Checking, Curating And Qualifying Chemistry

Checking, Curating and Checking, Curating and Qualifying Chemistry to Build Qualifying Chemistry to Build

a Structure Centric a Structure Centric Community for ChemistsCommunity for Chemists

Rutgers University 12/2/2008Rutgers University 12/2/2008

Antony WilliamsAntony Williams

Building a Structure Centric Community for Chemists

ChemSpider - A Search Engine for ChemSpider - A Search Engine for ChemistsChemists

Questions a chemist might ask…Questions a chemist might ask… What is the melting point of n-butanol? What is the melting point of n-butanol? What is the chemical structure of Xanax?What is the chemical structure of Xanax? Chemically, what is phenolphthalein?Chemically, what is phenolphthalein? What are the stereocenters of cholesterol?What are the stereocenters of cholesterol? Where can I find publications about xylene?Where can I find publications about xylene? What are the different trade names for What are the different trade names for

Ketoconazole?Ketoconazole? What is the NMR spectrum of Aspirin?What is the NMR spectrum of Aspirin? What are the safety handling issues for Thymol What are the safety handling issues for Thymol

Blue?Blue?

ChemSpider can answer all of these questionsChemSpider can answer all of these questions


Tell Me About GlutathioneTell Me About Glutathione


Link outsLink outs


Links out to KEGGLinks out to KEGGKyoto Encyclopedia of Genes and Kyoto Encyclopedia of Genes and

Genomes Genomes


How many names does a How many names does a compound have?compound have?


ChemSpider Data ContentChemSpider Data Content

Over 21.5 million unique chemical structures from Over 21.5 million unique chemical structures from ca. 150 data sourcesca. 150 data sources Online Databases –PubChem, Drugbank, KEGG, WikipediaOnline Databases –PubChem, Drugbank, KEGG, Wikipedia Literature – PubMed, J Het Chem, Nature, RSC, Open Literature – PubMed, J Het Chem, Nature, RSC, Open

AccessAccess Chemical Vendors – over 40 different vendors and Chemical Vendors – over 40 different vendors and

growinggrowing Personal Depositions – individual contributionsPersonal Depositions – individual contributions Content database vendorsContent database vendors Analytical data collectionsAnalytical data collections PatentsPatents Web scrapingWeb scraping

Content is linked back to the original data sourcesContent is linked back to the original data sources


Complex SearchComplex Search


The Quality of Data Online…The Quality of Data Online…

Aggregating data opens up quality issuesAggregating data opens up quality issues Structure-identifier associations are “dirty”Structure-identifier associations are “dirty” Structures are COMMONLY incorrectStructures are COMMONLY incorrect Manual curation of small databases is enough Manual curation of small databases is enough

work – what about millions of structures?work – what about millions of structures? Structures are far from perfect. What is a Structures are far from perfect. What is a

“correct structure”?“correct structure”? Full stereochemistry? Full stereochemistry? Historical timeline of structure?Historical timeline of structure? Who is the authority?Who is the authority?


Quality is a Major Issue- Search Quality is a Major Issue- Search ButanolButanol

OLD EXAMPLE..now fixedOLD EXAMPLE..now fixed


Wikipedia Chemistry Curation Wikipedia Chemistry Curation projectproject

Only ca. 5000 organic structures, Only ca. 5000 organic structures, 7000 total structures7000 total structures

Almost a year of work so far for a Almost a year of work so far for a team of 6 peopleteam of 6 people

Many errors removed in the process. Many errors removed in the process. Curation process is a daily event for Curation process is a daily event for users/depositorsusers/depositors

Slow and torturous processSlow and torturous process

http://en.wikipedia.org/wiki/Talk:Tachttp://en.wikipedia.org/wiki/Talk:Tacrolimus#IUPAC_Name_and_structurrolimus#IUPAC_Name_and_structuree


Wikipedia CurationWikipedia Curation

Looking for self-Looking for self-consistency across a consistency across a Wikipedia PageWikipedia Page

Primary key is the article Primary key is the article TITLETITLE

The chemical shown The chemical shown needs to match the titleneeds to match the title

