Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop.

Abstract:

:Alternative splicing (AS) is a widespread process underlying the generation of transcriptomic and proteomic diversity and is frequently misregulated in human disease. Accordingly, an important goal of biomedical research is the development of tools capable of comprehensively, accurately, and efficiently profiling AS. Here, we describe Whippet, an easy-to-use RNA-seq analysis method that rapidly-with hardware requirements compatible with a laptop-models and quantifies AS events of any complexity without loss of accuracy. Using an entropic measure of splicing complexity, Whippet reveals that one-third of human protein coding genes produce transcripts with complex AS events involving co-expression of two or more principal splice isoforms. We observe that high-entropy AS events are more prevalent in tumor relative to matched normal tissues and correlate with increased expression of proto-oncogenic splicing factors. Whippet thus affords the rapid and accurate analysis of AS events of any complexity, and as such will facilitate future biomedical research.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Sterne-Weiler T,Weatheritt RJ,Best AJ,Ha KCH,Blencowe BJ

doi

10.1016/j.molcel.2018.08.018

subject

Has Abstract

pub_date

2018-10-04 00:00:00

pages

187-200.e6

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(18)30678-6

journal_volume

72

pub_type

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