Building a Symbiotic Informatics Platform · Chemistry •Chemdraw •JChem ... • Import ELN reaction products 8 ChemAxon UGM 2015 Chemdraw drawing panel Excel radar plot of properties

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

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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

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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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email

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

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• Mira Patel

• Vincent Siu

• Michelle Lindstrom

• Jenny McKinnell

• ChemAxon