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