Sharing Chemical Data with Collaborators using Chemaxon Tools Julian Fowler Chemaxon UGM - September 26 th , 2012
Example Collaboration Constellation Pharmaceuticals and Genentech Enter Broad Epigenetics Drug Discovery Collaboration CAMBRIDGE, Mass. – January 17, 2012 – Constellation Pharmaceuticals, Inc., today announced that it has entered into a major strategic agreement with Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), to launch a broad collaboration based on the science of epigenetics and chromatin biology to discover and develop innovative treatments for cancer and other serious diseases. 2
Collaboration: Registration’s Role Challenge: Working as part of a collaboration • How can we enable Constellation to meet the requirements for registering new compounds? • How can we effectively share data? • Acknowledge a problem with existing registration system • How quickly can we implement a solution? Reliably Standard Determine Representation Uniqueness Chemical Registration Workflow Clean Robust Structures Searching Structure Submission Standardizer Staging Triage Registration Checker Chemical Database Structure Validation Rules 3
Expectations Compound Data Analysis Results • Registered correctly • Timely transfer of data • Clean structures • High confidence level CRO’s Physical Samples • Constant flow of • Reorder/Remake samples compound • Shipping samples • Inactive batch? 4
Compound Management Maturing Stage Start-Up Stage • MedChem scale up • Manageable number of • CRO scale up MedChem compounds • Small/midsize library addition • Small established screening • Registration impacts drug library discovery process • Registration a non-issue Unique Compounds Added vs. Year MedChem Compounds By Month 450 000 Number of Unique Compounds 400 000 Numbe of Compounds 350 000 300 000 250 000 Compounds 200 000 Registered 150 000 Total Library 100 000 Size 50 000 0 2009/09 2009/11 2010/01 2010/03 2010/05 2010/07 2010/09 2010/11 2011/01 2011/03 2011/05 2011/07 2011/09 2011/11 2012/01 2012/03 2012/05 2012/07 2012/09 2008 2009 2010 2011 2012 Year 5
Get registration right first time Compound submission, triage and registration completed in one day Lead MedChem Aggressive schedule leaves little room for error Discovery Get registration wrong then assay analysis and reporting could be affected 6
Problem: Challenging Stereochemistry Constellation New CPI-585.01 Batch CPI-585.02 X09345.01 X09345.02 CPI-585.03 X10945.01 Collaborator New ID CPI-585.04 X18345.01 7
Problem: Synchronize Registration Registration CPI-1198745 Constellation Collaborator Database Database X15667294 Results 8
How are we solving these problems? Chemical Database • New registration system • Robust and reliable • Clean structures • Fast efficient searching Stereochemistry • Handle stereochemistry consistently • Registrar plays a significant role • Registrar knows the chemical space • Provide tools to determine uniqueness Synchronize Registration • Implement the same registration rules as our collaborator • Rules are complex How can we incorporate these rules and create a system in less than 6 months? 9
Chemaxon Tools • Clean structures • Detect and fix issues Structure Checker • Customized checks • Integrated in batch • Canonical structure representation • Consistent standardization • Fully customized Standardizer • Integrated in batch • Chemical intelligence • Robust search capability JChem Cartridge • Oracle based 10
How does Structure Checker help us? Wedge Bonds <WedgeErrorChecker fixMode= “fix” fixerClassName="chemaxon.fixers.WedgeCleanFixer"/> Remove explicit Hydrogen atoms <ExplicitHydrogenChecker charged="true" fixMode="fix" fixerClassName="chemaxon.fixers.ExplicitHydrogenFixer" isotopic="false" lonely="true" mapped="true" radical="true" wedged="true"/> Images from Chemaxon User Documentation 11
How does Standardizer help us? Mesomers Transformation Transformation Images from Chemaxon User Documentation 12
How does Standardizer help us? Tautomers Transformation Transformation Images from Chemaxon User Documentation 13
Implementing Registration Rules Standardizer svc = new Standardizer(new File (“ constellation_rules.xml")); svc.standardize(mol); 14
Chemical Registration System Challenge: Build a robust and reliable chemical database • Transform chemical structures into a customized, canonical representation • Ensure CRO provides compound data in a consistent format • Share compound data with our collaboration colleagues in a consistent format Strategy: Select the right technologies • JChem Cartridge • Structure Checker • Standardizer Features : System attributes • Simple and easy to use • Registrar role in determining uniqueness • Register single/bulk compounds • Robust search capabilities • Easier to correct structures after registration 15
Successfully sharing chemical data with collaborators • For a small biotech company sharing chemical data within a collaboration setting can be especially challenging • Making Structure Checker and Standardizer part of our chemical registration workflow has been a smart move • These tools have allowed us to rapidly develop a new registration system and also address the more important issue of reliably sharing data with our collaborators 16
Team Structure Resource Primary Role Bill Amsbaugh Systems architecture design, component design, program management Director Ashan Tissera Architecture implementation, web applications, database design, lead offshore Senior Software Engineer team Julian Fowler Automation applications, web applications, Bioinformatics algorithm development, Lead Engineer lead offshore team Joe Marchionna Robotic integration, mechanical engineering, software design, application Principle Engineer development R-Systems (Delhi) Infrastructure development Jubilant (Bangalore) Scientific application development DBA Zone (Pittsburgh) Database Administration 17
Acknowledgements Automation R&D/ Jubilant Bill Amsbaugh Management Asath Fernando Julian Fowler JC Harmange Senthil Kumar Mike Cooper Ashan Tissera Jim Audia Joe Marchionna Medicinal Chemistry Chemaxon Brian Albrecht Doug Drake Mike Hewitt Jon Patterson Alex Taylor David Deng Victor Gehling Alex Cote Rishi Vaswani Yves Leblanc Alex Gagnon
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