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Delivering Curated Chemistry to the
World via Crowdsourced Deposition
and Annotation on ChemSpider
Antony WilliamsUniversity of Illinois in Chicago, January 27th 2012
The World of Online Chemistry
Property databases
Compound aggregators
Screening assay results
Scientific publications
Encyclopedic articles (Wikipedia)
Metabolic pathway databases
ADME/Tox data – eTOX for example
Blogs/Wikis and Open Notebook Science
Contributing Open Source code to projects
We Have …Too Much Data!!!
e-Science and Primary Data
How much data generated in a lab, that COULDgo public, is lost forever?
TotallySynthetic.com
e-Science and Primary Data
How much data generated in a lab, that COULDgo public, is lost forever?
Public Domain reference databases of value?
Syntheses
Properties
Spectra
CIFs
Images
PubChem
ChEMBL
Collaborative Knowledge Management
e-Science and Primary Data
How much data generated in a lab, that COULDgo public, is lost forever?
Public Domain reference databases of value?
Syntheses
Properties
Spectra
CIFs
Images
Much of chemistry is chemical structure-based –where and how could we host these data?
RSC’s ChemSpider
Available Information…
Linked to vendors, safety data, toxicity, metabolism
Available Information….
Crowdsourced “Annotations”
Users can add
Descriptions/Syntheses/Commentaries
Links to PubMed articles
Links to articles via DOIs
Add spectral data
Add Crystallographic Information Files
Add photos
Add MP3 files
Add Videos
Spectra
Spectra
Data on the Web
Chemistry Data online is messy
We have inherited errors
All public compound databases, including ours, have errors
“Incorrect” structures – assertions, timelines etc
“Incorrect” names associated with structures
Properties
Links
Publications
ENORMOUS CHALLENGE
The Structure of Vitamin K?
MeSH
A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K
The Structure of Vitamin K1?
What is the Structure of Vitamin K1?
CAS’s Common Chemistry
Wikipedia
ChEBI – Manual Curation
“2-methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione”
Variants of systematic names on PubChem
2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl
2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl
2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl
2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl
2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl
2-methyl-3-[(E)-3,7,11,15-tetramethyl
2-methyl-3-(3,7,11,15-tetramethyl
2-methyl-3-[(E)-3,7,11,15-tetramethyl
Question Everything online: www.dhmo.org
It’s all on Wikipedia…
Chemistry on The Internet Is Messy
It’s Methane…
What’s Methane?
What’s Methane?
What ELSE is Methane???
EPA’s DailyMed
EPA’s DailyMed
EPA’s DailyMed
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
With Great Fanfare…
NPC Browser http://tripod.nih.gov/npc/
NPC Browser http://tripod.nih.gov/npc/
Openness and Quality IssuesWilliams and Ekins, DDT, 16: 747-750 (2011)
Science Translational Medicine 2011
Public Domain Databases
Our databases are a mess…
Non-curated databases are proliferating errors
We source and deposit data between databases
Original sources of errors hard to determine
Curation is time-consuming and challenging
Stop Whining – Fix it
Crowdsourced Curation
Crowd-sourced curation: identify/tag errors, edit names, synonyms, identify records to deprecate
Search “Vitamin H”
“Curate” Identifiers
“Curate” Identifiers
“Curate” Identifiers
Standards : Structure Standardization
Standards : Structure Standardization
Standards : Structure Standardization
What needs to happen?
Standards
Standardization of structures ChEBI/PubChem sharing
InChI adoption
The InChI Identifier
Multiple Layers
InChIStrings Hash to InChIKeys
Vancomycin – Search the Internet
Vancomycin
Search Molecular
SKELETON
Search Full Molecule
Full Skeleton Search: 104 Hits
Full Molecule Search: 4 Hits
Crowdsourcing Works
>130 people have deposited data and participated in data curation
Different level curators check each other
More curators and depositors are encouraged!
What needs to happen?
Standards
Standardization of structures ChEBI/PubChem sharing
InChI adoption
Collaboration
Stop reinventing the wheel
Share data, share efforts and speed the process
Antony Williams vs Identifiers
Passport ID
Dad, Tony, others
SSN
Green Card
License5 email addresses
ChemSpiderman (blog,
Twitter account,
Facebook, Friendfeed)
OpenID
….
Aspirin names and synonyms
• Text searches depend on correct association
• 335 suggested identifiers for Aspirin just on PubChem!
• Disambiguation dictionaries are necessary, not just for authors!
The Final Search Strategy
All Those Names, One Structure
Ambiguity in Identifiers
Curated Dictionaries Matter
Success Depends on Dictionaries
Validated Name-Structure Dictionaries
Chemical name dictionaries are used for: Text-mining (publications, patents)
Used to index PubMed and link to Google Patents
Linking to other databases – think Biology! When structures are not available drug names link
Searching the web Names link to structures link to InChIs
I want to know about “Vincristine”
If all algorithms work then
everything on the page is
correct by default except the
name-structure relationship!
Vincristine: Identifiers and Properties
Vincristine: Vendors and SourcesLinked by Structure
Vincristine: PatentsLinked by Name
Vincristine: ArticlesLinked by Name
Challenges of Complex Molecules
Yohimbine
Originally 15 compounds “called” Yohimbine
54 Skeletons for Yohimbine
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
Literature Patents NewsPipeline SAR CSRs SafetyIn vivo Etc
Pharma Information Tombs
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?
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 -
ChemSpider Resources for Chemistry
Internet Data
The Future
Commercial Software
Pre-competitive Data
Open Science
Open Data
Publishers
Educators
Open Databases
Chemical Vendors
Small organic molecules
Undefined materials
Organometallics
Nanomaterials
Polymers
Minerals
Particle bound
Links to Biologicals
The Future of Chemistry on the Web?
Public compound databases federate & build a linked environment of validated data!
Data validation needs are not ignored
Publishers layer on information to make publications discoverable
Public-Private databases can be linked
Open Data proliferate
The “Semantic Web” in action
Acknowledgments
The ChemSpider team
Our data providers, depositors, collaborators and curators
Software providers – OpenEye, ChemDoodle, ACD/Labs, GGA Software, Open Source (Jmol, JSpecView, OpenBabel)
Sean Ekins @collabchem
Thank you
Email: [email protected]
Twitter: ChemConnector
Blog: www.chemspider.com/blog
Personal Blog: www.chemconnector.com
SLIDES: www.slideshare.net/AntonyWilliams
