Assessing the functional coherence of modules found in multiple-evidence networks from Arabidopsis

BMC Bioinformatics

Research Article

Charlie Hodgman¹  Jan Taubert²  Christopher J Rawlings²  Michael Defoin-Platel²  Mansoor Saqi²  Keywan Hassani-Pak²  Artem Lysenko³ 

[1] CPIB, Multidisciplinary Centre for Integrative Biology, School of Biosciences, University of Nottingham, Sutton Bonington, LE12 5RD, UK;Centre for Mathematical and Computational Biology, Rothamsted Research, AL5 2JQ, Harpenden, Herts, UK;Centre for Mathematical and Computational Biology, Rothamsted Research, AL5 2JQ, Harpenden, Herts, UK;CPIB, Multidisciplinary Centre for Integrative Biology, School of Biosciences, University of Nottingham, Sutton Bonington, LE12 5RD, UK;

关键词: Gene Ontology;    Functional Module;    Modular Structure;    Relationship Network;    Combine Network;   

DOI  :  10.1186/1471-2105-12-203

 received in 2010-08-20, accepted in 2011-05-25,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundCombining multiple evidence-types from different information sources has the potential to reveal new relationships in biological systems. The integrated information can be represented as a relationship network, and clustering the network can suggest possible functional modules. The value of such modules for gaining insight into the underlying biological processes depends on their functional coherence. The challenges that we wish to address are to define and quantify the functional coherence of modules in relationship networks, so that they can be used to infer function of as yet unannotated proteins, to discover previously unknown roles of proteins in diseases as well as for better understanding of the regulation and interrelationship between different elements of complex biological systems.ResultsWe have defined the functional coherence of modules with respect to the Gene Ontology (GO) by considering two complementary aspects: (i) the fragmentation of the GO functional categories into the different modules and (ii) the most representative functions of the modules. We have proposed a set of metrics to evaluate these two aspects and demonstrated their utility in Arabidopsis thaliana. We selected 2355 proteins for which experimentally established protein-protein interaction (PPI) data were available. From these we have constructed five relationship networks, four based on single types of data: PPI, co-expression, co-occurrence of protein names in scientific literature abstracts and sequence similarity and a fifth one combining these four evidence types. The ability of these networks to suggest biologically meaningful grouping of proteins was explored by applying Markov clustering and then by measuring the functional coherence of the clusters.ConclusionsRelationship networks integrating multiple evidence-types are biologically informative and allow more proteins to be assigned to a putative functional module. Using additional evidence types concentrates the functional annotations in a smaller number of modules without unduly compromising their consistency. These results indicate that integration of more data sources improves the ability to uncover functional association between proteins, both by allowing more proteins to be linked and producing a network where modular structure more closely reflects the hierarchy in the gene ontology.

【 授权许可】

CC BY   
© Lysenko et al; licensee BioMed Central Ltd. 2011