Allele-specific sequencing reads provide a powerful signal for identifying molecular quantitative trait loci (QTLs), but they are challenging to analyze and are prone to technical artifacts. Here researchers from the University of Chicago and Stanford University describe WASP, a suite of tools for unbiased allele-specific read mapping and discovery of molecular QTLs. Using simulated reads, RNA-seq reads and chromatin immunoprecipitation sequencing (ChIP-seq) reads, they demonstrate that WASP has a low error rate and is far more powerful than existing QTL-mapping approaches.
The WASP mapping pipeline – Reads are first mapped to the genome using a mapping tool of the user’s choice. The aligned reads are provided to WASP in SAM (sequence alignment/map) or BAM (binary alignment/map) format, along with a list of known polymorphisms. WASP identifies reads that overlap known polymorphisms, flips the alleles in the reads, and remaps them to the genome. Reads that map to a different location than the original read are then discarded. Finally, WASP can optionally remove reads that map to the same genomic location (‘duplicate reads’) without introducing a reference bias.