Cargando…

Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv

Potential drug targets of Mycobacterium tuberculosis H37Rv were identified through systematically integrated comparative genome and network centrality analysis. The comparative analysis of the complete genome of Mycobacterium tuberculosis H37Rv against Database of Essential Genes (DEG) yields a list...

Descripción completa

Detalles Bibliográficos
Autores principales: Melak, Tilahun, Gakkhar, Sunita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651637/
https://www.ncbi.nlm.nih.gov/pubmed/26618166
http://dx.doi.org/10.1155/2015/212061
_version_ 1782401666636578816
author Melak, Tilahun
Gakkhar, Sunita
author_facet Melak, Tilahun
Gakkhar, Sunita
author_sort Melak, Tilahun
collection PubMed
description Potential drug targets of Mycobacterium tuberculosis H37Rv were identified through systematically integrated comparative genome and network centrality analysis. The comparative analysis of the complete genome of Mycobacterium tuberculosis H37Rv against Database of Essential Genes (DEG) yields a list of proteins which are essential for the growth and survival of the pathogen. Those proteins which are nonhomologous with human were selected. The resulting proteins were then prioritized by using the four network centrality measures: degree, closeness, betweenness, and eigenvector. Proteins whose centrality value is close to the centre of gravity of the interactome network were proposed as a final list of potential drug targets for the pathogen. The use of an integrated approach is believed to increase the success of the drug target identification process. For the purpose of validation, selective comparisons have been made among the proposed targets and previously identified drug targets by various other methods. About half of these proteins have been already reported as potential drug targets. We believe that the identified proteins will be an important input to experimental study which in the way could save considerable amount of time and cost of drug target discovery.
format Online
Article
Text
id pubmed-4651637
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-46516372015-11-29 Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv Melak, Tilahun Gakkhar, Sunita Biomed Res Int Research Article Potential drug targets of Mycobacterium tuberculosis H37Rv were identified through systematically integrated comparative genome and network centrality analysis. The comparative analysis of the complete genome of Mycobacterium tuberculosis H37Rv against Database of Essential Genes (DEG) yields a list of proteins which are essential for the growth and survival of the pathogen. Those proteins which are nonhomologous with human were selected. The resulting proteins were then prioritized by using the four network centrality measures: degree, closeness, betweenness, and eigenvector. Proteins whose centrality value is close to the centre of gravity of the interactome network were proposed as a final list of potential drug targets for the pathogen. The use of an integrated approach is believed to increase the success of the drug target identification process. For the purpose of validation, selective comparisons have been made among the proposed targets and previously identified drug targets by various other methods. About half of these proteins have been already reported as potential drug targets. We believe that the identified proteins will be an important input to experimental study which in the way could save considerable amount of time and cost of drug target discovery. Hindawi Publishing Corporation 2015 2015-11-05 /pmc/articles/PMC4651637/ /pubmed/26618166 http://dx.doi.org/10.1155/2015/212061 Text en Copyright © 2015 T. Melak and S. Gakkhar. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Melak, Tilahun
Gakkhar, Sunita
Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title_full Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title_fullStr Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title_full_unstemmed Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title_short Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
title_sort comparative genome and network centrality analysis to identify drug targets of mycobacterium tuberculosis h37rv
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651637/
https://www.ncbi.nlm.nih.gov/pubmed/26618166
http://dx.doi.org/10.1155/2015/212061
work_keys_str_mv AT melaktilahun comparativegenomeandnetworkcentralityanalysistoidentifydrugtargetsofmycobacteriumtuberculosish37rv
AT gakkharsunita comparativegenomeandnetworkcentralityanalysistoidentifydrugtargetsofmycobacteriumtuberculosish37rv