title: A computational method for studying the relation between alternative splicing and DNA methylation.
abstract: Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non-trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large-scale data sets.
authors.affiliation: Bioinformatics Institute, Singapore 138671, Singapore.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Wei
authors.affiliation: Institut für Informatik, Johannes Gutenberg Universität Mainz, 55099 Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hildebrandt
authors.affiliation: Institut für Informatik, Johannes Gutenberg Universität Mainz, 55099 Mainz, Germany bertil.schmidt@uni-mainz.de.
authors.forename: Bertil
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D017398:Alternative Splicing; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D006801:Humans; D007438:Introns; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012984:Software; D059467:Transcriptome
chemical_list: D012313:RNA