Upload
bob-coner
View
89
Download
12
Embed Size (px)
Citation preview
4 Years In – How A Biotechnology Company Has Grown In Its Use Of
Dotmatics
Robert ConerMay 2016
May 20162NOT CONFIDENTIAL
Agenda
• Where we started• How we use Dotmatics now
– Design– Synthesis & Purification– Sample Logistics– Screening/Testing
• Extending Dotmatics Example
May 2016NOT CONFIDENTIAL
A Drug Discovery and Development CompanyOncology focused
3
• World class scientific founder and experienced drug discovery team• Novel oncology project pipeline based on innovative science• Strong funding and venture capital support
• Commenced operation in August 2011• Based at the BioCenter in UTSW Dallas• More information at
http://pelotontherapeutics.com
May 2016NOT CONFIDENTIAL
Experienced Scientific and Business Team
4
Multidisciplinary Drug Discovery Team• 33 employees, 17 Ph.D. level scientists, >100 years drug discovery experience• Scientific team members have delivered over 20 new chemical entities into
human clinical trials
Scientific Advisory BoardMichael S. Brown, M.D. Ralph J. DeBerardinis, M.D., Ph.D.William G. Kaelin, Jr., M.D. Thomas J. Kelly, M.D., Ph.D.David H. Johnson, M.D., F.A.C.P. Steven L. McKnight, Ph.D.
Board of DirectorsJohn CreecyDavid V. Goeddel, Ph.D.Leo Guthart, Ph.D.Tim Kutzkey, Ph.D.Frank McCormick, Ph.D.Brett Ringle, J.D.
Scientific CollaboratorsSally Comerford, Ph.D.Rick Bruick, Ph.D.Kevin Gardner, Ph.D.Robert Hammer, Ph.D.Ben Tu, Ph.D.
ManagementJohn Josey, Ph.D.James Rizzi, Ph.D.Eli Wallace, Ph.D.Michael Bakes, PMPNaseem Zojwalla, M.D.Tai Wong, Ph.D.
May 20165NOT CONFIDENTIAL
Where we started
Registry & Materials Inventory in Excel
Data Analysis inGraphpad
Data Shared inPowerPoint and stored on File Share
Paper notebooks for IP capture
May 20166NOT CONFIDENTIAL
Transitioning to Dotmatics
• Convert existing Excel file to SD file and Load with Register
• Start using ChemELN and Register compounds from there
• Setup assay data analysis protocols and start using Studies. Use BioELN to capture experiments.
• Use Browser to query and analyze data
May 20167NOT CONFIDENTIAL
Growth over time
• Use Nucleus to load HTS data and Vortex to analyze
• Added new projects• Added new assay data analysis protocols• “Side loaded” DMPK data• Barcode all reagent and sample containers
and use Inventory to manage location• Add custom extensions
May 20168NOT CONFIDENTIAL
Design Synthesis/Purification
Materials/Sample logisticsScreening/Testing
• Procure materials
• Synthesize
• Purify/characterize
• Prepare Sample
• Dissolve
• Dilute
• Distribute to screen
• Reduce raw data• Execute screen
• Develop the assay
• Select compounds to make
• Mine, search and invent analogs
• Analyze patternsProject Workflow & Tracking and
Decision making
• Assess design ideas
• Load data to dbs
• Procure reagents
Discovery Cycle
May 20169NOT CONFIDENTIAL
Initial load of HTS data
May 201610NOT CONFIDENTIAL
Initial load of HTS data
May 201611NOT CONFIDENTIAL
Initial load of HTS data
May 201612NOT CONFIDENTIAL
Initial load of HTS data
May 201613NOT CONFIDENTIAL
Initial load of HTS data
May 201614NOT CONFIDENTIAL
Analyze HTS data in Vortex
Next step: Resynthesize & test the hits…
May 201615NOT CONFIDENTIAL
Synthesis - ChemELN
May 201616NOT CONFIDENTIAL
Synthesis - ChemELN
May 201617NOT CONFIDENTIAL
Compound Registration – from ChemELN
May 201618NOT CONFIDENTIAL
Sample Logistics
May 201619NOT CONFIDENTIAL
Materials Management
May 201620NOT CONFIDENTIAL
Assay Data Processing and Publishing
May 201621NOT CONFIDENTIAL
Assay Data Processing and Publishing
May 201622NOT CONFIDENTIAL
Assay Data Processing and Publishing
May 201623NOT CONFIDENTIAL
Assay Data Processing and Publishing
May 201624NOT CONFIDENTIAL
Design – Analyze Data
Multiple tabs – all data in one place
May 201625NOT CONFIDENTIAL
Design – Analyze PK data (from Winnonlin)
May 201626NOT CONFIDENTIAL
Design – Analyze Stability Data
May 201627NOT CONFIDENTIAL
Behind the Scenes
May 201628NOT CONFIDENTIAL
Dotmatics Pivoter
Instead of trying to use Oracle’s PIVOT statement, you point and click
May 201629NOT CONFIDENTIAL
Example Pivot
