TY - JOUR A1 - Blanchette, Mathieu A1 - Kent, W. James A1 - Riemer, Cathy A1 - Elnitski, Laura A1 - Smit, Arian F.A. A1 - Roskin, Krishna M. A1 - Baertsch, Robert A1 - Rosenbloom, Kate A1 - Clawson, Hiram A1 - Green, Eric D. A1 - Haussler, David A1 - Miller, Webb T1 - Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner Y1 - 2004/04/01 JF - Genome Research JO - Genome Research SP - 708 EP - 715 DO - 10.1101/gr.1933104 VL - 14 IS - 4 UR - http://genome.cshlp.org/content/14/4/708.abstract N2 - 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. ER -