improving online chemistry one structure at a time filemetabolic pathway databases adme/tox data...

Improving Online Chemistry –

One Structure at a Time

Antony WilliamsAstraZeneca, February 10th 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?

Literature Patents NewsPipeline SAR CSRs SafetyIn vivo Etc

Pharma Information..and the web…

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 COULDgo public, is lost forever?

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

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

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-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

What’s Methane?

What’s Methane?

What ELSE is Methane???

EPA’s DailyMed

EPA’s DailyMed

EPA’s DailyMed

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

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, PubChemC&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

“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

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: PatentsLinked by Name

Vincristine: ArticlesLinked 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 -

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)

Thank you

Email: williamsa@rsc.org

Twitter: ChemConnector

Blog: www.chemspider.com/blog

Personal Blog: www.chemconnector.com

SLIDES: www.slideshare.net/AntonyWilliams