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                       BIOINFORMATICS COLLOQUIUM
                    School of Computational Sciences
                        George Mason University
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                Predicting Cis-acting Regulatory Regions
                     Using Multi-species Alignments

                            Laura Elnitski
                    Pennsylvania State University

                        Tuesday, April 13, 2004
                                4:30 pm
                 Verizon Auditorium, Prince William Campus


Conservation in noncoding regions of mammalian genomes has long been a
useful guide to predicting elements retained by selective pressure for
an important regulatory function. Additionally, clustering of
transcription factor binding sites is a hallmark of curated promoter and
enhancer sequences. These features, when combined with proximity to a
well-mapped transcription start site, augment the prediction of
promoters in whole genome alignments. However,  the identification of
distally located enhancer elements has proven to be more
elusive. Currently, the most useful scoring schemes for predicting
regulatory potential are based on human-rodent,  2- and 3-way whole
genome alignments. Known as L-scores (http://genome.ucsc.edu/) and
RP-scores, these measurements utilize information beyond sequence
conservation such as the local rate of neutral variation or patterns in
the alignment composition, respectively. Attempts at predicting putative
functional elements become increasingly effective when these scores are
considered together and when high scores in both correlate to the
location of conserved, clustered transcription factor binding sites. In
fact, experimental testing of putative regulatory regions in gene
expression assays confirms that this approach predicts novel regulatory
elements. These analyses will be used to highlight the benefits of
adding additional species to whole genome alignments for the purpose of
predicting /cis/-acting regulatory regions.

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