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Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

Vashisht, Rohit and Mondal, Anupam Kumar and Jain, Akanksha and Shah, Anup and Vishnoi, Priti and Priyadarshini, Priyanka and Bhattacharyya, Kausik and Rohira, Harsha and Bhat, Ashwini G and Passi, Anurag and Mukherjee, Keya and Choudhary, Kumari Sonal and Kumar, Vikas and Arora, Anshula and Munusamy, Prabhakaran and Subramanian, Ahalyaa and Venkatachalam, Aparna and Gayathri, S and Raj, Sweety and Chitra, Vijaya and Verma, Kaveri and Zaheer, Salman and Balaganesh, J and Gurusamy, Malarvizhi and Razeeth, Mohammed and Raja, Ilamathi and Thandapani, Madhumohan and Mevada, Vishal and Soni, Raviraj and Rana, Shruti and Ramanna, Girish Muthagadhalli and Raghavan, Swetha and Subramanya, Sunil N and Kholia, Trupti and Patel, Rajesh and Bhavnani, Varsha and Chiranjeevi, Lakavath and Sengupta, Soumi and Singh, Pankaj Kumar and Atray, Naresh and Gandhi, Swati and Avasthi, Tiruvayipati Suma and Nisthar, Shefin and Anurag, Meenakshi and Sharma, Pratibha and Hasija, Yasha and Dash, Debasis and Sharma, Arun and Scaria, Vinod and Thomas, Zakir and Chandra, Nagasuma and Brahmachari, Samir K. and Bhardwaj, Anshu and Consortium, OSDD (2012) Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis. In: PLOS ONE, 7 (7).

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Official URL: http://dx.doi.org/10.1371/journal.pone.0039808

Abstract

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative `Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed `3interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to PUBLIC LIBRARY SCIENCE
Keywords: MOLECULAR INTERACTION DATABASE;ANTI-SIGMA-FACTOR;SYSTEMS BIOLOGY;GENOME SEQUENCE;BINDING-SITES; NETWORKS;PROTEINS; BETWEENNESS;INHIBITOR;ALGORITHM
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 13 Aug 2012 09:46
Last Modified: 13 Aug 2012 09:46
URI: http://eprints.iisc.ernet.in/id/eprint/44943

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