Summary
Here, we describe the usage of Fastcompare, a simple and efficient comparative approach for finding short noncoding DNA (e.g., transcription factor binding sites) and mRNA (e.g., microRNA target sites) sequences that are globally conserved between two genomes. Fastcompare is based on the network-level conservation principle, according to which the connectivity of transcriptional regulatory networks should be largely conserved between two closely related genomes. We describe here the procedure for applying Fastcompare to large genomes (with an emphasis on metazoan genomes), including scoring of exhaustive motif lists, determination of conservation threshold using sequence randomizations, and discovery of interactions between regulatory elements.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Elemento, O. and Tavazoie, S. (2005) Fast and systematic genome-wide discovery of conserved regulatory elements using a non-alignment based approach.Genome Biol 6, R18.
Pritsker, M., Liu, Y., Beer, M., and Tavazoie, S. (2004) Whole-genome discovery of transcription factor binding sites by network-level conservation. Genome Res. 14, 99–108.
Chan, C. S., Elemento, O., and Tavazoie, S. (2005) Revealing posttranscriptional regulatory elements through network-level conservation. PLoS Computational Biology 1, e69.
Wasserman, W. W., Palumbo, M., Thompson, W., Fickett, J. W., and Lawrence, C. E. (2000) Human-mouse genome comparisons to locate regulatory sites. Nat. Genet. 26, 225–228.
Blanchette, M., and Tompa, M. (2002) Discovery of regulatory elements by a computational method for phylogenetic footprinting. Genome Res. 12, 739–748.
Xie, X., Lu, J., Kulbokas, E., et al. (2005) Systematic discovery of regulatory motifs in human promoters and 3’ UTRs by comparison of several mammals. Nature 434, 338–345.
Kellis, M., Patterson, N., Endrizzi, M., Birren, B., and Lander, E. S. (2003) Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254.
Cliften, P., Sudarsanam, P., Desikan, A., et al. (2003) Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 301, 71–76.
Lee, T. I., Rinaldi, N. J., Robert, F., et al. (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804.
Matys, V., Kel-Margoulis, O. V., Fricke, E., et al. (2006) TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 34, D108–D110.
Griffiths-Jones, S. (2004) The microRNA Registry. Nucleic Acids Res. 32, D109–D111.
Needleman, S. B. and Wunsch, C. D. (1970) A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48, 443–453.
Tavazoie, S., Hughes, J., Campbell, M., Cho, R., and Church, G. (1999) Systematic determination of genetic network architecture. Nat. Genet. 22, 281–285.
Thompson, J. D., Higgins, D. G., and Gibson, T. J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680.
Birney, E., Andrews, D., Caccamo, M., et al. (2006) Ensembl 2006. Nucl. Acids Res. 34, D556–D561.
Altschul, S., Madden, T., Schaffer, A., et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl. Acids Res. 25, 3389–3402.
Birney, E., Clamp, M., and Durbin, R. (2004) GeneWise and Genomewise. Genome Res 14, 988–995.
Jacobs Anderson, J. S., and Parker, R. (2000) Computational identification of cis-acting elements affecting post-transcriptional control of gene expression in Saccharomyces cerevisiae. Nucleic Acids Res. 28, 1604–1617.
O’Brien, K. P., Remm, M., and Sonnhammer, E. L. (2005) Inparanoid: a comprehensive database of eukaryotic orthologs. Nucl. Acids Res. 33, D476–D480.
Stein, L., Bao, Z., Blasiar, D., et al. (2003) The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol 1, E45.
Acknowledgments
The authors are grateful to Chang S. Chan and Kellen Olszewski for critical reading of preliminary versions of this document. The authors are also grateful to members of the Tavazoie group for insightful discussions. Saeed Tavazoie is supported by National Institutes of Health, National Science Foundation, and Defense Advanced Research Projects Agency.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Elemento, O., Tavazoie, S. (2007). Fastcompare. In: Bergman, N.H. (eds) Comparative Genomics. Methods in Molecular Biology™, vol 395. Humana Press. https://doi.org/10.1007/978-1-59745-514-5_22
Download citation
DOI: https://doi.org/10.1007/978-1-59745-514-5_22
Publisher Name: Humana Press
Print ISBN: 978-1-58829-693-1
Online ISBN: 978-1-59745-514-5
eBook Packages: Springer Protocols