Crowd sourcing a new paradigm for interactome driven drug target identification in Mycobacterium tuberculosis.
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 'interactome 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.
Council of Scientific and Industrial Research, Delhi, India.
Rohit
R
Vashisht
Anupam Kumar
AK
Mondal
Akanksha
A
Jain
Anup
A
Shah
Priti
P
Vishnoi
Priyanka
P
Priyadarshini
Kausik
K
Bhattacharyya
Harsha
H
Rohira
Ashwini G
AG
Bhat
Anurag
A
Passi
Keya
K
Mukherjee
Kumari Sonal
KS
Choudhary
Vikas
V
Kumar
Anshula
A
Arora
Prabhakaran
P
Munusamy
Ahalyaa
A
Subramanian
Aparna
A
Venkatachalam
S
S
Gayathri
Sweety
S
Raj
Vijaya
V
Chitra
Kaveri
K
Verma
Salman
S
Zaheer
J
J
Balaganesh
Malarvizhi
M
Gurusamy
Mohammed
M
Razeeth
Ilamathi
I
Raja
Madhumohan
M
Thandapani
Vishal
V
Mevada
Raviraj
R
Soni
Shruti
S
Rana
Girish Muthagadhalli
GM
Ramanna
Swetha
S
Raghavan
Sunil N
SN
Subramanya
Trupti
T
Kholia
Rajesh
R
Patel
Varsha
V
Bhavnani
Lakavath
L
Chiranjeevi
Soumi
S
Sengupta
Pankaj Kumar
PK
Singh
Naresh
N
Atray
Swati
S
Gandhi
Tiruvayipati Suma
TS
Avasthi
Shefin
S
Nisthar
Meenakshi
M
Anurag
Pratibha
P
Sharma
Yasha
Y
Hasija
Debasis
D
Dash
Arun
A
Sharma
Vinod
V
Scaria
Zakir
Z
Thomas
Nagasuma
N
Chandra
Samir K
SK
Brahmachari
Anshu
A
Bhardwaj
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D063045:Crowdsourcing; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial; D023281:Genomics; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D025941:Protein Interaction Mapping; D020543:Proteome; D015398:Signal Transduction
D001426:Bacterial Proteins; D020543:Proteome