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A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

Publication Type : Journal Article

Publisher : Frontiers in Cellular and Infection Microbiology, Frontiers Research Foundation.

Source : Frontiers in Cellular and Infection Microbiology, Frontiers Research Foundation, Volume 5, Number JAN (2016)

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Keywords : apoptosis, article, computer model, enzyme localization, gelatinase A, gelatinase B, gene interaction, gingivitis, high throughput screening, homeostasis, host cell, human, jun proto oncogene, matrix metalloproteinase, matrix metalloproteinase 14, neutrophil, nitric oxide, oncogene, oxidative stress, oxidoreductase, pathogenesis, periodontitis, protein c jun, Protein interaction, saliva analysis, Systems Biology, ubiquitin C

Campus : Amritapuri

School : School of Biotechnology

Department : biotechnology

Year : 2016

Abstract : Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions (BIOMARK interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with Experiments and Databases as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the BIOMARK members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

Cite this Research Publication : Fab Zeidán-Chuliá, Gürsoy, Mb, de Oliveira, B. - H. Na, Özdemir, Vcd, Könönen, Ebe, and Gürsoy, U. Kb, “A systems biology approach to reveal putative host-derived biomarkers of periodontitis by network topology characterization of MMP-REDOX/NO and apoptosis integrated pathways”, Frontiers in Cellular and Infection Microbiology, vol. 5, 2016.

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