Analysis of Multiple Genomic Sequence Alignments: A Web Resource, Online Tools, and Lessons Learned From Analysis of Mammalian SCL Loci

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Abstract
Comparative analysis of genomic sequences is becoming a standard technique for studying gene regulation. However, only a limited number of tools are currently available for the analysis of multiple genomic sequences. An extensive data set for the testing and training of such tools is provided by theSCLgene locus. Here we have expanded the data set to eight vertebrate species by sequencing the dogSCLlocus and by annotating the dog and ratSCLloci. To provide a resource for the bioinformatics community, allSCLsequences and functional annotations, comprising a collation of the extensive experimental evidence pertaining toSCLregulation, have been made available via a Web server. A Web interface to new tools specifically designed for the display and analysis of multiple sequence alignments was also implemented. The uniqueSCLdata set and new sequence comparison tools allowed us to perform a rigorous examination of the true benefits of multiple sequence comparisons. We demonstrate that multiple sequence alignments are, overall, superior to pairwise alignments for identification of mammalian regulatory regions. In the search for individual transcription factor binding sites, multiple alignments markedly increase the signal-to-noise ratio compared to pairwise alignments.