This article is part of the supplement: Proceedings of the Second Annual RECOMB Satellite Workshop on Massively Parallel Sequencing (RECOMB-seq 2012)
ISS PLICE: de-novo calling alternative splicing events from RNA-seq data
1 INRIA Grenoble Rhône-Alpes, France
2 Université de Lyon, F-69000, Lyon; Université Lyon 1; CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622, Villeurbanne, France
3 Centre de recherche INRIA Rennes - Bretagne Atlantique, IRISA, Campus universitaire de Beaulieu, Rennes, France
4 INRA UMR118, Amélioration des Plantes et Biotech. Végétales, Rennes, France
BMC Bioinformatics 2012, 13(Suppl 6):S5 doi:10.1186/1471-2105-13-S6-S5Published: 19 April 2012
In this paper, we address the problem of identifying and quantifying polymorphisms in RNA-seq data when no reference genome is available, without assembling the full transcripts. Based on the fundamental idea that each polymorphism corresponds to a recognisable pattern in a De Bruijn graph constructed from the RNA-seq reads, we propose a general model for all polymorphisms in such graphs. We then introduce an exact algorithm, called KISSPLICE, to extract alternative splicing events.
We show that KISSPLICE enables to identify more correct events than general purpose transcriptome assemblers. Additionally, on a 71 M reads dataset from human brain and liver tissues, KISSPLICE identified 3497 alternative splicing events, out of which 56% are not present in the annotations, which confirms recent estimates showing that the complexity of alternative splicing has been largely underestimated so far.
We propose new models and algorithms for the detection of polymorphism in RNA-seq data. This opens the way to a new kind of studies on large HTS RNA-seq datasets, where the focus is not the global reconstruction of full-length transcripts, but local assembly of polymorphic regions. KISSPLICE is available for download at http://alcovna.genouest.org/kissplice/ webcite.