1. LeadMarker – an integrated suite for managing chemical and biological information Tim Dudgeon Informatics Matters Ltd Oxford, UK Bob Bamford Managed Ventures LLC California, USA Chris Palmer Kcc Tech Pty Ltd Queensland, Australia

2. About LeadMarker A Modular suite of apps based on Java Enterprise Edition (J2EE) Management of core chemical and biological data for Life Science companies Allow deployment of different configurations to different customers Built around the objects you deal with and the workflows you operate with Designed around high performance and scaleability

3. LeadMarker Features chemMarker Chemical registration Chemical searching Manages compounds, batches, libraries sampleMarker Plate and/or vial sample management Liquid handling and transformation operations assayMarker Manages biological results Simplified data acquistion from instruments Data processing to generate biological results %INH IC50 Tabular and graphical reporting

4. LeadMarker Features (2) structShare a chemical spreadsheet, including its SDLoader plug-in that facilitates a simple mechanism for library registration into chemMarker. structShare has the ability to handle over 100,000 structures simultaneously runLoader A tool to read raw instrument data files, associate biological data with samples, and store the data in assayMarker. runLoader requires valid containers, registered via sampleMarker, to associate the data.

5. Goals for LeadMaker Increase software flexibility by A single code base from which we can push out multiple branded versions, each with its own configuration A working system that we can support Not a CD in an envelope Integration hotspots allowing extension and customisation Make the scientist's life easy by LeadMarker should correspond to real world objects Should support scientific workflows Adaptable Configurable

6. Technologies employed

7. LeadMarker architecture Web apps LeadMarker Web application Java Web Start apps runLoader structShare Service tier Domain tier Database tier chemService assayService sampleService chemistry schema Marvin JChem Standardizer chemMarker module assayMarker module sampleMarker module SDLoader externalQuery overlapAnalyser accountService JBoss Oracle 9i Oracle 10g cpdsbatcheslibrariessupplierssamplesplatesassaysrunstargetsresults sample schemaassay schemaadmin schema

8. Key benefits of ChemAxon to LeadMarker Single set of Java tools Designed to work in harmony All tools have been developed by ChemAxon since their inception No mergers of other partys code Flexibility Database vendor independence Molecule format neutral Configurable components e.g. standardizer Performance Support & documentation

9. Marvin Applets in web applications Use for display and editing structures Structures before and after standardization Sketching of structures for registration for searching onMouseOver previews

10. Use of JChem in LeadMarker JChem databases for compound and batch structures Choose not to use cartridge Allow other dbms vendors Maximise performance Keep cost to a minimum JChem Base provides sufficient functionality Two stage standardization Provides highly flexible definition of chemical business rules

11. Salts, stereochemistry and mixtures Typically this is the biggest headache for a chemical registration system Problem with standard salt stripping approaches Loss of information and/or data in multiple places Typically need to define salts up front Difficult to change your view of what is a salt and what isnt Problems with stereochemistry MDL chiral flag Absolute and relative stereochemistry Uncertainty Symptoms Changes in rules or data means (biological) data has to be moved around Database administrators and technical staff are kept busy fixing errors

12. LeadMarker approach to salts and mixtures Register what you have, salts and all Salts do not get stripped Compounds that are composite are broken into their parts and their components also registered Parent child relationships within composite compounds are maintained A user can flag any component as a salt and name it No data needs to be relocated

13. Batches, compounds, solvents and salts Batch Original structure Standardized structure Compound Original structure Standardized structure New Batch Batch standardizer Compound standardizer Fragmentation

14. Typical standardizer configs >" Exact="true"/> >[*:1]=[*:2]"/> >[*:1]#[*:2]"/> >[O:2]=[N:1]=O"/> >N=[N+:1]=[N-:2]"/> >[H:4][C:2][C:1]=[N:3]"/> >[H:4][C:2][C:1]=[O:3]"/> >[F,Cl,Br,I:3][H:2].[N:1][#6]"/> >[C,c:1][S:2](=[O:3])(=[O:4])[O-:5]"/> >[C,c:1][C:2](=[O:3])[O-:4]"/> Batch standardizer – remove common solvents Compound standardizer – common representation

15. Salts example B B IDNameParentType 1LM-0000011CPD IDNameParentTYPE 2LM-000003, HCl2CPD 3LM-0000032CPD 4HCl2SALT

16. chemMarker in action Demonstration….

17. structShare – chemical spreadsheet Alternative to form builders and office spreadsheets Neither of these are good solutions Office software limits performance and scaleability Installation and support involves Office suite licensing Platform specific libraries (windows DLLs) structShare designed to address this Large datasets: > 100,000 structures managed easily Rapid sorting and filtering Workbench for analysing and processing data Easy deployment through Java Web Start Provides workbench for LeadMarker functionality High volume data input or output Ability to persist files locally and collaborate informally

18. structShare features Embedded SQL database Fast sorting and filtering of large datasets Manage relational data Future use of JChem searching Memory only or disk based modes SDfile and text file import and export Plug-in architecture and API allows extension sdLoader for registering libraries into LeadMarker OverlapAnayzer for identifying structural overlap between your sample structures and what is already registered in LeadMarker ExternalQuery plug-in for querying LeadMarker and other SQL databases (under development)

19. Use of ChemAxon tools within structShare Marvin for molecule rendering MViewPane used as TableCellRenderer MarvinSketch as molecule editor MolImporter/MolExporter for reading/writing SDF JChem in ovelap analysis - classify according to exact match match to unsalted form no match Future use of JChem to allow structure filtering integration of Chemical Terms integration of Reactor for library enumeration

20. structShare in action Demonstration….

21. LeadMarker Team LeadMarker has been developed by a global team that provides regional customisation and expertise Organisation LeadMarker Licensor North America & Japan – Managed Ventures LLC Regional Agents Europe – Informatics Matters Ltd Australasia – KCC Tech Pty Ltd

22. Consortium History Managed Ventures Incorporated in 1999 Initially focused on custom informatics consulting Syrrx, Kalypsys, Triad, Anadys, Salk Institute, Merck, Medsn Genomics Institute of Novartis Eli Lilly and Company European expansion with Informatics Matters collaboration Recent expansion into Australasia with Kcc Tech agency Several custom chemical registration and screening software implementations led to the development of the LeadMarker integrated suite To be formally released at World Pharmaceutical Congress in Philadelphia Several custom chemical registration and screening software implementations led to the development of the LeadMarker integrated suite To be formally released at World Pharmaceutical Congress in Philadelphia

23. Contributors - Contacts Managed Ventures – Jack Crawford – Bob Bamford – Nadeem Bitar – Bob Thomas – Chris Novak – Matt Houser – Emma Davila – Brad Ziola – Arthur Clements KCC Tech Pty – Chris Palmer Informatics Matters – Tim Dudgeon – Jon North – Petr Hamernik – Svata Dedic – Milos Kleint 6 Venture, Suite 100 Irvine, CA 92618 USA Yew Tree Farm, High Street Charlton on Otmoor Kidlington, Oxon OX5 2UQ 2 Alpha Avenue Currumbin 4223 Queensland, Australia