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Updated: Jul 2, 2025

Improving Small RNA-seq: Less Bias and Better Detection of 2'-O-Methyl RNAs
Published on: September 16, 2019
STAR+WASP reduces reference bias in the allele-specific mapping of RNA-seq reads
Rebecca Asiimwe1, Dobin Alexander1
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA.
Abstract:
Allele-specific expression (ASE) is an important genetic phenomenon that impacts an individual's phenotype and is relevant in various biological and medical contexts. Next-generation RNA sequencing technologies provide an unprecedented opportunity to measure ASE genome-wide across all heterozygous alleles expressed in a given sample. One of the major obstacles to the accurate calculation of ASE from RNA-seq data is the reference mapping bias, i.e., the preferential misalignment of the reads to the reference allele. Here, we present STAR+WASP, our re-implementation of WASP, a highly accurate algorithm for reducing the reference bias (Van De Geijn et al. 2015). We show that STAR+WASP is an order of magnitude faster than WASP while significantly reducing reference bias and providing ASE estimations similar to the original WASP algorithm.

