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      Deciphering the Novel Target Genes Involved in the Epigenetics of Hepatocellular Carcinoma Using Graph Theory Approach

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          Abstract

          Background

          Even after decades of research, cancer, by and large, remains a challenge and is one of the major causes of death worldwide. For a very long time, it was believed that cancer is simply an outcome of changes at the genetic level but today, it has become a well-established fact that both genetics and epigenetics work together resulting in the transformation of normal cells to cancerous cells.

          Objective

          In the present scenario, researchers are focusing on targeting epigenetic machinery. The main advantage of targeting epigenetic mechanisms is their reversibility. Thus, cells can be reprogrammed to their normal state. Graph theory is a powerful gift of mathematics which allows us to understand complex networks.

          Methodology

          In this study, graph theory was utilized for quantitative analysis of the epigenetic network of hepato-cellular carcinoma (HCC) and subsequently finding out the important vertices in the network thus obtained. Secondly, this network was utilized to locate novel targets for hepato-cellular carcinoma epigenetic therapy.

          Results

          The vertices represent the genes involved in the epigenetic mechanism of HCC. Topological parameters like clustering coefficient, eccentricity, degree, etc. have been evaluated for the assessment of the essentiality of the node in the epigenetic network.

          Conclusion

          The top ten novel epigenetic target genes involved in HCC reported in this study are cdk6, cdk4, cdkn2a, smad7, smad3, ccnd1, e2f1, sf3b1, ctnnb1, and tgfb1.

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          Most cited references19

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          Emergence of scaling in random networks

          Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach preferentially to sites that are already well connected. A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.
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            A measure of betweenness centrality based on random walks

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              Cancer epigenetics comes of age.

              The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour-suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation.
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                Author and article information

                Journal
                Curr Genomics
                Curr. Genomics
                CG
                Current Genomics
                Bentham Science Publishers
                1389-2029
                1875-5488
                December 2019
                December 2019
                : 20
                : 8
                : 545-555
                Affiliations
                Department of Bioinformatics and Applied Sciences, Indian Institute of Information Technology , Allahabad, , Uttar Pradesh , India; Department of Biotechnology and Bioinformatics, NIIT University, Neemrana, Rajasthan, India; Division of Biotechnology, Netaji Subhas Institute of Technology, University of Delhi , New Delhi, , India
                Author notes
                [* ]Address correspondence to this author at the Department of Bioinformatics and Applied Sciences, Indian Institute of Information Technology, Allahabad, Uttar Pradesh, India; Tel: 9236666060; E-mail: pritish@ 123456iiita.ac.in
                Article
                CG-20-545
                10.2174/1389202921666191227100441
                7290056
                f4bf884b-7f0c-4c7e-83fa-e358a3cb8d00
                © 2019 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 25 April 2019
                : 25 September 2019
                : 10 November 2019
                Categories
                Artile

                Genetics
                graph theory,clustering coefficient,eccentricity,epigenome,stress centrality,hepatocellular carcinoma

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