RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2004 
FD April 01 
VO 14 
IS 4 
SP 708 
OP 715 
DO 10.1101/gr.1933104 
UL http://genome.cshlp.org/content/14/4/708.abstract 
AB 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.