Team India Consortium with Global Partnership

1. Team India Consortium with Global Partnership A CSIR-led initiative for affordable healthcare to the developing world Council of Scientific and Industrial Research INDIA http://www.osdd.net

2. “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

3. One person • every 20 seconds • 1.7 Million people • every year • In India • Nearly 1000 people • every day • Two people • every 3 minutes TB Kills Image Credits:  Teseum/Flickr

4. Deaths due to Tuberculosis in 2008 Source: GlobalHealthFacts.org • More than 2 billion people (~1/3 of world population) is affected with the • tubercle bacilli

5. TB Drug Discovery

6. “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

7. 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

9. 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).

10. 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

11. OSDD View on Patents • Two patent applied molecules in hit to lead phase • Patentonly to ensure that: • Quality assurance in downstream processes • Subsequent innovations remain in open source • Affordability : through non exclusive licenses

12. OSDD – Multipronged approaches DRUG TARGET BASED (18 Drug Targets) NATURAL PRODUCT BASED (135 Phytomolecules ) LIGAND BASED (Pubchem Bioassay Data/New inhibitors/) Lead Optimization Potential hit

13. Community peer reviewOpen Funding Review

14. OSDD Open Access Resources Assembly line for drug discovery • I Biological Repository • i. Open access clinical strains repository • ii. Open access clone repository • iii. Open access protein repository • II Chemical Repository • i. Open access small molecule repository • III Open Screening Facility • i. Submit your compounds for anti-tuberculosis screening

15. Computational Resources developed with Community participation http://tbrowse.osdd.net http://sysborg2.osdd.net Bhardwaj et al. Tuberculosis (Edinb). 2009 Sep;89(5):386-7 Bhardwaj et al. 2011 John Wiley & Sons, Inc. Chembio Toolkit TrapTB Mtb drug targets database Workflow engine with federated resources AmPhyDB AntimycobacterialPhytomolecule Database Mtb essen\tial genes database

16. COG Easy RNA Profile IdentificatioN Database of Conditionally Regulated Proteins Pathway network & Unique pathways Drug Targets (TDR/Plos/TDI) Databases Do not “talk” to each other Mycobacterial Genome Divergence Database Operon predictions (DOOR/VIMSS/Rutherford) * This is representative set of post-genomics data available on TB

17. COG Easy RNA Profile IdentificatioN Database of Conditionally Regulated Proteins Pathway network & Unique pathways Drug Targets (TDR/Plos/TDI) Databases now do “talk” to each other !! Mycobacterial Genome Divergence Database Operon predictions (DOOR/VIMSS/Rutherford) More than 100 datasetsencompassing a million data points

18. Publication in Tuberculosis 2009 AnshuBhardwaj DeekshaBhartiya VinodScaria NitinKumar OpenLabNoteBook on SysBorgTB http://sysborgtb.osdd.net/bin/view/OpenLabNotebook/TBMapDataset Deeksha Bhartiya Nitin Kumar

19. The “Connect to Decode” Programme Collaborative Curation Curated Annotations OSDD C2D Community 800+ Student Researchers Literature Annotation Tools Raw Annotations Pathway/Interactome | Gene Ontology | Protein Structure/Fold | Glycomics| Immunome Genomic Databases

20. “Given enough eyeballs, all bugs are shallow” -Linus Torvalds Errors are Discussed by the Community Errors are corrected by the Community Errors are marked by the Community for Correction

21. Innovative Crowd Sourcing Model for Mtb Systems Biology Collaborative Curation Curated Annotations Literature Annotation Tools Raw Annotations Community of >800 student researchers 87% of Mtb genome annotated Genomic Databases Generated the largest Interactome & Metabolic Map of Mtb

22. 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&D Repower 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 Headway J Natl Cancer Inst. 2010 Aug 18;102(16):1221-3

23. Nagasuma Chandra, Indian Institute of Science, Bangalore

24. OSDD SInCRe 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

25. Ongoing: Cheminformatics Community of About 400 PubChem ChEMBL DrugBank HT Virtual screening Cheminformatics Models Experimental Assays Curated molecule datasets Data Mining and Analysis • Other Active Communities: • OSDD Women Scientists Forum • OSDD Junior Scientists Forum

26. Cheminformatics – Large Scale Data Analysis Data Processing Size increases Heap Size issues Software Power MV and WEKA Output

27. Cheminformatics – Large Scale Data Analysis • Accessing large data files from online repository such as Pub Chem. • Basic computational resources – 4Gb RAM Pub Chem Database 1.04Pb Max bandwidth - 1-4 Mbps Local Systems 4Gb RAM

28. 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

29. Garuda Usage by OSDD:Job Accounting

30. OSDD - Linking Institutions and Competencies 45 Hits Selected for Screening Hits identified through virtual screening are synthesized and tested for enzyme assay

31. Creation of Library of Drug Like Compounds Filtering Criteria for Pruning 50,000 compounds from Chembridge Database • 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) Whole cell screening

32. OSDD Open Chemistry Led by CSIR- CDRI, India’s National Drug Research Laboratory

33. 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

34. 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

35. POC for downstream experiments • 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)

37. Status: OSDD Projects 18 Other projects aim to develop tools, databases and repositories for the OSDD community 19 9 6 2

38. OSDD Publications • Bhardwaj A, et al. Open Source Drug Discovery- a new paradigm of collaborative research in Tuberculosis drug development. Tuberculosis, 2011 (in press) • 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. • 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. • Sharma S, et al. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J AntimicrobChemother. 2010 Aug;65(8):1694-701. • Mishra NK, et al. Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule. BMC Pharmacol. 2010 Jul 16; 10:8. • Mathew R, et al. Inhibition of mycobacterial growth by plumbagin derivatives. ChemBiol Drug Des. 2010 Jul 76(1); 34-42. • Garg A, et al. KiDoQ: using docking based energy scores to developligand based model for predicting antibacterials. BMC Bioinformatics. 2010 Mar 11;11:125. • 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. • 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.

39. 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..” “..The West may think India is still in the gutter, but it is looking at the stars..” Author, Angela Saini

40. Responses from the OSDD Community • 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

41. Together we can … • .. and weshould ! http://www.osdd.net http://c2d.osdd.net http://sysborg2.osdd.net Matt Smadley | Flickr.com