MATS: A Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data

Shihao Shen, Juw Won Park, Jian Huang, Kimberly A. Dittmar, Zhi Xiang Lu, Qing Zhou, Russ P. Carstens, Yi Xing

Research output: Journal article publicationJournal articleAcademic researchpeer-review

176 Citations (Scopus)

Abstract

Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate analysis of transcript splicing), a Bayesian statistical framework for flexible hypothesis testing of differential alternative splicing patterns on RNA-Seq data. MATS uses a multivariate uniform prior to model the between-sample correlation in exon splicing patterns, and a Markov chain Monte Carlo (MCMC) method coupled with a simulation-based adaptive sampling procedure to calculate the P-value and false discovery rate (FDR) of differential alternative splicing. Importantly, the MATS approach is applicable to almost any type of null hypotheses of interest, providing the flexibility to identify differential alternative splicing events that match a given user-defined pattern. We evaluated the performance of MATS using simulated and real RNA-Seq data sets. In the RNA-Seq analysis of alternative splicing events regulated by the epithelial-specific splicing factor ESRP1, we obtained a high RT-PCR validation rate of 86 for differential exon skipping events with a MATS FDR of <10. Additionally, over the full list of RT-PCR tested exons, the MATS FDR estimates matched well with the experimental validation rate. Our results demonstrate that MATS is an effective and flexible approach for detecting differential alternative splicing from RNA-Seq data.
Original languageEnglish
JournalNucleic Acids Research
Volume40
Issue number8
DOIs
Publication statusPublished - 1 Apr 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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