May 201630NOT CONFIDENTIAL
Dotmatics Pivoter converts PK data from this
May 201631NOT CONFIDENTIAL
To this
Data here is output of Dotmatics Pivoter
May 201632NOT CONFIDENTIAL
Extending Dotmatics Example
• Several of our chemists came from other companies that had a method for automatically adding analytical data to their notebooks
• Requirements: - Take no longer than 24 hours to add spectra to Dotmatics after creation- Exclude certain spectra from being added- Indicate which spectra goes with which notebook and page- Work for both LC and NMR instruments- Never add spectra to a closed notebook page- Never add a spectra that has been removed manually from a page
May 201633NOT CONFIDENTIAL
Analytical instrumentation setup
Agilent LCMS
Agilent LC
Agilent NMR
Replication scripts
run twice daily
Windows File Share
Backup at Offsite Data
Center
Dotmatics Server
DotmaticsELN
Analytical attachment script runs once per day
May 201634NOT CONFIDENTIAL
Extending Dotmatics Example
• Several of our chemists came from other companies that had a method for automatically adding analytical data to their notebooks
• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after
creation- Exclude certain spectra from being added- Indicate which spectra goes with which notebook and page- Work for both LC and NMR instruments- Never add spectra to a closed notebook page- Never add a spectra that has been removed manually from a page
May 201635NOT CONFIDENTIAL
Agilent NMR
May 201636NOT CONFIDENTIAL
Agilent LC
May 201637NOT CONFIDENTIAL
Extending Dotmatics Sample
• Several of our chemists came from other companies that had a method for automatically adding analytical data to their notebooks
• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after creation ✓ Exclude certain spectra from being added
✓ Indicate which spectra goes with which notebook and page ✓ Work for both LC and NMR instruments
- Never add spectra to a closed notebook page - Never add a spectra that has been removed manually from a page
May 201638NOT CONFIDENTIAL
Processing Algorithm
• Python script runs periodically (using cron) on our Dotmatics server
• It walks the directory tree of the shared folder that contains all of our analytical data
• For each analytical pdf:– A SHA512 hash is calculated for the pdf and checked vs. the database, if found,
pdf is skipped. If not found, hash added to database.– Filename of pdf is analyzed to look for a notebook-page pattern. If not found,
skipped.– Using notebook and page, experiment is located in TM_EXPERIMENTS table
and EXPERIMENT ID extracted. If experiment is closed or not found, skip.– PDF is added to ELN_QCDATA table with EXPERIMENT ID– Studies ChemELN will read the PDF from the ELN_QCDATA table when the
experiment is opened
May 201639NOT CONFIDENTIAL
Table to record hashes of analytical pdfs
May 201640NOT CONFIDENTIAL
ELN_QCDATA table
May 201641NOT CONFIDENTIAL
CHEMELN page example
May 201642NOT CONFIDENTIAL
Overview
• Several of our chemists came from other companies that had a method for automatically adding analytical data to their notebooks
• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after creation ✓ Exclude certain spectra from being added
✓ Indicate which spectra goes with which notebook and page ✓ Work for both LC and NMR instruments ✓ Never add spectra to a closed notebook page ✓ Never add a spectra that has been removed manually from a page
May 201643NOT CONFIDENTIAL
Summary of Dotmatics
• Grows with us• Supports the Discovery Cycle• Can be extended
May 2016NOT CONFIDENTIAL
Acknowledgments
Peloton Therapeutics, Inc. DotmaticsZhaodan CaoTzuling ChengRobert CzerwinskiXinlin DuBarry GogginJonas GrinaGuangzhou HanHeli HuangJohn Josey
James RizziStephen SchlachterHuiling TanBin WangKeshi WangPaul WehnShanhai XieRui XuHanbiao Yang
Alister CampbellPhil MounteneyDan Ormsby
Jason CastanadaTheresa Smith
May 201645NOT CONFIDENTIAL
Q & A
• Contact Information:– Robert Coner– Peloton Therapeutics– Manager, R&D Informatics– 2330 Inwood Drive, Suite 226, Dallas, TX 75235– [email protected]– Phone: +1-469-271-7811– https://www.linkedin.com/in/bobconer– Skypeid: conerbob