Improving online chemistry one structure at a time

Improving Online Chemistry – One Structure at a Time Antony Williams AstraZeneca, February 10 th 2012

We Have …Too Much Data!!!

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?

Pharma Information..and the web… Literature Patents News Pipeline SAR CSRs Safety In vivo Etc

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

PubChem

ChEMBL

Collaborative Knowledge Management

e-Science and Primary Data
How much data generated in a lab, that COULD go public, is lost forever?

Public Domain reference databases of value?
Syntheses
Properties
Spectra
CIFs
Images

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

We Want to Answer Questions
Questions a chemist might ask…
What is the melting point of n-heptanol?
What is the chemical structure of Xanax?
Chemically, what is phenolphthalein?
What are the stereocenters of cholesterol?
Where can I find publications about xylene?
What are the different trade names for Ketoconazole?
What is the NMR spectrum of Aspirin?
What are the safety handling issues for Thymol Blue?

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

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

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. ”
Consider drug structures ONLY…

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-tetramethyl hexadec-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

What’s Methane?

What ELSE is Methane???

EPA’s DailyMed

With Great Fanfare…

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

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

Content is King and Quality Costs
Curated Chemistry “content” is expensive to create
Patent searching
Structures and properties
Drug databases
Literature databases
Chemical Abstracts Service (CAS), the “Gold Standard” in Chemistry related information
104 years of content
>50 million substances
Proprietary platform

The EXPERTS must get it right?!

Wikipedia, C&E News, PubChem
C&E News (from ACS)

Feedback from Steve Ritter
“ Although CAS and C&EN are both part of the ACS Publications Division, we at C&EN still have to pay for our SciFinder access, strangely enough.”
“ It would be nice to have an authoritative web-based source of standard, well-drawn structures for chemists to go to so they can freely cut and paste structures into their papers, PowerPoint presentations, and anything else they might need. Maybe Wikipedia will be that source one day .”

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

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 License 5 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

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: Patents Linked by Name

Vincristine: Articles Linked by Name

ChemSpider Everywhere: What do computers want?
Web services

Mass Spec Analysis

ChemSpider Interface

Tinuvin 328

Position sorted by references

Position 1 only

Web Services

Web Services Open Up Collaboration
Agilent, Bruker, Waters and Thermo all use our web-based services for compound lookup
Many academic sites integrating directly – metabonomics, name lookup, semantic markup
Mobile app integration
Commercial structure drawing packages

ChemSpider Everywhere : Embed

ChemSpider Everywhere: Spectral Game

ChemSpider Everywhere Crowdsourced Curation of Spectra

ChemSpider Everywhere : ChemMobi

Structure Database Lookup

ChemSpider Resources for Chemistry

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 -

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 Internet Data

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)

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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Improving online chemistry one structure at a time

by Antony Williams, ChemConnector on Feb 13, 2012

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Improving online chemistry one structure at a time — Presentation Transcript