Abstract

BackgroundAlternative splicing increases proteome diversity by expressing multiple gene isoforms that often differ in function. Identifying alternative splicing events from RNA-seq experiments is important for understanding the diversity of transcripts and for investigating the regulation of splicing.ResultsWe developed Alt Event Finder, a tool for identifying novel splicing events by using transcript annotation derived from genome-guided construction tools, such as Cufflinks and Scripture. With a proper combination of alignment and transcript reconstruction tools, Alt Event Finder is capable of identifying novel splicing events in the human genome. We further applied Alt Event Finder on a set of RNA-seq data from rat liver tissues, and identified dozens of novel cassette exon events whose splicing patterns changed after extensive alcohol exposure.ConclusionsAlt Event Finder is capable of identifying de novo splicing events from data-driven transcript annotation, and is a useful tool for studying splicing regulation.

Highlights

  • Alternative splicing increases proteome diversity by expressing multiple gene isoforms that often differ in function

  • We developed a tool, Alt Event Finder, for generating de novo annotation for alternative splicing events from a map of transcripts and isoforms reconstructed from RNA sequencing (RNA-seq) experiments

  • In conjunction with upstream alignment and isoform reconstruction tools, we demonstrated that Alt Event Finder has the ability to identify novel cassette exon events that are not documented in the established databases

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Summary

Introduction

Alternative splicing increases proteome diversity by expressing multiple gene isoforms that often differ in function. Identifying alternative splicing events from RNA-seq experiments is important for understanding the diversity of transcripts and for investigating the regulation of splicing. Alternative splicing is an important level of gene regulation that greatly contributes to proteome diversity [1]. It enables one gene to produce multiple isoforms that can have different biological functions. More than 90% of genes encode multiple protein isoforms [2], and many diseases are caused by the dysregulation of splicing patterns [3]. EST (Expressed Sequence Tags) databases and microarray technologies have been utilized to study splicing regulation [4,5,6,7]. In addition to previously known splicing events, RNA-seq technology can be used to identify novel splicing events

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