Cyclic self-consistency – Cyclic self-consistency – and decisions must get and decisions must get mademade


Other issues…Other issues…


ChargesCharges


Sugars – Machine Readable vs Sugars – Machine Readable vs AestheticsAesthetics

Haworth Stereo Fischer


Wikipedia – Crowdsourcing Wikipedia – Crowdsourcing ChemistryChemistry


Thymol Blue on ChemSpiderThymol Blue on ChemSpider

Data online includes:Data online includes: UV-vis spectrumUV-vis spectrum Measured experimental propertiesMeasured experimental properties Link to Wikipedia articleLink to Wikipedia article Links to chromatography detailsLinks to chromatography details Multiple identifiers/trade names etc.Multiple identifiers/trade names etc. Links to vendors/suppliers/other databasesLinks to vendors/suppliers/other databases Safety informationSafety information

http://www.chemspider.com/q/thymol%20bluehttp://www.chemspider.com/q/thymol%20blue


Crowd-sourcing CurationCrowd-sourcing Curation

How to curate data for millions of How to curate data for millions of structures? structures?

Robot processes can clean up depositionsRobot processes can clean up depositions Search for Chloride and check molecular formula Search for Chloride and check molecular formula

for Clfor Cl Check for stereochemistry and remove names Check for stereochemistry and remove names

with stereo with stereo Provide a simple-to-use platform to curate, Provide a simple-to-use platform to curate,

annotate and tag data annotate and tag data Provide curator administration to prevent Provide curator administration to prevent

vandalism (Veropedia)vandalism (Veropedia)


Post CommentsPost Comments Anyone can “Post Comments” associated Anyone can “Post Comments” associated

with a structure. To curate data we with a structure. To curate data we require login to trackrequire login to track


Multi-level Curation and Multi-level Curation and ApprovalApproval


Crowd-sourcing ChemistryCrowd-sourcing Chemistry

Crowd-sourced curation: identify and tag Crowd-sourced curation: identify and tag errors, edit names, synonyms, identify errors, edit names, synonyms, identify records for deprecationrecords for deprecation

ALSOALSO

Crowd-sourced deposition: anyone can Crowd-sourced deposition: anyone can deposit data (structures, text, images, deposit data (structures, text, images, analytical data)analytical data)


VancomycinVancomycin

Originally 12 structures Originally 12 structures with vancomycin with vancomycin Incomplete Incomplete

stereochemistrystereochemistry Complete but different Complete but different

stereochemistrystereochemistry Different charge statesDifferent charge states

1 remains after 1 remains after community community collaboration with collaboration with ChEBIChEBI


““Collaboration” with ChEBICollaboration” with ChEBI


Ginkgolide BGinkgolide B


DailyMedDailyMed


Quality of StructuresQuality of Structures


Quality of Structures!!!Quality of Structures!!!


““Entity Extraction”Entity Extraction”

Rule-based recognition of systematic names:Rule-based recognition of systematic names: Use a lexeme of name fragmentsUse a lexeme of name fragments Rules for identifying bounds of a nameRules for identifying bounds of a name

Look-up dictionary:Look-up dictionary: Drug NamesDrug Names Trivial NamesTrivial Names Numbers : Registry IDs, EINECS/ELINCSNumbers : Registry IDs, EINECS/ELINCS Massive look-up dictionary of validated Massive look-up dictionary of validated

identifiers on ChemSpideridentifiers on ChemSpider


Name RecognitionName Recognition

Azo aldehyde Azo aldehyde 22 was synthesized according to a was synthesized according to a reported method [17]. To a stirred solution of azo reported method [17]. To a stirred solution of azo aldehyde aldehyde 22 (1.08 g, 3.76 mmol ) in dry CH2Cl2 (1.08 g, 3.76 mmol ) in dry CH2Cl2 (30.00 mL) at 0 oC were successively added (3,4-(30.00 mL) at 0 oC were successively added (3,4-diaminophenyl)phenyl methanone diaminophenyl)phenyl methanone 11(0.40 g, 1.88 (0.40 g, 1.88 mmol) and a excces of anhydrous MgSO4 (2.00 mmol) and a excces of anhydrous MgSO4 (2.00 g,16.67 mmol) . g,16.67 mmol) .

