	13	9
Signaling by ALK in cancer	-1.674926	65	37
Signaling by ALK fusions and activated point mutants	-1.674926	65	37
PRC2 methylates histones and DNA	-1.667802	16	7
SLC-mediated transmembrane transport	-1.667667	100	26
Class A/1 (Rhodopsin-like receptors)	-1.664491	47	13
Role of LAT2/NTAL/LAB on calcium mobilization	-1.661828	10	8
RAC3 GTPase cycle	-1.660552	60	23
HSF1 activation	-1.657144	11	2
FLT3 signaling in disease	-1.651469	18	10
Signaling by FGFR3	-1.638074	18	7
Signaling by FGFR4	-1.638074	18	7
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	-1.629110	37	13
RHOB GTPase cycle	-1.623881	45	22
Downstream signaling of activated FGFR2	-1.620808	11	7
Signaling by FGFR1 in disease	-1.619984	18	13
Hemostasis	-1.618392	289	96
RAF-independent MAPK1/3 activation	-1.615505	13	10
Signaling by ERBB2 ECD mutants	-1.615229	13	8
Syndecan interactions	-1.613136	17	6
Signaling by ERBB2 in Cancer	-1.607487	14	8
Signaling by ERBB2 KD Mutants	-1.607487	14	8
G alpha (q) signalling events	-1.603283	58	23
Platelet activation, signaling and aggregation	-1.603022	134	47
Signaling by ALK	-1.599328	17	11
GPVI-mediated activation cascade	-1.595708	22	11
ROS and RNS production in phagocytes	-1.590936	18	9
Signaling by FGFR	-1.581584	46	17
Integrin cell surface interactions	-1.576134	39	14
Downstream signaling of activated FGFR3	-1.575990	10	6
Downstream signaling of activated FGFR4	-1.575990	10	6
Signaling by TGF-beta Receptor Complex	-1.571323	63	25
Epigenetic regulation of gene expression	-1.565754	104	38
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	-1.565482	20	10
IGF1R signaling cascade	-1.565482	20	10
Interferon gamma signaling	-1.549480	30	15
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	-1.540638	25	12
Interleukin-37 signaling	-1.539840	10	8
G alpha (12/13) signalling events	-1.535679	39	17
Signaling by CSF3 (G-CSF)	-1.529843	22	12
GPCR ligand binding	-1.529233	61	14
G alpha (i) signalling events	-1.520189	61	13
rRNA modification in the nucleus and cytosol	-1.512065	54	26
Fcgamma receptor (FCGR) dependent phagocytosis	-1.502643	59	18
Signaling by Interleukins	-1.501554	216	86
Diseases of signal transduction by growth factor receptors and second messengers	-1.492363	279	82
Extracellular matrix organization	-1.475897	124	30
Signaling by Receptor Tyrosine Kinases	-1.437949	277	76
RHO GTPase cycle	-1.426424	289	78
CDC42 GTPase cycle	-1.417491	97	34
Cytokine Signaling in Immune system	-1.333779	338	112
Metabolism of lipids	1.362471	436	114
SLC transporter disorders	1.500487	53	13
Diseases of metabolism	1.515116	131	36
Complex I biogenesis	1.525126	42	17
Metabolism of amino acids and derivatives	1.530165	260	99
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	1.530984	42	25
p53-Independent DNA Damage Response	1.530984	42	25
p53-Independent G1/S DNA damage checkpoint	1.530984	42	25
AUF1 (hnRNP D0) binds and destabilizes mRNA	1.554179	44	27
Regulation of activated PAK-2p34 by proteasome mediated degradation	1.559095	42	25
Biological oxidations	1.559514	85	43
Somitogenesis	1.577357	40	24
Autodegradation of the E3 ubiquitin ligase COP1	1.579467	44	27
Disorders of transmembrane transporters	1.580149	114	22
Regulation of Apoptosis	1.587880	43	26
Mitochondrial protein degradation	1.594150	75	30
Sulfur amino acid metabolism	1.619725	22	10
ABC transporter disorders	1.625230	61	31
Regulation of beta-cell development	1.625786	19	4
Respiratory electron transport	1.626783	78	33
Metabolism of nucleotides	1.651396	69	18
Asymmetric localization of PCP proteins	1.651439	47	23
Aquaporin-mediated transport	1.658361	17	5
Pyruvate metabolism	1.667465	31	14
RHO GTPases activate CIT	1.667608	10	3
Degradation of DVL	1.667783	45	27
Diseases of carbohydrate metabolism	1.681234	22	8
Drug ADME	1.682511	36	10
Degradation of AXIN	1.686945	45	27
Regulation of Glucokinase by Glucokinase Regulatory Protein	1.693556	24	6
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1.693556	24	6
Nucleotide catabolism	1.696699	22	8
RHO GTPases activate PAKs	1.697307	13	4
Triglyceride catabolism	1.699835	10	4
Lysine catabolism	1.713094	12	8
Hedgehog ligand biogenesis	1.729542	49	30
Regulation of pyruvate dehydrogenase (PDH) complex	1.729713	10	5
Cristae formation	1.742941	24	13
Visual phototransduction	1.748230	35	14
Hh mutants abrogate ligand secretion	1.749674	47	29
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.751881	94	41
Aerobic respiration and respiratory electron transport	1.753255	147	58
Hh mutants are degraded by ERAD	1.758956	46	29
Peroxisomal protein import	1.759622	44	28
Formation of ATP by chemiosmotic coupling	1.788182	12	7
Branched-chain amino acid catabolism	1.846272	17	9
Defective CFTR causes cystic fibrosis	1.891005	51	32
Degradation of cysteine and homocysteine	1.894221	11	6
Triglyceride metabolism	1.898246	18	7
Initial triggering of complement	1.912913	12	3
Complement cascade	1.960510	28	5
The canonical retinoid cycle in rods (twilight vision)	2.335860	10	8

IV-HD

Description	NES	setSize	Count
tRNA modification in the nucleus and cytosol	-2.177561	21	14
tRNA processing	-2.114216	64	33
Activation of the pre-replicative complex	-2.092571	23	13
Interleukin-4 and Interleukin-13 signaling	-2.024606	39	13
DNA strand elongation	-1.991399	25	13
rRNA modification in the nucleus and cytosol	-1.951206	54	23
Activation of ATR in response to replication stress	-1.881421	26	13
Synthesis of DNA	-1.771895	89	30
Regulation of actin dynamics for phagocytic cup formation	-1.769697	41	11
Fcgamma receptor (FCGR) dependent phagocytosis	-1.733032	57	15
Amplification of signal from the kinetochores	-1.721040	54	22
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	-1.721040	54	22
Recruitment of mitotic centrosome proteins and complexes	-1.718997	41	13
Centrosome maturation	-1.718997	41	13
Cell Cycle, Mitotic	-1.711076	306	100
RHO GTPases Activate Formins	-1.688922	68	29
DNA Replication	-1.674303	95	30
S Phase	-1.672746	116	37
Mitotic Prometaphase	-1.671646	107	38
Response to elevated platelet cytosolic Ca2+	-1.664125	70	17
Cell Cycle	-1.606754	363	110
Platelet degranulation	-1.604579	66	15
G1/S Transition	-1.598515	94	30
Mitotic G1 phase and G1/S transition	-1.573187	103	32
Cell Cycle Checkpoints	-1.571586	156	52
M Phase	-1.538726	216	67
Sphingolipid metabolism	1.648678	51	20
NCAM signaling for neurite out-growth	1.803092	21	10
Regulation of beta-cell development	1.899808	17	5
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1.952205	14	5
FOXO-mediated transcription	2.146193	33	14

