Functional homogeneity and specificity of topological modules in human proteome
Background: Functional modules in protein-protein interaction networks (PPIN) are defined by maximal sets of functionally associated proteins and are vital to understanding cellular mechanisms and identifying disease associated proteins. Topological modules of the human proteome have been shown to b...
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sg-ntu-dr.10356-1054912019-12-06T21:52:23Z Functional homogeneity and specificity of topological modules in human proteome Kaalia, Rama Rajapakse, Jagath Chandana School of Computer Science and Engineering Topological Modules Functional Modules DRNTU::Engineering::Computer science and engineering Background: Functional modules in protein-protein interaction networks (PPIN) are defined by maximal sets of functionally associated proteins and are vital to understanding cellular mechanisms and identifying disease associated proteins. Topological modules of the human proteome have been shown to be related to functional modules of PPIN. However, the effects of the weights of interactions between protein pairs and the integration of physical (direct) interactions with functional (indirect expression-based) interactions have not been investigated in the detection of functional modules of the human proteome. Results: We investigated functional homogeneity and specificity of topological modules of the human proteome and validated them with known biological and disease pathways. Specifically, we determined the effects on functional homogeneity and heterogeneity of topological modules (i) with both physical and functional protein-protein interactions; and (ii) with incorporation of functional similarities between proteins as weights of interactions. With functional enrichment analyses and a novel measure for functional specificity, we evaluated functional relevance and specificity of topological modules of the human proteome. Conclusions: The topological modules ranked using specificity scores show high enrichment with gene sets of known functions. Physical interactions in PPIN contribute to high specificity of the topological modules of the human proteome whereas functional interactions contribute to high homogeneity of the modules. Weighted networks result in more number of topological modules but did not affect their functional propensity. Modules of human proteome are more homogeneous for molecular functions than biological processes. MOE (Min. of Education, S’pore) Published version 2019-06-13T06:09:54Z 2019-12-06T21:52:23Z 2019-06-13T06:09:54Z 2019-12-06T21:52:23Z 2019 Journal Article Kaalia, R., & Rajapakse, J. C. (2019). Functional homogeneity and specificity of topological modules in human proteome. BMC Bioinformatics, 19(S13), 553-. doi:10.1186/s12859-018-2549-8 https://hdl.handle.net/10356/105491 http://hdl.handle.net/10220/48724 http://dx.doi.org/10.1186/s12859-018-2549-8 en BMC Bioinformatics © 2019 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 14 p. application/pdf |
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Topological Modules Functional Modules DRNTU::Engineering::Computer science and engineering Kaalia, Rama Rajapakse, Jagath Chandana Functional homogeneity and specificity of topological modules in human proteome |
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Background: Functional modules in protein-protein interaction networks (PPIN) are defined by maximal sets of functionally associated proteins and are vital to understanding cellular mechanisms and identifying disease associated proteins. Topological modules of the human proteome have been shown to be related to functional modules of PPIN. However, the effects of the weights of interactions between protein pairs and the integration of physical (direct) interactions with functional (indirect expression-based) interactions have not been investigated in the detection of functional modules of the human proteome. Results: We investigated functional homogeneity and specificity of topological modules of the human proteome and validated them with known biological and disease pathways. Specifically, we determined the effects on functional homogeneity and heterogeneity of topological modules (i) with both physical and functional protein-protein interactions; and (ii) with incorporation of functional similarities between proteins as weights of interactions. With functional enrichment analyses and a novel measure for functional specificity, we evaluated functional relevance and specificity of topological modules of the human proteome. Conclusions: The topological modules ranked using specificity scores show high enrichment with gene sets of known functions. Physical interactions in PPIN contribute to high specificity of the topological modules of the human proteome whereas functional interactions contribute to high homogeneity of the modules. Weighted networks result in more number of topological modules but did not affect their functional propensity. Modules of human proteome are more homogeneous for molecular functions than biological processes. |
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School of Computer Science and Engineering |
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School of Computer Science and Engineering Kaalia, Rama Rajapakse, Jagath Chandana |
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Article |
author |
Kaalia, Rama Rajapakse, Jagath Chandana |
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Kaalia, Rama |
title |
Functional homogeneity and specificity of topological modules in human proteome |
title_short |
Functional homogeneity and specificity of topological modules in human proteome |
title_full |
Functional homogeneity and specificity of topological modules in human proteome |
title_fullStr |
Functional homogeneity and specificity of topological modules in human proteome |
title_full_unstemmed |
Functional homogeneity and specificity of topological modules in human proteome |
title_sort |
functional homogeneity and specificity of topological modules in human proteome |
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2019 |
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https://hdl.handle.net/10356/105491 http://hdl.handle.net/10220/48724 http://dx.doi.org/10.1186/s12859-018-2549-8 |
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