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

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

Tell Me About Glutathione

Tell Me About Glutathione

Tell Me About Glutathione

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

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?

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

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

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

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)

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

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)

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

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

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 %)

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 %)

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

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

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?

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 ?

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?

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

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