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gene :: disease lookup. #571
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For humans, OMIM is certainly where I check first. For extending to other organisms, I suspect Monarch Initiative is the place to start (e.g. Exomiser uses model organism phenotype data curated by Monarch Initiative). I would guess you would want to be able to limit the "associated phenotype" to only those phenotypes that are actually known to be caused by mutations in the gene (vs GWAS signals, etc -- or at least a gene associated with a phenotype by GWAS is a different level of evidence/information than a gene in which mutations cause a Mendelian phenotype). |
One way to do this currently would be to create a bed file with a pipe delimited disease list for each gene and then use gemini annotate. |
Yeah I have an old file I made from OMIM that I'll use for now. Actually it occurs to me that this is the more general solution for this is also applicable to integrating pathway info -- I know pathways is currently a separate tool within Gemini, but ideally when doing variant filtration, you'd want to be able to output the pathway/KEGG/etc information for the gene that the variant is affecting. |
Oh hey! I think this appears to be implemented in VEP v82 with the VEP option This appears to be multi-species. List of phenotype sources: http://uswest.ensembl.org/info/genome/variation/sources_phenotype_documentation.html I have not had time to test yet though. |
According to the VEP devs, |
is there an additional column that indicates the phenotype? if so, this wont require any change to gemini. |
Apparently not... they said:
I'm debating whether to argue that it should be an option to output the phenotype name (though the above response makes me think they're reluctant to add it) |
hrm. without that, it's not very helpful and with it, it'd be very helpful... and the more disease annotations they get, the bigger that divide in helpfulness becomes. |
I emailied the VEP dev mailing list to ask. You have a good point, right now a "1" tells me almost nothing -- for humans I'd already have to search nearly 20 databases to see which DB is the source of the "1" and it might have been wasted effort if the phenotype isn't even relevant. |
Will McLaren on the ENSEMBL dev list replied:
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This would also be a good method to use the resulting BED file either as a On Tue, Nov 10, 2015 at 1:43 PM, Jessica Chong notifications@github.com
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That is useful. I couldn't figure out the invocation for 82_37 ... |
Current plan is to use VEP "annotation dump" to support this. |
another couple of sources are: http://ctdbase.org/downloads/ both of which seem to have licenses that would allow us to use them in gemini |
FYI when using VEP (v83+) with here are some examples from running VEP v83 on some known pathogenic variants in CFTR:
There's a little weirdness with them using |
If Example:
This means that rs2691305 and rs75062661 are not associated with a phenotype, disease, or trait, but COSM4144171 is. This is sort of like a super-set that includes clinvar_sig (since VEP includes ClinVar) |
@jxchong any ideas on how to handle this
but not sure I grok enough to understand how useful that is. |
I think both of these keys can be added as-is to the GEMINI database using GEMINI's current standard handling of extra fields. (except for minor issue that blank values are not being output by GEMINI as
Personally I don't envision filtering on the results of VEP's |
via @jxchong cc @arq5x
A user may find a variant that is not itself associated with disease, but is in a gene known to be associated with the disease. There is no way to store or query this info in gemini at this time.
clinvar is an obvious choice and omim seems to be available to download for academic (http://omim.org/downloads).
Design
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