VariantClassifier

VariantClassifier performs hierarchical classification of genetic variants using genome annotation data to assign variants by genomic context and predict potential functional consequences.

Key Features:

• Hierarchical Classification: Employs a hierarchical approach to organize and prioritize variants based on genomic context and feature-based criteria.
• Input Handling: Accepts polymorphism lists alongside genome annotations generated from high-throughput DNA sequencing technologies.
• Comprehensive Annotation Integration: Assigns each variant to feature types including location-based categories (intergenic, genic, upstream promoter, intronic, exonic, downstream transcript), functional impact categories (5' splice site, 3' splice site, 5' UTR, 3' UTR, coding sequence (CDS)), mutation types (substitution, insertion, deletion), consequences on protein function (synonymous, non-synonymous, conserved, unconserved, frameshift, amino acid indel), and protein domain impact with prediction of truncated or altered protein sequences when applicable.
• Annotation Source Flexibility: Optimized for Ensembl annotations but can process properly formatted annotation data from alternative sources.
• Implementation: Implemented in Perl.

Scientific Applications:

• Large-scale variant evaluation: Enables rapid evaluation and prioritization of hundreds of thousands of variations across multiple genomes.
• Resequencing and variant prioritization: Supports prioritizing variants in resequencing studies based on genomic context and predicted impact.
• Functional interpretation: Provides annotations to aid interpretation of variant functional consequences for applications in personalized medicine, evolutionary biology, and population genetics.

Methodology:

Implemented in Perl, the software accepts polymorphism lists and genome annotations, applies a hierarchical classification by genomic context to assign variants to specified feature types (location-based, functional impact, mutation type), detects mutation types (substitution, insertion, deletion) and predicts consequences on protein function (synonymous/non-synonymous, conserved/unconserved, frameshift, amino acid indel) and protein domain impact including truncated or altered protein sequence prediction; it is optimized for Ensembl annotations but can process properly formatted alternative annotation sources.