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The Royal Society of Chemistry hosts a growing collection of online chemistry content. For much of our work the InChI identifier is an important component underpinning our projects. This enables the integration of chemical compounds with our archive of scientific publications, the delivery of a reaction database containing millions of reactions as well as a chemical validation and standardization platform developed to help improve the quality of structural representations on the internet. The InChI has been a fundamental part of each of our projects and has been pivotal in our support of international projects such as the Open PHACTS semantic web project integrating chemistry and biology data and the PharmaSea project focused on identifying novel chemical components from the ocean with the intention of identifying new antibiotics. This presentation will provide an overview of the importance of InChI in the development of many of our eScience platforms and how we have used it to provide integration across hundreds of websites and chemistry databases across the web. We will discuss how we are now expanding our efforts to develop a platform encompassing efforts in Open Source Drug Discovery and the support of data management for neglected diseases.
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How the InChI identifier is used to underpin our online chemistry
databases at RSC
Antony Williams, Valery Tkachenko
and Ken Karapetyan
ACS San Francisco
August 2014
What can I say that I haven’t said?
What can I say that I haven’t said?
What can I say that I haven’t said?YouTube InChIKey Collision Movie
What can I say that I haven’t said?
InChI is for machines but do have a human aspect…
Many Names, One Structure
Structure Identifiers
OPSIN (chemical name to structure) http://opsin.ch.cam.ac.uk/
• InChI support systems…
InChI mapping helps a lot!
• We wanted to map together chemical data on the web
• We knew that chemical name mapping was difficult but dictionaries were useful
• It is InChI that became the foundation technology for our database…
• We accepted all the limitations of InChI• We lived with the “Useful but not ideal”• And so….
• ~32 million chemicals and growing
• Data sourced from >500 different sources
• Crowd sourced curation and annotation
• Ongoing deposition of data from our journals and our collaborators
• Structure centric hub for web-searching
• …and a really big dictionary!!!
ChemSpider
So where can we travel???
InChI String Search via GoogleSo give me InChIKeys…
And where can we travel???
And where can we travel???
And where can we travel???
And where can we travel???
NEW15th
Edition
*The name THE MERCK INDEX is owned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., and is licensed to The Royal Society of Chemistry for use in the U.S.A. and Canada.
Where else is RSC using InChIs
Text Mining
The N-(β-hydroxyethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)urea prepared in Example 6 , thionyl chloride ( 5 ml ) and benzene ( 50 ml ) were charged into a glass reaction vessel equipped with a mechanical stirrer , thermometer and reflux condenser .
The reaction mixture was heated at reflux with stirring , for a period of about one-half hour .
After this time the benzene and unreacted thionyl chloride were stripped from the reaction mixture under reduced pressure to yield the desired product N-(β-chloroethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-thiaidazol-5-yl)urea as a solid residue
Text Mining
The N-(β-hydroxyethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)urea prepared in Example 6 , thionyl chloride ( 5 ml ) and benzene ( 50 ml ) were charged into a glass reaction vessel equipped with a mechanical stirrer , thermometer and reflux condenser .
The reaction mixture was heated at reflux with stirring , for a period of about one-half hour .
After this time the benzene and unreacted thionyl chloride were stripped from the reaction mixture under reduced pressure to yield the desired product N-(β-chloroethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-thiaidazol-5-yl)urea as a solid residue
SO MANY reactions!
Extracting our Archive
• What could we get from our archive?• Find chemical names and generate structures• Find chemical images and generate structures• Find reactions• Find data (MP, BP, LogP) and deposit• Find figures and database them• Find spectra (and link to structures)• And of course InChIfy the entire collection
After we mine the Archive
Models published from data
Text-mining Data to compare
Progress to date
• We have text-mined all 21st century articles… >100k articles from 2000-2013
• Marked up with XML and published onto the HTML forms of the articles
• Required multiple iterations based on dictionaries, markup, text mining iterations
• New visualization tools in development – not just chemical names. Add chemical and biomedical terms markup also!
MedChemComm markup
MedChemComm markup
MedChemComm markup
InChIs under our “repository”
• Scientific publications are a summary of work• Is all work reported?• How much science is lost to pruning?• What of value sits in notebooks and is lost?• Publications offering access to “real data”?
• How much data is lost?• How many compounds never reported?• How many syntheses fail or succeed?• How many characterization measurements?
