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BUILDING A SYMBIOTIC INFORMATICS PLATFORM TO SUPPORT DRUG DISCOVERY
GETTING HETEROGENEOUS TOOLS TO “PLAY NICELY” IN THE INFORMATICS SANDBOX
ChemAxon UGM 2015San Diego CA
ALL I REALLY NEED TO KNOW I LEARNED IN KINDERGARTEN
• Share everything, play fair, don’t hit people
• Put things back where you found them
• Clean up your own mess
• Don’t take things that aren’t yours
• Say you’re sorry when you hurt somebody
• Wash your hands before you eat, flush
• Warm cookies and cold milk are good for you
• Live a balanced life – learn, drink, draw, paint , sing, dance, play, and work some everyday
• Take a nap every afternoon
• When you go out into the world, watch out for traffic, hold hands and stick together
By Robert Fulghum
ChemAxon UGM 20152
Symbiotic Relationships
INFORMATICS “SANDBOX”
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Capture
Analysis
Visualization
Pharmacology
Biology
Chemistry
Fit
Interact
BACKGROUND & FOUNDATION
Chemistry• Chemdraw
• JChem/IJC/JC4XL
Data Analysis
• Prism/R
• XLFit
Data
Visualization
• Excel
• Vortex
IntegrationServices
• Startup environment• Poor understanding & choices• Lack of expertise• Diversity of stake holders• Overlapping group demands
FOCUS!
• Strategy & Architecture• Important tasks• Realistic expectations• Senior mgmt. buy in & support• “Take care of business”
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RESEARCH INFORMATICS WORKFLOW
Concept
Compound
AssayData
Progression
Knowledge Sources
Data Warehouse
Per Project
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JSON COMMUNICATION LANGUAGE
• Oracle Database
– JSON CLOB field
– PL/JSON (JSON Object, jtl, jql packages)
• Java & JSON.org
• Visual Basic & JSON Modules
• Web Services JSON
• JSON Configuration
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Examples
STRUCTURE DRAWING & NAME SERVICE
Input chemical identifier and return molecular structure
• GBT Compound ID• GBT Concept ID• GBT Reagent ID• CAS• Common Name• IUPAC• Smiles
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Web service to display input structure
COMPOUND REGISTRATION/SEARCHING
• Chemical image web services
• Chemical descriptor property calculations JChem
• Structure searching via cartridge
• Excel plotting of descriptor properties
• Excel export of query results
• API library include (Chemdraw)
• Import ELN reaction products
ChemAxon UGM 20158
Chemdrawdrawing
panel
Excel radar plot of
properties
GBT/ChemAxonimage service
ChemAxondescriptor
calculations
ChemAxoncartridge searching
ELN product import
Excel export to
worksheet
HEMOX DATA WORKFLOW (LIFE CYCLE)
• Input parameters
• Run patient sample
• Upload data file
Lab
• Secured temporary file storage
Cloud • Scan data folder
• Parse & analyze HEMOX files
• Import HEMOX files
• Send warning notification
Server
• View & query analysis
• Update analysis parameters
• Import meta-data
Desktop
CRO GBT
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HEMOX CLINICAL ANALYSIS TOOLS
• Linux CRON job
• Java executable (Rcaller)– Scan for files in Dropbox
– Call R and execute script
– Import calc. values & files
– Send email alerts
• Excel review & data verification
• Excel meta-data import
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Review & Verification
Report ImportVisualization
ASSAY DATA ANALYSIS WORKFLOW
• Plate Maps
• Sample Mgmt.
Sample Association
• Engine (Xlfit)
• Charts
• Excel
Data Analysis• QC
• Publication
• Report
Data Capture
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Assay Data Management
Instrument Files
Assay Results
Assay Results
Database
Automated data analysis:• Streamline result generation• Minimize human error• Consistent data reporting• Structured format for data
capture
Optional
ASSAY MANAGEMENT & PLATE IC50 PROCESSOR
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Assay tracking & searching
Attributes
Samples
Sample results
Sample repeats
Notes & status
COMPOUND PROGRESS WORKFLOW
Registration
• Compound registration by chemist
• Status (New, Active, Hold, Standard, Lead, NFI)
• Action (empirical result)
Testing
• Action executed by biologist & pharmacologist
• Data analysis, visualization & association
• Data capture (result) into central database
Decisions
• Team focus & action oriented
• Team empowerment, decision tracking & transparency
• Individual accountability to project team
Continual vetting by
project team
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Requirement: Integrated Informatics Platform
Wheat & Chaff
Important focus
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COMPOUND PROGRESSION
• PDF progress packet generation (status)
• Team meeting (status & actions update)
• Action email & follow-up
• Administrator tools– Action configuration
– Action tracking (queue, CRO)
– Project specific data (JSON config.)
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SUMMARY
• Utilizing MS Office 365 as a foundation, we have built Add-ins to enable drug discovery operations and data workflows.
– Integrating standard industry software tools e.g. ChemDraw, XLFit, ChemAxon Cartridge
– Replacing costly dated LIMS e.g. CISPro, Accord
– Establishing a framework for third party tools to participate in the Informatics ecosystem
• Reduced our licensing costs and maximized our ROI of core software tools
• Streamlined drug discovery processes e.g. compound progression, result publication
• Fulfill our vision
Science dedicated to patientsEmbrace open communication & debateTrust, respect, and accountabilityOne team, one purpose
…always do the right thing
ChemAxon UGM 201515
Analyst Excel WinNonLin PowerPointExcel In Vivo PK Report
ACKNOWLEDGEMENTS
• Hing Sham
• Zhe Li
• Lina Setti
• Chul Yu
• Calvin Yee
• Qing Xu
• Steve Gwaltney
• Matt Lardy
• Steve Richards
ChemAxon UGM 201516
• Mira Patel
• Vincent Siu
• Michelle Lindstrom
• Jenny McKinnell
• ChemAxon