Computational screening of conserved genomic DNA in search of functional noncoding elements

tools. The protocol is divided into four major steps: defining the genomic region of interest, based on the user’s starting point (gene of interest, a region between two genetic markers, and other regions); selecting a subset of cross-species conserved elements within this region, based on a hidden Markov model that defines and scores genomic intervals for conservation; mapping the different properties of the interval set (such as transcript overlap and species coverage extent); and, finally, ranking the set for further analysis, based on a characteristic profile of the functional class of interest. The same protocol may be used to search for different functional classes of elements in all branches of the tree of life available in the UCSC Genome Browser, including vertebrate, insect, nematode and yeast. It can also easily incorporate custom types of information that the user has access to and allows for easy replacement of parts of the protocol, as our understanding of the relationship between function and sequence conservation, and of the different functional classes, improves. As an example, we present an informatic profile of vertebrate enhancer sequences and discuss a case for which such a method has led to the discovery of several functional enhancers. An accompanying protocol describes a complementary approach to identification of cis-regulatory DNA regions in complex genome assemblies by clustering of sequence motifs corresponding to known transcription factor binding sites 9 .

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