Bioinformatics Analyses of Alternative Splicing

This thesis investigates three aspects of alternativesplicing by means of computational large-scale analyses. In thefirst part, we introduce a new approach for the ab initioprediction of alternative splice events. We introduce an efficientalgorithm to reduce the computational complexity during the searchfor new splice events. Applying this algorithm to the human genome,we predict and verify novel splice events. In the second part, weinvestigate the influence of mRNA secondary structures on theregulation of the splicing process. We show that experimentallyverified binding sites of splicing regulatory proteins have ahigher single-strandedness. Then, we develop a new motif findingmethod that benefits from taking the single-strandedness of motifoccurrences into account. In the third part, we analyze a group ofsplice events that occur at tandem splice sites and result in minorchanges of the mRNA and the protein. Genome-wide analyses provideevidence for a non-random distribution of these splice events, fortissue-specific regulation, and for evolutionary conservation. Weconclude that these splice events represent one major mechanism toincrease the proteome diversity.