USUGM 2014 - Erin Bolstad (ChemAxon): Consultancy report - New capabilities and reviewing some major...
Transcript of USUGM 2014 - Erin Bolstad (ChemAxon): Consultancy report - New capabilities and reviewing some major...
Consultancy ServicesInformatics Pick-n-Mix
Erin Bolstad
Global Consulting TeamSkills, Resources, Experience:
● Project Management● Solutions/packaging● Customizations/Integration of
existing/3rd party software● Rich scientific background● Software design and development
(Java, Groovy, JS, .NET, mobile, etc.)● Toolkit development (ETL, DSL, API,
ORM, etc)
ConsultantsAppScis
Dedicated consulting developers
ConsultantsAppScis
Developers (100+)
Dedicated consulting developers
Hungary
USA
CzechRepublic
Argentina
Project Examples● Migrations: database migration, PM of customized development, form and data-access design,
customized training.
Project Examples● Migrations: database migration, PM of customized development, form and data-access design,
customized training.
● Customized developer and end-user training
Project Examples● Migrations: database migration, PM of customized development, form and data-access design,
customized training.
● Customized solutions: thin clients, integration of existing and in-house tech
● Customized developer and end-user training
DuPont Doc2DB Database● System to trawl DuPont ELN + stored documents (PDF, Doc, etc)
● WebApp for complex queries
● Based on Doc2DB technology
Novartis Reactions Database● Reactions data warehouse
o Import from various legacy databases (ISIS)
o Live feed from CambridgeSoft ELN
● Database migration: ISIS -> ChemAxon
● CambridgeSoft ELN chemistry -> ChemAxon
● AJAX-style web application providing query and filtering capabilities
● Web services interface for fitting into SOA
Project Examples● Migrations: database migration, PM of customized development, form and data-access design,
customized training.
● Customized solutions: thin clients, integration of existing and in-house tech
● Spotfire integration (GSK)
● Customized developer and end-user training
Project Examples
● Customized project incubator
● Migrations: database migration, PM of customized development, form and data-access design, customized training.
● Customized solutions: thin clients, integration of existing and in-house tech
● Spotfire integration (GSK)
● Customized developer and end-user training
Customized Product Incubator
Compound Registration
● Customizable business rules ○ Tautomers, solvents, isotopes,
formulations, alternate identifications
● Salt and solvent multiplicity● Templated bulk registrations● API for updating downstream
processes, integrating to other products (like ELN)
● Sits on database with thin client interface - IT required
● Enterprise level: 1000’s of users
MiniReg
Customized Product Incubator● Simple compound registration system sitting
within IJC. No IT overhead or support needed.● Chemistry handling
○ Single salts○ Batches○ Samples Properties
● Biology assay handling○ Aggregation at db level
● Highly customizable at database level● Small - medium companies
(currently in ~10 companies)
Project Examples
● Customized project incubator
● Migrations: database migration, PM of customized development, form and data-access design, customized training.
● Customized solutions: thin clients, integration of existing and in-house tech
● Spotfire integration (GSK)
● Customized developer and end-user training
● Large scale global project management
Large Scale PM for Global Pharma● GSK: IJC rollout as a global reporting tool, assisted/trained,
customization of IJC, additional admin software creation. (3+ yrs)
● BMS: IJC customization/development for global roll-out needs,
training, migration of data, consulting on data-mart integration. Thin
client development. (2+ yrs)
Project Examples
● Customized project incubator
● Migrations: database migration, PM of customized development, form and data-access design, customized training.
● Customized solutions: thin clients, integration of existing and in-house tech
● Spotfire integration (GSK)
● Customized components of large initiatives (OIDD, IMI)
● Customized developer and end-user training
● Large scale global project management
European Lead Factory is part of IMI
● Innovative Medicines Initiative● http://www.imi.europa.eu/IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe.
