Aligning multiple genomic sequences with the threaded blockset aligner
Aligning multiple genomic sequences with the threaded blockset aligner
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DOI：
10.1101/gr.1933104
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发表时间：
2004-04-01
期刊：
影响因子：
7
通讯作者：
Miller, W
中科院分区：
文献类型：
--
作者：
Blanchette, M;Kent, WJ;Miller, W
我们定义了一个“穿线块集”，它是对多重比对经典概念的一种新颖的推广。一个名为TBA（“穿线块集比对器”）的新计算机程序在假定所有匹配片段在给定序列中以相同顺序和方向出现的情况下构建一个穿线块集；倒位和重复未被处理。TBA被设计用于比对许多（但绝不是所有）哺乳动物多个基因组的百万碱基大小的区域。TBA的输出可以投射到任何被选作参考的基因组上，从而保证不同的投射对哪些基因组位置是直系同源的给出一致的预测。利用一种新的可视化工具从哺乳动物和鱼类的角度查看TBA生成的脊椎动物Hox簇比对，说明了这种能力。使用一个模拟基因组序列进化变化的程序对比对质量进行的实验评估表明，TBA比早期的程序更准确。为了执行动态规划比对步骤，TBA运行一个名为MULTIZ的独立程序，该程序可用于比对高度重排或不完全测序的基因组。我们描述了我们使用MULTIZ在圣克鲁斯基因组浏览器上生成全基因组多重比对的情况。
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.