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monarch-initiative / gpsea

A Python library for discovery of genotype-phenotype associations
https://monarch-initiative.github.io/gpsea/stable
MIT License
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Create a predicate to test if variant affects a codon that encodes an aminoacid of interest #326

Open ielis opened 1 month ago

ielis commented 1 month ago

Create a predicate to test if variant affects a codon that encodes an aminoacid of interest.

pnrobinson commented 2 weeks ago

ZMYM3, amino acid 441 might be a good test, although the cohort size is small

pnrobinson commented 2 weeks ago

There is a significant result here:

r441w = VariantPredicates.variant_key("X_71249610_71249610_G_A") #c.1321C>T p.Arg441Trp
r441q = VariantPredicates.variant_key("X_71249609_71249609_C_T") #c.1322G>A p.Arg441Gln 
r441 = r441w | r441q

is_r441 = monoallelic_predicate(
    a_predicate=r441,
    b_predicate=~r441,
    a_label="R441",
    b_label="other"
)
r441_result = analysis.compare_genotype_vs_phenotypes(
    cohort=cohort,
    gt_predicate=is_r441,
    pheno_predicates=pheno_predicates,
)
summarize_hpo_analysis(hpo=hpo, result=r441_result)

yields a corrected p value of 0.003839 for Cupped ear [HP:0000378].

Note that I added a lot of curation for this cohort, which previously was one of the early efforts and did not include all of the HPOs. The data is not yet in an official phenopacket-store release.