motif map of genome wide motifs

motif map of genome wide motifs - BIOINFORMATICS ORIGINAL...

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Unformatted text preview: BIOINFORMATICS ORIGINAL PAPER Vol. 25 no. 2 2009, pages 167–174 doi:10.1093/bioinformatics/btn605 Genome analysis MotifMap: a human genome-wide map of candidate regulatory motif sites Xiaohui Xie 1 , 2 , ∗ , Paul Rigor 1 , 2 and Pierre Baldi 1 , 2 , ∗ 1 Department of Computer Sciences and 2 Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697, USA Received on May 20, 2008; revised and accepted on November 17, 2008 Advance Access publication November 18, 2008 Associate Editor: Dmitrij Frishman ABSTRACT Motivation: Achieving a comprehensive map of all the regulatory elements encoded in the human genome is a fundamental challenge of biomedical research. So far, only a small fraction of the regulatory elements have been characterized, and there is great interest in applying computational techniques to systematically discover these elements. Such efforts, however, have been significantly hindered by the overwhelming size of non-coding DNA regions and the statistical variability and complex spatial organizations of mammalian regulatory elements. Results: Here we combine information from multiple mammalian genomes to derive the first fairly comprehensive map of regulatory elements in the human genome. We develop a procedure for identifying regulatory sites, with high levels of conservation across different species, using a new scoring scheme, the Bayesian branch length score (BBLS). Using BBLS, we predict 1.5 million regulatory sites, corresponding to 380 known regulatory motifs, with an estimated false discovery rate (FDR) of < 50%. We demonstrate that the method is particularly effective for 155 motifs, for which 121 056 sites can be mapped with an estimated FDR of < 10%. Over 28K SNPs are located in regions overlapping the 1.5 million predicted motif sites, suggesting potential functional implications for these SNPs. We have deposited these elements in a database and created a user-friendly web server for the retrieval, analysis and visualization of these elements. The initial map provides a systematic view of gene regulation in the genome, which will be refined as additional motifs become available. Availability: http://motifmap.ics.uci.edu Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online. 1 INTRODUCTION Among the 3 billion bases of the haploid human genome, only a small portion ( < 2%) corresponds to protein-coding regions. A central challenge of biology is to map and understand the role of the remaining 98% non-coding regions of the human genome. It is commonly believed that many of these non-coding regions are involved in gene regulation, but their specific roles and organization, ∗ To whom correspondence should be addressed....
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motif map of genome wide motifs - BIOINFORMATICS ORIGINAL...

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