Team India Consortium with Global Partnership
Council of Scientific and Industrial Research INDIA
A CSIR-led initiative for affordable healthcare to the developing world
http://www.osdd.net
“When it comes to health, we need to have a
balanced view between health as a right and
health as a business”
Prof Samir Brahmachari
Director General, CSIR and
Chief Mentor, OSDD
(Ref: Cell (2008) v.133, pp. 201-203)
50
One personevery 20 seconds
1.7 Million people every year
In IndiaNearly 1000 people every day
Two peopleevery 3 minutes
TB Kills
Image Credits: Teseum/Flickr
More than 2 billion people (~1/3 of world population) is affected with the tubercle bacilli
Deaths due to Tuberculosis in 2008 Source: GlobalHealthFacts.org
TB Drug Discovery
“Generations of advances in research and technology have bypassed TB research” - Anthony Fauci, NIAID .
“The field has been too isolated and inward-looking” Dr. Margaret Chan, head WHO
Why Open Source Drug discovery ?
Many eye balls make the bug shallow!
Lack of market incentive for TB
Successful Open Source Models
Human Genome Sequencing Initiative
Open Source Software Initiative (eg: Linux OS)
Android
The WWW
OSDD Platform
System Architecture
Collaborative tools to accelerate neglected diseases research” in the book “Collaborative Computational Technologies for Biomedical Research”. Wiley and Sons. 2011 (in press).
OSDD: Attribution and IP
• All contributions on the OSDD portal attributed to the authors with date and time stamp
• Real time data sharing
• Click wrap license agreement– All contributions treated as Protected Collective
Information• mandates sharing, • attribution, • contribute back
OSDD View on Patents
• Two patent applied molecules in hit to lead phase
• Patent only to ensure that:
– Quality assurance in downstream processes
– Subsequent innovations remain in open source
– Affordability : through non exclusive licenses
OSDD – Multipronged approaches
Potential hit Lead Optimization
DRUG TARGET BASED(18 Drug Targets)
LIGAND BASED(Pubchem Bioassay Data/New inhibitors/)
NATURAL PRODUCT BASED (135 Phytomolecules )
Community peer reviewOpen Funding Review
Assembly line for drug discovery
I Biological Repository
i. Open access clinical strains repositoryii. Open access clone repositoryiii. Open access protein repository
II Chemical Repositoryi. Open access small molecule repository
III Open Screening Facility i. Submit your compounds for anti-tuberculosis
screening
OSDD Open Access Resources
Bhardwaj et al. Tuberculosis (Edinb). 2009 Sep;89(5):386-7
http://tbrowse.osdd.net
Computational Resources developed with Community participation
Bhardwaj et al. 2011 John Wiley & Sons, Inc.
Mtb essen\tial genes database
TrapTBMtb drug targets database
Chembio ToolkitWorkflow engine with federated resources
AmPhyDBAntimycobacterial Phytomolecule Database
http://sysborg2.osdd.net
Databases Do not “talk” to each other
COG Mycobacterial Genome Divergence Database
Easy RNA Profile IdentificatioN
Database of Conditionally Regulated Proteins
Pathway network & Unique pathways
Drug Targets (TDR/Plos/TDI)
Operon predictions (DOOR/VIMSS/Rutherford)
* This is representative set of post-genomics data available on TB
Databases now do “talk” to each other !!
Mycobacterial Genome Divergence Database
COG
Easy RNA Profile IdentificatioN
Database of Conditionally Regulated Proteins
Pathway network & Unique pathways
Drug Targets (TDR/Plos/TDI)
Operon predictions (DOOR/VIMSS/Rutherford)
More than 100 datasets
encompassing a million data points
AnshuBhardwaj
DeekshaBhartiya
NitinKumar
VinodScaria
OpenLabNoteBook on SysBorgTBhttp://sysborgtb.osdd.net/bin/view/OpenLabNotebook/TBMapDataset
Publication in Tuberculosis 2009
Deeksha Bhartiya Nitin Kumar
Literature
Annotation Tools
Genomic Databases
Curated Annotations
Raw Annotations
OSDD C2DCommunity
800+ Student
Researchers
Collaborative Curation
Pathway/Interactome | Gene Ontology | Protein Structure/Fold | Glycomics| Immunome
Pathway/Interactome | Gene Ontology | Protein Structure/Fold | Glycomics| Immunome
The “Connect to Decode” Programme
“Given enough eyeballs, all bugs are shallow”
Errors are marked by the Community for Correction
Errors are corrected by the Community
-Linus Torvalds
Errors are Discussed by the Community
Literature
Annotation Tools
Genomic Databases
Curated Annotations
Raw Annotations
Community of >800 student researchers
Collaborative Curation
Innovative Crowd Sourcing Model for Mtb Systems Biology
Generated the largest Interactome & Metabolic Map of Mtb
87% of Mtb genome annotated
Within weeks, 830 volunteered to re-annotate the entire M. tuberculosis genome. The work started in December 2009 and was completed by April 2010, packing nearly 300 man-years into 4 months!
Source: Munos B. Can Open-Source Drug R&DRepower Pharmaceutical Innovation?Clin Pharmacol Ther 2010;87:534–536
The Open-Source Drug Discovery (OSDD), which is dedicated to discovering treatments for diseases that plague the developing world, surprised many when more than 400 of its volunteer researchers reannotated the tuberculosis bacterium genome, wiki style, in just 4 months—record time for such an endeavor
Source: Margie Patlak. Open-Source Science Makes HeadwayJ Natl Cancer Inst. 2010 Aug 18;102(16):1221-3
Nagasuma Chandra, Indian Institute of Science, Bangalore
An Open Source Integrated Computational Resource for the Analysis of the Structural Interactome to predict Off-Site Interactions of Drug Candidates
Nagasuma Chandra, R. Sowdhamini, N. Srinivasan & Sir Tom Blundell
OSDD SInCRe
Ongoing: Cheminformatics
Curated molecule datasets
Curated molecule datasets
Cheminformatics Models
Cheminformatics Models
Data Mining and AnalysisData Mining and Analysis
HT Virtual screeningHT Virtual screening
PubChemPubChem
ChEMBL ChEMBL
DrugBankDrugBank
Experimental Assays
Experimental Assays
Community of About 400
Other Active Communities:•OSDD Women Scientists Forum•OSDD Junior Scientists Forum
Software
Processing
Power MV and WEKAPower MV and WEKA
Output
Size increases
Size increasesHeap Size
issuesHeap Size
issues
Data
Cheminformatics – Large Scale Data Analysis
Cheminformatics – Large Scale Data Analysis
• Accessing large data files from online repository such as Pub Chem.
• Basic computational resources – 4Gb RAM
Database
Local Systems
Pub ChemPub Chem
4Gb RAM4Gb RAM
Max bandwidth - 1-4 Mbps
Max bandwidth - 1-4 Mbps
1.04Pb
C-DAC’s Garuda Grid – Indian Grid Computing Initiative
• C-DAC is R&D organization under Ministry of Communication & Information Technology, India
• C-DAC’s Garuda Grid is targeted at providing a facility for the scientific community, which would enable them to seamlessly access the distributed resources.
• Compute Power of GARUDA: ~ 70TFs (6000 CPUs)
• Currently there are 55 Garuda Partners
• Has NKN (National Knowledge Network) connectivity at 10Gbps
Garuda Usage by OSDD:Job Accounting
45 Hits Selected for Screening
OSDD - Linking Institutions and Competencies
Hits identified through virtual screening are synthesized and tested for enzyme assay
Molecular Weight < 400 Remove molecules other than H,C,N,O,F,S,P,Cl,Br, or I
ADME properties (Principle descriptors & Prediction of properties) based on 1712 drugs.
