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
About LeadMarker™
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A Modular suite of apps based on Java
Enterprise Edition (J2EE)
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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
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chemMarker
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sampleMarker
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Chemical registration
Chemical searching
Manages compounds, batches, libraries
Plate and/or vial sample management
Liquid handling and transformation operations
assayMarker
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Manages biological results
Simplified data acquistion from instruments
Data processing to generate biological results
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%INH
IC50
Tabular and graphical reporting
LeadMarker Features (2)
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structShare
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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
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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
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Increase software flexibility by
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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
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Not a CD in an envelope
Integration hotspots allowing extension and
customisation
Make the scientist's life easy by
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LeadMarker™ should correspond to real world objects
Should support scientific workflows
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Adaptable
Configurable
Technologies employed
LeadMarker™ architecture
Web apps
Marvin
Java Web Start apps
LeadMarker™ Web application
chemMarker
module
sampleMarker
module
structShare
runLoader
assayMarker
module
SDLoader
externalQuery
overlapAnalyser
JBoss
Service tier
chemService
sampleService
assayService
accountService
Domain tier
cpds
batches
libraries
suppliers
samples
plates
assays
runs
targets
results
JChem
Standardizer
Database tier
chemistry schema
sample schema
assay schema
admin schema
Oracle 9i
Oracle 10g
Key benefits of ChemAxon to
LeadMarker
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Single set of Java tools
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Designed to work in harmony
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Flexibility
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All tools have been developed by ChemAxon since
their inception
No mergers of other party’s code
Database vendor independence
Molecule format neutral
Configurable components e.g. standardizer
Performance
Support & documentation
Marvin Applets in web applications
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Use for display and editing structures
Structures
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Sketching of structures
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before and after standardization
for registration
for searching
onMouseOver previews
Use of JChem in LeadMarker
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JChem databases for compound and batch
structures
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Choose not to use cartridge
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Allow other dbms vendors
Maximise performance
Keep cost to a minimum
JChem Base provides sufficient functionality
Two stage standardization
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Provides highly flexible definition of chemical
business rules
Salts, stereochemistry and mixtures
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Typically this is the biggest headache for a chemical
registration system
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Problem with standard “salt stripping” approaches
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Problems with stereochemistry
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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
MDL chiral flag
Absolute and relative stereochemistry
Uncertainty
Symptoms
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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
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Register what you have, salts and all
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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
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No data needs to be relocated
Batches, compounds, solvents
and salts
New Batch
Batch
Original structure
Batch
standardizer
Standardized structure
Compound
Original structure
Standardized structure
Fragmentation
Compound
standardizer
Typical standardizer configs
Batch standardizer – remove common solvents
<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>
Compound standardizer – common representation
<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>
Salts example
ID
1
ID
2
3
4
Name
LM-000001
Name
LM-000003, HCl
LM-000003
HCl
Parent
1
Type
CPD
Parent
2
2
2
TYPE
CPD
CPD
SALT
B
B
chemMarker in action
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Demonstration….
structShare – chemical spreadsheet
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Alternative to form builders and office
spreadsheets
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Neither of these are good solutions
Office software limits performance and scaleability
Installation and support involves
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structShare designed to address this
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Office suite licensing
Platform specific libraries (windows DLLs)
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
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High volume data input or output
Ability to persist files locally and collaborate informally
structShare features
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Embedded SQL database
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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
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sdLoader for registering libraries into
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OverlapAnayzer for identifying structural
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LeadMarker™
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
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Marvin for molecule rendering
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MViewPane used as TableCellRenderer
MarvinSketch as molecule editor
MolImporter/MolExporter for
reading/writing SDF
JChem in ovelap analysis - classify
according to
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exact match
match to unsalted form
no match
Future
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use of JChem to allow structure filtering
integration of Chemical Terms
integration of Reactor for library enumeration
structShare in action
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Demonstration….
LeadMarker™ Team
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LeadMarker™ has been developed by a
global team that provides regional
customisation and expertise
Organisation
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LeadMarker™ Licensor
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North America & Japan – Managed Ventures LLC
Regional Agents
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Europe – Informatics Matters Ltd
Australasia – KCC Tech Pty Ltd
Consortium History
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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
Contributors - Contacts
●
Informatics Matters
Yew Tree Farm, High Street
Charlton on Otmoor
Kidlington, Oxon OX5 2UQ
●
Managed Ventures
6 Venture, Suite 100
Irvine, CA 92618 USA
–
Tim Dudgeon
–
Jack Crawford
–
Jon North
–
Bob Bamford
–
Petr Hamernik
–
Nadeem Bitar
–
Svata Dedic
–
Bob Thomas
–
Milos Kleint
–
Chris Novak
–
Matt Houser
–
Emma Davila
–
Brad Ziola
–
Arthur Clements
●
KCC Tech Pty
2 Alpha Avenue
Currumbin 4223
Queensland, Australia
–
Chris Palmer