Metabolic pathway alignment between species using a comprehensive and flexible similarity measure.

Metabolic pathway alignment between species using a comprehensive and flexible similarity measure.
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DOI:
10.1186/1752-0509-2-111
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发表时间:
2008-12-24
影响因子:
--
通讯作者:
Reinders MJ
Reinders MJ
中科院分区:
生物2区
文献类型:
--
作者:
Li Y;de Ridder D;de Groot MJ;Reinders MJ

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对不同物种的代谢网络进行比较分析,可以提供其进化的重要信息,在代谢工程、人类疾病分析、药物设计等方面具有重要的实用价值。在这项工作中,我们的目标是系统地寻找两个物种的保守通路,量化它们的相似性,并关注它们之间的差异。我们提出了一个有效的框架,代谢途径比对和评分(M-PAS),用于识别和排序保守的代谢途径。M-PAS将两个物种的整个代谢网络中的所有反应对齐,并将它们组装成途径,将不匹配、间隙和交叉考虑在内。它使用了一个综合评分函数,它量化了途径的相似性,这样我们就可以关注不同的途径,给出不同的生物动机。利用M-PAS,我们在酿酒酵母和大肠杆菌之间发现了1198条完全保守的长度- 4通路,并在其他高度保守的通路中发现了1399例使用独特途径的物种。我们的方法有效地自动化了探索物种之间和物种内部反应排列可能性的过程,以找到保守的途径。我们不仅重建了KEGG中发现的传统途径,而且还发现了新的途径可能性。我们的研究结果有助于对缺失反应产生假设,并在高度保守的途径中表现出差异,这对生物学和生命科学应用是有用的。
Comparative analysis of metabolic networks in multiple species yields important information on their evolution, and has great practical value in metabolic engineering, human disease analysis, drug design etc. In this work, we aim to systematically search for conserved pathways in two species, quantify their similarities, and focus on the variations between them. We present an efficient framework, Metabolic Pathway Alignment and Scoring (M-PAS), for identifying and ranking conserved metabolic pathways. M-PAS aligns all reactions in entire metabolic networks of two species and assembles them into pathways, taking mismatches, gaps and crossovers into account. It uses a comprehensive scoring function, which quantifies pathway similarity such that we can focus on different pathways given different biological motivations. Using M-PAS, we detected 1198 length-four pathways fully conserved between Saccharomyces cerevisiae and Escherichia coli, and also revealed 1399 cases of a species using a unique route in otherwise highly conserved pathways. Our method efficiently automates the process of exploring reaction arrangement possibilities, both between species and within species, to find conserved pathways. We not only reconstruct conventional pathways such as those found in KEGG, but also discover new pathway possibilities. Our results can help to generate hypotheses on missing reactions and manifest differences in highly conserved pathways, which is useful for biology and life science applications.
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