ChemSpider – The Vision and Challenges Associated with Building a Free Online Community Resource for Chemists

ChemSpider – The Vision and Challenges Associated with Building a Free Online Community Resource for Chemists Antony Williams AZ, February 2011

What’s the Status of Chemistry online?
Encyclopedic articles (Wikipedia)
Chemical vendor databases
Metabolic pathway databases
Virtual Screening databases
Property databases
Screening assay results
Patents with chemical structures
ADME/Tox data
Scientific publications
Compound aggregators
Blogs/Wikis and Open Notebook Science

For Synthesis…TotallySynthetic.com

Org Prep Daily (Blog)

Molbank (Open Access Journal)

Lots of “Public Compound” Databases
PubChem
Drugbank
ChEBI/ChEMBL
KEGG
LipidMAPs
ChemIDPlus
eMolecules
ZINC
Lots of chemical vendors
ChemSpider

Where Would You look? What Do You Trust?

Linked Data on the Web

What is a compound? “ARTAs”

Vision: Connect Chemistry on the Web
The internet is searchable by chemical structure and substructure (e.g.Wikipedia, Google Scholar)
Chemistry articles are indexed and searchable by a free online service
The web is linked together through the “language of chemistry”
Publicly funded research data is linked

We Have Delivered the Vision
“ Build a Structure Centric Community to
Serve Chemists”
Integrate chemical structure data on the web
Create a “structure-based hub” to information, data and algorithmic predictions
Let chemists contribute their own data
Allow the community to curate/correct data

How Was ChemSpider Built?
ChemSpider was a “hobby project”
Housed in a basement and running off three servers – one bought, two built
Sensitive to weather and power stability
Went live at ACS Spring 2007 in Chicago

How Did We Build It?
We deal in Molfiles or SDF files
We do rudimentary filtering – valence checking, charge imbalance – prior to deposition
We have our own “business logic” to standardize
Link out to external sites where possible using IDs

www.chemspider.com

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?

Search for a Chemical…by name

Link off a structure in ChemSpider
Chemical suppliers
Other publications
Analytical Data
Related Reactions
Wikipedia
Patents
“ Everything”

Available Information…
Linked to vendors, safety data, toxicity, metabolism

Available Information….

Clickthrough to Patent (SureChem)

Crowdsourced “Annotations”
Registered 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 Linked

Search for a chemical…by structure Substructure search coming…

Inherited Errors
Inherited errors from every database… all public compound databases, including ours, have errors
“ Incorrect” structures – assertions, timelines etc
“ Incorrect” names associated with structures
ENORMOUS CHALLENGE

What is 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

What is the Structure of Vitamin K1?

Vitamin K1

“ 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

Question Everything online: www.dhmo.org

It’s all on Wikipedia…

Chemistry on The Internet Is Messy

It’s Methane…

What’s Methane?

What ELSE is Methane???

EPA’s DailyMed

Public Domain Chemistry 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, challenging and exacting
An examination of quality in databases – inter/intra lab comparison of processes for 150 drugs

Drug Name Generic Name ChEBI ChemSpider CAS Com. Chem ChemIDPlus DailyMed DrugBank PubChem Wikipedia Spiriva Tiotropium Bromide No Hits  No Hits    4/0  Depakote Valproate semisodium        No Structure Basen Voglibose   No Hits  No Hits  2/1  Symbicort 1) Budesonide       8/1  Symbicort 2) Formoterol WRONG  No Hits    6/1  Vytorin 1) Ezetimibe   No Hits      Vytorin 2) Simvastatin       2/1  Taxol Paclitaxel       44/1  Thalidomid Thalidomide No Hits        Zocor Simvastatin       2/1  Crestor Rosuvastatin   No Hits    2/1 

Symbicort: Budesonide + Formoterol

Symbicort: Budesonide + Formoterol ChemIDPlus Wikipedia

DrugBank: Search Symbicort…

Symbicort: Budesonide + Formoterol
PubChem
8 structures called Budesonide. 1 “correct”
6 structures called Formoterol. 1 “correct”
Search on “Symbicort” gives 1 structure.

Taxol: Paclitaxel 44 structures

Taxol: Paclitaxel Bioassay Data

Taxol: Paclitaxel Bioassay Data
Most Bioassay data associated with structure with one ambiguous stereocenter

Consider searching each of these chemical databases by chemical name (systematic name, trade name or synonym). Please mark each online resource according to how much you generally trust the results.

The Final Search Strategy

All Those Names, One Structure

Searching Chemistry on the Internet
How complete a result set will we get if we search for “chemicals” by name?
Is there a better way to link chemistry databases? Linking by “names” is dangerous
Chemists want structure and SUBstructure searching

The InChI Identifier

Multiple Layers

InChIStrings Hash to InChIKeys

Oleoylethanolamine

InChIs have traction…

Vancomycin

Vancomycin Search Molecular SKELETON Search Full Molecule

Full Molecule Search: 4 Hits

Full Skeleton Search: 104 Hits

Vancomycin
Who will curate?
How would you clean such a large dataset?

Vancomycin on ChemSpider

Name Searching is “Easier”

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 .”

Search OEA

Semantic Mark-up for Chemistry
Semantic mark-up for chemistry is here
RSC project prospect (structure linking, IUPAC Gold Book ontology and other ontologies
Nature publishing group compound linking

Nature Chemistry Compound Pages

Project Prospect

Entity-Extraction, Mark-up, Annotate

And linked to STITCH…

Success Depends on Dictionaries

Online Curation
Online databases generally do NOT allow curation or annotation
If you find errors they stay there!
ChemSpider allows immediate curation

Search “Vitamin H”

“ Curate” Identifiers

Crowd-sourcing Chemistry Curation

Crowdsourcing Works
>130 people have deposited data and participated in data curation
Different level curators check each other
Wikipedia is the modern primary example

ChemSpider and Publishing
The curation efforts on ChemSpider led to a set of validated dictionaries
Integrate best-in-class entity extraction with validated name dictionaries
Already text-mined the RSC archive and presently linking!

Crowdsourcing Synthesis ChemSpider SyntheticPages

ChemSpider Everywhere: What do computers want?
Web services

Web Services

ChemSpider Everywhere
Linked from Wikipedia and many Public Databases
Linked from Open Notebook Science sites
Linked from Blogs using Structure/Spectra EMBED
Integrated into structure drawing packages
Integrated to software offerings from Thermo, Waters, Agilent, Bruker

ChemSpider Everywhere : Embed

ChemSpider Everywhere: Spectral Game

ChemSpider Everywhere Crowdsourced Curation of Spectra

ChemSpider Everywhere : ChemMobi

Structure Database Lookup

Reaction Database Look-up

There will always be gaps...
What ChemSpider does not deal with, yet...
Materials
Minerals
Polymers
Biological macromolecules

Collaborative Data Curation
How can we COLLECTIVELY clean online data?
Developing ways to share curation actions back to original data sources
A mindset of bigger is better is problematic. How many “real chemicals” are in the public databases?

Future Work
Continue curation work
Extend search capabilities
Expand existing databases
Text-mine RSC archive and link chemistry
Project: pre-competitive data sharing and linking for Life Sciences
Integrate to metabolic pathways tools

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

It’s a long road ahead…

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

ChemSpider – The Vision and Challenges Associated with Building a Free Online Community Resource for Chemists

by Antony Williams, ChemConnector on Feb 02, 2011

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ChemSpider – The Vision and Challenges Associated with Building a Free Online Community Resource for Chemists Presentation Transcript

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