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LeadMarker™ – an integrated suite for managing chemical and biological information
Tim DudgeonInformatics Matters Ltd
Oxford, UK
Bob BamfordManaged Ventures LLC
California, USA
Chris PalmerKcc Tech Pty Ltd
Queensland, Australia
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
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
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.
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
Technologies employed
LeadMarker™ architecture
Web apps
LeadMarker™ Web application
Java Web Start apps
runLoader structShare
Service tier
Domain tier
Database tier
chemService assayServicesampleService
chemistry schema
Marvin
JChemStandardizer
chemMarker module
assayMarker module
sampleMarker module
SDLoader externalQuery
overlapAnalyser
accountService
JBoss
Oracle 9i Oracle 10g
cpds batches libraries suppliers samples plates assays runs targets results
sample schema assay schema admin schema
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 party’s code
Flexibility Database vendor independence Molecule format neutral Configurable components e.g. standardizer
Performance Support & documentation
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
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
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 isn’t 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
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
Batches, compounds, solvents and salts
Batch
Original structure
Standardized structure
Compound
Original structure
Standardized structure
New Batch
Batchstandardizer
Compoundstandardizer
Fragmentation
Typical standardizer configs
<StandardizerConfiguration Version ="0.1"> <Actions> <Reaction ID="Water" Structure="O>>" Exact="true"/> <Reaction ID="DMSO" Structure="CS(C)=O>>" Exact="true"/> <Reaction ID="Methanol" Structure="CO>>" Exact="true"/> <Reaction ID="Acetonitrile" Structure="CC#N>>" Exact="true"/> </Actions></StandardizerConfiguration>
<StandardizerConfiguration Version ="0.1"> <Actions>
<Aromatize/><Reaction ID="PlusMinus" Structure="[*+:1][*-:2]>>[*:1]=[*:2]"/><Reaction ID="PlusMinusDouble" Structure="[*+:1]=[*-:2]>>[*:1]#[*:2]"/><Reaction ID="nitro" Structure="[O-:2][N+:1]=O>>[O:2]=[N:1]=O"/><Reaction ID="azide" Structure="N=[N:1]#[N:2]>>N=[N+:1]=[N-:2]"/><Reaction ID="enamine" Structure="[H:4][N:3][C:1]=[C:2]>>[H:4][C:2][C:1]=[N:3]"/><Reaction ID="enol" Structure="[H:4][O:3][C:1]=[C:2]>>[H:4][C:2][C:1]=[O:3]"/><Reaction ID="ammoniumhalide" Structure="[F,Cl,Br,I;-:3].[H:2][N+:1][#6]>>[F,Cl,Br,I:3][H:2].[N:1][#6]"/><Reaction ID="sulphate" Structure="[C,c:1][S:2](=[O:3])(=[O:4])[O;H1:5]>>[C,c:1][S:2](=[O:3])(=[O:4])[O-:5]"/><Reaction ID="carboxylate" Structure="[C,c:1][C:2](=[O:3])[O;H1:4]>>[C,c:1][C:2](=[O:3])[O-:4]"/><ImplH ID="implh" Charged="true" Radical="true" Mapped="true"/><Sgroups ID="ungroup" Act="Ungroup"/><Clean ID="cleanIfNeeded"/>
</Actions></StandardizerConfiguration>
Batch standardizer – remove common solvents
Compound standardizer – common representation
Salts example
B
B
ID Name Parent Type1 LM-000001 1 CPD
ID Name Parent TYPE2 LM-000003, HCl 2 CPD3 LM-000003 2 CPD4 HCl 2 SALT
chemMarker in action
Demonstration….
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
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)
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
structShare in action
Demonstration….
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
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
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 100Irvine, CA 92618 USA
Yew Tree Farm, High StreetCharlton on OtmoorKidlington, Oxon OX5 2UQ
2 Alpha AvenueCurrumbin 4223Queensland, Australia