KATK

KATK calls genetic variants directly from raw next-generation sequencing (NGS) FASTQ reads by using predefined k-mers to retrieve relevant reads for local alignment and genotype determination.

Key Features:

• Direct Variant Calling: Operates on raw NGS FASTQ reads without requiring pre-mapped reads or prior reference genome alignments.
• K-mer-based Read Filtering: Uses predefined k-mers to efficiently retrieve only reads pertinent to variant analysis from FASTQ files.
• Local Alignment for Genotyping: Performs local alignment of retrieved reads to determine genotypes without relying on prior knowledge of known polymorphisms.
• Genotype Confidence and No-Call Policy: Assigns a genotype only when there is sufficient evidence for the reference or variant allele and reports NC (No Call) when evidence is lacking.
• Performance Metrics: In simulated datasets, reports a false negative rate of 0.23%, a false discovery rate of 0.19%, and a sensitivity of 99.77%.
• Human Exome Processing Time: Can process all human exonic regions within approximately 1–2 hours depending on sequencing coverage.

Scientific Applications:

• Genomic Studies: Facilitates discovery of rare genetic variants and de novo mutations from raw sequencing data.
• Clinical Genomics: Enables rapid and accurate variant detection directly from patient sequencing data for clinical analyses.
• Population Genetics: Supports analyses of genetic diversity and evolutionary patterns across populations using raw NGS reads.

Methodology:

Predefined k-mers are used to filter and retrieve relevant reads from FASTQ files, retrieved reads undergo local alignment for genotype determination, genotypes are called only when sufficient evidence for reference or variant alleles exists and otherwise reported as NC, and the approach does not rely on prior knowledge of known polymorphisms.