IV-LD

Description	NES	setSize	Count
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	-1.963323	21	10
Downregulation of SMAD2/3:SMAD4 transcriptional activity	-1.922826	21	6
RHO GTPases Activate NADPH Oxidases	-1.921551	17	8
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	-1.917286	37	9
Fcgamma receptor (FCGR) dependent phagocytosis	-1.880702	64	28
Amino acid transport across the plasma membrane	-1.879409	18	7
Transport of inorganic cations/anions and amino acids/oligopeptides	-1.856819	45	15
Signaling by ERBB2 in Cancer	-1.838310	14	6
Signaling by ERBB2 KD Mutants	-1.838310	14	6
FCGR3A-mediated IL10 synthesis	-1.836638	21	9
Platelet activation, signaling and aggregation	-1.835522	145	52
Cell surface interactions at the vascular wall	-1.833250	66	26
Signaling by ERBB2 ECD mutants	-1.804882	13	6
Regulation of insulin secretion	-1.802926	26	9
FCERI mediated Ca+2 mobilization	-1.802784	19	10
ROS and RNS production in phagocytes	-1.792430	19	7
Signaling by ERBB2 TMD/JMD mutants	-1.765167	11	5
VEGFA-VEGFR2 Pathway	-1.754364	70	18
RHO GTPases Activate ROCKs	-1.741422	12	9
PI3K/AKT Signaling in Cancer	-1.737552	46	26
G alpha (q) signalling events	-1.729742	62	19
Netrin-1 signaling	-1.724029	17	6
Signaling by VEGF	-1.718570	74	18
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	-1.714377	25	7
Semaphorin interactions	-1.709944	40	20
G alpha (i) signalling events	-1.706816	65	19
Platelet calcium homeostasis	-1.702921	11	5
Effects of PIP2 hydrolysis	-1.700834	11	6
Cholesterol biosynthesis	-1.695521	23	11
EPHA-mediated growth cone collapse	-1.688049	14	11
Interleukin-4 and Interleukin-13 signaling	-1.686119	43	25
Hemostasis	-1.685229	305	119
RAF-independent MAPK1/3 activation	-1.677323	14	10
G-protein mediated events	-1.672555	22	6
Sema4D induced cell migration and growth-cone collapse	-1.668424	13	9
Signaling by FGFR1	-1.667585	25	14
Role of phospholipids in phagocytosis	-1.666463	16	11
Nuclear Receptor transcription pathway	-1.663007	32	11
Sema4D in semaphorin signaling	-1.658031	17	10
Smooth Muscle Contraction	-1.646729	24	14
RAC3 GTPase cycle	-1.644313	64	24
Signaling by ERBB2	-1.644090	29	12
Signaling by CSF1 (M-CSF) in myeloid cells	-1.643930	22	8
PLC beta mediated events	-1.640126	19	5
GPCR downstream signalling	-1.636954	170	49
Constitutive Signaling by Aberrant PI3K in Cancer	-1.634688	28	14
Signaling by GPCR	-1.634416	184	53
Muscle contraction	-1.633358	64	24
Negative regulation of the PI3K/AKT network	-1.617022	49	25
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	-1.615472	46	23
SLC-mediated transmembrane transport	-1.615031	104	29
Signaling by ALK in cancer	-1.614893	66	26
Signaling by ALK fusions and activated point mutants	-1.614893	66	26
Activation of gene expression by SREBF (SREBP)	-1.612002	38	17
Class A/1 (Rhodopsin-like receptors)	-1.609446	51	14
Platelet degranulation	-1.603596	74	22
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	-1.599137	31	5
Negative regulation of MAPK pathway	-1.593495	27	14
Parasite infection	-1.591010	46	18
Leishmania phagocytosis	-1.591010	46	18
FCGR3A-mediated phagocytosis	-1.591010	46	18
Fc epsilon receptor (FCERI) signaling	-1.573421	93	24
Anti-inflammatory response favouring Leishmania parasite infection	-1.571348	36	17
Leishmania parasite growth and survival	-1.571348	36	17
Response to elevated platelet cytosolic Ca2+	-1.569407	78	31
Ca2+ pathway	-1.567243	27	10
Signaling by Interleukins	-1.561478	224	82
Costimulation by the CD28 family	-1.547630	35	16
RAC2 GTPase cycle	-1.542744	66	16
Signaling by Receptor Tyrosine Kinases	-1.523483	296	95
Transcriptional regulation by RUNX1	-1.500291	122	41
RHO GTPase Effectors	-1.491957	170	58
RAC1 GTPase cycle	-1.474237	128	49
Diseases of signal transduction by growth factor receptors and second messengers	-1.456128	289	105
Cytokine Signaling in Immune system	-1.443442	352	125
Adaptive Immune System	-1.396534	409	120
RHO GTPase cycle	-1.353014	305	101
Signaling by Rho GTPases	-1.336077	429	134
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	-1.332690	439	139
rRNA processing in the nucleus and cytosol	1.276087	157	75
Major pathway of rRNA processing in the nucleolus and cytosol	1.422418	147	77
Metabolism of amino acids and derivatives	1.426549	264	122
Metabolism of nucleotides	1.469857	72	22
Translation	1.475773	237	117
Cellular response to starvation	1.561049	117	45
Aerobic respiration and respiratory electron transport	1.664542	151	77
Regulation of expression of SLITs and ROBOs	1.668917	132	50
Selenoamino acid metabolism	1.730473	93	56
Retrograde neurotrophin signalling	1.807523	11	6
Response of EIF2AK4 (GCN2) to amino acid deficiency	1.812629	80	54
Respiratory electron transport	1.818833	80	44
The canonical retinoid cycle in rods (twilight vision)	1.819757	10	8
Formation of ATP by chemiosmotic coupling	1.848615	12	9
SARS-CoV-2 modulates host translation machinery	1.861811	38	25
SARS-CoV-1 modulates host translation machinery	1.885818	29	21
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.982287	96	54
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	2.004224	50	31
Ribosomal scanning and start codon recognition	2.013422	50	31
Nonsense-Mediated Decay (NMD)	2.013986	89	57
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2.013986	89	57
Cristae formation	2.016761	24	16
Translation initiation complex formation	2.024032	49	31
Eukaryotic Translation Termination	2.154457	73	51
Formation of the ternary complex, and subsequently, the 43S complex	2.157697	44	30
SRP-dependent cotranslational protein targeting to membrane	2.237501	88	58
Eukaryotic Translation Initiation	2.271027	97	63
Cap-dependent Translation Initiation	2.271027	97	63
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.283325	74	52
Selenocysteine synthesis	2.335805	73	52
L13a-mediated translational silencing of Ceruloplasmin expression	2.347708	90	61
GTP hydrolysis and joining of the 60S ribosomal subunit	2.348593	91	61
Peptide chain elongation	2.375799	69	51
Eukaryotic Translation Elongation	2.390348	71	53
Formation of a pool of free 40S subunits	2.400952	82	58
Viral mRNA Translation	2.415355	69	51

