Online Resources to Support Open Drug Discovery Systems

Online Resources to Support Open Drug Discovery Systems Antony Williams 3 rd Annual Drug Discovery Partnership: Filling the Pipeline, October 2011

Open Drug Discovery
Pharma Companies spend >$50 billion annually on R&D
How much historical data/knowledge/information is in the public domain? And where is it?
How much generated data is truly competitive?
Pre-competitive and public domain data could deliver high value to drug discovery
Data mining
Model-building
Integrating into in-house and online systems

Internal and external content
Built to meet primary use-case
Tailored indexes and GUIs
Internal unique language & metadata
Poor interoperability/integration
Powerpoint, Documents, Excel
Many suppliers of systems and content in a single workflow
Pharma Information Tombs Literature Patents News Pipeline SAR CSRs Safety In vivo Etc

What could create change?
Harvard Business Review (2010)
“ One change would make a substantial difference [ to drug R&D ] : the creation of agreed-upon standards for digitally representing drug assets. ”

It is so difficult to navigate… What’s the structure? Are they in our file? What’s similar? What’s the target? Pharmacology data? Known Pathways? Working On Now? Connections to disease? Expressed in right cell type? Competitors? IP?

Where is chemistry online?
Encyclopedic articles (Wikipedia)
Chemical vendor databases
Metabolic pathway databases
Property databases
Patents with chemical structures
Drug Discovery data
Scientific publications
Compound aggregators
Blogs/Wikis and Open Notebook Science

PubChem

ChEMBL

ChemSpider

SciDBs Wiki

Pharma are accessing, processing, storing & re-processing Public Domain Drug Discovery Data

New trend: Set Data Free on the Web

Open Algorithms, Descriptors and Closed Data – Can We Unlock It?

The Innovative Medicines Initiative
EC funded public-private partnership for pharmaceutical research
Focus on key problems
Efficacy
Safety
Education & Training
Knowledge Management

Open PHACTS Project
Develop a set of robust standards…
Implement the standards in a semantic integration hub
Deliver services to support drug discovery programs in pharma and public domain
22 partners, 8 pharmaceutical companies, 3 biotechs
36 months project
Guiding principle is open access, open usage, open source - Key to standards adoption -

Open PHACTS Project Partners

Example Research questions
Give all compounds with IC50 < xxx for target Y in species W and Z plus assay data
What substructures are associated with readout X (target, pathway, disease, …)
Give all experimental and clinical data for compound X
Give all targets for compound X or a compound with a similarity > y%

Prioritised Research Questions Analysis
Prevalent Concepts
Compound
Bioassay
Target
Pathway
Disease
Prevalent data relationships
Compound – target
Compound – bioassay
Bioassay – target
Compound – target – mode of action
Target – target classification
Target – pathway and disease
Required cheminformatics functionality
Chemical substructure searching
Chemical similarity searching
Required bioinformatics functionality
Sequence and similarity searching
Bioprofile similarity searching

Selection of prioritised data sources
Chemistry
ChEMBL
DrugBank
ChEBI
PubChem
ChemSpider
Human Metabolome DB
Wombat (commercial)
Ontologies
AmiGo (The Gene Ontology)
KEGG ( Kyoto Encyclopedia of Genes and Genomes)
OBI ( The Ontology for Biomedical Investigations)
Bioassay Ontology EFO ( Experimental Factor Ontology)
Biology
EntrezGene
HGNC
Uniprot
Interpro
SCOP
Wikipathways
OMIM
IUPHAR

Linking “Flavors” of Chemistry

Improve Linked Data Access…
Coordinate effort to clean up chemistry related data
Open tools – require good validation studies
Support scientists making data open
Support companies/groups promoting software for data sharing
Engage community to help create what they want.

Openness and Quality Issues Williams and Ekins, DDT, 16: 747-750 (2011) Science Translational Medicine 2011

Chemistry Databases on the Internet
Some public databases are “trusted” as primary sources
Trust is granted without investigation or understanding of the content
What do we know about some of the online resources?

PHYSPROP Database
The freely downloadable database under the EPI Suite prediction software
Very Basic filters suggest data quality issues

The Stereochemistry challenge. 12500 chemicals with “missed” stereo

Searches on ChemSpider
Most searches are text-based: people searching for information about known chemicals
Creating accurate name-structure dictionaries is critical

NIST Webbook

PubChem

NPC Browser http://tripod.nih.gov/npc/

Cyclic Data Sharing
Data-sharing between open databases is cyclic

Synonyms on PubChem
1,3-DICHLORO-PROPAN-2-ONE
(2R,3R)-Butanediol bis(methanesulfonate)
Ethyl-1-propenyl ether, mixture of cis and trans
PSS-[2-[(Chloromethyl)phenyl]ethyl]-Heptaisobutyl substituted
1-Chlorobenzylethyl-3,5,7,9,11,13,15-heptaisobutylpentacyclo [9.5.1.1(3,9).1(5,15).1(7,13)]octasiloxane

Synonyms on PubChem

Data Proliferation

www.chemspider.com

ChemSpider…
>26 million unique molecules
Links together >400 internet resources
Linking patents, publications, chemical vendors and online chemical compound databases
Crowdsourced depositions and curations

ChemSpider…
>26 million unique molecules
Links together >400 internet resources
Linking patents, publications, chemical vendors and online chemical compound databases
Crowdsourced depositions and curations
A focus on data quality – cleaning data on the web
The structure database under Open PHACTS

Acknowledgments
Sean Ekins – Collaborations in Chemistry
RSC|ChemSpider team
Open PHACTS consortium – especially Lee Harland and Carole Goble
Data depositors and curators
Software providers – ACD/Labs, OpenEye, GGA Software Inc, Open Source Cheminformatics

Thank you Email: williamsa@rsc.org Twitter: ChemConnector Blog: www.chemspider.com/blog Personal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams

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Online Resources to Support Open Drug Discovery Systems

by Antony Williams, ChemConnector on Oct 17, 2011

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