PoolHap2

PoolHap2 infers haplotype frequencies from pooled sequencing samples to enable analysis of within-sample genetic variation in mixed-strain populations and pooled-sample genetic mapping.

Key Features:

• Haplotype inference from pooled samples: Determines haplotype frequencies when individual subtypes cannot be experimentally separated prior to sequencing.
• Utilization of genome-wide SNP coverage: Uses genome-wide single nucleotide polymorphism (SNP) coverage to compensate for uneven sequencing coverage across genomic regions, improving haplotype frequency estimation accuracy.
• Application in various biological contexts: Applicable to naturally occurring pools, such as pooled pathogen samples, and to artificially pooled samples used in genetic mapping approaches like bulked segregant analysis.
• Performance validation: Validated on simulated and real data, estimating haplotype proportions with less than 2% error in a 34-strain Arabidopsis thaliana whole-genome polymorphism mixture at 2X total coverage.

Scientific Applications:

• Within-host polymorphism analysis: Enables analysis of within-host polymorphisms in mixed infections without prior separation of individual strains.
• Pathogen population studies: Supports characterization of mixed pathogen populations from pooled sequencing data.
• Genetic mapping / bulked segregant analysis: Supports use in bulked segregant analysis and other pooled-sample genetic mapping approaches.
• Cancer genomics: Applicable to analyses of pooled tumor-derived samples to assess intra-tumor heterogeneity.
• mRNA isoform studies: Can be applied to pooled-sample analyses involving mRNA isoforms.

Methodology:

Determines haplotype frequencies from pooled sequencing samples by leveraging genome-wide single nucleotide polymorphism (SNP) coverage to compensate for uneven sequencing depth across genomic regions.