New Repository Architecturedoi: 10.1007/s10822-014-9784-5
What are we building?
• We are building the “RSC Data Repository”
• Containers for compounds, reactions, analytical data, tabular data
• Algorithms for data validation and standardization
• Flexible indexing and search technologies
• A platform for modeling data and hosting existing models and predictive algorithms
New Repository Architecture
Compounds Reactions Spectra Materials Documents
CompoundsAPI
ReactionsAPI
SpectraAPI
MaterialsAPI
DocumentsAPI
CompoundsWidgets
ReactionsWidgets
SpectraWidgets
MaterialsWidgets
DocumentsWidgets
Data tier
Data access tier
User interface
components tier
Analytical Laboratory application
User interface tier
(examples) Electronic Laboratory Notebook
Paid 3rd party integrations (various platforms – SharePoint, Google, etc)
Chemical Inventory application
Deposition of Data
Compounds
Reactions
Analytical data
Crystallography data
InChIs under the repository
• All compound-based data handling will of course connect with InChIs• Compounds• Reactions• Compound-spectra matching • Etc. etc. etc…
For Deposition of Data
• Developing systems that provides feedback to users regarding data quality• Validate/standardize chemical compounds• Check for balanced reactions• Checks spectral data
• EXAMPLE Future work• Properties – compare experimental to pred.• Automated structure verification - NMR
RSC Cheminformatics Projects
• RSC as a provider of support for grant-based projects• Utilizing ChemSpider initially as a platform• Developing Chemical Registry Service• Utilizing core architecture and widgets to
serve the projects
The PharmaSea Website
• ChemSpider IDs and InChIs/InChIKeys made open and available for linking
• Exposed via the Open PHACTS RDF export
• A structure ID standard to enable further linking across the semantic web of science
InChIs and DDP
Electronic Notebook Data
• Development work integrating chemistry into the Southampton Labtrove notebook• Stoichiometry table development• Analytical data integration
• “ChemTrove” includes chemistry widgets and InChI as an important data field
Side Effects of InChI Usage
SMILES by comparison…
Side Effects of InChI Usage
Standardization IssuesDepiction based on molfile
Standardize
• Use the SRS as guidance for standardization• Adjust as necessary to our needs
Nitro groups
Salt and Ionic Bonds
What needs to happen?
• If we could validate• Catch errors in databases (and clean)• Proactively catch errors in publications/patents• Reduce junk in the ether – improve QUALITY!
• If we standardized• Interlinking should improve
Validate and Standardize
CVSP Filtering
CVSP Filtering of DrugBank
DrugBank (ca. 6000 records)
• 38 records with InChI not matching the structure, e.g. DB08521, DB08187
• 24 records where names (IUPAC_NAME) did not match the structure, e.g. DB08346
• 38 records with SMILES not matching the structure, e.g. DB08293
• 53 records with unusual valence, e.g. DB01983 with boron(V)
ChEMBL (1.3 million records)
• 11,020 records with 4 bonds and zero charge, e.g. CHEMBL501101 or CHEMBL501973
• 271 records with hypervalent oxygen (e.g. , CHEMBL2219679), carbon (e.g. 1005895), boron, chlorine, iodine or phosphine
• 6,177 records where direction of bond makes no sense, e.g. CHEMBL12760 and CHEMBL34704
ChemSpider Standardization
• Entire ChemSpider database will be standardized using modified FDA rule set
• Original Molfiles will be standardized and all properties (predicted properties, SMILES, InChIs, Names) will all be regenerated
• CLEAN’ed database to compounds repository
• Standardization procedures automatically applied to all future depositions
Recent Data (last week)
Internet Data
Data Repositories and InChI
Commercial SoftwarePre-competitive Data
Open ScienceOpen DataPublishersEducators
Open DatabasesChemical Vendors
Small organic moleculesUndefined materialsOrganometallicsNanomaterialsPolymersMineralsParticle boundLinks to Biologicals
If InChI was not developed…
• Database linking would suffer dramatically
• The web would not be “structure searchable”
• Cheminformatics tools would likely not be linking to public domain databases in the same way
• We wouldn’t be here discussing….
• And ChemSpider would not have been built
Acknowledgments
• The InChI team
• The entire RSC cheminformatics team…
• Daniel Lowe for the text mining work
• Igor Tetko for OCHEM modeling
Thank you
Email: [email protected]: 0000-0002-2668-4821 Twitter: @ChemConnectorPersonal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams
