Journal Article

Position-dependent motif characterization using non-negative matrix factorization

Lucie N. Hutchins, Sean M. Murphy, Priyam Singh and Joel H. Graber

in Bioinformatics

Volume 24, issue 23, pages 2684-2690
Published in print December 2008 | ISSN: 1367-4803
Published online October 2008 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btn526

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Motivation: Cis-acting regulatory elements are frequently constrained by both sequence content and positioning relative to a functional site, such as a splice or polyadenylation site. We describe an approach to regulatory motif analysis based on non-negative matrix factorization (NMF). Whereas existing pattern recognition algorithms commonly focus primarily on sequence content, our method simultaneously characterizes both positioning and sequence content of putative motifs.

Results: Tests on artificially generated sequences show that NMF can faithfully reproduce both positioning and content of test motifs. We show how the variation of the residual sum of squares can be used to give a robust estimate of the number of motifs or patterns in a sequence set. Our analysis distinguishes multiple motifs with significant overlap in sequence content and/or positioning. Finally, we demonstrate the use of the NMF approach through characterization of biologically interesting datasets. Specifically, an analysis of mRNA 3′-processing (cleavage and polyadenylation) sites from a broad range of higher eukaryotes reveals a conserved core pattern of three elements.

Contact: joel.graber@jax.org

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  5651 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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