MutCombinator

MutCombinator identifies mutated peptides from tandem mass spectra by searching combinatorial point mutations on a nucleotide-based variant graph to support proteogenomic analyses.

Key Features:

• Combinatorial Mutation Search: Considers combinations of point mutations during database searches of tandem mass spectra to detect a broader spectrum of peptide variants.
• Variant Graph Utilization: Employs a nucleotide-based variant graph that maintains reading-frame information and is indexed by nine nucleotides for rapid access.
• Integration with Mutation Databases: Uses large mutation databases such as COSMIC to generate candidate variant peptides for searching.
• In-Frame and Three-Frame Search: Supports in-frame searches for coding regions and three-frame searches for non-coding regions.
• Genomics–Proteomics Integration: Leverages next-generation sequencing (NGS) and proteomic data to infer protein expression and detect mutation-derived peptide variants.

Scientific Applications:

• Proteogenomic peptide discovery: Identifies novel peptides that arise from genetic mutations for proteogenomic studies.
• Detection of combinatorial variant peptides: Detects peptide variants resulting from multiple concurrent point mutations that conventional searches may miss.
• Cancer proteomics: Supports analysis of protein variations linked to somatic mutations cataloged in COSMIC and other cancer-related mutation datasets.

Methodology:

Performs a nucleotide-based graph search using a variant graph indexed by nine nucleotides that preserves frame information; considers combinatorial point mutations during database searches of tandem mass spectra; supports in-frame and three-frame searches and incorporates mutation databases such as COSMIC to generate candidate peptides.