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Cancer Inform. 2015 Feb 16;14:45-53. doi: 10.4137/CIN.S24832. eCollection 2015.

Mapping Splicing Quantitative Trait Loci in RNA-Seq.

Cancer informatics

Cheng Jia, Yu Hu, Yichuan Liu, Mingyao Li


  1. Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

PMID: 25733796 PMCID: PMC4333812 DOI: 10.4137/CIN.S24832


BACKGROUND: One of the major mechanisms of generating mRNA diversity is alternative splicing, a regulated process that allows for the flexibility of producing functionally different proteins from the same genomic sequences. This process is often altered in cancer cells to produce aberrant proteins that drive the progression of cancer. A better understanding of the misregulation of alternative splicing will shed light on the development of novel targets for pharmacological interventions of cancer.

METHODS: In this study, we evaluated three statistical methods, random effects meta-regression, beta regression, and generalized linear mixed effects model, for the analysis of splicing quantitative trait loci (sQTL) using RNA-Seq data. All the three methods use exon-inclusion levels estimated by the PennSeq algorithm, a statistical method that utilizes paired-end reads and accounts for non-uniform sequencing coverage.

RESULTS: Using both simulated and real RNA-Seq datasets, we compared these three methods with GLiMMPS, a recently developed method for sQTL analysis. Our results indicate that the most reliable and powerful method was the random effects meta-regression approach, which identified sQTLs at low false discovery rates but higher power when compared to GLiMMPS.

CONCLUSIONS: We have evaluated three statistical methods for the analysis of sQTLs in RNA-Seq. Results from our study will be instructive for researchers in selecting the appropriate statistical methods for sQTL analysis.

Keywords: RNA-Seq; alternative splicing; quantitative trait loci


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