51. mountainClimber Identifies Alternative Transcription Start and Polyadenylation Sites in RNA-Seq
- Author
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Xinshu Xiao and Ashley A. Cass
- Subjects
Untranslated region ,Histology ,Transcription, Genetic ,Polyadenylation ,Messenger ,RNA-Seq ,Computational biology ,Biology ,Article ,Pathology and Forensic Medicine ,Alternative transcription ,03 medical and health sciences ,0302 clinical medicine ,Genetic ,RNA Isoforms ,Protein biosynthesis ,Genetics ,Humans ,tissues ,RNA, Messenger ,human ,Gene ,3' Untranslated Regions ,030304 developmental biology ,0303 health sciences ,Sequence Analysis, RNA ,Gene Expression Profiling ,alternative polyadenylation ,Human Genome ,RNA ,Cell Biology ,change point ,GTEx ,Biochemistry and Cell Biology ,RNA-seq ,alternative transcription start site ,Sequence Analysis ,Transcription ,030217 neurology & neurosurgery ,Software - Abstract
Alternative transcription start (ATS) and alternative polyadenylation (APA) create alternative RNA isoforms and modulate many aspects of RNA expression and protein production. However, ATS and APA remain difficult to detect in RNA sequencing (RNA-seq). Here, we developed mountainClimber, a de novo cumulative-sum-based approach to identify ATS and APA as change points. Unlike many existing methods, mountainClimber runs on a single sample and identifies multiple ATS or APA sites anywhere in the transcript. We analyzed 2,342 GTEx samples (36 tissues, 215 individuals) and found that tissue type is the predominant driver of transcript end variations. 75% and 65% of genes exhibited differential APA and ATS across tissues, respectively. In particular, testis displayed longer 5' untranslated regions (UTRs) and shorter 3' UTRs, often in genes related to testis-specific biology. Overall, we report the largest study of transcript ends across human tissues to our knowledge. mountainClimber is available at github.com/gxiaolab/mountainClimber.
- Published
- 2019