Nucleic Acids Research, 2003, Vol. 31, No. 13 3518-3524
© 2003 Oxford University Press
MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences
1 Department of Computer Science and Engineering, The Pennsylvania State University, University Park, PA 2 Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 3 Department of Biology, The Pennsylvania State University, University Park, PA 4 Institute for Systems Biology, Seattle, WA 5 National Human Genome Research Institute, Bethesda, MD, USA
*To whom correspondence should be addressed at Department of Computer Science and Engineering, Pond Laboratory, The Pennsylvania State University, University Park, PA 16802, USA. Tel: +1 814 865 4551; Fax: +1 814 865 3176; Email: webb{at}bio.cse.psu.edu
Analysis of multiple sequence alignments can generate important, testable hypotheses about the phylogenetic history and cellular function of genomic sequences. We describe the MultiPipMaker server, which aligns multiple, long genomic DNA sequences quickly and with good sensitivity (available at http://bio.cse.psu.edu/ since May 2001). Alignments are computed between a contiguous reference sequence and one or more secondary sequences, which can be finished or draft sequence. The outputs include a stacked set of percent identity plots, called a MultiPip, comparing the reference sequence with subsequent sequences, and a nucleotide-level multiple alignment. New tools are provided to search MultiPipMaker output for conserved matches to a user-specified pattern and for conserved matches to position weight matrices that describe transcription factor binding sites (singly and in clusters). We illustrate the use of MultiPipMaker to identify candidate regulatory regions in WNT2 and then demonstrate by transfection assays that they are functional. Analysis of the alignments also confirms the phylogenetic inference that horses are more closely related to cats than to cows.
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