FlexTyper

FlexTyper performs k-mer based reverse mapping against an FM-indexed next-generation sequencing short-read dataset to extract coverage, SNP genotypes, pathogen sequences, and population-specific alleles without reference-guided alignment.

Key Features:

• FM-index Creation: Builds an FM-index from raw NGS short-read data to enable rapid, searchable sequence queries.
• Reverse Mapping: Queries indexed reads directly rather than aligning reads to a reference genome.
• k-mer Queries: Supports high-throughput k-mer searches against indexed short-read datasets for targeted sequence detection.
• Genotyping and Coverage Analysis: Recovers depth of coverage and genotypes single nucleotide polymorphism (SNP) sites, including from unmapped reads to inform sample ancestry, sex, and familial relatedness.
• Pathogen Detection: Detects pathogen sequences in RNA-seq data with sensitivity and accuracy comparable to existing methods.
• Analysis of Complex Genome Features: Enables interrogation of contigs from African genome sequencing studies and detection of alleles at loci poorly represented by linear references, such as the killer immune receptor locus.
• Population-Reference Integration: Supports selection of population-specific references and weighting of edges in pan-population reference genome graphs for population-aware analyses.

Scientific Applications:

• Human Genomics: Identifies sample ancestry, sex, and familial relationships from whole-genome sequencing and unmapped reads.
• Pathogen Detection: Detects viral and other pathogen sequences within RNA-seq datasets.
• Population-Specific Analysis: Analyzes genomic regions and contigs enriched in specific populations, such as African genomes, and interrogates alleles at loci underrepresented in global references.

Methodology:

Creates an FM-index of short-read NGS data and performs user-guided k-mer based reverse mapping queries against that index to recover coverage, genotype SNP sites, detect pathogen sequences, and interrogate contigs or alleles without reference-guided alignment.