CompoundHetVIP

CompoundHetVIP identifies compound heterozygous (CH) variants in Illumina whole-genome sequencing data to elucidate genetic contributions to disease heritability and other phenotypes.

Key Features:

• Integration of multiple tools: Encapsulates a suite of computational tools for phasing, annotating, and analyzing compound heterozygous, homozygous alternate, and de novo variants.
• Input compatibility: Accepts Illumina whole-genome sequencing from individual samples or trios (child and both parents) in VCF or gVCF formats.
• Phasing and parental origin assignment: Phases variants and distinguishes maternally and paternally derived alleles.
• Comprehensive workflow: Operates through a series of 13 steps, each producing analysis-ready output files.
• Modular design: Modular pipeline architecture enables stepwise processing and focused identification of CH variants, homozygous alternate variants, and de novo mutations.

Scientific Applications:

• Missing heritability investigation: Identifying CH variants to investigate missing heritability in human diseases and complex traits.
• Familial inheritance analysis: Resolving inheritance patterns in trio data and assigning parental origin of alleles.
• Empirical demonstration: Applied to publicly available Ashkenazim trio whole-genome sequencing data, identifying candidate CH variants in two genes and a candidate homozygous alternate variant in one gene after filtering.

Methodology:

Processes VCF or gVCF inputs through a 13-step modular pipeline that performs phasing and annotation to distinguish maternal and paternal alleles and to identify compound heterozygous, homozygous alternate, and de novo variants.