delivering curated chemistry to the world via crowdsourced ... filemetabolic pathway databases...

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: williamsa@rsc.org

Twitter: ChemConnector

Blog: www.chemspider.com/blog

Personal Blog: www.chemconnector.com

SLIDES: www.slideshare.net/AntonyWilliams