Head-kidney

4 WPC

DNA vaccine

Description	NES	setSize	Count
Peptide ligand-binding receptors	-1.898369	37	16
Class A/1 (Rhodopsin-like receptors)	-1.868515	79	31
GPCR ligand binding	-1.851556	101	37
Cellular hexose transport	-1.717279	11	5
Sensory processing of sound by inner hair cells of the cochlea	-1.714307	33	15
Signaling by GPCR	-1.686628	258	85
Sensory processing of sound	-1.674182	36	17
RORA activates gene expression	-1.668492	16	5
Constitutive Signaling by Aberrant PI3K in Cancer	-1.667587	35	14
Nitric oxide stimulates guanylate cyclase	-1.665922	10	5
Glutamate Neurotransmitter Release Cycle	-1.641438	15	10
HS-GAG biosynthesis	-1.634413	18	8
Long-term potentiation	-1.619079	10	5
IRS-related events triggered by IGF1R	-1.601692	28	12
GPCR downstream signalling	-1.596801	241	78
Receptor-type tyrosine-protein phosphatases	-1.588085	12	5
Sensory processing of sound by outer hair cells of the cochlea	-1.587560	25	14
NCAM1 interactions	-1.586362	16	6
G alpha (12/13) signalling events	-1.580873	53	34
Metal ion SLC transporters	-1.576531	14	7
NRAGE signals death through JNK	-1.572897	43	16
Class B/2 (Secretin family receptors)	-1.551199	21	6
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	-1.550559	29	14
IGF1R signaling cascade	-1.550559	29	14
G alpha (i) signalling events	-1.548316	100	35
Negative regulation of the PI3K/AKT network	-1.546372	62	22
Potassium Channels	-1.545506	23	9
Dopamine Neurotransmitter Release Cycle	-1.544575	14	6
Metabolism of fat-soluble vitamins	-1.543244	25	12
Activation of SMO	-1.540024	11	6
Signaling by WNT in cancer	-1.515090	21	10
Laminin interactions	-1.507777	18	5
RHOB GTPase cycle	-1.502878	64	27
NCAM signaling for neurite out-growth	-1.499037	33	10
NGF-stimulated transcription	-1.496005	24	11
Disassembly of the destruction complex and recruitment of AXIN to the membrane	-1.492778	20	10
Transport of bile salts and organic acids, metal ions and amine compounds	-1.485597	37	17
Defective B3GALT6 causes EDSP2 and SEMDJL1	-1.481914	10	4
CDC42 GTPase cycle	-1.480730	125	60
SLC-mediated transmembrane transport	-1.470681	129	53
Sensory Perception	-1.469184	80	30
Ca2+ pathway	-1.459038	34	11
Protein-protein interactions at synapses	-1.457523	43	14
Muscle contraction	-1.443707	90	24
Signaling by NTRKs	-1.421794	98	38
Sphingolipid metabolism	-1.417192	70	11
G alpha (q) signalling events	-1.414677	88	44
RHOA GTPase cycle	-1.409192	127	48
PI3K/AKT Signaling in Cancer	-1.406538	57	20
Signaling by NTRK1 (TRKA)	-1.380517	84	34
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	-1.379232	78	34
Toll Like Receptor TLR1:TLR2 Cascade	-1.379232	78	34
Toll Like Receptor TLR6:TLR2 Cascade	-1.379232	78	34
Toll Like Receptor 2 (TLR2) Cascade	-1.379232	78	34
Neuronal System	-1.361198	164	57
Transmission across Chemical Synapses	-1.353636	117	40
Axon guidance	1.138802	361	94
Adaptive Immune System	1.201348	488	108
Neutrophil degranulation	1.208304	296	116
SARS-CoV Infections	1.311292	305	94
RHO GTPases Activate Formins	1.336346	97	45
SARS-CoV-2 Infection	1.346521	214	68
UCH proteinases	1.378611	75	24
SARS-CoV-1 Infection	1.391961	111	44
CLEC7A (Dectin-1) signaling	1.407009	81	20
Downstream TCR signaling	1.412984	70	22
KEAP1-NFE2L2 pathway	1.416750	102	23
RNA Polymerase II Pre-transcription Events	1.441413	71	20
Global Genome Nucleotide Excision Repair (GG-NER)	1.450598	70	18
ER-Phagosome pathway	1.450672	63	23
Transport of Mature mRNAs Derived from Intronless Transcripts	1.454109	35	9
Mitotic Prometaphase	1.456858	153	61
Protein localization	1.459801	121	34
Neddylation	1.460006	193	46
SUMOylation of chromatin organization proteins	1.470953	47	12
Formation of paraxial mesoderm	1.473598	54	17
PTEN Regulation	1.476454	117	28
RHO GTPase Effectors	1.481098	198	76
Antigen processing-Cross presentation	1.481510	75	29
C-type lectin receptors (CLRs)	1.483194	95	23
EML4 and NUDC in mitotic spindle formation	1.487638	84	42
Transport of Mature mRNA Derived from an Intronless Transcript	1.488959	34	9
Nucleotide Excision Repair	1.490695	91	23
ISG15 antiviral mechanism	1.498335	55	12
Export of Viral Ribonucleoproteins from Nucleus	1.502679	27	8
NEP/NS2 Interacts with the Cellular Export Machinery	1.502679	27	8
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1.503871	32	8
Transport of the SLBP independent Mature mRNA	1.506275	28	8
Glycolysis	1.512998	51	15
HCMV Early Events	1.516398	54	15
Mitotic Spindle Checkpoint	1.521303	90	40
Amplification of signal from the kinetochores	1.522766	76	36
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1.522766	76	36
ATF4 activates genes in response to endoplasmic reticulum stress	1.529761	22	9
Nuclear Envelope (NE) Reassembly	1.534652	51	24
TCR signaling	1.538692	87	28
SARS-CoV-2-host interactions	1.540857	139	58
Cellular response to chemical stress	1.542184	159	54
mRNA Splicing	1.543553	180	73
BBSome-mediated cargo-targeting to cilium	1.546516	15	7
Mitotic G2-G2/M phases	1.546591	150	48
Signaling by the B Cell Receptor (BCR)	1.547450	93	25
Transcription of the HIV genome	1.547464	61	19
Transcriptional regulation by RUNX1	1.549167	142	32
G2/M Transition	1.552014	149	48
Vpr-mediated nuclear import of PICs	1.552132	26	8
Somitogenesis	1.554455	46	17
Deposition of new CENPA-containing nucleosomes at the centromere	1.554581	21	6
Nucleosome assembly	1.554581	21	6
Regulation of Glucokinase by Glucokinase Regulatory Protein	1.563185	25	8
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1.563185	25	8
Metabolism of amino acids and derivatives	1.563329	267	112
mRNA Splicing - Minor Pathway	1.563560	44	12
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1.563972	27	12
Meiotic synapsis	1.564023	23	5
SUMOylation of RNA binding proteins	1.565725	38	11
mRNA 3'-end processing	1.570448	51	27
HIV Transcription Initiation	1.570483	40	11
RNA Polymerase II HIV Promoter Escape	1.570483	40	11
RNA Polymerase II Promoter Escape	1.570483	40	11
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1.570483	40	11
RNA Polymerase II Transcription Initiation	1.570483	40	11
RNA Polymerase II Transcription Initiation And Promoter Clearance	1.570483	40	11
Signaling by FGFR2 IIIa TM	1.576421	16	6
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1.580540	10	8
mRNA Splicing - Major Pathway	1.581028	173	71
Termination of translesion DNA synthesis	1.582349	25	7
Transport of Mature mRNA derived from an Intron-Containing Transcript	1.587545	61	29
mRNA decay by 3' to 5' exoribonuclease	1.596144	14	7
Telomere Maintenance	1.596961	62	16
APC/C:Cdc20 mediated degradation of Cyclin B	1.602951	20	6
Resolution of Sister Chromatid Cohesion	1.603552	94	45
FCERI mediated NF-kB activation	1.610498	65	21
Mitochondrial protein import	1.611419	50	24
Dual Incision in GG-NER	1.612127	33	8
Removal of the Flap Intermediate from the C-strand	1.617365	14	10
SUMOylation of DNA replication proteins	1.617774	39	13
Downstream signaling events of B Cell Receptor (BCR)	1.621439	68	23
Transport of Mature Transcript to Cytoplasm	1.626752	69	33
MHC class II antigen presentation	1.629213	78	19
Processing of Capped Intron-Containing Pre-mRNA	1.631444	239	99
NS1 Mediated Effects on Host Pathways	1.632671	32	10
MAPK6/MAPK4 signaling	1.639220	76	22
SUMOylation of SUMOylation proteins	1.640954	29	9
Gap-filling DNA repair synthesis and ligation in TC-NER	1.641227	53	13
Hedgehog 'off' state	1.643923	81	27
HIV elongation arrest and recovery	1.644714	30	9
Pausing and recovery of HIV elongation	1.644714	30	9
Chromosome Maintenance	1.645756	80	28
PERK regulates gene expression	1.652403	27	11
Pausing and recovery of Tat-mediated HIV elongation	1.653135	29	9
Tat-mediated HIV elongation arrest and recovery	1.653135	29	9
Interconversion of nucleotide di- and triphosphates	1.655394	19	8
Regulation of PTEN stability and activity	1.660899	59	19
tRNA processing in the nucleus	1.662955	48	13
DNA Damage Bypass	1.663316	41	12
Base Excision Repair	1.671815	37	22
Cell Cycle, Mitotic	1.674286	407	163
Formation of TC-NER Pre-Incision Complex	1.675714	45	11
Dual incision in TC-NER	1.678389	53	13
SARS-CoV-1-host interactions	1.679226	74	34
Interactions of Vpr with host cellular proteins	1.679614	27	9
Formation of tubulin folding intermediates by CCT/TriC	1.680516	12	10
Late Phase of HIV Life Cycle	1.683110	115	37
Prefoldin mediated transfer of substrate to CCT/TriC	1.688304	18	11
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1.688304	18	11
rRNA processing	1.688988	172	58
Condensation of Prometaphase Chromosomes	1.691717	11	5
Translesion synthesis by POLI	1.693945	15	4
M Phase	1.695185	287	119
RNA Polymerase II Transcription Termination	1.703843	56	30
Translesion Synthesis by POLH	1.709257	17	5
Disorders of transmembrane transporters	1.709713	116	32
SUMOylation of ubiquitinylation proteins	1.720380	31	10
SUMOylation of DNA damage response and repair proteins	1.721382	61	16
Regulation of mRNA stability by proteins that bind AU-rich elements	1.721465	75	26
Collagen degradation	1.722414	31	10
snRNP Assembly	1.726941	44	13
Metabolism of non-coding RNA	1.726941	44	13
Gap-filling DNA repair synthesis and ligation in GG-NER	1.728069	20	8
Unwinding of DNA	1.730626	11	3
Nuclear events mediated by NFE2L2	1.732387	76	31
ABC-family proteins mediated transport	1.735827	76	25
Regulation of RUNX2 expression and activity	1.739000	56	19
Cell Cycle Checkpoints	1.741388	215	98
Translesion synthesis by REV1	1.741781	14	4
Condensation of Prophase Chromosomes	1.742712	16	10
Maternal to zygotic transition (MZT)	1.746421	42	3
Activation of NF-kappaB in B cells	1.752844	57	20
TNFR2 non-canonical NF-kB pathway	1.755333	60	21
Lagging Strand Synthesis	1.757589	18	8
Metabolic disorders of biological oxidation enzymes	1.763286	17	6
HIV Life Cycle	1.764963	123	41
Abortive elongation of HIV-1 transcript in the absence of Tat	1.767302	22	12
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1.769134	65	19
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1.772279	21	11
Glutathione conjugation	1.792277	17	10
G1/S DNA Damage Checkpoints	1.793583	58	21
ATF6 (ATF6-alpha) activates chaperone genes	1.802080	10	7
Hh mutants abrogate ligand secretion	1.803321	50	20
p53-Dependent G1 DNA Damage Response	1.806012	57	21
p53-Dependent G1/S DNA damage checkpoint	1.806012	57	21
Signaling by NOTCH4	1.807572	66	23
rRNA processing in the nucleus and cytosol	1.808687	162	57
Cyclin A:Cdk2-associated events at S phase entry	1.813637	76	25
Inhibition of DNA recombination at telomere	1.818177	21	7
Mitochondrial translation termination	1.832632	76	43
Cyclin E associated events during G1/S transition	1.835220	74	25
G2/M Checkpoints	1.836895	115	55
Maturation of TCA enzymes and regulation of TCA cycle	1.837153	17	12
Transcriptional regulation by small RNAs	1.842060	45	14
Mitochondrial translation initiation	1.842166	76	44
Mitotic Anaphase	1.844995	184	80
Mitotic Metaphase and Anaphase	1.849734	185	81
Hedgehog ligand biogenesis	1.852418	52	21
PCNA-Dependent Long Patch Base Excision Repair	1.871621	17	8
Host Interactions of HIV factors	1.874978	107	36
Complex I biogenesis	1.875018	44	22
Mitochondrial translation	1.876080	82	46
Mitochondrial translation elongation	1.887312	76	45
Dectin-1 mediated noncanonical NF-kB signaling	1.895239	52	19
HIV Infection	1.896702	191	64
Heme biosynthesis	1.899694	11	7
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1.901211	65	22
Viral Messenger RNA Synthesis	1.905425	38	14
ATF6 (ATF6-alpha) activates chaperones	1.907050	12	8
Major pathway of rRNA processing in the nucleolus and cytosol	1.907547	152	55
AUF1 (hnRNP D0) binds and destabilizes mRNA	1.912492	47	18
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1.921740	48	19
FGFR2 alternative splicing	1.923406	21	10
Cellular response to starvation	1.923815	125	41
Degradation of GLI1 by the proteasome	1.925014	50	20
PCP/CE pathway	1.925900	70	37
APC/C-mediated degradation of cell cycle proteins	1.927213	77	28
Regulation of mitotic cell cycle	1.927213	77	28
Metabolism of polyamines	1.938700	53	27
Activation of the pre-replicative complex	1.941105	28	18
Cellular response to hypoxia	1.941721	65	23
NIK-->noncanonical NF-kB signaling	1.945799	51	19
Activation of Matrix Metalloproteinases	1.954516	11	4
GLI3 is processed to GLI3R by the proteasome	1.968317	51	20
Activation of ATR in response to replication stress	1.970960	33	21
Switching of origins to a post-replicative state	1.978475	81	41
Citric acid cycle (TCA cycle)	1.981681	30	18
SCF-beta-TrCP mediated degradation of Emi1	1.984259	48	19
Asymmetric localization of PCP proteins	1.984539	52	28
Mitotic G1 phase and G1/S transition	1.988280	125	62
Separation of Sister Chromatids	1.988696	148	74
DNA strand elongation	1.994820	29	11
Degradation of GLI2 by the proteasome	1.997713	50	20
Stabilization of p53	2.004577	48	18
ABC transporter disorders	2.006541	61	24
Cristae formation	2.019671	24	17
Regulation of APC/C activators between G1/S and early anaphase	2.029764	71	27
Nonsense-Mediated Decay (NMD)	2.031480	92	48
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2.031480	92	48
Vpu mediated degradation of CD4	2.031771	45	19
RHO GTPases activate PKNs	2.032475	30	18
SCF(Skp2)-mediated degradation of p27/p21	2.045367	54	22
Orc1 removal from chromatin	2.046792	64	36
Negative regulation of NOTCH4 signaling	2.048350	47	20
Recognition of DNA damage by PCNA-containing replication complex	2.062587	25	11
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	2.062993	46	19
Degradation of DVL	2.076107	50	29
G1/S Transition	2.078545	113	60
S Phase	2.082303	144	46
Respiratory electron transport	2.088733	83	41
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2.090415	65	24
Autodegradation of the E3 ubiquitin ligase COP1	2.097057	46	18
Aerobic respiration and respiratory electron transport	2.113940	161	74
Formation of ATP by chemiosmotic coupling	2.114518	12	7
APC/C:Cdc20 mediated degradation of mitotic proteins	2.121036	66	25
Selenoamino acid metabolism	2.125163	95	52
Regulation of ornithine decarboxylase (ODC)	2.130723	46	25
Translation	2.132676	249	124
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	2.149238	58	21
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2.152249	67	26
Degradation of AXIN	2.168457	48	19
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.169438	98	48
Cross-presentation of soluble exogenous antigens (endosomes)	2.169850	42	25
SARS-CoV-1 modulates host translation machinery	2.171885	30	17
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	2.179124	64	33
CDK-mediated phosphorylation and removal of Cdc6	2.189034	64	33
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	2.195298	45	18
p53-Independent DNA Damage Response	2.195298	45	18
p53-Independent G1/S DNA damage checkpoint	2.195298	45	18
The role of GTSE1 in G2/M progression after G2 checkpoint	2.200940	58	25
APC/C:Cdc20 mediated degradation of Securin	2.201093	58	22
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	2.205780	64	24
Assembly of the pre-replicative complex	2.206283	76	27
Regulation of activated PAK-2p34 by proteasome mediated degradation	2.211546	44	18
Selenocysteine synthesis	2.220933	75	52
Ubiquitin-dependent degradation of Cyclin D	2.222888	46	19
Metabolism of porphyrins	2.223918	17	11
Regulation of Apoptosis	2.232589	47	27
Autodegradation of Cdh1 by Cdh1:APC/C	2.244973	56	21
Eukaryotic Translation Termination	2.252142	74	53
Regulation of RUNX3 expression and activity	2.253519	47	18
Synthesis of DNA	2.253831	106	40
Influenza Infection	2.259532	126	70
Vif-mediated degradation of APOBEC3G	2.266014	47	20
Detoxification of Reactive Oxygen Species	2.266782	22	18
DNA Replication	2.269363	115	62
SARS-CoV-2 modulates host translation machinery	2.287955	39	21
Influenza Viral RNA Transcription and Replication	2.298649	111	61
Hh mutants are degraded by ERAD	2.304187	48	28
Peptide chain elongation	2.307492	71	52
DNA Replication Pre-Initiation	2.321567	90	49
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	2.323919	51	24
Eukaryotic Translation Elongation	2.335797	73	53
Translation initiation complex formation	2.343264	50	24
Response of EIF2AK4 (GCN2) to amino acid deficiency	2.344863	82	46
Defective CFTR causes cystic fibrosis	2.364787	52	31
Ribosomal scanning and start codon recognition	2.389005	51	25
Formation of the ternary complex, and subsequently, the 43S complex	2.391335	45	24
Signaling by ROBO receptors	2.439710	166	95
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.440381	75	53
Viral mRNA Translation	2.456060	70	52
SRP-dependent cotranslational protein targeting to membrane	2.459457	89	52
Eukaryotic Translation Initiation	2.477005	98	66
Cap-dependent Translation Initiation	2.477005	98	66
L13a-mediated translational silencing of Ceruloplasmin expression	2.513564	91	55
Formation of a pool of free 40S subunits	2.519407	83	61
GTP hydrolysis and joining of the 60S ribosomal subunit	2.535719	92	56
Regulation of expression of SLITs and ROBOs	2.575939	136	83
Mitochondrial protein degradation	2.577030	81	50