Shrinking the CLogP window between 1.5 & 5
A physical compound library of drug like compounds. (20,000 compounds)
Creation of Library of Drug Like Compounds
Filtering Criteria for Pruning 50,000 compounds from Chembridge Database
Whole cell screening
OSDD Open Chemistry
Led by CSIR- CDRI, India’s National Drug Research Laboratory
OSDD Open Chemistry
Challenge Need novel molecules for screening against
TB/Malaria
OSDD Approach
Open source small molecule synthesis involving 40 chemistry departments from colleges across India
Web based collaboration and discussion
OSDD Team at work in SASTRA
Project implementation through students selected via pan India online primer designing exercise
More than 30 genes cloned in
less than 3 months
• Fifteen undergraduate students were given hands on training in various Molecular biology techniques
• So far, 11 genes have been cloned in pGEM-T easy vector • 20 have been cloned in pET28 a/b/c and expressed (Verified by SDS –PAGE)
POC for downstream experiments
18
19
9
6
2
Status: OSDD Projects
Other projects aim to develop tools, databases and repositories for the OSDD community
1) Bhardwaj A, et al. Open Source Drug Discovery- a new paradigm of collaborative research in Tuberculosis drug development. Tuberculosis, 2011 (in press)
2) Bhardwaj A, et al. Collaborative Tools to Accelerate Neglected Disease Research: the Open Source Drug Discovery Model [Book Chapter]in Collaborative Computational Technologies for Biomedical Research, Wiley and Sons, May 2011.
3) Bhat AG, et al. Modeling metabolic adjustment in Mycobacterium tuberculosis upon treatment with Isoniazid. Systems and Synthetic Biology. 2011 Volume 4, Number 4, 299-309.
4) Sharma S, et al. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J Antimicrob Chemother. 2010 Aug;65(8):1694-701.
5) Mishra NK, et al. Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule. BMC Pharmacol. 2010 Jul 16; 10:8.
6) Mathew R, et al. Inhibition of mycobacterial growth by plumbagin derivatives. Chem Biol Drug Des. 2010 Jul 76(1); 34-42.
7) Garg A, et al. KiDoQ: using docking based energy scores to developligand based model for predicting antibacterials. BMC Bioinformatics. 2010 Mar 11;11:125.
8) Bhardwaj A, et al. Open Source Drug Discovery Consortium, TBrowse: an Integrative Genomics Map of Mycobacterium tuberculosis. Tuberculosis (Edinb). 2009 Sep; 89(5):386-7.
9) Bhardwaj A, et al . Open source drug discovery: a global collaborative drug discovery model for tuberculosis. Science and culture, January-February, 2011, vol. 77, nos. 1–2, 22-26.
OSDD Publications
Author, Angela Saini
Geek Nation: How Indian Science Is Taking Over The World
“..a journey to meet the inventors,
engineers and young scientists behind this
nation built not on conquest, oil or minerals,
but on the scientific ingenuity of its people..”
“.. explores the reason why the government of the most religious country on earth has put its faith in science and technology..”
“.. explores the reason why the government of the most religious country on earth has put its faith in science and technology..”
“..The West may think India is still in the gutter, but it is looking at the stars..”
“..The West may think India is still in the gutter, but it is looking at the stars..”
•I have had a thrilling experience with OSDD for the past 2 years and now I am ready to pursue my PHD at Indiana University Abhik Seal, SBI Employee, Calcutta
•I can access the CDAC supercomputing facility The Garuda Grid sitting at any place from anywhere in the world. Rajdeep Poddar, Bio IT Application Specialist
•OSDD is a boon to me, giving me a platform to research when I was at cross roads regarding career ,family and research
Swati Gandhi ,Baroda, Gujrat
•It has been a dream come true and a great learning experience after becoming a part of OSDD
Dr Preetha Anil, SIAS, Kerala
•I still remember what I said to myself on second day of OSDD conference looking into the mirror... “Is this the Shamsudheen from that remote village?????....!!!!!”
Shamsudheen K.V ,IGIB
Responses from the OSDD Community
Together we can ….. and we should !
Matt Smadley | Flickr.com
http://www.osdd.nethttp://c2d.osdd.net
http://sysborg2.osdd.net