cheminformatics workflows using mobile apps for drug discovery
DESCRIPTION
talk for SLAS 2014 slidesTRANSCRIPT
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Alex M. Clark1, Antony J. Williams2 and Sean Ekins3,4
1 Molecular Materials Informatics, 2 Royal Society of Chemistry, 3Collaborations in
Chemistry, 4 Collaborative Drug Discovery, Inc.,
Cheminformatics Workflows Using Mobile
Apps for Drug Discovery
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• mobile is revolutionary: a clean break
entirely new user interface
no backward compatibility
highly constrained resources
applicable to entirely new situations
mainframes
minicomputers
personal computers
portable laptops
mobile tablets
smartphones
?
The Computing Revolution #3
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Williams et al DDT
16:928-939, 2011
Arnold and Ekins, PharmacoEconomics 28: 1-5, 2010
Williams et al., In collaborative computational technologies for
biomedical research 2011
Fitting Mobile Apps into R&D Workflow
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Chemistry Apps • Reference data
• Education
• Structure drawing
• Database searching
• 3D viewing
• Reactions & collections
• Property calculation
• Model building
• Graphical presentation
• Data sharing
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http://goo.gl/Goa4e
Need for dedicated website / store for science Apps
– find out more at www.scimobileapps.com
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Simple App Workflows
• 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
Clark AM, Williams AJ and Ekins S, Chem-Bio Informatics Journal, 13: 1-18 2013.
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A Bigger Vision
• Mobile chemistry originally intended to support
desktop workflows
• Mobile+Cloud can be a total replacement
• Entirely new user expectations for apps:
- easy to learn
- delightful to use
- trivial to install
- inexpensive or FREE
• Extremely disruptive to existing software vendors!
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APPIFYING DATA - From PDF to Mobile App
Lots of data
but how to
make it useful
for chemists?
Chemists see
structures
PDF not
accessible,
small text- too
much data
http://bit.ly/GzQ5ty
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Green Solvents and Lab Solvents FREE Apps
Alex Clark made the App in 3 days
Android version – Lab Solvents
Includes GSK solvent data
ACS Sustain Chem Eng 1: 8-13 (2013)
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TB Kills 1.6-1.7m/yr (~1 every 8 seconds)
1/3rd of worlds population infected!!!!
Multi drug resistance in 4.3% of cases
Extensively drug resistant increasing incidence
No new drugs in over 40 yrs until Bedaquiline
Drug-drug interactions and Co-morbidity with HIV
Increase in HTS phenotypic screening
1000’s of hits no idea of target Use of computational methods with TB is rare
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30 years with little TB mouse in vivo data MIND THE TB GAP
IN V
IVO
INA
CT
IVE
IN V
IVO
AC
TIV
E
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Pathway analysis
Binding site similarity to Mtb proteins
Docking
Bayesian Models - ligand similarity
Predicting the target/s for small molecules
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TB molecules and target information database connects
molecule, gene, pathway and literature for >700 molecules
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iPhone Android
TB Mobile layout on iPhone and Android
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TB Mobile Molecule Detail and Links
iPhone Android
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Molecules active against Mtb evaluated in TB Mobile app
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Workflow from sketching molecules in MMDS mobile app
to exporting and opening with TB Mobile
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http://goo.gl/UTTH0
TB Mobile – poster on Jan 2013
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http://goo.gl/vPOKS http://goo.gl/iDJFR
TB Mobile – Is on iTunes and Google play
and it is FREE
http://goo.gl/7fGFW
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What next ?
Update with more data
Add a weighting or scoring function to account
for heavily populated targets
Expand beyond the similarity measure
Add algorithms to predict activity
Could we appify data for other diseases/ targets
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Connecting
data/tools
like a TB Spider
In vitro data
In vivo data
Target data
ADME/Tox data
& models
Drug-like scaffold creation
TB prediction tools TB publications
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• 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
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Source Materials • 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……
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Open Drug Discovery Teams
• Curation of open data, e.g. Twitter & RSS feeds
• Rare & neglected diseases, precompetitive
areas
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Harvested Tweet
• Tweet got harvested into Tuberculosis topic
• Inline preview browsed, with other
thumbnails
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What we can do now… Take HTS screening hits Query public databases Propose targets Design / purchase analogs Predict activity All on a mobile device / anywhere
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Conclusion
• 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
• Other advantages:
- anywhere/anytime portability
- excellent collaboration and sharing
- non-existent installation or maintenance burden
27
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Malabika Sarker, Carolyn Talcott, Joel Freundlich, Barry Bunin
2R42AI088893-02 “from the National Institute of Allergy And
Infectious Diseases. (PI: S. Ekins)
You can find me @. CDD Booth 653..
Poster 224
PAPER TITLE: “Dual Response and dataset Fusion for
Machine Learning Models for Hit to lead Optimization in
Mycobacterium Tuberculosis Drug Discovery”
Monday, January 20, 2014
Presentation Time: 1:00 PM – 3:00 PM
Acknowledgments