title: Aligning multiple genomic sequences with the threaded blockset aligner.
abstract: We define a "threaded blockset," which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for "threaded blockset aligner") builds a threaded blockset under the assumption that all matching segments occur in the same order and orientation in the given sequences; inversions and duplications are not addressed. TBA is designed to be appropriate for aligning many, but by no means all, megabase-sized regions of multiple mammalian genomes. The output of TBA can be projected onto any genome chosen as a reference, thus guaranteeing that different projections present consistent predictions of which genomic positions are orthologous. This capability is illustrated using a new visualization tool to view TBA-generated alignments of vertebrate Hox clusters from both the mammalian and fish perspectives. Experimental evaluation of alignment quality, using a program that simulates evolutionary change in genomic sequences, indicates that TBA is more accurate than earlier programs. To perform the dynamic-programming alignment step, TBA runs a stand-alone program called MULTIZ, which can be used to align highly rearranged or incompletely sequenced genomes. We describe our use of MULTIZ to produce the whole-genome multiple alignments at the Santa Cruz Genome Browser.
authors.affiliation: Howard Hughes Medical Institute, University of California at Santa Cruz, Santa Cruz, California 95064, USA.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Blanchette
authors.forename: W James
authors.initials: WJ
authors.lastname: Kent
authors.forename: Cathy
authors.initials: C
authors.lastname: Riemer
authors.forename: Laura
authors.initials: L
authors.lastname: Elnitski
authors.forename: Arian F A
authors.initials: AF
authors.lastname: Smit
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Roskin
authors.forename: Robert
authors.initials: R
authors.lastname: Baertsch
authors.forename: Kate
authors.initials: K
authors.lastname: Rosenbloom
authors.forename: Hiram
authors.initials: H
authors.lastname: Clawson
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: David
authors.initials: D
authors.lastname: Haussler
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
mesh_terms: D000818:Animals; D001483:Base Sequence; D002415:Cats; D002417:Cattle; D019295:Computational Biology / Q000379:methods / Q000592:standards / Q000639:trends; D003198:Computer Simulation; D004285:Dogs; D005069:Evaluation Studies as Topic; D019143:Evolution, Molecular; D005801:Genes, Homeobox / Q000235:genetics; D016762:Genes, fos / Q000235:genetics; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D051381:Rats; D012269:Ribosomal Proteins / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods* / Q000592:standards / Q000639:trends*; D012984:Software / Q000639:trends*
chemical_list: D012269:Ribosomal Proteins; C041672:ribosomal protein L34