title: MultiPipMaker and supporting tools: Alignments and analysis of multiple genomic DNA sequences.
abstract: 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.
authors.affiliation: Department of Computer Science and Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Schwartz
authors.forename: Laura
authors.initials: L
authors.lastname: Elnitski
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Matt
authors.initials: M
authors.lastname: Weirauch
authors.forename: Cathy
authors.initials: C
authors.lastname: Riemer
authors.forename: Arian
authors.initials: A
authors.lastname: Smit
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
mesh_terms: D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D002415:Cats; D023281:Genomics / Q000379:methods*; D006736:Horses / Q000145:classification / Q000235:genetics; D020407:Internet; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D014157:Transcription Factors / Q000378:metabolism; D051154:Wnt2 Protein
chemical_list: D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051154:Wnt2 Protein