EOMES

Description	NES	setSize	Count
Sensory processing of sound by inner hair cells of the cochlea	-1.748837	31	17
Long-term potentiation	-1.688954	10	5
Dopamine Neurotransmitter Release Cycle	-1.664041	13	7
Sensory processing of sound	-1.663711	34	16
Protein-protein interactions at synapses	-1.581498	42	15
Transmission across Chemical Synapses	-1.479524	115	34
Metabolism of carbohydrates	1.578805	189	49
Response to elevated platelet cytosolic Ca2+	1.581291	78	21
Metabolism of steroids	1.584888	97	24
rRNA processing	1.593360	172	64
Diseases of metabolism	1.595154	144	35
Platelet degranulation	1.596438	74	20
Extracellular matrix organization	1.600723	155	29
Glucose metabolism	1.634594	54	14
Disorders of transmembrane transporters	1.636374	114	33
rRNA processing in the nucleus and cytosol	1.664360	162	75
Translation	1.667454	249	105
Maternal to zygotic transition (MZT)	1.700397	40	4
Pyruvate metabolism	1.705549	37	14
Cellular response to starvation	1.706554	124	57
Degradation of the extracellular matrix	1.718058	66	14
Glycogen metabolism	1.732991	20	8
Plasma lipoprotein assembly, remodeling, and clearance	1.733256	46	15
Collagen biosynthesis and modifying enzymes	1.735078	30	15
Metabolism of nucleotides	1.742821	74	21
Nucleotide catabolism	1.743800	24	7
Formation of ATP by chemiosmotic coupling	1.747353	12	11
Amyloid fiber formation	1.750055	34	13
Lysine catabolism	1.756481	11	7
Peroxisomal lipid metabolism	1.757965	19	12
Metabolism of vitamins and cofactors	1.758470	131	35
Activation of Matrix Metalloproteinases	1.758975	11	5
Arachidonic acid metabolism	1.759124	30	14
Phase II - Conjugation of compounds	1.784450	48	16
Assembly of active LPL and LIPC lipase complexes	1.800929	11	5
Major pathway of rRNA processing in the nucleolus and cytosol	1.801319	152	73
Formation of Fibrin Clot (Clotting Cascade)	1.802891	13	3
Fatty acid metabolism	1.807310	118	43
Integrin cell surface interactions	1.809870	47	11
Metabolism of folate and pterines	1.831727	11	6
Degradation of cysteine and homocysteine	1.840771	13	8
SARS-CoV-2 modulates host translation machinery	1.845231	39	26
SARS-CoV-1 modulates host translation machinery	1.851809	30	21
Attachment and Entry	1.864010	11	7
Protein localization	1.884595	121	39
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1.888422	27	10
Respiratory electron transport	1.896364	83	41
Metabolism of porphyrins	1.897188	17	11
Sulfur amino acid metabolism	1.897366	24	12
Binding and Uptake of Ligands by Scavenger Receptors	1.907952	23	7
Metabolic disorders of biological oxidation enzymes	1.925527	17	7
Nonsense-Mediated Decay (NMD)	1.928087	92	56
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1.928087	92	56
Heme biosynthesis	1.951164	11	8
Plasma lipoprotein remodeling	1.955769	19	9
Translation initiation complex formation	1.964003	50	26
Post-translational protein phosphorylation	1.966010	50	18
Scavenging by Class A Receptors	1.980234	14	5
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1.992614	51	27
Cytochrome P450 - arranged by substrate type	1.993397	22	10
Peroxisomal protein import	1.994364	44	18
Detoxification of Reactive Oxygen Species	2.005465	22	13
Ribosomal scanning and start codon recognition	2.007552	51	27
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	2.015502	98	50
Formation of the ternary complex, and subsequently, the 43S complex	2.025754	45	26
Metabolism of fat-soluble vitamins	2.035588	25	12
Influenza Infection	2.037178	125	67
Influenza Viral RNA Transcription and Replication	2.066656	110	64
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	2.092458	56	21
Aerobic respiration and respiratory electron transport	2.110440	160	78
Retinoid metabolism and transport	2.147202	21	9
Glutathione conjugation	2.149258	17	7
Collagen degradation	2.163898	30	11
Signaling by ROBO receptors	2.178178	165	91
Eukaryotic Translation Termination	2.188410	74	51
Selenoamino acid metabolism	2.193095	95	61
Regulation of expression of SLITs and ROBOs	2.201981	135	78
Selenocysteine synthesis	2.230963	75	50
Visual phototransduction	2.236597	36	15
Peptide chain elongation	2.250277	71	50
SRP-dependent cotranslational protein targeting to membrane	2.268162	89	60
Eukaryotic Translation Elongation	2.279521	73	51
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.287740	75	51
Response of EIF2AK4 (GCN2) to amino acid deficiency	2.295444	82	53
Mitochondrial protein degradation	2.316663	81	46
Eukaryotic Translation Initiation	2.333654	98	59
Cap-dependent Translation Initiation	2.333654	98	59
Viral mRNA Translation	2.342171	70	50
L13a-mediated translational silencing of Ceruloplasmin expression	2.359260	91	56
GTP hydrolysis and joining of the 60S ribosomal subunit	2.378197	92	57
Metabolism of amino acids and derivatives	2.381380	265	125
Formation of a pool of free 40S subunits	2.401536	83	56
Phase I - Functionalization of compounds	2.407338	41	18
Biological oxidations	2.417072	94	36

