Functional homogeneity and specificity of topological modules in human proteome
Abstract 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 sh...
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doaj-8e208748b34f4e0882b03ba5bbd4b8de2020-11-25T03:20:12ZengBMCBMC Bioinformatics1471-21052019-02-0119S1312513810.1186/s12859-018-2549-8Functional homogeneity and specificity of topological modules in human proteomeRama Kaalia0Jagath C. Rajapakse1School of Computer Science and Engineering, Nanyang Technological UniversitySchool of Computer Science and Engineering, Nanyang Technological UniversityAbstract 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.http://link.springer.com/article/10.1186/s12859-018-2549-8Topological modulesFunctional modulesPhysical PPIFunctional PPIFunctional enrichment analysisProtein-protein interaction networks |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rama Kaalia Jagath C. Rajapakse |
spellingShingle |
Rama Kaalia Jagath C. Rajapakse Functional homogeneity and specificity of topological modules in human proteome BMC Bioinformatics Topological modules Functional modules Physical PPI Functional PPI Functional enrichment analysis Protein-protein interaction networks |
author_facet |
Rama Kaalia Jagath C. Rajapakse |
author_sort |
Rama Kaalia |
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 |
publisher |
BMC |
series |
BMC Bioinformatics |
issn |
1471-2105 |
publishDate |
2019-02-01 |
description |
Abstract 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. |
topic |
Topological modules Functional modules Physical PPI Functional PPI Functional enrichment analysis Protein-protein interaction networks |
url |
http://link.springer.com/article/10.1186/s12859-018-2549-8 |
work_keys_str_mv |
AT ramakaalia functionalhomogeneityandspecificityoftopologicalmodulesinhumanproteome AT jagathcrajapakse functionalhomogeneityandspecificityoftopologicalmodulesinhumanproteome |
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1724618814269685760 |