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Weighted Cohesiveness for Identification of Functional Modules and Their Interconnectivity

Zelmina Lubovac1, 2 Contact Information, David CorneContact Information, Jonas Gamalielsson1, 2 Contact Information and Björn OlssonContact Information

(1)  University of Skövde, School of Humanities and Informatics, Box 408, 54128 Skövde, Sweden
(2)  Heriot-Watt University, School of Mathematical and Computer Sciences, EH14 4AS Edinburgh, UK
Abstract
Systems biology offers a holistic perspective where individual proteins are viewed as elements in a network of protein-protein interactions (PPI), in which the proteins have contextual functions within functional modules. In order to facilitate the identification and analysis of such modules, we have previously proposed a Gene Ontology-weighted clustering coefficient for identification of modules in PPI networks and a method, named SWEMODE (Semantic WEights for MODule Elucidation), where this measure is used to identify network modules. Here, we introduce novel aspects of the method that are tested and evaluated. One of the aspects that we consider is to use the k-core graph instead of the original protein-protein interaction graph.Also, by taking the spatial aspect into account, by using the GO cellular component annotation when calculating weighted cohesiveness, we are able to improve the results compared to previous work where only two of the GO aspects (molecular function and biological process) were combined. We here evaluate the predicted modules by calculating their overlap with MIPS functional complexes. In addition, we identify the “most frequent” proteins, i.e. the proteins that most frequently participate in overlapping modules. We also investigate the role of these proteins in the interconnectivity between modules. We find that the majority of identified proteins are involved in the assembly and arrangement of cell structures, such as the cell wall and cell envelope.

Keywords  systems biology - functional modules - Gene Ontology -  SWEMODE - interconnectivity


Contact Information Zelmina Lubovac
Email: zelmina.lubovac@his.se

Contact Information David Corne
Email: dwcorne@macs.hw.ac.uk

Contact Information Jonas Gamalielsson
Email: jonas.gamalielsson@his.se

Contact Information Björn Olsson
Email: bjorn.olsson@his.se
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