SRPRISM

SRPRISM performs non-spliced alignment of next-generation sequencing reads to reference genome assemblies, providing explicit search-sensitivity guarantees and support for assemblies containing primary and alternate sequences to enable accurate mapping to complex genomes such as GRCh38.

Key Features:

• Support for Genome Assemblies with Alternate Sequences: Supports genome assemblies containing both primary and alternate sequences and provides placement information for alternates relative to primary sequences, enabling mapping to assemblies such as GRCh38.
• Partial Alignment Capabilities: Allows specification of regions within reads for alignment to perform partial alignments.
• Flexible Ranking Schemes for Alignments: Provides customizable ranking schemes to prioritize alignments according to specified criteria.
• Explicit Criteria for Search Sensitivity: Defines clear criteria and guarantees for search sensitivity to enable informed trade-offs between sensitivity and computational performance.

Scientific Applications:

• Mapping to Complex Genome Assemblies: Aligns reads to genome assemblies with alternate sequences to improve placement accuracy in complex references such as GRCh38.
• Genetic and Structural Variation Analysis: Supports analyses of genetic variation and structural variants by enabling alignments to alternate sequences and placement-aware mappings.
• Variant Discovery and Personalized Medicine: Facilitates variant discovery and personalized-medicine studies where precise, sensitivity-controlled alignments are required.

Methodology:

Evaluated using benchmark sets of paired and single reads of lengths 100 and 250 base pairs generated by DWGSIM and compared against GEM, Kart, STAR, BWA-MEM, Bowtie2, Hobbes, and Yara; demonstrated superior performance across most benchmark sets with error rates up to approximately 2.5% and higher sensitivity even when sensitivity was reduced to improve run time.