PASS

PASS aligns short DNA sequences to reference genomes for rapid, sensitive mapping of high-throughput and bisulfite-treated sequencing data.

Key Features:

• Efficient alignment mechanism: Performs both gapped and ungapped alignments of short reads using an index of seed words (11-12 bases) and precomputed scores for shorter flanking regions (7-8 bases) to rapidly locate and verify matches.
• Performance: Achieves gap alignment hundreds of times faster than BLAST and outperforms SOAP, particularly when gaps are allowed, while maintaining high sensitivity for short-read mapping.
• Compatibility with sequencing technologies: Handles large datasets generated by Solexa, SOLiD, and 454 sequencing platforms.
• Bisulfite-treated DNA (Bi-Seq) support: Implements an algorithm optimized for Bi-Seq reads from SOLiD and Illumina, addressing C/T conversions in SOLiD color space, and includes a methylation-caller that reports methylated and unmethylated cytosines on both strands.
• Implementation and platforms: Implemented in C++ and supports Linux and Windows operating systems.
• Benchmarking integration: Used with CuReSim and CuReSimEval for benchmarking mapper accuracy, robustness, and computational efficiency.

Scientific Applications:

• Whole genome sequencing: Mapping short reads to reference genomes for WGS projects.
• Methylation analysis: Mapping bisulfite-treated reads and calling cytosine methylation states on both DNA strands.
• Variant detection: Precise detection and reporting of indels and substitutions from short-read data.
• Small genome projects: High-sensitivity, high-throughput mapping suitable for analyses of small genomes.
• Mapper evaluation: Benchmarking and comparison of mappers using simulated datasets and evaluation tools such as CuReSim and CuReSimEval.

Methodology:

Indexes genomic positions of 11–12 base seed words and stores precomputed scores for 7–8 base flanking regions, locates seed matches via the index, verifies candidates using precomputed alignments and exact dynamic alignment within a narrow region, supports gapped and ungapped alignments, and applies a specialized algorithm for bisulfite-treated reads (including handling C/T conversions in SOLiD color space) with a methylation-caller that reports methylation per cytosine on both strands.