GATA3

Description	NES	setSize	Count
Synthesis of very long-chain fatty acyl-CoAs	-1.684479	19	9
Sensory processing of sound	-1.668433	32	14
Sensory processing of sound by inner hair cells of the cochlea	-1.629033	29	15
HS-GAG biosynthesis	-1.626025	17	8
Sensory processing of sound by outer hair cells of the cochlea	-1.608837	21	9
Metabolism of fat-soluble vitamins	-1.606457	25	16
Nicotinamide salvaging	-1.595758	13	7
Plasma lipoprotein remodeling	-1.594360	19	11
Bile acid and bile salt metabolism	-1.591882	22	9
Synthesis of PIPs at the late endosome membrane	-1.553295	11	6
RHOB GTPase cycle	-1.541174	63	21
NRAGE signals death through JNK	-1.535744	42	19
Peptide ligand-binding receptors	-1.517745	34	12
Class A/1 (Rhodopsin-like receptors)	-1.513317	74	31
G alpha (12/13) signalling events	-1.508970	52	33
Muscle contraction	-1.501913	88	21
Signaling by GPCR	-1.499479	245	105
GPCR ligand binding	-1.484694	91	33
GPCR downstream signalling	-1.476687	230	98
Metabolism of vitamins and cofactors	-1.474144	131	48
SLC-mediated transmembrane transport	-1.441127	127	34
G alpha (q) signalling events	-1.429814	86	40
Metabolism of lipids	-1.257625	500	139
Neutrophil degranulation	1.283297	293	96
Nervous system development	1.287317	363	112
SARS-CoV Infections	1.300935	303	82
Axon guidance	1.317153	350	110
SARS-CoV-2-host interactions	1.342103	138	40
Signaling by NOTCH	1.349235	139	43
Adaptive Immune System	1.351711	481	135
Mitotic Prometaphase	1.363991	151	46
Cellular response to chemical stress	1.377313	159	52
G2/M Checkpoints	1.403760	115	35
mRNA Splicing	1.416873	179	64
CLEC7A (Dectin-1) signaling	1.428114	80	26
Cell Cycle Checkpoints	1.435963	215	70
Mitotic G2-G2/M phases	1.443498	148	54
G2/M Transition	1.450079	147	54
Amplification of signal from the kinetochores	1.461076	76	27
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1.461076	76	27
Cell Cycle	1.462536	497	149
Metabolism of amino acids and derivatives	1.476012	264	106
Switching of origins to a post-replicative state	1.480159	81	31
ABC-family proteins mediated transport	1.482829	74	27
rRNA processing	1.489591	172	63
mRNA Splicing - Major Pathway	1.505290	172	64
Regulation of TNFR1 signaling	1.508306	37	11
FCERI mediated NF-kB activation	1.511784	65	24
UCH proteinases	1.515172	75	28
Processing of Capped Intron-Containing Pre-mRNA	1.522370	236	84
Hedgehog 'off' state	1.526536	80	30
HCMV Late Events	1.533330	45	12
SUMOylation of DNA replication proteins	1.535361	38	15
Transport of the SLBP independent Mature mRNA	1.536768	27	7
Citric acid cycle (TCA cycle)	1.545413	30	15
Postmitotic nuclear pore complex (NPC) reformation	1.545697	23	9
Chromosome Maintenance	1.546066	79	33
SARS-CoV-1-host interactions	1.547713	74	32
Regulation of PTEN stability and activity	1.551231	59	22
Late Phase of HIV Life Cycle	1.551941	114	46
Nuclear Envelope (NE) Reassembly	1.552482	50	20
Transport of Ribonucleoproteins into the Host Nucleus	1.555139	25	7
rRNA processing in the nucleus and cytosol	1.557445	162	58
MAPK6/MAPK4 signaling	1.560974	75	27
Base Excision Repair	1.561452	37	13
Transport of Mature mRNA derived from an Intron-Containing Transcript	1.569210	60	25
Resolution of Sister Chromatid Cohesion	1.569948	93	33
APC/C-mediated degradation of cell cycle proteins	1.577802	77	32
Regulation of mitotic cell cycle	1.577802	77	32
Nuclear signaling by ERBB4	1.580528	18	6
Vpr-mediated nuclear import of PICs	1.583347	25	7
RNA Polymerase II Transcription Termination	1.584898	55	24
Export of Viral Ribonucleoproteins from Nucleus	1.586452	26	7
NEP/NS2 Interacts with the Cellular Export Machinery	1.586452	26	7
RHO GTPase Effectors	1.587712	196	71
Cyclin A/B1/B2 associated events during G2/M transition	1.590258	18	13
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1.592961	21	8
MHC class II antigen presentation	1.593630	76	20
Disorders of transmembrane transporters	1.593917	114	40
Transport of Mature mRNAs Derived from Intronless Transcripts	1.595779	34	11
Abortive elongation of HIV-1 transcript in the absence of Tat	1.603469	22	12
Respiratory electron transport	1.604512	83	41
TCR signaling	1.605577	86	33
SUMOylation of SUMOylation proteins	1.612490	28	8
Transport of Mature Transcript to Cytoplasm	1.613353	68	28
Signaling by the B Cell Receptor (BCR)	1.615003	92	29
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1.617468	27	8
Regulation of Glucokinase by Glucokinase Regulatory Protein	1.618194	24	7
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1.618194	24	7
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1.620695	17	9
Cell Cycle, Mitotic	1.621489	403	131
Translation	1.623650	249	89
Meiotic synapsis	1.625306	23	6
Transcriptional regulation by RUNX1	1.630654	142	45
Transport of Mature mRNA Derived from an Intronless Transcript	1.632642	33	11
Regulation of RAS by GAPs	1.633814	56	21
Metabolic disorders of biological oxidation enzymes	1.637941	16	5
Degradation of the extracellular matrix	1.638710	63	17
Antigen processing-Cross presentation	1.640411	75	30
M Phase	1.641700	284	97
ER-Phagosome pathway	1.641933	63	25
PCNA-Dependent Long Patch Base Excision Repair	1.642133	17	8
SUMOylation of RNA binding proteins	1.647227	37	13
HIV Life Cycle	1.657428	121	51
Recognition of DNA damage by PCNA-containing replication complex	1.662703	25	8
Collagen chain trimerization	1.663230	14	6
Major pathway of rRNA processing in the nucleolus and cytosol	1.667105	152	56
Activation of NF-kappaB in B cells	1.668749	57	22
Inhibition of DNA recombination at telomere	1.676651	21	12
SUMOylation of ubiquitinylation proteins	1.677816	30	9
Assembly of the pre-replicative complex	1.678062	76	31
Cellular response to starvation	1.680600	124	53
Regulation of APC/C activators between G1/S and early anaphase	1.685531	71	31
RHO GTPases activate IQGAPs	1.689130	12	7
Synthesis of DNA	1.692688	106	39
RHO GTPases activate PKNs	1.694726	30	18
FGFR2 alternative splicing	1.695097	20	12
G1/S DNA Damage Checkpoints	1.701501	58	23
Lysine catabolism	1.702366	11	4
p53-Dependent G1 DNA Damage Response	1.703777	57	23
p53-Dependent G1/S DNA damage checkpoint	1.703777	57	23
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1.707925	22	13
APC/C:Cdc20 mediated degradation of Securin	1.714550	58	24
Condensation of Prophase Chromosomes	1.715310	16	8
CDK-mediated phosphorylation and removal of Cdc6	1.715389	64	29
Deposition of new CENPA-containing nucleosomes at the centromere	1.716501	21	9
Nucleosome assembly	1.716501	21	9
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.717929	98	49
Downstream signaling events of B Cell Receptor (BCR)	1.718758	67	25
Mitotic G1 phase and G1/S transition	1.726049	125	44
snRNP Assembly	1.728076	43	13
Metabolism of non-coding RNA	1.728076	43	13
Hedgehog ligand biogenesis	1.728994	51	21
Autodegradation of Cdh1 by Cdh1:APC/C	1.729243	56	23
S Phase	1.730262	143	49
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1.732901	64	27
Orc1 removal from chromatin	1.734179	64	26
SUMOylation of DNA damage response and repair proteins	1.736060	60	19
APC/C:Cdc20 mediated degradation of mitotic proteins	1.738294	66	29
Nuclear events mediated by NFE2L2	1.740403	76	30
Hh mutants abrogate ligand secretion	1.743268	49	21
GLI3 is processed to GLI3R by the proteasome	1.743908	51	21
Regulation of RUNX2 expression and activity	1.750065	56	21
Interactions of Vpr with host cellular proteins	1.752998	26	8
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1.755729	65	29
Aerobic respiration and respiratory electron transport	1.756970	160	74
Degradation of GLI1 by the proteasome	1.758707	50	21
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1.764399	67	30
Translesion Synthesis by POLH	1.767317	16	5
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1.773473	48	21
tRNA processing in the nucleus	1.775782	47	12
Dectin-1 mediated noncanonical NF-kB signaling	1.780723	52	21
Degradation of GLI2 by the proteasome	1.790817	50	21
Detoxification of Reactive Oxygen Species	1.792689	22	16
Host Interactions of HIV factors	1.800631	105	40
Metabolism of polyamines	1.802143	53	22
Transcriptional regulation by small RNAs	1.806275	44	20
G1/S Transition	1.806739	113	46
Mitotic Anaphase	1.808689	182	70
Mitotic Metaphase and Anaphase	1.809050	183	70
DNA Replication	1.812655	115	44
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1.817971	64	29
Cellular response to hypoxia	1.823028	65	26
Cyclin A:Cdk2-associated events at S phase entry	1.828468	76	29
Separation of Sister Chromatids	1.829491	147	57
NS1 Mediated Effects on Host Pathways	1.830066	31	10
Viral Messenger RNA Synthesis	1.832078	37	12
HIV Infection	1.838232	188	71
Signaling by NOTCH4	1.838687	66	25
DNA Replication Pre-Initiation	1.842178	90	36
Cyclin E associated events during G1/S transition	1.852647	74	29
Stabilization of p53	1.856818	48	20
NIK-->noncanonical NF-kB signaling	1.864619	51	21
SCF-beta-TrCP mediated degradation of Emi1	1.866171	48	21
Regulation of mRNA stability by proteins that bind AU-rich elements	1.870693	74	32
ABC transporter disorders	1.870972	60	26
PCP/CE pathway	1.872663	69	27
The role of GTSE1 in G2/M progression after G2 checkpoint	1.877632	58	26
The phototransduction cascade	1.880133	11	4
Inactivation, recovery and regulation of the phototransduction cascade	1.880133	11	4
SARS-CoV-1 modulates host translation machinery	1.891711	30	20
Autodegradation of the E3 ubiquitin ligase COP1	1.897373	46	20
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1.905666	65	26
Formation of ATP by chemiosmotic coupling	1.906061	12	7
Activation of Matrix Metalloproteinases	1.908897	11	3
Selenoamino acid metabolism	1.910420	95	59
Negative regulation of NOTCH4 signaling	1.911847	47	23
TNFR2 non-canonical NF-kB pathway	1.913089	58	24
SCF(Skp2)-mediated degradation of p27/p21	1.914750	54	24
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	1.920061	46	21
Vpu mediated degradation of CD4	1.923179	45	21
Degradation of DVL	1.942347	50	22
Asymmetric localization of PCP proteins	1.959794	51	22
Regulation of Apoptosis	1.969835	47	23
Cristae formation	1.981851	24	11
Heme biosynthesis	1.986583	11	7
ATF6 (ATF6-alpha) activates chaperone genes	1.992543	10	8
SARS-CoV-2 modulates host translation machinery	1.993772	39	23
Translation initiation complex formation	1.993920	50	32
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	2.011257	51	33
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	2.014222	58	24
Nonsense-Mediated Decay (NMD)	2.020740	92	59
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2.020740	92	59
Cross-presentation of soluble exogenous antigens (endosomes)	2.021573	42	20
Ribosomal scanning and start codon recognition	2.032561	51	33
Hh mutants are degraded by ERAD	2.037604	48	21
Formation of the ternary complex, and subsequently, the 43S complex	2.037911	45	21
Regulation of activated PAK-2p34 by proteasome mediated degradation	2.050765	44	20
Ubiquitin-dependent degradation of Cyclin D	2.065511	46	21
Degradation of AXIN	2.067437	48	22
Regulation of ornithine decarboxylase (ODC)	2.069842	46	21
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	2.075990	45	20
p53-Independent DNA Damage Response	2.075990	45	20
p53-Independent G1/S DNA damage checkpoint	2.075990	45	20
Selenocysteine synthesis	2.096711	75	51
Mitochondrial protein degradation	2.108916	81	39
AUF1 (hnRNP D0) binds and destabilizes mRNA	2.115587	46	21
Eukaryotic Translation Termination	2.123653	74	52
Collagen degradation	2.124877	30	11
Vif-mediated degradation of APOBEC3G	2.128310	47	22
ATF6 (ATF6-alpha) activates chaperones	2.144804	12	9
Response of EIF2AK4 (GCN2) to amino acid deficiency	2.146668	82	56
Maternal to zygotic transition (MZT)	2.147872	40	5
Regulation of RUNX3 expression and activity	2.153411	47	20
Defective CFTR causes cystic fibrosis	2.153644	52	24
Influenza Viral RNA Transcription and Replication	2.159789	110	58
Influenza Infection	2.174912	125	58
Peptide chain elongation	2.176142	71	51
Eukaryotic Translation Elongation	2.197829	73	52
Metabolism of porphyrins	2.211398	17	10
SRP-dependent cotranslational protein targeting to membrane	2.220490	89	61
Signaling by ROBO receptors	2.257215	165	76
Viral mRNA Translation	2.257290	70	51
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.298739	75	53
Eukaryotic Translation Initiation	2.312568	98	65
Cap-dependent Translation Initiation	2.312568	98	65
L13a-mediated translational silencing of Ceruloplasmin expression	2.371951	91	62
Regulation of expression of SLITs and ROBOs	2.388212	135	67
Formation of a pool of free 40S subunits	2.389773	83	59
GTP hydrolysis and joining of the 60S ribosomal subunit	2.392154	92	63

