Collaboraive sharing of molecules and data in the mobile age
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Collaboraive sharing of molecules and data in the mobile age

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An overview of using collaborative software in small and large scale collaborations in drug discovery. A focus on Tuberculosis. Also analysis of collaboration and mobile apps for science

An overview of using collaborative software in small and large scale collaborations in drug discovery. A focus on Tuberculosis. Also analysis of collaboration and mobile apps for science

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Collaboraive sharing of molecules and data in the mobile age Collaboraive sharing of molecules and data in the mobile age Presentation Transcript

  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Collaborative Sharing of Molecules and Data in the Mobile Age Sean Ekins1,2*, Alex M. Clark3 and Joel S. Freundlich4,5 * 1 Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA. 2 Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay-Varina, NC 27526, USA. 3 Molecular Materials Informatics, 1900 St. Jacques #302, Montreal, Quebec, Canada H3J 2S1 4 Department of Medicine, Center for Emerging and Reemerging Pathogens, Rutgers University – New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. 5 Department of Pharmacology & Physiology, Rutgers University – New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Collaboration
  • “by provisioning the right amount of storage and compute resources, cost can be significantly reduced with no significant impact on application performance”
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. CDD 2004 - present
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. CDD- a decade of drug discovery collaborations 2004 - present SaaS Easy to use Used by Academia Industry, Biotech Private Selective collaboration 100’s of published datasets
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Online Zendesk • CDD Models • CDD Vision • Integration of CDD Public, ChemSpider, Zinc, and PubChem. Benefits of CDD Vault
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Applications of CDD
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Three collaborations within Rutgers–NJMS • Collaboration with Johns Hopkins, SRI, and CDD • Collaboration with Johns Hopkins • Collaboration with CDD Supported by 7 Active NIH Grants Chemical Probe Evolution Drug Discovery Compound Evolution Target Identification & Validation Freundlich Laboratory Collaborations Rely on CDD for Data Tracking!
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Project overview Phase I STTR – Proof of concept of mimic strategy Phase II STTR – Expand mimic strategy and validation of phase I hits
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Examples of vault used for STTR
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Examples of vault used for STTR Computationally searched >80,000 molecules – and used Bayesian models for filter - narrowed to 842 hits -tested 23 compounds in vitro (3 picked as inactives), lead to 2 proposed as mimics of D-fructose 1,6 bisphosphate Sarker et al., Pharm Res 2012, 29: 2115-2127 a. b. 1R41AI088893-01
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. NIH Blueprint – CDD Partnership Securely sharing data New Old
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Another example of a big TB collaboration 7 Big Pharma and 4 academic institutes will open up targeted sections of their compound libraries and share data with each other. • Abbott • AstraZeneca • Bayer • Eli Lilly • GlaxoSmithKline • Merck • Sanofi • Infectious Disease Research Institute (IDRI) • NIH National Institute of Allergy and Infectious Diseases • Texas A&M University • Weill Cornell Medical College TB Drug Accelerator
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. MM4TB 5 yr project – develop new medicines for tuberculosis
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Pharma with 24 Organizations in Single, Secure MM4TB-CDD Vault® • Text
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. MM4TB • Provide CDD Vault • Vault Support • Cheminformatics support to project • Example using CDD Vault to share docking data for Topo I project • Dock compounds in homology model of Mtb Topo I then import data in CDD Godbole et al., Biochem Biophys Res Comm 446:916-20, 2014.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. MM4TB – Topo I • Mtb Topo I docking identified new inhibitors – collaboration With Nagaraja group in India - Amsacrine Godbole et al., Biochem Biophys Res Comm 446:916-20, 2014.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Drug discovery is repetitive and there are 1000s of diseases Drug discovery is high risk Do we need robots or just smarter programs that discover the ideas we test?
  • MoDELS RESIDE IN PAPERS NOT ACCESSIBLE…THIS IS UNDESIRABLE How do we share them? How do we use Them?
  • Open ExtendedConnectivity Fingerprints ECFP_6 FCFP_6 • Collected, deduplicated, hashed • Sparse integers • Invented for Pipeline Pilot: public method, proprietary details • Often used with Bayesian models: many published papers • Built a new implementation: open source, Java, CDK – stable: fingerprints don't change with each new toolkit release – well defined: easy to document precise steps – easy to port: already migrated to iOS (Objective-C) for TB Mobile app • Provides core basis feature for CDD open source model service
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Data + One Click = Uses Bayesian algorithm and FCFP_6 fingerprints
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. “Beautifully Simple” and equally fast to apply
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Single point data > 300K molecules
