期刊
RNA
卷 21, 期 1, 页码 14-27出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.046037.114
关键词
3 ' UTR; APA; RNA-seq; IsoSCM
资金
- Tr-Institutional Training Program in Computational Biology and Medicine
- Canadian Institutes of Health Research
- Burroughs Wellcome Fund
- National Institute of General Medical Sciences of the National Institutes of Health (National Institute of Neurological Disorders and Stroke) [R01-NS074037, R01-NS083833]
- NATIONAL CANCER INSTITUTE [P30CA008748] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS074037, R01NS083833] Funding Source: NIH RePORTER
Major applications of RNA-seq data include studies of how the transcriptome is modulated at the levels of gene expression and RNA processing, and how these events are related to cellular identity, environmental condition, and/or disease status. While many excellent tools have been developed to analyze RNA-seq data, these generally have limited efficacy for annotating 3' UTRs. Existing assembly strategies often fragment long 3' UTRs, and importantly, none of the algorithms in popular use can apportion data into tandem 3' UTR isoforms, which are frequently generated by alternative cleavage and polyadenylation (APA). Consequently, it is often not possible to identify patterns of differential APA using existing assembly tools. To address these limitations, we present a new method for transcript assembly, Isoform Structural Change Model (IsoSCM) that incorporates change-point analysis to improve the 3' UTR annotation process. Through evaluation on simulated and genuine data sets, we demonstrate that IsoSCM annotates 3' termini with higher sensitivity and specificity than can be achieved with existing methods. We highlight the utility of IsoSCM by demonstrating its ability to recover known patterns of tissue-regulated APA. IsoSCM will facilitate future efforts for 3' UTR annotation and genome-wide studies of the breadth, regulation, and roles of APA leveraging RNA-seq data.
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