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Locally Adjust Networks Based on Connectivity and Semantic Similarities for Disease Module Detection

ABSTRACT: For studying the pathogenesis of complex diseases, it is important to identify the disease modules in the system level. Since the protein-protein interaction (PPI) networks contain a number of incomplete and incorrect interactome, most existing methods often lead to many disease proteins isolating from disease modules. In this paper, we propose an effective disease module identification method IDMCSS, where the used human PPI networks are obtained by adding some potential missing interactions from existing PPI networks, as well as removing some potential incorrect interactions. In IDMCSS, a network adjustment strategy is developed to add or remove links around disease proteins based on both topological and semantic information. Next, neighboring proteins of disease proteins are prioritized according to a suggested similarity between each of them and disease proteins, and the protein with the largest similarity with disease proteins is added into a candidate disease protein set one by one. The stopping criterion is set to the boundary of the disease proteins. Finally, the connected subnetwork having the largest number of disease proteins is selected as a disease module. Experimental results on asthma demonstrate the effectiveness of the method in comparison to existing algorithms for disease module identification. It is also shown that the proposed IDMCSS can obtain the disease modules having crucial biological processes of asthma and 12 targets for drug intervention can be predicted.

SUBMITTER: Liu J

PROVIDER: S-EPMC8575408 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Biological networks catalog the complex web of interactions happening between different molecules, typically proteins, within a cell. These networks are known to be highly modular, with groups of proteins associated with specific biological functions. Human diseases often arise from the dysfunction of one or more such proteins of the biological functional group. The ability, to identify and automatically extract these modules has implications for understanding the etiology of different diseases as well as the functional roles of different protein modules in disease. The recent DREAM challenge posed the problem of identifying disease modules from six heterogeneous networks of proteins/genes. There exist many community detection algorithms, but all of them are not adaptable to the biological context, as these networks are densely connected and the size of biologically relevant modules is quite small. The contribution of this study is 3-fold: first, we present a comprehensive assessment of many classic community detection algorithms for biological networks to identify non-overlapping communities, and propose heuristics to identify small and structurally well-defined communities-core modules. We evaluated our performance over 180 GWAS datasets. In comparison to traditional approaches, with our proposed approach we could identify 50% more number of disease-relevant modules. Thus, we show that it is important to identify more compact modules for better performance. Next, we sought to understand the peculiar characteristics of disease-enriched modules and what causes standard community detection algorithms to detect so few of them. We performed a comprehensive analysis of the interaction patterns of known disease genes to understand the structure of disease modules and show that merely considering the known disease genes set as a module does not give good quality clusters, as measured by typical metrics such as modularity and conductance. We go on to present a methodology leveraging these known disease genes, to also include the neighboring nodes of these genes into a module, to form good quality clusters and subsequently extract a "gold-standard set" of disease modules. Lastly, we demonstrate, with justification, that "overlapping" community detection algorithms should be the preferred choice for disease module identification since several genes participate in multiple biological functions.

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Locally Adjust Networks Based on Connectivity and Semantic Similarities for Disease Module Detection

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