Mapping Splicing Quantitative Trait Loci in RNA-Seq

Cancer Informatics
Cheng JiaMingyao Li

Abstract

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. 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. 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 GLi...Continue Reading

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Citations

Sep 20, 2018·Diabetes, Obesity & Metabolism·Maria Inês AlvelosDécio L Eizirik
Oct 3, 2018·Nucleic Acids Research·Nuno Saraiva-Agostinho, Nuno L Barbosa-Morais
Jan 11, 2020·Frontiers in Genetics·Jed J LyeDiana Baralle

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Methods Mentioned

BETA
RNA-Seq
of

Software Mentioned

lme4
PSGLMM
Cufflinks
UCSC Genome Browser
Flux Simulator
PSMeta
JIP
Stata
betareg
GLiMMPS

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Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.