Abstract

SummaryAn alternative splicing isoform switch is where a pair of transcript isoforms reverse their relative expression abundances in response to external or internal stimuli. Although computational methods are available to study differential alternative splicing, few tools for detection of isoform switches exist and these are based on pairwise comparisons. Here, we provide the TSIS R package, which is the first tool for detecting significant transcript isoform switches in time-series data. The main steps of TSIS are to search for the isoform switch points in the time-series, characterize the switches and filter the results with user input parameters. All the functions are integrated into a Shiny App for ease of implementation of the analysis.Availability and implementationThe TSIS package is available on GitHub: https://github.com/wyguo/TSIS.

Highlights

  • Regulation of gene expression by alternative splicing (AS) generates changes in abundance of different transcript isoforms

  • Computational methods are available to study differential alternative splicing, few tools for detection of isoform switches exist and these are based on pairwise comparisons

  • We provide the time-series isoform switch (TSIS) R package, which is the first tool for detecting significant transcript isoform switches in time-series data

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Summary

Introduction

Regulation of gene expression by alternative splicing (AS) generates changes in abundance of different transcript isoforms. One particular splicing phenotype is isoform switching where the relative abundance of different isoforms of the same gene is reversed in different cell types or in response to stimuli. Isoform switches often play pivotal roles in re-programming of gene expression and isoform switches of functionally different transcript isoforms between normal and tumor tissues provide signatures for cancer diagnostics and prognostics (Sebestyen et al, 2015). There are limited tools designed for inference of isoform switches and currently there is no software available for detecting alternative splicing isoform switches for time-series data. To detect and characterize temporal and complex isoform switches, we developed the time-series isoform switch (TSIS) R package, which incorporates score schemes from current methods and includes a number of new metrics which capture the characteristics of the isoform switches

Methods and application
Determine the switch points
Filter and visualize the results
Define the switch metrics

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