The resulting mixture was stirred for 6 hours at The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and room temperature [18]. The mixture was filtered and washed with dichloromethane . Then the solvent was washed with dichloromethane . Then the solvent was evaporated under reduced pressure to give azo evaporated under reduced pressure to give azo Schiff base Schiff base 33 as a red solid which was recrystalized as a red solid which was recrystalized from ethanol 95% from ethanol 95% (1.28 g, 91 %) (1.28 g, 91 %)


Name RecognitionName Recognition

Azo aldehyde Azo aldehyde 22 was synthesized according to a was synthesized according to a reported method [17]. To a stirred solution of azo reported method [17]. To a stirred solution of azo aldehyde aldehyde 22 (1.08 g, 3.76 mmol ) in dry (1.08 g, 3.76 mmol ) in dry CH2Cl2CH2Cl2 (30.00 mL) at 0 oC were successively added (30.00 mL) at 0 oC were successively added (3,4-(3,4-diaminophenyl)phenyl methanonediaminophenyl)phenyl methanone 11(0.40 g, 1.88 (0.40 g, 1.88 mmol) and a excess of anhydrous mmol) and a excess of anhydrous MgSOMgSO44 (2.00 (2.00 g,16.67 mmol) . g,16.67 mmol) .

The resulting mixture was stirred for 6 hours at The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and room temperature [18]. The mixture was filtered and washed with washed with dichloromethanedichloromethane . Then the solvent . Then the solvent was evaporated under reduced pressure to give azo was evaporated under reduced pressure to give azo Schiff base Schiff base 33 as a red solid which was recrystalized as a red solid which was recrystalized from from ethanolethanol 95% 95% (1.28 g, 91 %) (1.28 g, 91 %)


ChemMantisChemMantis

ChemChemical ical MMarkup arkup AAnd nd NNomenclature omenclature TTransformation ransformation IIntegrated ntegrated SSystemystem


Document markupDocument markup


Markup – 3 seconds!Markup – 3 seconds!


On the fly conversionOn the fly conversion


Shorthand Formulae Shorthand Formulae SupportedSupported


One Click to more Info…One Click to more Info…


Names and StructuresNames and Structures

DichloroacetoneDichloroacetone

TrichloromethylsilaneTrichloromethylsilane


AmbiguityAmbiguity


Ambiguity in Abbreviations - Ambiguity in Abbreviations - DPADPA


IUPAC PAC ArticlesIUPAC PAC Articles


PatentsPatents


Single Configuration File Single Configuration File defines entities for markupdefines entities for markup

Algorithms can be built for Algorithms can be built for certain entities but the certain entities but the majority are dictionaries – majority are dictionaries – vendors, Phys Properties, vendors, Phys Properties, AnalyticalAnalytical

We can extend our system – We can extend our system – should we integrate to PDB should we integrate to PDB somehow?somehow?


Nature PublicationsNature Publications


Entity BalloonsEntity Balloons

Structures are the Structures are the language of language of chemistrychemistry

Show structures to Show structures to chemists and chemists and search/link from search/link from therethere

Link to PDBLink to PDB??


Other Dictionaries - SpeciesOther Dictionaries - Species

We are considering We are considering BacteriaBacteria FungiFungi EnzymesEnzymes VirusesViruses PDB codes?PDB codes?


Integrations Out to Other Integrations Out to Other SourcesSources


ReactionsReactions


ConclusionsConclusions

The quality of structure-based data online The quality of structure-based data online should always be questioned – that should always be questioned – that includes ChemSpiderincludes ChemSpider

Data on ChemSpider are being added and Data on ChemSpider are being added and curated on a daily basis but we need more curated on a daily basis but we need more eyeballs helping alwayseyeballs helping always

ChemSpider has a large validated ChemSpider has a large validated structure-name dictionarystructure-name dictionary

Chemical name extraction and document Chemical name extraction and document markup is very enablingmarkup is very enabling

Checking, Curating And Qualifying Chemistry

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