KmerSignificance score: A discriminative and biologically informed framework for viral k-mer prioritization.

KmerSignificance Score (KSS) prioritizes viral k-mers on a shared [0,1] scale, achieving a mean F1 of 0.881 for strain discrimination across viral datasets.

• Why it matters: Existing k-mer selection methods emphasize statistical discriminative power but lack a standardized framework that integrates biological context for identifying informative genomic regions.
• What they did: KSS combines an information-theoretic discriminative component, a MIYATA_EVO amino-acid substitution matrix optimized by a genetic algorithm, and a UniProt-derived protein characterization score; it also reports Kendall’s τ=0.775 across 17,471 viral proteins.
• The result: Top-ranked k-mers for SARS-CoV-2, HIV-1, and human cytomegalovirus map to established variant-defining mutations, subtype-specific polymorphisms, and genotype markers, supporting KSS for variant surveillance and molecular epidemiology.