Checking, Curating And Qualifying Chemistry

Checking, Curating and Qualifying Chemistry to Build a Structure Centric Community for Chemists Rutgers University 12/2/2008 Antony Williams

ChemSpider - A Search Engine for Chemists
Questions a chemist might ask…
What is the melting point of n-butanol?
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?
ChemSpider can answer all of these questions

Tell Me About Glutathione

Link outs

Links out to KEGG Kyoto Encyclopedia of Genes and Genomes

How many names does a compound have?

ChemSpider Data Content
Over 21.5 million unique chemical structures from ca. 150 data sources
Online Databases –PubChem, Drugbank, KEGG, Wikipedia
Literature – PubMed, J Het Chem, Nature, RSC, Open Access
Chemical Vendors – over 40 different vendors and growing
Personal Depositions – individual contributions
Content database vendors
Analytical data collections
Patents
Web scraping
Content is linked back to the original data sources

Complex Search

The Quality of Data Online…
Aggregating data opens up quality issues
Structure-identifier associations are “dirty”
Structures are COMMONLY incorrect
Manual curation of small databases is enough work – what about millions of structures?
Structures are far from perfect. What is a “correct structure”?
Full stereochemistry?
Historical timeline of structure?
Who is the authority?

Quality is a Major Issue- Search Butanol OLD EXAMPLE..now fixed

Wikipedia Chemistry Curation project
Only ca. 5000 organic structures, 7000 total structures
Almost a year of work so far for a team of 6 people
Many errors removed in the process. Curation process is a daily event for users/depositors
Slow and torturous process
http://en.wikipedia.org/wiki/Talk:Tacrolimus#IUPAC_Name_and_structure

Wikipedia Curation
Looking for self-consistency across a Wikipedia Page
Primary key is the article TITLE
The chemical shown needs to match the title
Cyclic self-consistency – and decisions must get made

Other issues…

Charges

Sugars – Machine Readable vs Aesthetics Haworth Stereo Fischer

Wikipedia – Crowdsourcing Chemistry

Thymol Blue on ChemSpider
Data online includes:
UV-vis spectrum
Measured experimental properties
Link to Wikipedia article
Links to chromatography details
Multiple identifiers/trade names etc.
Links to vendors/suppliers/other databases
Safety information
http://www.chemspider.com/q/thymol%20blue

Crowd-sourcing Curation
How to curate data for millions of structures?
Robot processes can clean up depositions
Search for Chloride and check molecular formula for Cl
Check for stereochemistry and remove names with stereo
Provide a simple-to-use platform to curate, annotate and tag data
Provide curator administration to prevent vandalism (Veropedia)

Post Comments
Anyone can “Post Comments” associated with a structure. To curate data we require login to track

Multi-level Curation and Approval

Crowd-sourcing Chemistry
Crowd-sourced curation: identify and tag errors, edit names, synonyms, identify records for deprecation
ALSO
Crowd-sourced deposition: anyone can deposit data (structures, text, images, analytical data)

Vancomycin
Originally 12 structures with vancomycin
Incomplete stereochemistry
Complete but different stereochemistry
Different charge states
1 remains after community collaboration with ChEBI

“ Collaboration” with ChEBI

Ginkgolide B

DailyMed

Quality of Structures

Quality of Structures!!!

“Entity Extraction”
Rule-based recognition of systematic names:
Use a lexeme of name fragments
Rules for identifying bounds of a name
Look-up dictionary:
Drug Names
Trivial Names
Numbers : Registry IDs, EINECS/ELINCS
Massive look-up dictionary of validated identifiers on ChemSpider

Name Recognition
Azo aldehyde 2 was synthesized according to a reported method [17]. To a stirred solution of azo aldehyde 2 (1.08 g, 3.76 mmol ) in dry CH2Cl2 (30.00 mL) at 0 oC were successively added (3,4-diaminophenyl)phenyl methanone 1 (0.40 g, 1.88 mmol) and a excces of anhydrous MgSO4 (2.00 g,16.67 mmol) .
The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and washed with dichloromethane . Then the solvent was evaporated under reduced pressure to give azo Schiff base 3 as a red solid which was recrystalized from ethanol 95% (1.28 g, 91 %)

Name Recognition
Azo aldehyde 2 was synthesized according to a reported method [17]. To a stirred solution of azo aldehyde 2 (1.08 g, 3.76 mmol ) in dry CH2Cl2 (30.00 mL) at 0 oC were successively added (3,4-diaminophenyl)phenyl methanone 1 (0.40 g, 1.88 mmol) and a excess of anhydrous MgSO 4 (2.00 g,16.67 mmol) .
The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and washed with dichloromethane . Then the solvent was evaporated under reduced pressure to give azo Schiff base 3 as a red solid which was recrystalized from ethanol 95% (1.28 g, 91 %)

ChemMantis
Chem ical M arkup A nd N omenclature T ransformation I ntegrated S ystem

Document markup

Markup – 3 seconds!

On the fly conversion

Shorthand Formulae Supported

One Click to more Info…

Names and Structures
Dichloroacetone
Trichloromethylsilane

Ambiguity

Ambiguity in Abbreviations - DPA

IUPAC PAC Articles

Patents

Single Configuration File defines entities for markup
Algorithms can be built for certain entities but the majority are dictionaries – vendors, Phys Properties, Analytical
We can extend our system – should we integrate to PDB somehow?

Nature Publications

Entity Balloons
Structures are the language of chemistry
Show structures to chemists and search/link from there
Link to PDB ?

Other Dictionaries - Species
We are considering
Bacteria
Fungi
Enzymes
Viruses
PDB codes?

Integrations Out to Other Sources

Reactions

Conclusions
The quality of structure-based data online should always be questioned – that includes ChemSpider
Data on ChemSpider are being added and curated on a daily basis but we need more eyeballs helping always
ChemSpider has a large validated structure-name dictionary
Chemical name extraction and document markup is very enabling

Checking, Curating And Qualifying Chemistry

by Antony Williams, ChemConnector on Dec 02, 2008

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Checking, Curating And Qualifying Chemistry — Presentation Transcript