A statistical method for the detection of alternative splicing using RNA-seq

Liguo Wang, Yuanxin Xi, Jun Yu, Liping Dong, Laising Yen, Wei Li

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Deep sequencing of transcriptome (RNA-seq) provides unprecedented opportunity to interrogate plausible mRNA splicing patterns by mapping RNA-seq reads to exon junctions (thereafter junction reads). In most previous studies, exon junctions were detected by using the quantitative information of junction reads. The quantitative criterion (e.g. minimum of two junction reads), although is straightforward and widely used, usually results in high false positive and false negative rates, owning to the complexity of transcriptome. Here, we introduced a new metric, namely Minimal Match on Either Side of exon junction (MMES), to measure the quality of each junction read, and subsequently implemented an empirical statistical model to detect exon junctions. When applied to a large dataset (>200M reads) consisting of mouse brain, liver and muscle mRNA sequences, and using independent transcripts databases as positive control, our method was proved to be considerably more accurate than previous ones, especially for detecting junctions originated from low-abundance transcripts. Our results were also confirmed by real time RT-PCR assay. The MMES metric can be used either in this empirical statistical model or in other more sophisticated classifiers, such as logistic regression.

Original languageEnglish (US)
Article numbere8529
JournalPLoS One
Volume5
Issue number1
DOIs
StatePublished - Jan 8 2010
Externally publishedYes

Fingerprint

alternative splicing
Alternative Splicing
exons
Exons
Statistical methods
statistical analysis
RNA
Statistical Models
statistical models
Transcriptome
transcriptome
High-Throughput Nucleotide Sequencing
Messenger RNA
Liver
Muscle
Logistics
Real-Time Polymerase Chain Reaction
control methods
Assays
Brain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A statistical method for the detection of alternative splicing using RNA-seq. / Wang, Liguo; Xi, Yuanxin; Yu, Jun; Dong, Liping; Yen, Laising; Li, Wei.

In: PLoS One, Vol. 5, No. 1, e8529, 08.01.2010.

Research output: Contribution to journalArticle

Wang, Liguo ; Xi, Yuanxin ; Yu, Jun ; Dong, Liping ; Yen, Laising ; Li, Wei. / A statistical method for the detection of alternative splicing using RNA-seq. In: PLoS One. 2010 ; Vol. 5, No. 1.
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