Is your feature request related to a problem? Please describe.
After #72 we have AutoPM1. We need to finish it's implementation and test it.
Describe the solution you'd like
Implement the _get_uniprot_domain method
Add unit tests
Add integration tests
Rewrite docstrings
Describe alternatives you've considered
N/A
Additional context
Some information for PM1
PM1 (hotspot)
Original Definition
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
-- Richards et al. (2015); Table 4
Preconditions / Precomputations
If the variant is on chrMT then this criterion is skipped according to McCormick et al. (2020).
Implemented Criterion
If the variant is within a hotspot (at least 4 pathogenic missense/in-frame variants within 25bp radius) then this criterion is triggered.
If the variant is within an annotated UniProt domain and the domain contains at least 2 pathogenic variants then this criterion is triggered.
User Report
The hotspot region definition and the number of pathogenic variants in the region.
Literature
McCormick et al. (2020) describe the ACMG criteria for chrMT variants.
Caveats
We currently use the threshold from PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.
Intervar
PM1 by Automated Scoring
Many protein domains play essential roles for protein function, so missense variants in these domains tend to be pathogenic. The domain information can be inferred from dbNSFP by ANNOVAR through the “dbnsfp31a_interpro” database. We first annotated all ClinVar variants (subject to the same data-cleaning procedure described above) with protein-domain information and then compiled a list in which domains contained only pathogenic or likely pathogenic variants without benign or common (allele frequency > 5%) variants. This list is provided within the InterVar package and will be updated regularly. If the user’s input variants are located in these domains, then PM1 will be applied.
Is your feature request related to a problem? Please describe. After #72 we have AutoPM1. We need to finish it's implementation and test it.
Describe the solution you'd like
_get_uniprot_domainmethodDescribe alternatives you've considered N/A
Additional context Some information for PM1
PM1 (hotspot)
Original Definition
Preconditions / Precomputations
Implemented Criterion
User Report
Literature
Caveats
PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.Intervar
PM1 by Automated Scoring Many protein domains play essential roles for protein function, so missense variants in these domains tend to be pathogenic. The domain information can be inferred from dbNSFP by ANNOVAR through the “dbnsfp31a_interpro” database. We first annotated all ClinVar variants (subject to the same data-cleaning procedure described above) with protein-domain information and then compiled a list in which domains contained only pathogenic or likely pathogenic variants without benign or common (allele frequency > 5%) variants. This list is provided within the InterVar package and will be updated regularly. If the user’s input variants are located in these domains, then PM1 will be applied.