[HTML][HTML] Allelic mapping bias in RNA-sequencing is not a major confounder in eQTL studies
Genome biology, 2014•Springer
Background RNA sequencing (RNA-seq) is the current gold-standard method to quantify
gene expression for expression quantitative trait locus (eQTL) studies. However, a potential
caveat in these studies is that RNA-seq reads carrying the non-reference allele of variant
loci can have lower probability to map correctly to the reference genome, which could bias
gene quantifications and cause false positive eQTL associations. In this study, we analyze
the effect of this allelic mapping bias in eQTL discovery. Results We simulate RNA-seq read …
gene expression for expression quantitative trait locus (eQTL) studies. However, a potential
caveat in these studies is that RNA-seq reads carrying the non-reference allele of variant
loci can have lower probability to map correctly to the reference genome, which could bias
gene quantifications and cause false positive eQTL associations. In this study, we analyze
the effect of this allelic mapping bias in eQTL discovery. Results We simulate RNA-seq read …
Background
RNA sequencing (RNA-seq) is the current gold-standard method to quantify gene expression for expression quantitative trait locus (eQTL) studies. However, a potential caveat in these studies is that RNA-seq reads carrying the non-reference allele of variant loci can have lower probability to map correctly to the reference genome, which could bias gene quantifications and cause false positive eQTL associations. In this study, we analyze the effect of this allelic mapping bias in eQTL discovery.
Results
We simulate RNA-seq read mapping over 9.5 M common SNPs and indels, with 15.6% of variants showing biased mapping rate for reference versus non-reference reads. However, removing potentially biased RNA-seq reads from an eQTL dataset of 185 individuals has a very small effect on gene and exon quantifications and eQTL discovery. We detect only a handful of likely false positive eQTLs, and overall eQTL SNPs show no significant enrichment for high mapping bias.
Conclusion
Our results suggest that RNA-seq quantifications are generally robust against allelic mapping bias, and that this does not have a severe effect on eQTL discovery. Nevertheless, we provide our catalog of putatively biased loci to allow better controlling for mapping bias to obtain more accurate results in future RNA-seq studies.
Springer