IV-HD

Description	NES	setSize	Count
Signaling by CSF1 (M-CSF) in myeloid cells	-1.869259	25	13
PPARA activates gene expression	-1.810673	75	27
Regulation of lipid metabolism by PPARalpha	-1.774851	77	27
Negative regulation of MET activity	-1.772842	13	10
Interleukin-6 family signaling	-1.764369	11	6
Downregulation of SMAD2/3:SMAD4 transcriptional activity	-1.760074	19	8
Plasma lipoprotein remodeling	-1.753294	17	8
Signal amplification	-1.749093	13	6
XBP1(S) activates chaperone genes	-1.720464	35	19
Signaling by EGFR in Cancer	-1.712812	14	8
FLT3 signaling in disease	-1.705644	19	12
SUMOylation of DNA methylation proteins	-1.696502	12	5
IRE1alpha activates chaperones	-1.688171	36	19
Signaling by ERBB2	-1.678333	25	10
Sensory processing of sound by outer hair cells of the cochlea	-1.669455	17	9
Signaling by FLT3 fusion proteins	-1.634968	14	9
Platelet sensitization by LDL	-1.625555	13	6
Signaling by FGFR3	-1.609945	17	8
Signaling by FGFR4	-1.609945	17	8
Negative regulation of the PI3K/AKT network	-1.606407	45	16
Plasma lipoprotein assembly, remodeling, and clearance	-1.602755	37	12
RHOBTB2 GTPase cycle	-1.595576	17	3
Listeria monocytogenes entry into host cells	-1.593565	11	6
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	-1.591690	42	15
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	-1.572422	13	7
Signaling by Ligand-Responsive EGFR Variants in Cancer	-1.572422	13	7
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	-1.565189	28	10
Sensory processing of sound by inner hair cells of the cochlea	-1.559412	20	12
Spry regulation of FGF signaling	-1.556017	10	4
Negative regulation of FGFR1 signaling	-1.556017	10	4
Negative regulation of FGFR3 signaling	-1.556017	10	4
Negative regulation of FGFR4 signaling	-1.556017	10	4
Sensory processing of sound	-1.551170	23	13
Chondroitin sulfate/dermatan sulfate metabolism	-1.533951	17	6
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	-1.521704	56	22
Toll Like Receptor TLR1:TLR2 Cascade	-1.521704	56	22
Toll Like Receptor TLR6:TLR2 Cascade	-1.521704	56	22
Toll Like Receptor 2 (TLR2) Cascade	-1.521704	56	22
Constitutive Signaling by Aberrant PI3K in Cancer	-1.518995	24	10
Interferon gamma signaling	-1.510473	30	14
G alpha (12/13) signalling events	-1.502975	38	21
Transcriptional regulation of white adipocyte differentiation	-1.487524	55	16
Platelet homeostasis	-1.483787	30	14
GPCR downstream signalling	-1.376518	160	63
Signaling by GPCR	-1.346686	168	66
Metabolism of lipids	-1.289286	384	98
Adaptive Immune System	1.209229	414	107
Nervous system development	1.250303	301	107
Transcriptional Regulation by TP53	1.259967	242	88
mRNA Splicing	1.283339	172	71
Processing of Capped Intron-Containing Pre-mRNA	1.291811	226	89
Axon guidance	1.320393	292	106
mRNA Splicing - Major Pathway	1.332344	168	70
Signaling by Nuclear Receptors	1.339471	130	27
Late Phase of HIV Life Cycle	1.357150	108	38
Resolution of Sister Chromatid Cohesion	1.360317	88	35
Signaling by Hedgehog	1.368366	83	25
Host Interactions of HIV factors	1.385170	101	40
Biological oxidations	1.398811	67	21
Mitotic Prophase	1.403700	64	23
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1.407687	61	20
Downstream signaling events of B Cell Receptor (BCR)	1.427761	63	18
Cellular response to chemical stress	1.429464	145	53
Regulation of RUNX2 expression and activity	1.433935	53	20
Cell Cycle Checkpoints	1.437531	196	63
Nuclear Envelope (NE) Reassembly	1.442580	49	16
HIV Life Cycle	1.455856	114	42
Degradation of DVL	1.464981	47	22
Mitotic G2-G2/M phases	1.470910	134	48
G2/M Transition	1.470910	134	48
Regulation of RAS by GAPs	1.473905	53	21
Complex I biogenesis	1.478627	42	19
Respiratory electron transport	1.485687	78	30
Diseases of programmed cell death	1.494375	35	11
Pre-NOTCH Transcription and Translation	1.503348	24	8
ECM proteoglycans	1.505102	29	10
Hedgehog 'off' state	1.510686	68	29
Deadenylation-dependent mRNA decay	1.513691	40	24
Extension of Telomeres	1.515992	39	16
Maternal to zygotic transition (MZT)	1.518402	34	18
Branched-chain amino acid catabolism	1.542656	15	8
Signaling by NOTCH4	1.546589	60	23
Reproduction	1.546975	42	14
Polymerase switching on the C-strand of the telomere	1.547057	17	8
Degradation of GLI2 by the proteasome	1.551086	48	20
GLI3 is processed to GLI3R by the proteasome	1.551086	48	20
MAPK6/MAPK4 signaling	1.557136	66	27
Chromatin modifications during the maternal to zygotic transition (MZT)	1.560145	10	5
G2/M Checkpoints	1.562135	107	36
ATF6 (ATF6-alpha) activates chaperones	1.567495	12	6
Dectin-1 mediated noncanonical NF-kB signaling	1.568827	50	20
HIV Infection	1.574117	179	70
Stabilization of p53	1.574576	46	19
Condensation of Prometaphase Chromosomes	1.580346	10	6
Diseases of mitotic cell cycle	1.580636	25	7
Degradation of GLI1 by the proteasome	1.581502	47	20
Meiosis	1.584745	36	12
M Phase	1.584761	260	67
Regulation of PTEN stability and activity	1.590671	54	23
Cell Cycle	1.592066	445	110
Regulation of mRNA stability by proteins that bind AU-rich elements	1.592218	68	27
TNFR2 non-canonical NF-kB pathway	1.594814	55	23
Transcriptional regulation by RUNX1	1.595005	134	32
APC/C-mediated degradation of cell cycle proteins	1.598256	72	29
Regulation of mitotic cell cycle	1.598256	72	29
Autodegradation of the E3 ubiquitin ligase COP1	1.598353	45	19
Activation of ATR in response to replication stress	1.598869	33	13
Hedgehog 'on' state	1.601294	54	23
Removal of the Flap Intermediate from the C-strand	1.602114	14	7
Neddylation	1.602366	164	46
G0 and Early G1	1.604597	22	8
PCP/CE pathway	1.617148	62	24
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	1.619491	92	37
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1.621595	46	20
ESR-mediated signaling	1.622440	100	25
Recognition of DNA damage by PCNA-containing replication complex	1.631508	24	8
SCF-beta-TrCP mediated degradation of Emi1	1.631579	47	20
Cellular response to hypoxia	1.631995	62	25
NFE2L2 regulating anti-oxidant/detoxification enzymes	1.632816	13	8
Lagging Strand Synthesis	1.632984	18	9
Mitochondrial iron-sulfur cluster biogenesis	1.635088	11	7
AUF1 (hnRNP D0) binds and destabilizes mRNA	1.645605	45	19
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1.647523	63	26
Cyclin A/B1/B2 associated events during G2/M transition	1.649633	17	8
NIK-->noncanonical NF-kB signaling	1.650658	49	20
Orc1 removal from chromatin	1.653949	62	24
Telomere C-strand (Lagging Strand) Synthesis	1.654943	25	12
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	1.655468	45	20
DNA Damage Bypass	1.655633	37	11
Activation of the pre-replicative complex	1.657165	28	12
Formation of ATP by chemiosmotic coupling	1.658186	12	10
Switching of origins to a post-replicative state	1.660390	76	25
MET activates PTK2 signaling	1.662472	12	4
Mitotic Anaphase	1.663883	172	53
Beta-catenin independent WNT signaling	1.666858	84	33
Formation of tubulin folding intermediates by CCT/TriC	1.668526	12	7
Cellular response to starvation	1.672384	118	61
p53-Dependent G1 DNA Damage Response	1.678593	51	21
p53-Dependent G1/S DNA damage checkpoint	1.678593	51	21
RHO GTPases activate IQGAPs	1.681201	11	3
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1.682871	23	5
Mitotic Metaphase and Anaphase	1.683770	173	54
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1.684261	20	8
Vpu mediated degradation of CD4	1.686267	44	20
Aberrant regulation of mitotic cell cycle due to RB1 defects	1.688310	23	7
Resolution of Abasic Sites (AP sites)	1.690718	26	11
Telomere Maintenance	1.691783	56	23
PCNA-Dependent Long Patch Base Excision Repair	1.693297	17	8
Estrogen-dependent gene expression	1.695618	67	19
Depolymerization of the Nuclear Lamina	1.697760	11	6
Chromosome Maintenance	1.698144	72	28
M-decay: degradation of maternal mRNAs by maternally stored factors	1.703932	16	11
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1.705562	60	25
Transcriptional regulation by small RNAs	1.708220	42	16
G1/S DNA Damage Checkpoints	1.708472	52	22
Citric acid cycle (TCA cycle)	1.709215	27	14
Hedgehog ligand biogenesis	1.710239	49	20
Maturation of TCA enzymes and regulation of TCA cycle	1.710956	15	12
Nuclear events mediated by NFE2L2	1.713082	71	32
Hh mutants are degraded by ERAD	1.717536	47	20
Hh mutants abrogate ligand secretion	1.717536	47	20
Negative regulation of NOTCH4 signaling	1.721080	45	21
Separation of Sister Chromatids	1.726248	138	44
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1.729533	10	4
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1.729533	10	4
Meiotic synapsis	1.730601	20	4
Cell Cycle, Mitotic	1.734849	368	99
Glutathione conjugation	1.734893	13	8
Mitotic Telophase/Cytokinesis	1.735760	11	2
APC/C:Cdc20 mediated degradation of mitotic proteins	1.741056	61	25
Regulation of APC/C activators between G1/S and early anaphase	1.748150	66	28
G1/S-Specific Transcription	1.754016	23	9
Gastrulation	1.757620	59	25
Translation	1.762651	230	130
rRNA processing	1.768383	164	85
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1.771163	62	26
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1.775303	60	25
APC/C:Cdc20 mediated degradation of Securin	1.778978	54	23
The phototransduction cascade	1.783309	11	4
Inactivation, recovery and regulation of the phototransduction cascade	1.783309	11	4
Aerobic respiration and respiratory electron transport	1.784765	140	57
Transcriptional regulation by RUNX3	1.790810	66	25
Metabolism of polyamines	1.794662	51	25
Regulation of activated PAK-2p34 by proteasome mediated degradation	1.794734	43	19
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1.796957	59	25
Regulation of ornithine decarboxylase (ODC)	1.804391	46	23
The role of GTSE1 in G2/M progression after G2 checkpoint	1.809942	56	25
SCF(Skp2)-mediated degradation of p27/p21	1.810370	51	22
Autodegradation of Cdh1 by Cdh1:APC/C	1.817242	52	23
CDK-mediated phosphorylation and removal of Cdc6	1.822288	59	25
Regulation of Apoptosis	1.830192	44	20
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1.835191	15	12
Assembly of the pre-replicative complex	1.841773	72	26
Cristae formation	1.843428	24	14
rRNA processing in the nucleus and cytosol	1.862370	156	83
Mitotic G1 phase and G1/S transition	1.865521	116	32
Ubiquitin-dependent degradation of Cyclin D	1.867879	45	20
SARS-CoV-1 modulates host translation machinery	1.870299	29	21
DNA strand elongation	1.875665	29	13
Degradation of AXIN	1.881169	47	22
Cyclin E associated events during G1/S transition	1.883151	68	29
Condensation of Prophase Chromosomes	1.884843	15	9
Asymmetric localization of PCP proteins	1.898340	46	21
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1.902168	55	25
Cyclin A:Cdk2-associated events at S phase entry	1.903061	70	30
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A	1.905882	43	20
p53-Independent DNA Damage Response	1.905882	43	20
p53-Independent G1/S DNA damage checkpoint	1.905882	43	20
Base Excision Repair	1.917680	32	14
Major pathway of rRNA processing in the nucleolus and cytosol	1.926930	146	78
Influenza Infection	1.933389	122	70
Regulation of RUNX3 expression and activity	1.948693	46	20
Influenza Viral RNA Transcription and Replication	1.967828	108	66
Synthesis of DNA	1.972000	101	37
SARS-CoV-2 modulates host translation machinery	1.982142	37	22
Cross-presentation of soluble exogenous antigens (endosomes)	2.001799	41	20
Vif-mediated degradation of APOBEC3G	2.007795	45	22
Nonsense-Mediated Decay (NMD)	2.013469	89	50
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2.013469	89	50
DNA Replication Pre-Initiation	2.015885	86	33
SRP-dependent cotranslational protein targeting to membrane	2.017591	88	53
G1/S Transition	2.026620	107	42
DNA Replication	2.039751	110	43
Somitogenesis	2.052897	40	20
Mitochondrial protein degradation	2.057051	73	37
Detoxification of Reactive Oxygen Species	2.057222	20	12
Translation initiation complex formation	2.087305	49	31
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	2.088340	50	32
Formation of paraxial mesoderm	2.096674	46	22
Signaling by ROBO receptors	2.098334	156	85
Metabolism of amino acids and derivatives	2.111932	224	117
Formation of the ternary complex, and subsequently, the 43S complex	2.126980	44	30
Heme biosynthesis	2.128247	11	7
Ribosomal scanning and start codon recognition	2.140236	50	32
S Phase	2.163457	133	46
Selenoamino acid metabolism	2.168885	91	57
Selenocysteine synthesis	2.171936	72	46
Viral mRNA Translation	2.178346	69	46
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2.206450	74	52
Eukaryotic Translation Termination	2.209620	72	47
Peptide chain elongation	2.240268	69	48
Eukaryotic Translation Elongation	2.250433	71	47
Metabolism of porphyrins	2.263622	16	11
Response of EIF2AK4 (GCN2) to amino acid deficiency	2.265917	80	51
Eukaryotic Translation Initiation	2.325314	97	64
Cap-dependent Translation Initiation	2.325314	97	64
L13a-mediated translational silencing of Ceruloplasmin expression	2.365928	90	61
Regulation of expression of SLITs and ROBOs	2.373838	131	76
GTP hydrolysis and joining of the 60S ribosomal subunit	2.394554	91	57
Formation of a pool of free 40S subunits	2.394803	82	55