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. The Mobile Age
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Examples of vault used for STTR mainframes minicomputers personal computers portable laptops mobile tablets smartphones ? • mobile is revolutionary: a clean break  entirely new user interface  no backward compatibility  highly constrained resources  applicable to entirely new situations
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Reference data • Education • Structure drawing • Database searching • 3D viewing • Reactions & collections • Property calculation • Model building • Graphical presentation • Data sharing Chemistry Apps
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Ekins et al., J Cheminform 5:13, 2013 Clark et al., J Cheminform 6:38 2014 Predict targets Cluster molecules http://goo.gl/vPOKS http://goo.gl/iDJFR Open fingerprints and bayesian method used in TB Mobile Vers.2
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Workflow from sketching molecules in MMDS mobile app to exporting and opening with TB Mobile
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Look up structure in ChemSpider • Saving structure as molfile - open in MMDS • Run substructure search in ChEBI using MMDS webservice • Open molecule from MMDS and assign scaffolds in SAR Table Generate substituents • Predict missing activities for compounds in SAR Table • Suggest compounds to make in SAR Table • Find a reaction in SPRESImobile • Use Yield101 to calculate synthesis yield • Share data with Dropbox using MolSync app • Tweet a reaction with MolSync • Read the data with ODDT mobile app Simple App Workflows Clark AM, Williams AJ and Ekins S, Chem-Bio Informatics Journal, 13: 1-18 2013.
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Preliminary work done with desktop software: com.mmi • Fragment TB Mobile structures, scaffold-like • Perform scaffold-substructure vs. 7000 in vitro • Derive R-groups, tidy, present graphically, browse... TB Mobile in a TB Workflow
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. • Scaffold: • Scaffold origin: inhibitor of Glf target • 87 molecules with in vitro activity (yes/no) • Scaffold seems to elicit an activity pattern • Next step: load it into the app ecosystem... http://molmatinf.com/ venice.html To see the rest of the TB workflow…… Source Materials
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Open Drug Discovery Teams • Curation of open data, e.g. Twitter & RSS feeds • Rare & neglected diseases, precompetitive areas • Tweet got harvested into Tuberculosis topic • Inline preview browsed, with other thumbnails Ekins et al., Mol Informatics, 31: 585-597, 2012
  • Rare diseases inspired an App that may be a new kind of database upload molecules by tweeting them- 1 tweet upload Take our data with us anywhere Bring data off the cloud into device Advantages you get to analyze it in the Cloud on a plane Future: how do we deliver data
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. Conclusions • Cheminformatics workflows historically the role of specialists: expensive and/or complex • Mobile apps are much cheaper and much more accessible to experimentalists • Mobile+cloud can: - replace simple-to-medium tasks - coexist with complex tasks run on desktop software Desktop+Mobile+cloud = best case • Other advantages: - anywhere/anytime portability - excellent collaboration and sharing - non-existent installation or maintenance burden
  • Archive, Mine, Collaborate© 2009 Collaborative Drug Discovery, Inc. PAPER ID: 22104 “Collaborative sharing of molecules and data in the mobile age” (final paper number: 43) DIVISION: COMP; DAY & TIME OF PRESENTATION: August 10, 2014 from 4:45 pm to 5:15 pm LOCATION: Moscone Center, West Bldg., Room: 2005 PAPER ID: 22094 “Expanding the metabolite mimic approach to identify hits for Mycobacterium tuberculosis ” (final paper number: 78) DIVISION: COMP: DAY & TIME OF PRESENTATION: August 11, 2014 from 9:00 am to 9:30 am LOCATION: Moscone Center, West Bldg., Room: 2005 PAPER ID: 22120 “Why there needs to be open data for ultrarare and rare disease drug discovery” (final paper number: 48) DIVISION: CINF:SESSION DAY & TIME OF PRESENTATION: August 11, 2014 from 10:50 am to 11:20 am LOCATION: Palace Hotel, Room: Marina PAPER ID: 22183 “Progress in computational toxicology” (final paper number: 125) DIVISION: TOXI: DAY & TIME OF PRESENTATION: August 12, 2014 from 6:30 pm to 10:30 pm LOCATION: Moscone Center, North Bldg. , Room: 134 PAPER ID: 22091 “Examples of how to inspire the next generation to pursue computational chemistry/cheminformatics” (final paper number: 100) DIVISION: CINF: Division of Chemical Information DAY & TIME OF PRESENTATION: August 13, 2014 from 8:25 am to 8:50 am LOCATION: Palace Hotel, Room: Presidio PAPER ID: 22176 “Applying computational models for transporters to predict toxicity” (final paper number: 132) DIVISION: TOXI: DAY & TIME OF PRESENTATION: August 13, 2014 from 9:45 am to 10:05 am LOCATION: InterContinental San Francisco, Room: Grand Ballroom A PAPER ID: 22186 “New target prediction and visualization tools incorporating open source molecular fingerprints for TB mobile version 2” (final paper number: 123) DIVISION: CINF: DAY & TIME OF PRESENTATION: August 13, 2014 from 1:35 pm to 2:05 pm LOCATION: Palace Hotel, Room: California Parlor You can find me @...
  • All at CDD, SRI, MM4TB and many others …Funding: Bill and Melinda Gates Foundation (Grant#49852) 1R41AI088893-01, 2R42AI088893-02, R43 LM011152-01, 9R44TR000942-02, 1R41AI108003-01, MM4TB, Software: Biovia
  •  Email: ekinssean@yahoo.com  Slideshare: http://www.slideshare.net/ekinssean  Twitter: collabchem  Blog: http://www.collabchem.com/  Website: http://www.collaborations.com/CHEMISTRY.HTM