title: Combinations of histone modifications mark exon inclusion levels.
abstract: Splicing is a complex process regulated by sequence at the classical splice sites and other motifs in exons and introns with an enhancing or silencing effect. In addition, specific histone modifications on nucleosomes positioned over the exons have been shown to correlate both positively and negatively with exon expression. Here, we trained a model of "IF … THEN …" rules to predict exon inclusion levels in a transcript from histone modification patterns. Furthermore, we showed that combinations of histone modifications, in particular those residing on nucleosomes preceding or succeeding the exon, are better predictors of exon inclusion levels than single modifications. The resulting model was evaluated with cross validation and had an average accuracy of 72% for 27% of the exons, which demonstrates that epigenetic signals substantially mark alternative splicing.
authors.affiliation: The Linnaeus Centre for Bioinformatics, Department of Cell and Molecular Biology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Enroth
authors.forename: Susanne
authors.initials: S
authors.lastname: Bornelöv
authors.forename: Claes
authors.initials: C
authors.lastname: Wadelius
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
mesh_terms: D030562:Databases, Protein; D005091:Exons / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones