Automatic detection of subsystem/pathway variants in genome analysis
Automatic detection of subsystem/pathway variants in genome analysis
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DOI：
10.1093/bioinformatics/bti1052
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发表时间：
2005-06-01
期刊：
影响因子：
5.8
通讯作者：
Godzik, A
中科院分区：
文献类型：
--
作者：
Ye, YZ;Osterman, A;Godzik, A
动机：蛋白质在通路和网络中协同工作，共同构成细胞机器。子系统（通路概念的概括）是一组共同参与细胞机器特定方面的相关功能角色（例如酶）。子系统为比较基因组分析和功能注释提供了一个自然的框架。一个子系统可以在各个物种中以多种不同的功能变体实现。为了可靠地预测跨多个基因组的功能分配，我们必须能够识别每个基因组中实现的变体。对不同物种的此类变异的分析本身就是一个有趣的问题，并且可能提供新的进化见解。然而，目前还没有可用于自动检测和分析子系统变体的计算技术。 结果：这里我们将子系统变体检测问题表述为寻找子系统的最小子图数（以图表示），并通过整数规划方法解决优化问题。我们的方法的性能在 SEED 中编码的子系统上进行了测试，SEED 是由基因组解释研究员开发的基因组集成平台，作为对多个不同基因组进行比较分析和注释的大规模工作的组成部分。在这里，我们展示了辅酶 A 和 FMN/FAD 辅因子生物合成的两个专家编码子系统获得的结果。在这些普遍保守且重要的代谢子系统的背景下，简要讨论了变异检测的应用，以支持基因组注释和评估物种的差异。
Motivation: Proteins work together in pathways and networks, collectively comprising the cellular machinery. A subsystem ( a generalization of pathway concept) is a group of related functional roles ( such as enzymes) jointly involved in a specific aspect of the cellular machinery. Subsystems provide a natural framework for comparative genome analysis and functional annotation. A subsystem may be implemented in a number of different functional variants in individual species. In order to reliably project functional assignments across multiple genomes, we have to be able to identify the variants implemented in each genome. The analysis of such variants across diverse species is an interesting problem by itself and may provide new evolutionary insights. However, no computational techniques are presently available for an automated detection and analysis of subsystem variants.Results: Here we formulate the subsystem variant detection problem as finding the minimum number of subgraphs of a subsystem, which is represented as a graph, and solve the optimization problem by integer programming approach. The performance of our method was tested on subsystems encoded in the SEED, a genomic integration platform developed by the Fellowship for Interpretation of Genomes as a component of a large-scale effort on comparative analysis and annotation of multiple diverse genomes. Here we illustrate the results obtained for two expert-encoded subsystems of the biosynthesis of Coenzyme A and FMN/FAD cofactors. Applications of variant detection, to support genomic annotations and to assess divergence of species, are briefly discussed in the context of these universally conserved and essential metabolic subsystems.