trioPhaser

trioPhaser phases genetic variants in parent-child trios by combining Mendelian inheritance logic and the SHAPEIT4 algorithm to increase completeness and accuracy of haplotype phasing.

Key Features:

• Integration of Mendelian Inheritance Logic: Applies Mendelian inheritance principles to phase approximately 67–83% of an individual's heterozygous nucleotide positions when genotypes for both parents are available.
• Utilization of SHAPEIT4 Algorithm: Uses the SHAPEIT4 phasing algorithm to resolve positions that remain unphased, specifically where all trio members are heterozygous.
• Input and Output Formats: Accepts gVCF files from the proband and both parents as input and outputs a phased VCF file.
• Performance Improvement: In whole-genome sequencing data from 52 trios, increases the total number of phased positions by 21.0% compared to SHAPEIT4 alone and by 10.5% compared to Mendelian inheritance logic alone.
• Comparative Accuracy: Produces phased calls with accuracy comparable to linked-read and read-backed phasing methods.
• Containerized Implementation: Distributed as a containerized implementation.

Scientific Applications:

• Mendelian disorder studies: Improves haplotype resolution for analyses of inherited single-gene disorders using parent-offspring trios.
• Complex trait genetics: Enhances phasing completeness for studies of polygenic traits that benefit from accurate haplotype information.
• Personalized medicine: Provides more complete phased genotypes to support clinical genomic interpretation and variant assessment.
• Variant association and genomic interpretation: Increases reliability of downstream analyses such as association studies and haplotype-based interpretation.

Methodology:

Performs a two-step computational phasing: first applies Mendelian inheritance logic to phase as many positions as possible, then applies the SHAPEIT4 algorithm to phase positions remaining unphased (notably sites where all trio members are heterozygous).