MACARON

MACARON re-annotates multi-base affected codons from VCF files to improve prediction of amino acid consequences of SNV combinations in whole-genome or whole-exome next-generation sequencing data.

Key Features:

• Input format: Accepts Variant Call Format (VCF) files originating from next-generation sequencing projects.
• Multi-base codon detection: Identifies codons affected by multiple single nucleotide variants (SNVs).
• Re-annotation of codons: Re-annotates multi-base affected codons to determine the composite codon sequence and resultant amino acid.
• Comparison to single-SNV annotation: Compares re-annotated amino acid consequences to predictions from conventional base-to-base single-SNV annotation methods to detect discrepant outcomes.
• Genomic scope: Applies to whole genome and whole exome sequencing datasets.
• Variant prioritization: Supports filtering of deleterious coding variants and identification of candidate variants potentially impacting disease risk.
• Implementation: Implemented in Python.

Scientific Applications:

• Coding variant annotation: Improves accuracy of coding consequence annotation in whole-exome and whole-genome analyses.
• Detection of intracodon interactions: Reveals cases where multiple SNVs within a codon interact to produce amino acid changes not predicted by single-SNV annotations.
• Variant filtering for disease studies: Refines identification and prioritization of deleterious coding variants for follow-up in human disease research.
• Empirical example: In a whole-exome study of 573 individuals, MACARON identified 114 codons where multiple SNVs led to amino acid changes distinct from standard single-SNV predictions.

Methodology:

Starts from a VCF file, identifies codons containing multiple SNVs, re-annotates those multi-base codons to determine composite codon sequences and resultant amino acids, and compares these outcomes to conventional single-SNV annotations; implemented in Python.