Maqola

Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner

Mathieu BlanchetteHoward Hughes Medical Institute, University of California at Santa Cruz, Santa Cruz, California 95064, USAW. James KentCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Cathy RiemerCenter for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA;Laura ElnitskiCenter for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA;Arian F. A. SmitInstitute for Systems Biology, Seattle, Washington 98103, USA;Krishna M. RoskinCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Robert BaertschCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Kate R. RosenbloomCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Hiram ClawsonCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Eric D. GreenGenome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USADavid HausslerCenter for Biomolecular Science and Engineering, University of California at Santa Cruz, Santa Cruz, California 95064, USA;Webb MillerCenter for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA;

2004en

ABI

Annotatsiya

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.

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Identifikatorlar

DOI: 10.1101/gr.1933104

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