Martin Tompa, University of Washington, Seattle, USA

Comparative Sequence Analysis in Molecular Biology
In computational molecular biology, "phylogenetic footprinting" is a standard idea that is used to predict functional regions within a biological sequence (DNA, RNA, or protein). The procedure is to find corresponding sequences from several related species, and within these to identify those regions that have mutated less than expected over the course of evolution, suggesting that these regions are under selective pressure due to biological functionality.

We will discuss various algorithms for and applications of phylogenetic footprinting and demonstrate some of these using software available on the web. We will then turn our attention to the larger problem of doing phylogenetic footprinting on a whole-genome scale, demonstrating the use of a genome browser available on the web and discussing the issue of assessing its reliability.

These lectures will be self-contained. No prior knowledge of molecular biology is necessary.

References
Blanchette M, Tompa M. Discovery of Regulatory Elements by a Computational Method for Phylogenetic Footprinting. Genome Research, vol. 12, no. 5, May 2002, 739-748.

Karlin S, Altschul SF. Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proceedings of the National Academy of Sciences USA, vol. 87, 1990, 2264-2268.

Kuhn RM, Karolchik D, Zweig AS, Trumbower H, Thomas DJ, Thakkapallayil A, Sugnet CW, Stanke M, Smith KE, Siepel A, Rosenbloom KR, Rhead B, Raney BJ, Pohl A, Pedersen JS, Hsu F, Hinrichs AS, Harte RA, Diekhans M, Clawson H, Bejerano G, Barber GP, Baertsch R, Haussler D, Kent, WJ. The UCSC Genome Browser database: update 2007. Nucleic Acids Research, vol. 35, January 2007, D668-73.

Kumar S, Filipski A. Multiple sequence alignment: In pursuit of homologous DNA positions. Genome Research, vol. 17, February 2007, 127-135.

Neph S, Tompa M. MicroFootPrinter: a Tool for Phylogenetic Footprinting in Prokaryotic Genomes. Nucleic Acids Research, vol. 34, July 2006, W366-W368.

Prakash A, Tompa M. Measuring the Accuracy of Genome-Size Multiple Alignments. Genome Biology, vol. 8, June 2007, R124.