A procedure for identifying homologous alternative splicing events
1 Molecular Modelling and Bioinformatics Unit, Institut de Recerca Biomèdica (IRB), Parc Científic de Barcelona (PCB), Barcelona, Spain
2 Protein Structure and Modelling Node, Instituto Nacional de Bioinfomática, Genoma España, Parc Científic de Barcelona, Barcelona, Spain
3 Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain
4 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
5 Computational Biology Program, Barcelona Supercomputing Center, Barcelona, Spain
BMC Bioinformatics 2007, 8:260 doi:10.1186/1471-2105-8-260Published: 19 July 2007
The study of the functional role of alternative splice isoforms of a gene is a very active area of research in biology. The difficulty of the experimental approach (in particular, in its high-throughput version) leaves ample room for the development of bioinformatics tools that can provide a useful first picture of the problem. Among the possible approaches, one of the simplest is to follow classical protein function annotation protocols and annotate target alternative splice events with the information available from conserved events in other species. However, the application of this protocol requires a procedure capable of recognising such events. Here we present a simple but accurate method developed for this purpose.
We have developed a method for identifying homologous, or equivalent, alternative splicing events, based on the combined use of neural networks and sequence searches. The procedure comprises four steps: (i) BLAST search for homologues of the two isoforms defining the target alternative splicing event; (ii) construction of all possible candidate events; (iii) scoring of the latter with a series of neural networks; and (iv) filtering of the results. When tested in a set of 473 manually annotated pairs of homologous events, our method showed a good performance, with an accuracy of 0.99, a precision of 0.98 and a sensitivity of 0.93. When no candidates were available, the specificity of our method varied between 0.81 and 0.91.
The method described in this article allows the identification of homologous alternative splicing events, with a good success rate, indicating that such method could be used for the development of functional annotation of alternative splice isoforms.