10 WPI

DNA vaccine

Description	NES	setSize	Count
Striated Muscle Contraction	-2.078391	27	12
Cell Cycle, Mitotic	1.325285	426	288
RHO GTPase Effectors	1.394363	214	124

EOMES

Description	NES	setSize	Count
Neuronal System	1.394553	283	99

GATA3

Description	NES	setSize	Count
rRNA modification in the nucleus and cytosol	-1.761944	57	55
Striated Muscle Contraction	-1.626816	27	9
Signaling by GPCR	1.191060	389	198
GPCR downstream signalling	1.193191	348	168
SLC-mediated transmembrane transport	1.225929	177	72
Transmission across Chemical Synapses	1.241173	189	89
GPCR ligand binding	1.250982	200	99
G alpha (i) signalling events	1.259988	156	81
Neuronal System	1.287592	283	142
Class A/1 (Rhodopsin-like receptors)	1.299060	139	71
Protein-protein interactions at synapses	1.312714	65	36
Degradation of the extracellular matrix	1.321021	86	32
Potassium Channels	1.328675	65	34
Post-translational protein phosphorylation	1.334892	66	20
Sensory processing of sound by inner hair cells of the cochlea	1.353306	54	26
Sensory processing of sound	1.355838	57	27
Visual phototransduction	1.372641	59	30
Cell-cell junction organization	1.374837	64	30
Sensory Perception	1.394828	134	65
Adherens junctions interactions	1.405572	45	20

IV-HD

Description	NES	setSize	Count
Striated Muscle Contraction	-2.643247	27	15

IV-LD

Description	NES	setSize	Count
DNA strand elongation	-2.954534	29	20
Activation of the pre-replicative complex	-2.823981	28	20
Activation of ATR in response to replication stress	-2.664441	33	19
Unwinding of DNA	-2.513751	11	10
Processive synthesis on the lagging strand	-2.438397	14	10
Lagging Strand Synthesis	-2.432991	18	10
Removal of the Flap Intermediate	-2.412073	13	10
Telomere C-strand (Lagging Strand) Synthesis	-2.368757	28	13
Polymerase switching on the C-strand of the telomere	-2.212591	20	10
Polymerase switching	-2.190069	12	7
Leading Strand Synthesis	-2.190069	12	7
tRNA processing	-2.178221	88	31
tRNA modification in the nucleus and cytosol	-2.166711	33	18
mRNA decay by 3' to 5' exoribonuclease	-2.158842	14	7
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	-2.108978	13	7
Nuclear import of Rev protein	-2.061305	29	12
Chromosome Maintenance	-2.025494	80	36
Mitochondrial translation	-2.003138	82	40
Synthesis of glycosylphosphatidylinositol (GPI)	-1.990159	14	7
Interactions of Vpr with host cellular proteins	-1.976322	27	11
Extension of Telomeres	-1.967876	45	23
Mitochondrial translation elongation	-1.967231	76	29
Transport of the SLBP Dependant Mature mRNA	-1.957045	29	12
Mitochondrial translation initiation	-1.952516	76	28
Transcriptional regulation by small RNAs	-1.933773	45	29
Mitochondrial translation termination	-1.923750	76	37
Postmitotic nuclear pore complex (NPC) reformation	-1.913919	24	10
tRNA processing in the nucleus	-1.905964	48	17
HDR through Homologous Recombination (HRR)	-1.900717	56	20
Mismatch Repair	-1.894024	14	7
Diseases of DNA repair	-1.889344	43	13
Regulation of Glucokinase by Glucokinase Regulatory Protein	-1.883906	25	10
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	-1.883906	25	10
Telomere Maintenance	-1.878765	62	28
Transport of Ribonucleoproteins into the Host Nucleus	-1.860285	26	10
RNA Polymerase I Promoter Escape	-1.843944	30	11
Transport of the SLBP independent Mature mRNA	-1.841741	28	11
Vpr-mediated nuclear import of PICs	-1.825700	26	10
Transport of Mature mRNAs Derived from Intronless Transcripts	-1.821860	35	13
snRNP Assembly	-1.819523	44	19
Metabolism of non-coding RNA	-1.819523	44	19
SUMOylation of SUMOylation proteins	-1.814853	29	11
DNA Replication Pre-Initiation	-1.805919	90	43
Interactions of Rev with host cellular proteins	-1.801442	31	12
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	-1.781758	10	4
Rev-mediated nuclear export of HIV RNA	-1.722768	29	11
Deposition of new CENPA-containing nucleosomes at the centromere	-1.716512	21	9
Nucleosome assembly	-1.716512	21	9
Transport of Mature mRNA Derived from an Intronless Transcript	-1.710378	34	12
E2F mediated regulation of DNA replication	-1.703348	16	7
Export of Viral Ribonucleoproteins from Nucleus	-1.701043	27	10
NEP/NS2 Interacts with the Cellular Export Machinery	-1.701043	27	10
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	-1.691194	13	6
Resolution of D-loop Structures through Holliday Junction Intermediates	-1.685023	30	11
Presynaptic phase of homologous DNA pairing and strand exchange	-1.675385	32	12
Resolution of D-Loop Structures	-1.663293	31	11
Meiotic recombination	-1.660692	22	8
SUMOylation of ubiquitinylation proteins	-1.643981	31	11
Diseases of DNA Double-Strand Break Repair	-1.640567	33	12
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	-1.640567	33	12
Homologous DNA Pairing and Strand Exchange	-1.628077	35	12
Nuclear Pore Complex (NPC) Disassembly	-1.610885	31	11
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	-1.605874	20	8
Defective homologous recombination repair (HRR) due to PALB2 loss of function	-1.605874	20	8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	-1.605874	20	8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	-1.605874	20	8
Impaired BRCA2 binding to PALB2	-1.605874	20	8
Gap-filling DNA repair synthesis and ligation in GG-NER	-1.583184	20	7
DNA Replication	-1.578501	115	45
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	-1.570014	22	8
RNA Polymerase I Transcription Termination	-1.552286	26	8
Gap-filling DNA repair synthesis and ligation in TC-NER	-1.539402	53	29
Dual incision in TC-NER	-1.537704	53	28
Viral Messenger RNA Synthesis	-1.529689	38	11
Negative epigenetic regulation of rRNA expression	-1.509520	46	13
Synthesis of DNA	-1.504299	106	44
NS1 Mediated Effects on Host Pathways	-1.489298	32	10
Fanconi Anemia Pathway	-1.487228	33	12
NoRC negatively regulates rRNA expression	-1.486856	43	12
SUMOylation of DNA replication proteins	-1.478088	39	14
RNA Polymerase I Promoter Clearance	-1.458619	48	17
RNA Polymerase I Transcription	-1.443085	49	17
Formation of the ternary complex, and subsequently, the 43S complex	-1.421806	45	44
Transport of Mature mRNA derived from an Intron-Containing Transcript	-1.408246	61	18
Transport of Mature Transcript to Cytoplasm	-1.403856	69	20
Assembly of the pre-replicative complex	-1.391016	76	33
Homology Directed Repair	-1.349732	89	28
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	-1.325622	83	23
DNA Double-Strand Break Repair	-1.314092	114	34
Axon guidance	1.239477	361	103
Hemostasis	1.249844	362	101
MAPK1/MAPK3 signaling	1.251507	175	64
Nervous system development	1.264132	376	110
RAF/MAP kinase cascade	1.265024	172	63
Extracellular matrix organization	1.266893	157	59
Signaling by GPCR	1.267244	258	111
GPCR downstream signalling	1.267495	241	104
RAC1 GTPase cycle	1.286911	148	79
RHO GTPase cycle	1.310042	363	180
Adipogenesis	1.324017	81	34
Ion channel transport	1.333062	89	23
Cargo recognition for clathrin-mediated endocytosis	1.351754	65	18
Factors involved in megakaryocyte development and platelet production	1.353268	98	40
Cell-Cell communication	1.354079	87	44
G alpha (q) signalling events	1.356045	88	32
Transport of small molecules	1.361181	417	116
CDC42 GTPase cycle	1.376493	125	75
SLC-mediated transmembrane transport	1.376789	129	35
Transcriptional regulation of white adipocyte differentiation	1.387855	62	25
Cell surface interactions at the vascular wall	1.396451	77	39
Fatty acid metabolism	1.396874	119	40
Degradation of the extracellular matrix	1.404099	67	27
Peptide ligand-binding receptors	1.413956	37	15
RHOD GTPase cycle	1.422377	45	28
NRAGE signals death through JNK	1.423426	43	20
RHOJ GTPase cycle	1.425257	48	31
L1CAM interactions	1.431323	67	32
Circadian Clock	1.436316	56	23
RND3 GTPase cycle	1.436619	36	14
TBC/RABGAPs	1.439978	34	17
Signaling by NOTCH3	1.449675	33	9
RHOA GTPase cycle	1.451754	127	53
Cardiac conduction	1.459053	49	15
Arachidonic acid metabolism	1.462290	31	5
Metabolism of water-soluble vitamins and cofactors	1.466094	88	27
Sensory processing of sound by outer hair cells of the cochlea	1.478480	25	9
Signaling by ERBB2 in Cancer	1.481454	17	8
Signaling by ERBB2 KD Mutants	1.481454	17	8
Uptake and actions of bacterial toxins	1.484117	16	6
Nucleotide catabolism	1.486791	24	4
EGFR downregulation	1.490518	21	7
Constitutive Signaling by Aberrant PI3K in Cancer	1.491620	35	17
Regulation of lipid metabolism by PPARalpha	1.492182	93	40
Ion transport by P-type ATPases	1.494421	32	13
Sensory Perception	1.494804	80	33
Glycogen synthesis	1.494930	10	2
PPARA activates gene expression	1.497057	91	40
Bile acid and bile salt metabolism	1.497313	22	10
Signal transduction by L1	1.497539	20	3
Endogenous sterols	1.500532	13	7
Assembly of active LPL and LIPC lipase complexes	1.504366	11	5
Glyoxylate metabolism and glycine degradation	1.504830	14	8
Non-integrin membrane-ECM interactions	1.508077	35	26
Syndecan interactions	1.509090	21	13
Biological oxidations	1.511144	94	27
Interaction between L1 and Ankyrins	1.514887	11	6
Attachment and Entry	1.524825	11	8
Basigin interactions	1.525764	20	7
SUMOylation of intracellular receptors	1.530752	19	10
Sulfur amino acid metabolism	1.533032	24	10
Glycosphingolipid biosynthesis	1.533504	10	4
NR1H2 and NR1H3-mediated signaling	1.546182	32	13
Nitric oxide stimulates guanylate cyclase	1.564377	10	6
Degradation of cysteine and homocysteine	1.564391	13	6
Signaling by ERBB2 TMD/JMD mutants	1.568626	14	8
Plasma lipoprotein clearance	1.569191	26	11
Ion homeostasis	1.569326	27	10
Metabolism of vitamins and cofactors	1.576338	131	38
CD209 (DC-SIGN) signaling	1.588426	17	9
Erythropoietin activates RAS	1.590764	12	8
Metabolism of folate and pterines	1.597534	11	5
Visual phototransduction	1.606751	37	20
Phase I - Functionalization of compounds	1.608231	41	13
Keratinization	1.608706	21	11
Formation of the cornified envelope	1.608706	21	11
Serotonin Neurotransmitter Release Cycle	1.610092	10	2
SHC1 events in ERBB2 signaling	1.617309	13	10
NOTCH3 Activation and Transmission of Signal to the Nucleus	1.625611	18	5
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1.626696	11	1
Nuclear Receptor transcription pathway	1.628092	32	17
Post-translational protein phosphorylation	1.634458	51	14
BMAL1:CLOCK,NPAS2 activates circadian gene expression	1.640093	22	11
Gluconeogenesis	1.641454	14	7
Activation of Matrix Metalloproteinases	1.648243	11	4
Triglyceride metabolism	1.649731	20	10
Cellular hexose transport	1.662707	11	6
Metabolism of fat-soluble vitamins	1.665754	25	13
Triglyceride catabolism	1.666912	13	6
Cytochrome P450 - arranged by substrate type	1.671828	22	7
Regulation of Complement cascade	1.673959	11	3
Plasma lipoprotein assembly, remodeling, and clearance	1.681026	46	22
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1.690045	57	17
Scavenging by Class A Receptors	1.691384	15	7
Binding and Uptake of Ligands by Scavenger Receptors	1.704992	24	8
Retinoid metabolism and transport	1.709875	21	8
Metabolism of steroids	1.721594	97	36
Plasma lipoprotein remodeling	1.736262	19	9
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1.743377	48	21
Activation of gene expression by SREBF (SREBP)	1.821012	37	20
Cholesterol biosynthesis	1.868195	22	14
Complement cascade	1.892080	17	6
Initial triggering of complement	1.915240	11	6

Interpretation of GSEA Results

In summary, a negative NES in GSEA indicates that the gene set is significantly downregulated in the condition of interest compared to the control, reflecting a negative correlation with the phenotype being studied. This information can provide valuable insights into the biological processes that are less active or suppressed in the experimental condition.

• Positive NES:
  • Indicates that the gene set is enriched at the top of the ranked list, suggesting that genes in the set are upregulated in the condition of interest.
• Negative NES:
  • Indicates that the gene set is enriched at the bottom of the ranked list, suggesting that genes in the set are downregulated in the condition of interest.

Most studies related to viral infection use qPCR to 'measure' gene expression of target genes in relation to a housekeeping gene. The approach of using RNAseq as a tool to study immune responses is inherently different, in the sense that it does not compare gene expression against a housekeeping gene. Instead, it requires using a reference, such as a control group. This control group provides the baseline gene expression against which all other groups are compared to.

Because with RNAseq one looks at thousands of genes simultaneously, it makes more sense to have a holistic view of gene expression. Any emerging patterns in gene expression tend to stand out during pathway analysis, since pathways, by definition, incorporate hundreds, or even thousands, of differentially regulated genes.

WHAT GENES ARE EXPECTED TO BE DIFFERENTIALLY REGULATED BY EOMES, GATA3, AND DNA VACCINE?

CREATE A TIMELINE PLOT OF GENE EXPRESSION, I.E. 1WPC VS 10WPI, 4WPC VS 1WPC, 6WPC VS 4WPC, 10WPC VS 6WPC FOR CONTROL

Immune-related genes

Housekeeping: β-actin (ACTB): AF012125, ENSSSAG00000116649. A lot of reads everywhere.

SasaIFN-α: AY216594, no Ensembl

Μx: U66475, ENSSSAG00070007970 (mxa). No hits in read files.

ISG15: AY926456, ENSSSAG00000105254 (UBIL). Mapped but mostly no reads.

IFN-γ: AY795563, ENSSSAG00000105299. Mapped but no reads.

ΤΝF-α (1&2): NM_001123589 & NM_001123590, ENSSSAG00000065312 (mapped but no reads) & ENSSSAG00000053783 (no hits)

IL12-β: BT049114, ENSSSAG00000009655. Mapped but with few reads.

IL-10: EF165029, ENSSSAG00000107544. Mapped but with no reads.

IL-8: NM_001140710, ENSSSAG00000006498. Mapped but with no reads.

CD3-ε: NM_001123622, ENSSSAG00000076824. A lot of reads in s and hk. Fewer reads in h.

CD4: NM_001124539, rainbow trout gene

CD8-α: NM_001123583, ENSSSAG00000065860. Mapped but with few reads.

TCR-α: BT050114, no Ensembl. ENSSSAG00070030723 for T-cell receptor alpha/delta variable 31.0. No hits.

MHC I: AF508864, no Ensembl. ENSSSAG00000077407 for a novel gene. A lot of hits in h, hk, and s.

MHC II: BT049430, no Ensembl. ENSSSAG00000004635 for a novel gene. A LOT of hits everywhere.

How did you look at specific genes in the RNAseq data (genes in Table 1, for example)? Are these manually curated, and you get their respective raw counts from gene count files?

So these were manually curated and then extracted into a table where we included the FC values from Deseq2 and then used total counts and the house keeping gene EF1a to make a normalised expression. It's maybe not the best way of doing it, but was a useful proxy of the genes expression. (Shahmir Naseer)

About normalising expression

Expression values were obtained by normalising gene count against total raw counts and then the ratio to ELF1a multiplied by 1000, trout (ENSOMYG00000038328) and salmon (ENSSSAG00000077892) counts,

blank cells = no counts for the gene.