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Discovery of regulatory elements in vertebrates through comparative genomics

Abstract

We have analyzed issues of reliability in studies in which comparative genomic approaches have been applied to the discovery of regulatory elements at a genome-wide level in vertebrates. We point out some potential problems with such studies, including difficulties in accurately identifying orthologous promoter regions. Many of these subtle analytical problems have become apparent only when studying the more complex vertebrate genomes. By determining motif reliability, we compared existing tools when applied to the discovery of vertebrate regulatory elements. We then used a statistical clustering method to produce a computational catalog of high quality putative regulatory elements from vertebrates, some of which are widely conserved among vertebrates and many of which are novel regulatory elements. The results provide a glimpse into the wealth of information that comparative genomics can yield and suggest the need for further improvement of genome-wide comparative computational techniques.

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Figure 1: Potential hazards in choosing orthologous promoter regions in vertebrates.
Figure 2: Performance of alignment tools.
Figure 3

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Acknowledgements

We thank Mathieu Blanchette, Nan Li, Michal Linial, Larry Ruzzo, Saurabh Sinha, Zasha Weinberg, Zizhen Yao, the Ensembl Help Desk (in particular, Michael Schuster and Ewan Birney) and the anonymous reviewers for their contributions to this work. This material is based upon work supported in part by the National Science Foundation under grant DBI-0218798 and by the National Institutes of Health under grant R01 HG02602.

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Correspondence to Martin Tompa.

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Prakash, A., Tompa, M. Discovery of regulatory elements in vertebrates through comparative genomics. Nat Biotechnol 23, 1249–1256 (2005). https://doi.org/10.1038/nbt1140

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