Part of Framework 7
Approx 25 projects covering many aspects of healthcare, also including:
● eTox● Open PHACTS
European Lead Factory
EFPIA membersAZBayerLundbeckJanssenMerck KGaASanofiUCB
SME membersBioAscentChemAxonEdelrisGABO:miLead Discovery CenterMerachemPivot Park Screening CentreSygnature DiscoverySyncomTaros ChemicalsTI Pharma
Academic membersUniversity of DundeeLeiden UniversityMax Planck Institute of Molecular PhysiologyNetherlands Cancer InstituteRadbound University, NijmegenUniversity of GroningenTechnical University of DenmarkUniversity of Duisburg-EssenUniversity of LeedsUniversity of NottinghamVU University Amsterdam
An alliance of participants collaborating on identifying novel leads
ELF philosophy
NovelLeads
NovelCompounds
300,000 from EFPIA members internal collections
200,000 from newly synthesized libraries
NovelScreens
13 Work packages
1. Programme Recruitment HTS2. Compound Logistics3. Assay Development4. High Throughput Screening5. Hit Characterisation6. Medicinal Chemistry7. Publication Policy / External Relations8. Information Technology9. Sourcing chemical library proposals
10. Review/selection of chemical library proposals11. Experimental Validation12. Library Production13. Project Management
Library generation workflow
Crowdsourcing Consortium participant
Library selection committee
Assessed on:1. Molecular properties2. Structural features3. Novelty4. Diversity potential5. Synthetic tractability6. Innovative design
Experimental validation Design optimisation
Library production
Architecture
2 x Intel(R) Xeon(R) CPU E5-2620 v2 @ 2.10GHz (2 x 6 core + HT)64GB RAM
Tomcat 7 MySQLFilesystem
Web App
WebBrowser Workflow engine
Job queuing systemDocument storeReport generationAutomated email notificationRole managementDynamically generated UI
Workflows and Roles
Three workflows for different types of user:1. Consortium member2. Non-EU/EAA citizen3. EU/EAA citizen
Supported by workflow engine
Different levels of access1. Submitter2. LSC member3. LSC Chair4. ….
UI dynamically generated to ensure that you only see what you’re supposed to see and only do what you’re supposed to do
Step 1: registration
Users register themselves and provide personal and affiliation details
Step 2: enter library
Define your library in one of three ways:
1. Upload SDF
2. Upload MRV with Markush library
3. Pick R-groups from within pre-defined lists and Markush Enumeration is used to generate the library
Sketch scaffold with Marvin JS
Give it a title
Provide accompanying info including rationale and synthesis validation info
Step 3: initial property calculations
SSS for scaffold against reference set of 12M structures using JChem SearchExact match search for enumerated structures against reference set of 12M structures
Property distributions of enumerated structures. Properties generated with Chemical Terms expressions with Calculator Plugins
Checking enumerated structures against UK MDA legislation database from Compliance Checker
Matching enumerated structures against sets of SMARTS filters provided by EFPIA members using Chemical Terms match() and matchCount() functions
Step 4: submit library
Further round of property calculations performed and library now visible to Library Selection Committee for consideration
At this stage user has handed over ownership of the library idea to the European Lead Factory
Step 5: final property calculationsECFP4 fingerprint comparison with 12M structures from reference set
Fuzzy Pharmacophore fingerprint comparison with 12M structures from reference set
Generate histogram of most similar structure in reference set for each compound in the library.
~1000 x 12M x 2 comparisons.
“Old” molecular descriptor tables:
● For each search read descriptors from database -> very IO bound.
● Single threaded.
● -> days for completion
“New” fast similarity search:
● Descriptors generated as binary file.
● Read into memory once
● Search fully multi-threaded.
● -> minutes for completion
● (1M x 1M completes in ~25 min)
Step 6: assessment
Approve Reject
Refine
Library Selection Committee
Status summary
"The Library Selection Committee has been using the web tool since the start of 2014 to support the selection of library proposals. Since then, well over 100 library proposals have been considered, around 80 of which have been approved for synthetic validation. The procedure for assessing and processing the proposals has been straightforward. The tool has allowed the proposals to be handled confidentially and to be assessed rigorously; it has saved huge time for both library proposal submitters and members of the Library Selection Committee."
Adam NelsonChair Library Selection Committee
ChemAxon and Open Innovation
Professional Services (BINGO!)● Product development
● Product customization
● Product Integration
● Workflow design/management
● Project management
● Creative solutions