The Expansive Reach of ChemSpider as a Resource for

the Chemistry Community

Antony WilliamsUniversity of Oregon, April 24th 2013

The World of Online Chemistry• Property databases• Compound aggregators• Screening assay results• Scientific publications • Encyclopedic articles (Wikipedia)• Metabolic pathway databases• ADME/Tox data – eTOX for example• Blogs/Wikis and Open Notebook Science

We Have …Too Much Data!!!

e-Science and Primary Data• How much data generated in a lab, that COULD go public, is

lost forever?

TotallySynthetic.com

e-Science and Primary Data• How much data generated in a lab, that COULD go public, is

lost forever?• Public Domain reference databases of value?

– Syntheses– Properties– Spectra– CIFs– Images

Collaborative Knowledge Management

e-Science and Primary Data• How much data generated in a lab, that COULD go public, is

lost forever?• Public Domain reference databases of value?

– Syntheses– Properties– Spectra– CIFs– Images

• Much of chemistry is chemical structure-based – where and how could we host these data?

RSC’s ChemSpider

Crowdsourced “Annotations”• 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

Chemistry Data online is messy• We have inherited errors• All public compound databases, including ours, have

errors• “Incorrect” structures – assertions, timelines etc• “Incorrect” names associated with structures• Properties• Links• Publications• ENORMOUS CHALLENGE

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

The Structure of Vitamin K1?

What is the Structure of Vitamin K1?

CAS’s Common Chemistry

Wikipedia

“2-methyl-3-(3,7,11,15-tetramethylhexadec-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’s Methane?

What ELSE is Methane???

With Great Fanfare…

NPC Browser http://tripod.nih.gov/npc/

NPC Browser http://tripod.nih.gov/npc/

Public Domain 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 and challenging

Stop Whining – Fix it

Crowdsourced Curation

• Crowd-sourced curation: identify/tag errors, edit names, synonyms, identify records to deprecate

Search “Vitamin H”

“Curate” Identifiers

“Curate” Identifiers

“Curate” Identifiers

Standards : Structure Standardization

Standards : Structure Standardization

Standards : Structure Standardization

The InChI Identifier

Multiple Layers

InChIStrings Hash to InChIKeys

Vancomycin – Search the Internet

Vancomycin

Search Molecular SKELETON

Search Full Molecule

Full Skeleton Search: 104 Hits

Full Molecule Search: 4 Hits

Validated Name-Structure Dictionaries• Chemical name dictionaries are used for:

• Text-mining (publications, patents)– Used to index PubMed and link to Google Patents

• Linking to other databases – think Biology!– When structures are not available drug names link

• Searching the web– Names link to structures link to InChIs

I want to know about “Vincristine”

If all algorithms work then everything on the page is correct by default except the name-structure relationship!

Vincristine: Identifiers and Properties

Vincristine: Vendors and SourcesLinked by Structure

Vincristine: PatentsLinked by Name

Vincristine: ArticlesLinked by Name

ChemSpider Resources for Chemistry

Micropublishing Syntheses

ChemSpider SyntheticPages

Olympicene

So you Want a Profile???

Interactive Data

PharmaSea

• Dereplication via ChemSpider• Segregation of natural products datasets• Analytical data algorithms & integration

– Mass spec searching – predicted fragmentation

– NMR feature searching – NMR prediction– Computer-assisted structure elucidation

It is so difficult to navigate…

What’s the structure?What’s the structure?

Are they in our file?

Are they in our file?

What’s similar?What’s similar?

What’s the target?

What’s the target?Pharmacology

data?Pharmacology

data?

Known Pathways?

Known Pathways?

Working On Now?

Working On Now?Connections to

disease?Connections to

disease?

Expressed in right cell type?

Expressed in right cell type?

Competitors?Competitors?

IP?IP?

• 3-year Innovative Medicines Initiative project

• Integrating chemistry and biology data using semantic web technologies

• Open source code, open data and open standards

• Academics, Pharma companies, Publishers….

ChemSpider Contributions

• The host of the chemistry services– Supplier of “standardized” chemical data files– Chemistry searching (structure, substructure etc)– Provider of data in RDF format – Curator and data quality checking

• Now building the Open PHACTS chemical registration system

ChemSpider Contributions

• Supplier of chemistry UI components• “Quality Police” for data checking • Chemical Validation and Standardization Platform• Nanopublications from RSC publications

Integrate to instruments and software

• Integration to analytical instrumentation vendors already in place – Agilent, Bruker, Thermo, Waters

• Also, Cheminformatics vendors link to ChemSpider– Accelrys, ACD/Labs, ChemAxon, iChemLabs, and…

Natural Products Updates

• Names hard, Structures “Obvious”

• New content based on monthly updates of the database

• Click through to the Natural Products Updates entry

National Chemical Database Service

Chemical Database Service• National Chemical Database

Service for UK Academics

• Integrating Commercial Databases and Services

• Chemicals, analytical data, prediction algorithms

• Development of data repository

Publications - a summary of work

• 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?

• How much data is lost?– How many compounds never reported?– How many syntheses fail or succeed?– How many characterization measurements?

Community Repository for Data• Funding agencies encourage sharing of data• Increasing availability of “Open Data”• Institutional repositories no specific domain

support • Develop a community repository for chemistry

data – private, public, embargoed• Provides data to develop models/algorithms

Community Repository for Data• Automated depositions of data• DOI’ed data objects for citation purposes• A database of reference data, but validated by

the community • National services feeding the repository –

crystallography, mass spectrometry• Integrate to blogging tools for chemistry• Integrate to Electronic Lab Notebooks as feeds

Model Building with Community Data

• Community data as a basis of model building– Consume data from available databases, community

data, new publications and build predictive algorithms for the community

– How many algorithms are reported and lost? How much repeat work is done in the domain of algorithmic development?

Pulling Data from our Archive

• Our contribution to the world of chemistry data• DERA – digitally enabling the RSC archive

– Text mining• Find chemicals, reactions, analytical data, properties

– Algorithmic checking• Validate algorithmically what we can - robots

– “Web 2.0 interfaces” for curating and validating

What if we could capture it all?Digitally Enhancing the RSC Archive

Data Validation and Curation Required

Encouraging Participation with Rewards and RECOGNITION

Manual Curation

• Integrated commenting, curating and validation platform across ALL eScience and publishing platforms

• All integrated to a central RSC profile and feeding the AltMetrics tools

Structure Review

Maybe Hybrid Man-Machine

Where we are now…

Rewards and Recognition

Congratulations! Your 1st CSSP article has been published. Philosopher Lao Tzu said “A journey of a thousand miles begins with a single step”. In the same way we hope that this will be the first of many submissions that you make to CSSP.

The First Step badge is awarded when a user submits (& has published) their 1st CSSP article.

Future Recognition in AltMetrics?

ChemSpider

Internet Data

The Future

Commercial SoftwarePre-competitive Data

Open ScienceOpen DataPublishersEducators

Open DatabasesChemical Vendors

Small organic moleculesUndefined materialsOrganometallicsNanomaterialsPolymersMineralsParticle boundLinks to Biologicals

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

Acknowledgments

• Valery Tkachenko and the eScience team• Our data providers, depositors, collaborators

and curators• Software providers – OpenEye, ChemDoodle,

ACD/Labs, GGA Software, Open Source (Jmol, JSpecView, OpenBabel)

Thank you

Email: williamsa@rsc.org Twitter: @ChemConnectorPersonal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams