Update OMIM gene references #8624

twhetzel · 2025-01-24T13:56:17Z

Update OMIM gene references.

matentzn · 2025-01-24T18:08:25Z

src/ontology/mondo-edit.obo

@@ -143773,8 +143773,8 @@ intersection_of: MONDO:0015281 ! atrial standstill
 intersection_of: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 ! SCN5A
 intersection_of: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/4279 ! GJA5
 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 {source="OMIM:108770"} ! SCN5A
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/4279 {source="MONDO:mim2gene_medgen", source="OMIM:108770"} ! GJA5
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 ! SCN5A


I thought we decided not to preserve gene references if there is no provenance at all? This goes for various examples in this PR..

This gene association is for MONDO:0007171 'atrial standstill 1'.

OMIM:108770 has "digenic" in the disease description. @joeflack4 I thought those were being filtered out and added into the "review.tsv" file in the OMIM repo, is that not the case in general?

I am also not finding this association in the data file from the 2025-01-19 OMIM ingest release https://github.com/monarch-initiative/omim/releases/tag/2025-01-19.

We did note that any updates where there is >1 subclassof gene association will need to be reviewed manually

In this case it seems like both the gene associations added as a logical definition and a subclassOf relation should be removed.

@joeflack4 after thinking a bit more about this, can you remind me:
(1) if any disease description that includes "digenic" is added into the review.tsv file
(2) if it is also added into the ROBOT file in order to create the gene association
(3) how confirmed disease defining "digenic" like https://omim.org/entry/601067 are handled

If this is in the docs, feel free to point me to that first and I can then add any follow-up questions.

I can start looking into this in a couple hours. For right now, just wanted to let you know that the documentation for the review.tsv is on the omim repo readme towards the bottom.

If something is not in the January 19th data files, and the Mondo ingest build is newer than that, and that is problematic.

For digenic, we did for a short time have a special rule where we were adding associations when digenic was in the label, even if there was more than one association. So it was an exception rule. But we removed that exception. However, we do not have any explicit filtering. So if something is, perhaps erroneously, labeled as digenic, but only has one association, and meets the other logical conditions for a disease defining Gene, then the association will be created. That's my guess as to why this one is appearing here but I will look into it further.

RE: OMIM:108770

So, we had to exclude this case specifically. Because, even though it is marked "digenic", it meets all of the conditions for a disease-defining gene (including 1 entry in morbidmap.txt, which is unusual for one marked 'digenic').

Thus, this is why it is not appearing in the data release, as Trish mentioned.

And, if you look at the diff highlighted in this thread, you can see that the OMIM source evidence indeed is removed. This is correct. However, relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 still remains, even without any source evidence. So this does not appear to be a bug with omim or mondo-ingest, but with the mondo pipeline. Perhaps it needs to be adjusted such that if there is no evidence for the gene association, it is removed?

I didn't work on this pipeline previously but if you want I can tweak the pipeline.

(1) if any disease description that includes "digenic" is added into the review.tsv file

Answer: Yes

Just to clarify, by "description", what you mean is the Phenotype label in the "Phenotype-Gene" table on the OMIM entry page, or the title in the "Phenotype" column of morbidmap.txt.

So, what's added to the review.tsv for 'digenic' is described here.

Basically, if it's marked digenic, but has >1 association, we filter it out. It won't appear in the review.tsv. If is marked digenic but has only 1 association and meets the other requirements for disease-defining (no [, {, or ?, not in our explicit exclusions, and mapping key = 3), then we do add it as a disease-defining association AND we add an entry for it in review.tsv.

(2) if it is also added into the ROBOT file in order to create the gene association

Answer: Yes (described more above)

(3) how confirmed disease defining "digenic" like https://omim.org/entry/601067 are handled

There is no logic for "confirmed" cases of disease-defining associations (digenic or otherwise). We only have exclusions. How the exclusions work is that even if something otherwise meets the conditions for disease-defining, it will be excluded if it appears in that TSV.

Since MONDO:0007171 is in the exclusion file a gene association was not intended to be added. It has now been manually removed.

twhetzel · 2025-01-27T08:39:17Z

src/ontology/mondo-edit.obo

-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/29090 {source="MONDO:mim2gene_medgen", source="OMIM:158901"} ! SMCHD1
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 {source="OMIM:158901"} ! DUX4
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/29090 {source="MONDO:mim2gene_medgen"} ! SMCHD1
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 ! DUX4


These gene associations are for MONDO:0008031 'facioscapulohumeral muscular dystrophy 2'.

OMIM:158901 also has "digenic" in the disease description.

It seems these gene associations should also be removed.

See my tentative explanation above #8624 (comment)

If it is the case that these are, perhaps erroneously labeled as digenic, but otherwise meet all of the logical conditions for which we would normally add a disease defining association, do you want me to add an explicit filter to remove anything that happens to have digenic in the label?

Since MONDO:0008031 is in the exclusion file a gene association was not intended to be added. It has now been manually removed.

twhetzel · 2025-01-27T08:52:07Z

src/ontology/mondo-edit.obo

@@ -270747,7 +270751,7 @@ xref: UMLS:C3693482 {source="MEDGEN:811326", source="MONDO:equivalentTo", source
 is_a: MONDO:0000653 {source="MONDO:Redundant", source="MONDO:indirect"} ! integumentary system cancer
 is_a: MONDO:0005164 {source="DOID:3507"} ! fibrosarcoma
 relationship: excluded_subClassOf MONDO:0019300 {source="Orphanet:31112", source="https://orcid.org/0000-0001-5208-3432"} ! obsolete rare skin tumor or hamartoma
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/8800 {source="MONDO:mim2gene_medgen", source="OMIM:607907"} ! PDGFB
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/8800 {source="MONDO:mim2gene_medgen"} ! PDGFB


This is for MONDO:0011934 'dermatofibrosarcoma protuberans'. Based on OMIM:607907 and that the mapping key is 4, this gene association should also be removed.

Evidence was removed, but the mondo pipeline likely needs to be updated now (see: thoughts).

Ok, so the OMIM evidence was removed since this has a mapping key of 4 and does not meet the guidelines for disease defining, but due to the gene association also having source="MONDO:mim2gene_medgen" and that the OMIM pipeline would not have removed the association even if there were no source provenance this gene association remains currently as a result of the pipeline.

This gene association was manually removed.

twhetzel · 2025-01-27T08:59:48Z

src/ontology/mondo-edit.obo

@@ -326240,7 +326244,7 @@ xref: Orphanet:397959 {source="MONDO:equivalentTo", source="OMIM:615387"}
 xref: UMLS:C3809332 {source="MONDO:equivalentTo", source="MONDO:MEDGEN", source="MEDGEN:815662"}
 is_a: MONDO:0018814 {source="Orphanet:397959", source="https://orcid.org/0000-0001-5208-3432"} ! non-SCID combined immunodeficiency
 relationship: curated_content_resource https://search.clinicalgenome.org/kb/conditions/MONDO:0014160 {source="MONDO:CLINGEN"}
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12029 {source="MONDO:mim2gene_medgen", source="OMIM:615387"} ! TRAC
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12029 {source="MONDO:mim2gene_medgen"} ! TRAC


Based on https://omim.org/entry/614102, I don't see why the OMIM gene was not updated to IGKC. @joeflack4 do you see why the gene association was not changed to IGKC with the source OMIM:614102?

Well, firstly, the gene-disease association evidence from OMIM was removed in this case.

If you were asking why the label TRAC wasn't changed to IGKC

I don't think this is what you were asking, but:

When you say "changed to IGKC", do you mean that you would expect to see an association to the HGNC class which has the label "IGKC" should be added (to this Mondo term, or another one)?
Or that you should see the label ! TRAC changed to ! IGKC in mondo-edit.obo on this highlighted line has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12029? If the latter, then I think that this is not a function of the mondo omim-genes pipeline, which uses omim-gene-equivalence.ru. It doesn't look like the pipeline has any functionality to update the labels for these associations.

Note that the evidence you have highlighted here was for OMIM:615387, not OMIM:614102.

MONDO:0013576 has relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/5716 {source="MONDO:mim2gene_medgen"} ! IGKC. MONDO:0014160 has relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12029 {source="MONDO:mim2gene_medgen"} ! TRAC

It took me a bit of time to see why there is no OMIM source evidence being added for IGKC.

The reason is that mim2gene.txt doesn't show a relationship to HGNC:5716 (or any HGNC symbol or ID) for the gene (OMIM:147200) mapped to OMIM:614102. It only has an NCBI gene entry:

MIM Number MIM Entry Type (see FAQ 1.3 at https://omim.org/help/faq) Entrez Gene ID (NCBI) Approved Gene Symbol (HGNC) Ensembl Gene ID (Ensembl)

147200 gene 3514 ENSG00000211592

For reference, the morbidmap.txt mapping:
Kappa light chain deficiency, 614102 (3) IGKC, IGKCD 147200 2p11.2

Note that you can see "IGCK" in that row, but it us under the "Gene/Locus And Other Related Symbols" column, which we do not parse.

This does result in the following entry added to omim.owl: AnnotationAssertion(<http://www.w3.org/2004/02/skos/core#exactMatch> <https://omim.org/entry/147200> <https://www.ncbi.nlm.nih.gov/gene/3514>)

However, we don't have any mappings between NCBI genes and HGNC IDs in OMIM. So this doesn't get captured by the omim-genes pipeline. See mondo-omim-genes.sparql:

SELECT DISTINCT ?mondo_id ?hgnc_id ?omim_disease_xref ?omim_gene WHERE { ?omim_disease a owl:Class . ?omim_disease skos:exactMatch ?mondo_id . ?omim_disease rdfs:subClassOf [ owl:onProperty RO:0004003 ; owl:someValuesFrom ?omim_gene ] . ?omim_gene skos:exactMatch ?hgnc_id . FILTER(STRSTARTS(STR(?hgnc_id), "http://identifiers.org/hgnc/"))

All of the conditions are met here, except that ?hgnc_id doesn't start with "http://identifiers.org/hgnc/". So it does not get added to mondo-omim-genes.robot.tsv. And therefore it doesn't get added to mondo-edit.obo.

NOTE: The comment about IGKC refers to this line for MONDO:0013576 and there is a HGNC identifier for this gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5716

NOTE: The gene association on this line should be maintained and with the OMIM source evidence. The OMIM source provenance was removed because of the missing data mapping in the mim2gene.txt file. Joe will email OMIM to let them know they are missing the HGNC gene identifier in the mim2gene.txt file.

NOTE: The gene association for MONDO:0014160 on this line should have also been maintained. The OMIM source provenance was not added back here because of missing data for the HGNC identifier in the mim2gene.txt file.

The issue w/ the data that Trish and I are discussing is that we see a label for the HGNC term in morbidmap.txt, but the ID for that term does not appear in mim2gene.txt. We will contact OMIM about this apparent discrepancy.

We also discussed a few programmatic solutions to this issue. Given the status of the project, I would like to get feedback on how to proceed.

The OMIM source provenance is now added back for these gene associations.

For these instances, I also sent an email to OMIM:

We're having an issue where we are processing mim2gene.txt and it appears there are missing HGNC symbols in the Approved Gene Symbol (HGNC) column. We are expecting to see them there because the gene has an entry in morbidmap.txt where the symbol appears.

So we're just thinking that this is a consistency problem. We are wondering if you agree; that if symbols appear in one of the files for an association, they should also appear in the other file.

I created a GitHub issue for Monarch purposes, but wanted to share it with you because it goes over an example in detail: OMIM:147200 <-> HGNC:5716 (IGKC).

There are other examples we found which also fit the same discrepancy / pattern:

OMIM:615387 <-> HGNC:12029 (TRAC)

OMIM:601495 <-> HGNC:5541 (IGHM)

And their response:

TRAC, IGKC, and IGHM are immunoglobin gene/regions. As such,
they are unusual and do not carry a standard a "gene" locus type
annotation in the browsers. We do not always have a 1-to-1 correlation
with HGNC for the immunoglobin entities. I will review these cases
and see if we can match a few more.

Of note, MIM:615387 and MIM:601495 shouldn't map to any HGNC ID.
They are phenotypes, not genes.

twhetzel · 2025-01-27T09:07:14Z

src/ontology/mondo-edit.obo

@@ -465430,7 +465434,7 @@ is_a: MONDO:0015977 {source="MESH:C538056", source="MONDO:Redundant", source="OM
 intersection_of: MONDO:0011096 ! autosomal agammaglobulinemia
 intersection_of: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/5541 ! IGHM
 relationship: curated_content_resource https://search.clinicalgenome.org/kb/conditions/MONDO:0020729 {source="MONDO:CLINGEN"}
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/5541 {source="MONDO:mim2gene_medgen", source="OMIM:601495"} ! IGHM
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/5541 {source="MONDO:mim2gene_medgen"} ! IGHM


It seems this OMIM source should have been maintained. @joeflack4 can you look into this?

So, the phenotype OMIM:601495 is mapped to the gene OMIM:147020 as shown in morbidmap.txt:

Agammaglobulinemia 1, 601495 (3) IGHM, MU, AGM1 147020 14q32.33

But as with my long explanation above, the reason we don't have any HGNC source evidence being added is because it only shows an NCBI gene entry in mim2gene.txt, not an HGNC one:

mim2gene.txt:
147020 gene 3507 ENSG00000211899

Which gets added like this in omim.owl:
`AnnotationAssertion(http://www.w3.org/2004/02/skos/core#exactMatch https://omim.org/entry/147020 https://www.ncbi.nlm.nih.gov/gene/3507)

Based on the issue with the data, the OMIM source provenance for MONDO:0020729 on this line should have also been kept.

The issue w/ the data that Trish and I are discussing is that we see a label for the HGNC term in morbidmap.txt, but the ID for that term does not appear in mim2gene.txt. We will contact OMIM about this apparent discrepancy.

The OMIM source provenance was added back to this gene association.

twhetzel · 2025-01-27T09:09:06Z

src/ontology/mondo-edit.obo

-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/2979 {source="OMIM:619478"} ! DNMT3B
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 {source="OMIM:619478"} ! DUX4
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/2979 ! DNMT3B
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 ! DUX4


This disease contains "digenic" in the description and the gene associations should be removed (not just the source provenance).

Per explanation here, just because it has digenic in the label doesn't necessarily mean it will be removed. Though in most cases it will. However it'll be removed because there are >1 associations, not because 'digenic' is in the label.

Regarding removing the entire association, this is part of the mondo pipeline that Nico created. I assume you or I will edit this to remove the association when no evidence remains? I can do that if you want.

MONDO:0030355 is in the exclusion file so these gene associations should not have existed in mondo-edit.obo. These gene associations should be removed.

The gene association was removed.

twhetzel · 2025-01-27T09:10:51Z

src/ontology/mondo-edit.obo

-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/253 {source="OMIM:619151"} ! ADH5
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/404 {source="OMIM:619151"} ! ALDH2
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/253 ! ADH5
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/404 ! ALDH2


The disease description contains "digenic" for OMIM:619151 and these gene associations should be removed.

See: response

This (MONDO:0030894) is in the exclusion file and the gene association should be removed.

twhetzel · 2025-01-27T09:12:32Z

src/ontology/mondo-edit.obo

-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12441 {source="OMIM:620040"} ! TYMS
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/30365 {source="OMIM:620040"} ! ENOSF1
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12441 ! TYMS
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/30365 ! ENOSF1


The disease description contains "digenic" for https://omim.org/entry/620040 and these gene associations should be removed.

See: response

This (MONDO:0031057) is in the exclusion file and the gene association should be removed.

twhetzel · 2025-01-30T06:04:10Z

This PR ready for re-review. Additional tickets based on the issues found here will be added.

twhetzel · 2025-01-30T06:24:26Z

src/ontology/mondo-edit.obo

 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 {source="OMIM:108770"} ! SCN5A
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/4279 {source="MONDO:mim2gene_medgen", source="OMIM:108770"} ! GJA5


@matentzn since these gene associations do not exist in master, do you know how the OMIM pipeline added these in?

If tehy are not in master, it means this branch is behind master and needs to be rebased.

I did a local test last night with a fresh pull from mondo master and created a new branch and ran the OMIM gene update as sh run.sh make update-omim-genes -B and the same thing happened.

This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

@sabrinatoro can you remind me what your expectation is for entries that you said should be in the exclusion file?? I thought these were Mondo classes where OMIM source provenance should not be added and therefore the gene association(s) should not be on the class.

@matentzn you mentioned in the first review "I thought we decided not to preserve gene references if there is no provenance at all? This goes for various examples in this PR."

@sabrinatoro the exclusion file is from the spreadsheet that you created and mentioned in the OMIM gene update in Nov.

That PR does not have any gene associations for MONDO:0015281 'atrial standstill'.

That PR does not have any gene associations for MONDO:0015281 'atrial standstill'.

@twhetzel I don't follow...
This PR show that the gene annotation (2 genes) are removed from atrial standstill 1 - MONDO:0007171
This should not happen.
Based on the notes from November "I also started this spreadsheet to keep track of the record that should be excluded from the pipeline because they do not fit the rules."
To me, it means that nothing should happen to this term, ie no gene removed, no gene added.

I went back to look at all the commits from the previous PR and the last two you did and added the exclude from qc checks were not originally showing up and making this a very confusing picture. Now that I am aware of those later commits, I hope that clear things up 🙏

Ok, I will manually add these back and @joeflack4 will update the OMIM ingest code to "protect" these so that nothing happens to this term, ie no gene removed, no gene added.

sabrinatoro

Please see comments.

sabrinatoro · 2025-01-30T16:17:31Z

src/ontology/mondo-edit.obo

 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/10593 {source="OMIM:108770"} ! SCN5A
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/4279 {source="MONDO:mim2gene_medgen", source="OMIM:108770"} ! GJA5


This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

sabrinatoro · 2025-01-30T16:19:31Z

src/ontology/mondo-edit.obo

 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/29090 {source="MONDO:mim2gene_medgen", source="OMIM:158901"} ! SMCHD1
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 {source="OMIM:158901"} ! DUX4


This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

sabrinatoro · 2025-01-30T16:20:08Z

src/ontology/mondo-edit.obo

@@ -500399,8 +500392,6 @@ xref: OMIM:619478 {source="MONDO:equivalentTo"}
 xref: UMLS:C5561960 {source="MEDGEN:1794170", source="MONDO:equivalentTo", source="MONDO:MEDGEN"}
 is_a: MONDO:0001347 {source="DOID:0060918", source="OMIM:619478"} ! facioscapulohumeral muscular dystrophy
 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/2979 {source="OMIM:619478"} ! DNMT3B
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/50800 {source="OMIM:619478"} ! DUX4


This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

So the presence of the http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql means necessarily, that this is a disease which is allowed to have multiple genes as causes - this will make our pipelines a little more complex..

yes, the http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql means a curator reviewed this and agreed that this disease has more than 1 disease defining gene associations

sabrinatoro · 2025-01-30T16:20:20Z

src/ontology/mondo-edit.obo

@@ -503207,8 +503198,6 @@ xref: Orphanet:611216 {source="MONDO:equivalentTo"}
 xref: UMLS:C5436906 {source="MONDO:equivalentTo", source="MONDO:MEDGEN", source="MEDGEN:1754257"}
 is_a: MONDO:0000159 {source="OMIM:619151"} ! bone marrow failure syndrome
 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/253 {source="OMIM:619151"} ! ADH5
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/404 {source="OMIM:619151"} ! ALDH2


This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

sabrinatoro · 2025-01-30T16:20:26Z

src/ontology/mondo-edit.obo

@@ -505014,8 +505003,6 @@ xref: OMIM:620040 {source="MONDO:equivalentTo"}
 xref: UMLS:C5774217 {source="MEDGEN:1823990", source="MONDO:equivalentTo", source="MONDO:MEDGEN"}
 is_a: MONDO:0015780 {source="OMIM:620040"} ! dyskeratosis congenita
 relationship: excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/12441 {source="OMIM:620040"} ! TYMS
-relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/30365 {source="OMIM:620040"} ! ENOSF1


This term has the annotation
excluded_from_qc_check http://purl.obolibrary.org/obo/mondo/sparql/qc/mondo/qc-multiple-gene-associations.sparql

These gene annotations should not be removed.

src/ontology/mondo-edit.obo

sabrinatoro · 2025-01-30T16:32:02Z

src/ontology/mondo-edit.obo

@@ -175530,6 +175521,7 @@ is_a: MONDO:0005138 {source="DOID:5409", source="EFO:0000702", source="MONDO:Red
 is_a: MONDO:0005454 {source="MONDO:Redundant", source="NCIT:C4917/inferred", source="ONCOTREE:SCLC"} ! lung neuroendocrine neoplasm
 intersection_of: MONDO:0000402 ! small cell carcinoma
 intersection_of: disease_has_location UBERON:0002048 ! lung
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/9884 {source="OMIM:182280"} ! RB1


According to omim, this term has a % in front of the name meaning that "Phenotype description or locus, molecular basis unknown"

Please confirm that this annotation should be added according to our rules and because it is in the file we used.
If it is, then the workflow works correctly, and I will remove it manually (as it is an error).

Yes, for the logic we set up, we allow addition of these associations regardless of the MIM type (#, %, etc).

If you want, it is simple for me to add logic such that we only allow additions of associations if the disease MIM is of type # (Phenotype).
I think this would be easy and better than handling these manually each time.

FYI regarding how unexpected types are currently handled:
We do however, "flag" cases where the MIM type is unexpected. We expect that the MIM type will be # (phenotype) or % (Phenotype description or locus, molecular basis unknown). By flag, I mean that if an association meets all of the conditions for disease-defining but isn't a # or %, an entry will get added to review.tsv in the release (documentation). Note that there have been no instances of a non # or % being added, though.

sabrinatoro · 2025-01-30T16:33:25Z

src/ontology/mondo-edit.obo

@@ -165662,6 +165652,7 @@ xref: SCTID:721307000 {source="MONDO:equivalentTo"}
 xref: UMLS:C1834582 {source="MEDGEN:331782", source="MONDO:equivalentTo", source="MONDO:MEDGEN"}
 is_a: MONDO:0020076 {source="DOID:0060888", source="Orphanet:420611"} ! myeloproliferative neoplasm
 relationship: disease_arises_from_feature MONDO:0008608 ! Down syndrome
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/4170 {source="OMIM:159595"} ! GATA1


Same comment as below.
If this annotation is expected as per our rules and the file we use, then all is well.
It should however be removed manually as it is not correct according to the website.

Ok, I see this is for MONDO:0008040 'transient myeloproliferative syndrome' and that the OMIM page shows this with a mapping key of 2. @joeflack4 mentioned this has 2 rows in the morbidmap.txt file and is found to be self-referential and somatic so for these reasons it is added into the review.txt file and needed curator review to decide whether the gene association should be added.

sabrinatoro

It looks good! I am approving this PR.

@twhetzel, feel free to merge, but first, please see my comment regarding the SOP for annotations that should not be updated. Thank you.

sabrinatoro · 2025-01-30T23:43:06Z

src/ontology/mondo-edit.obo

@@ -225590,6 +225591,7 @@ xref: OMIM:278850 {source="MONDO:equivalentTo"}
 xref: Orphanet:393 {source="OMIM:278850"}
 xref: UMLS:C2749215 {source="MONDO:equivalentTo", source="MONDO:MEDGEN", source="MEDGEN:411414"}
 is_a: MONDO:0100249 {source="DOID:0111763", source="Orphanet:393/btnt"} ! 46,XX testicular disorder of sex development
+relationship: has_material_basis_in_germline_mutation_in http://identifiers.org/hgnc/11204 {source="OMIM:278850"} ! SOX9


We should not have this relationship to the gene because
"(...) is caused by heterozygous duplication or triplication of a 68-kb regulatory region (XXSR) -584 to -516 kb upstream of the SOX9 gene on chromosome 17q24."

However, one would not be able to see without reading the details. (ie this has nothing to do with this workflow).

I will manually remove it in a follow-up PR (I have something else to update).

@twhetzel Could you please confirm: Should I add this Mondo/OMIM to the "excluded spreadsheet", so it will not be updated next time? What is the SOP? Thanks.

Generally, there will be another file that can be updated by curators for gene associations that should not be added even though they otherwise meet the rules. Joe is working on this now.

This update is based on [this PR](monarch-initiative/mondo#8624) NOTE: SOP is needed surrounding this exclusion document. (In addition, we need to create a standard for the exclusion reason).

[create-pull-request] automated change

882499d

twhetzel requested a review from sabrinatoro as a code owner January 24, 2025 13:56

twhetzel added the Automated label Jan 24, 2025

remove gene associations from obsolete classes

73b0d37

twhetzel requested a review from matentzn January 24, 2025 16:52

matentzn reviewed Jan 24, 2025

View reviewed changes

twhetzel commented Jan 27, 2025

View reviewed changes

joeflack4 mentioned this pull request Jan 29, 2025

Bug: Disease-Gene: missing HGNC links monarch-initiative/omim#186

Closed

twhetzel added 2 commits January 29, 2025 20:59

remove digenic gene association for MONDO:0007171

829ec8f

manual updates to gene associations

0111160

twhetzel requested review from matentzn and joeflack4 January 30, 2025 06:01

twhetzel assigned matentzn and sabrinatoro Jan 30, 2025

twhetzel commented Jan 30, 2025

View reviewed changes

sabrinatoro requested changes Jan 30, 2025

View reviewed changes

sabrinatoro assigned twhetzel and joeflack4 and unassigned matentzn and sabrinatoro Jan 30, 2025

address PR comments

525241b

twhetzel assigned sabrinatoro and unassigned twhetzel Jan 30, 2025

twhetzel unassigned joeflack4 Jan 30, 2025

twhetzel requested a review from sabrinatoro January 30, 2025 23:05

sabrinatoro approved these changes Jan 30, 2025

View reviewed changes

sabrinatoro merged commit 20ed165 into master Jan 30, 2025
1 check passed

sabrinatoro deleted the omim_gene_references-bdecdc6 branch January 30, 2025 23:57

sabrinatoro mentioned this pull request Jan 31, 2025

update exclusion-disease-gene.tsv monarch-initiative/omim#187

Merged

twhetzel mentioned this pull request Jan 31, 2025

Protected Disease-Gene monarch-initiative/omim#188

Merged

joeflack4 mentioned this pull request Jan 31, 2025

update exclusion-disease-gene.tsv monarch-initiative/omim#190

Closed

Update OMIM gene references #8624

Update OMIM gene references #8624

Conversation

twhetzel commented Jan 24, 2025

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

joeflack4 Jan 28, 2025 • edited Loading

Choose a reason for hiding this comment

joeflack4 Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 • edited by joeflack4 Loading

Choose a reason for hiding this comment

joeflack4 Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 • edited by joeflack4 Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 29, 2025 • edited Loading

Choose a reason for hiding this comment

twhetzel commented Jan 30, 2025

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

twhetzel Jan 30, 2025 • edited Loading

Choose a reason for hiding this comment

sabrinatoro left a comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

Choose a reason for hiding this comment

joeflack4 Jan 30, 2025 • edited Loading

Choose a reason for hiding this comment

twhetzel Jan 27, 2025 •

edited

Loading

joeflack4 Jan 28, 2025 •

edited

Loading

joeflack4 Jan 29, 2025 •

edited

Loading

twhetzel Jan 27, 2025 •

edited

Loading

twhetzel Jan 27, 2025 •

edited

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 27, 2025 •

edited by joeflack4

Loading

joeflack4 Jan 29, 2025 •

edited

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 27, 2025 •

edited by joeflack4

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 29, 2025 •

edited

Loading

twhetzel Jan 30, 2025 •

edited

Loading

joeflack4 Jan 30, 2025 •

edited

Loading

sabrinatoro Jan 30, 2025 •

edited by joeflack4

Loading

twhetzel Jan 30, 2025 •

edited

Loading