Genome-wide detection of alternative splicing in expressed sequences using partial order multiple sequence alignment graphs.
Genome-wide detection of alternative splicing in expressed sequences using partial order multiple sequence alignment graphs.
复制标题
使用偏序多序列比对图对表达序列中的选择性剪接进行全基因组检测。
DOI：
10.1142/9789812704856_0004
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发表时间：
2004
影响因子：
--
通讯作者：
Lee,C
中科院分区：
文献类型：
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作者：
Grasso,C;Modrek,B;Xing,Y;Lee,C
我们提出了一种在表达序列数据中进行高通量选择性剪接检测的方法。该方法有效地解决了基于EST序列推断剪接和选择性剪接所固有的许多问题，这些问题除了片段化和充满测序错误之外，还可能是嵌合的、方向错误的或被基因组序列污染的。我们的方法既依赖于偏序比对（POA）程序来构建多个序列比对，又依赖于其最重捆绑功能来生成共有序列，通过构建和分析包含与基因组序列比对的特定簇中的所有表达序列的单个多序列比对来解释表达序列数据的真正复杂性。我们举例说明了该方法在人类 UniGene Cluster Hs 中的应用。 1162，其中包含人类 HLA-DMB 基因的表达序列。我们已经使用这种方法生成了人类、小鼠和大鼠基因组的剪接和选择性剪接关系的数据库，并在其他地方发表。我们提供这些计算的统计数据，以及在不同大小的表达序列簇上运行我们的方法的 CPU 时间，以验证它是否真正扩展到完整的基因组。
We present a method for high-throughput alternative splicing detection in expressed sequence data. This method effectively copes with many of the problems inherent in making inferences about splicing and alternative splicing on the basis of EST sequences, which in addition to being fragmentary and full of sequencing errors, may also be chimeric, mis-oriented, or contaminated with genomic sequence. Our method, which relies both on the Partial Order Alignment (POA) program for constructing multiple sequence alignments, and its Heaviest Bundling function for generating consensus sequences, accounts for the real complexity of expressed sequence data by building and analyzing a single multiple sequence alignment containing all of the expressed sequences in a particular cluster aligned to genomic sequence. We illustrate application of this method to human UniGene Cluster Hs. 1162, which contains expressed sequences from the human HLA-DMB gene. We have used this method to generate databases, published elsewhere, of splices and alternative splicing relationships for the human, mouse and rat genomes. We present statistics from these calculations, as well as the CPU time for running our method on expressed sequence clusters of varying size, to verify that it truly scales to complete genomes.