Longshot

Longshot calls and phases single-nucleotide variants (SNVs) in diploid genomes using long-read single-molecule sequencing data from Pacific Biosciences (PacBio) SMRT and Oxford Nanopore Technologies (ONT) to improve variant detection and haplotype resolution in complex genomic regions.

Key Features:

• Long-read support: Operates on single-molecule sequencing (SMS) reads from PacBio SMRT and Oxford Nanopore Technologies (ONT).
• SNV detection and phasing: Detects and phases single-nucleotide variants by leveraging haplotype information within long reads.
• Input/output formats: Processes aligned BAM files and produces phased VCF files.
• Genotype and phase VCFs: Can genotype and phase variants provided in an input VCF file.
• Haplotype-separated BAMs: Can generate haplotype-separated BAM files for downstream analyses.
• Indel genotyping: Can genotype indels when they are supplied in an input VCF file.
• Performance in complex regions: Achieves high accuracy for SNV detection on whole-genome PacBio data, including duplicated and repetitive genomic regions where short reads have mapping challenges.

Scientific Applications:

• Diploid SNV calling: Accurate detection and phasing of SNVs in diploid genomes using long-read data.
• Phasing and genotyping of provided variants: Refinement of genotype and phase information for variants in existing VCFs.
• Phased data generation: Creation of haplotype-separated BAMs for analyses requiring phased read sets.
• Variant discovery in challenging regions: Improved SNV detection in duplicated and repetitive regions of the genome compared to short-read approaches.
• Indel genotyping from VCFs: Genotyping of indels when included in input VCF files.

Methodology:

Processes an aligned BAM to produce a phased VCF, can genotype and phase input VCF files, and can output haplotype-separated BAM files while leveraging haplotype information in single-molecule sequencing reads for SNV detection and phasing.