Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.
Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.
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DOI：
10.1016/j.jmb.2012.10.014
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发表时间：
2013-01-09
影响因子：
5.6
通讯作者：
Muggleton, Stephen H.
中科院分区：
文献类型：
--
作者：
Sternberg, Michael J. E.;Tamaddoni-Nezhad, Alireza;Lesk, Victor I.;Kay, Emily;Hitchen, Paul G.;Cootes, Adrian;van Alphen, Lieke B.;Lamoureux, Marc P.;Jarrelle, Harold C.;Rawlings, Christopher J.;Soo, Evelyn C.;Szymanski, Christine M.;Dell, Anne;Wren, Brendan W.;Muggleton, Stephen H.
越来越多的生物系统的实验数据是从几个来源和计算方法，需要整合这些信息，并推导出系统的功能模型。在这里，我们展示了一种基于逻辑的机器学习方法的力量，它可以为基因功能提出假设，整合来自两种不同实验方法的信息。具体来说，我们使用归纳逻辑编程，自动提出假设，解释经验数据的逻辑编码的背景知识。我们研究了人类主要胃肠道病原菌空肠弯曲菌的荚膜多糖生物合成途径。我们考虑了几个关键步骤，在形成的荚膜多糖组成的15个基因，其中8个已分配的功能，我们探索的程度，可以假设为其余7个功能。实验数据的两个来源提供了信息的学习-基因敲除实验的结果参与胶囊的形成和胶囊基因的存在/不存在在众多的菌株不同的血清型。机器学习使用通路结构作为背景知识。我们提出的特定基因的分配到五个以前未分配的反应步骤。对于这些步骤中的四个，存在基因对反应的明确的最佳分配，并且对于第五个，存在三个候选基因。其中一些分配与其他实验结果一致。因此，我们表明，基于逻辑的方法提供了一个强大的战略，整合不同的实验方法的结果，并提出假设的生物系统的行为。系统生物学建模的一个挑战是整合不同的数据源。采用基于逻辑的方法对C.空肠糖原将基因敲除和血清型菌株数据与途径信息整合。►假设了胶囊多糖生物合成途径基因的功能。基于逻辑的学习提出了生物系统行为的假设。
Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning—the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system. ► A challenge in systems biology modelling is to integrate different data sources. ► A logic-based approach was used to hypothesise gene function for the C. jejuni glycome. ► Gene knockout and serotype strain data were integrated with pathway information. ► Functions were hypothesised for capsule polysaccharide biosynthetic pathway genes. ► Logic-based learning proposed hypotheses for the behaviour of a biological system.
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影响因子：
5.7
作者：
Holst Sørensen MC;van Alphen LB;Fodor C;Crowley SM;Christensen BB;Szymanski CM;Brøndsted L
通讯作者：
Brøndsted L
影响因子：
4.3
作者：
Puchałka J;Oberhardt MA;Godinho M;Bielecka A;Regenhardt D;Timmis KN;Papin JA;Martins dos Santos VA
通讯作者：
Martins dos Santos VA
影响因子：
2
作者：
Bernot, G;Comet, JP;Guespin, J
通讯作者：
Guespin, J
DOI：
10.1073/pnas.0508647102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Hwang, D;Rust, AG;Bolouri, H
通讯作者：
Bolouri, H
DOI：
10.1073/pnas.0503252102
发表时间：
2005-11-01
影响因子：
11.1
作者：
Champion, OL;Gaunt, MW;Wren, BW
通讯作者：
Wren, BW