Using this approach, we attempted to identify key inflammatory genes and their core transcriptional regulators in coronary artery disease (CAD). Initially, we obtained 124 candidate genes associated with inflammation and CAD using Polysearch and CADgene database for which protein-protein interaction network was generated using STRING 9.0 (Search Tool for the Retrieval of Interacting Genes) and visualized using Cytoscape v 2.8.3. Based on betweenness centrality (BC) and node degree as key topological parameters, we identified interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), interleukin-1 beta (IL-1B), tumor necrosis factor (TNF) and prostaglandin-endoperoxide synthase 2 (PTGS2) as hub nodes. The backbone network constructed with these five hub genes showed 111 nodes connected via 348 edges, with IL-6 having the largest degree and highest BC. Nuclear factor kappa B1 (NFKB1), signal transducer and activator of transcription 3 (STAT3) and JUN were identified as the three core transcription factors from the regulatory network derived using MatInspector. Fallout 4 spring cleaning vs scrap everything Activator# For the purpose of validation of the hub genes, 97 test networks were constructed, which revealed the accuracy of the backbone network to be 0.7763 while the frequency of the hub nodes remained largely unaltered. Pathway enrichment analysis with ClueGO, KEGG and REACTOME showed significant enrichment of six validated CAD pathways - smooth muscle cell proliferation, acute-phase response, calcidiol 1-monooxygenase activity, toll-like receptor signaling, NOD-like receptor signaling and adipocytokine signaling pathways. Fallout 4 spring cleaning vs scrap everything verification#Įxperimental verification of the above findings in 64 cases and 64 controls showed increased expression of the five candidate genes and the three transcription factors in the cases relative to the controls (p<0.05). PLoS ONE 9(4):Įditor: Christian Schönbach, Nazarbayev University, Kazakhstan Thus, analysis of complex networks aid in the prioritization of genes and their transcriptional regulators in complex diseases.Ĭitation: Nair J, Ghatge M, Kakkar VV, Shanker J (2014) Network Analysis of Inflammatory Genes and Their Transcriptional Regulators in Coronary Artery Disease. Received: NovemAccepted: MaPublished: April 15, 2014Ĭopyright: © 2014 Nair et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: The authors gratefully acknowledge the support extended by the trustees of Thrombosis Research Institute, London and Bangalore, Weston Foundation, UK, Foundation Bey, Switzerland, the Tata Social Welfare Trust, India (TSWT/IG/SNB/JP/Sdm) and Department of Biotechnology, Ministry of Science and Technology, Government of India (BT/01/CDE/08/07). The sponsors did not participate in the design, conduct, sample collection analysis and interpretation of the data or in the preparation, review or approval of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭoronary Artery Disease (CAD) is a chronic inflammatory disease. There is ample evidence on the role of inflammation in all stages of the atherosclerotic disease process. Genetic studies have revealed many causal or susceptible inflammatory loci associated with CAD, the manifest form of atherosclerosis. Circulating inflammatory biomarkers such as C-reactive proteins (CRP) and certain cytokines are also elevated in acute coronary syndrome, which reflect the extent of myocardial necrosis and ischemia/reperfusion damage. Fallout 4 spring cleaning vs scrap everything verification#Īll these studies singularly demonstrate that inflammatory genes act in an interactive manner to orchestrate the disease associated risk.Fallout 4 spring cleaning vs scrap everything Activator#.
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