Leveraging transcript quantification for fast computation of alternative splicing profiles

Authors
Alamancos, Gael P.; Pages, Amadis; Trincado, Jose Luis; Bellora, Nicolás; Eyras, Eduardo
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
Alternative splicing plays an essential role in many cellular processes and bears major relevance in the understanding of multiple diseases, including cancer. High-throughput RNA sequencing allows genome-wide analyses of splicing across multiple conditions. However, the increasing number of available data sets represents a major challenge in terms of computation time and storage requirements. We describe SUPPA, a computational tool to calculate relative inclusion values of alternative splicing events, exploiting fast transcript quantification. SUPPA accuracy is comparable and sometimes superior to standard methods using simulated as well as real RNA-sequencing data compared with experimentally validated events. We assess the variability in terms of the choice of annotation and provide evidence that using complete transcripts rather than more transcripts per gene provides better estimates. Moreover, SUPPA coupled with de novo transcript reconstruction methods does not achieve accuracies as high as using quantification of known transcripts, but remains comparable to existing methods. Finally, we show that SUPPA is more than 1000 times faster than standard methods. Coupled with fast transcript quantification, SUPPA provides inclusion values at a much higher speed than existing methods without compromising accuracy, thereby facilitating the systematic splicing analysis of large data sets with limited computational resources. The software is implemented in Python 2.7 and is available under the MIT license at https://bitbucket.org/regulatorygenomicsupf/suppa. 
Fil: Alamancos, Gael P.. Universitat Pompeu Fabra; España
Fil: Pages, Amadis. Universitat Pompeu Fabra; España. Centre for Genomic Regulation; España
Fil: Trincado, Jose Luis. Universitat Pompeu Fabra; España
Fil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación En Biodiversidad y Medioambiente; Argentina
Fil: Eyras, Eduardo. Institució Catalana de Recerca I Estudis Avancats; España. Universitat Pompeu Fabra; España
Subject
bioinformatics
RNA-seq
splicing
cancer
Biología
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/11645