Journal of Materials Chemistry A - Royal Society of Chemistry
Ontology work at the Royal Society of Chemistry
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Transcript of Ontology work at the Royal Society of Chemistry
Ontology work at the Royal Society of ChemistryAntony J. Williams, Colin Batchelor, Peter Corbett, Jon Steele and Valery Tkachenko
ACS Dallas
March 16th 2014
Royal Society of Chemistry
• You know us as a publisher and society but
• We are a host of chemistry databases• We are a charity and community support• We are a provider of grant-based services• We are an innovator in cheminformatics
We have data to manage…
• Compounds
• Reactions
• Spectra
• Crystals
• Materials
• Assays
• Algorithms
• …
We have data to manage…
• Compounds
• Reactions
• Spectra
• Crystals
• Materials
• Assays
• Algorithms
• …
Properties - experimental
Physicochemical properties
LONG LIST: log P, log D (at pH 5.5, at pH 7.4), bioconcentration factor, KOC (at pH 5.5, at pH 7.4), index of refraction, polar surface area, molar refractivity, molar volume, polarizability, surface tension, density at STP, flash point at 1 atm, boiling point at 1 atm, enthalpy of vaporization at STP, vapour pressure at STP…
All are amenable to ontologiesand should blend standards
• Compounds and properties are handled (InChIs are important)
• Reactions are covered (and RInChIs help)• Spectra (JCAMP, AnIML, NetCDF, mzML)• Crystals (CIFs)• Materials (MatML)• Assays (MIAME)• Algorithms• …
ChemSpider Reactions
ChemSpider Spectra
ChemSpider is 7 years old
• When ChemSpider was developed ontologies were not directly implemented
• The ontologies and technologies have developed and more accepted in seven years
• Some efforts have been made to include ontologies – layer on MeSH. We support a lot of standards – InChI, RInChI, JCAMP, CIF
• The ChemSpider architecture is being rebuilt and considering new standards and ontologies
Some available ontologies…
• RSC has built and opened in-house ontologies:• Chemical methods (CHMO)• Name reactions (RXNO) • Molecular processes (MOP), largely auto-generated
from the corresponding ChEBI classes
• We have contributed to external ontologies:• Small molecules (ChEBI)• Cheminformatics (CHEMINF)
Chemistry ontologies 1
ChEBI (molecules, families of molecules, parts of molecules, 32128 fully annotated classes) (http://www.ebi.ac.uk/chebi/)
perylene (CHEBI:29861) a perylene (CHEBI:60201) perylene skeleton (CHEBI:60200)
ChEBI Ontology
RSC Ontologies
Chemistry ontologies 2
Chemical Methods Ontology (http://rsc-cmo.googlecode.com)
2745 classes describes methods used to: •collect data in chemical experiments, such as MS and NMR•prepare and separate material for further analysis, such as sample ionisation, chromatography, and electrophoresis •synthesise materials, such as continuous vapour deposition •also describes the instruments used in these experiments, such as mass spectrometers and chromatography columns and their outputs•Should be of value to chemical hazards and safety data
Chemistry ontologies 3
RSC Name Reaction Ontology
(http://rxno.googlecode.com/)
421 classes
Examples:
Diels–Alder cyclization
Chemistry ontologies 4
CHEMINF(http://code.google.com/p/semanticchemistry/)
638 classes Describes cheminformatics methods. Not presently used in text mining (see Open PHACTS usage later).
doi:10.1371/journal.pone.0025513
Limits of ontologies
Chemical space is very big:
‘The “small molecule universe” (SMU), the set of all synthetically feasible organic molecules of 500 Daltons molecular weight or less, is estimated to contain over 1060 structures, making exhaustive searches for structures of interest impractical.”
Virshup et al., J. Am. Chem. Soc., doi:10.1021/ja401184g
Why a named reaction ontology?
• Despite attempts to introduce systematic
nomenclature for organic reactions, lots of
chemists still prefer to attach human
names.
A big challenge
• Classification is based on what the experimenter intends
• Build the ontology around intended product molecules rather than might be by-products
• (Carbon dioxide, water, hydrolysed protecting groups, protons, etc. etc.)
Defining the skeleton
Limits of reaction classification
• Much of RXNO is still classified by hand
• Example: we can’t just define a cyclization as
a reaction where a cyclic compound is formed.
The Friedel–Crafts acylation produces a cyclic
compound but is not a cyclization!
RXNO in the wild
510 classes in the RXNO namespace
… and RXNO is built in to NextMove
Software’s reaction identification tool.
RXNO: next steps
• More reactions!
• More cross-references!
• More example reactions!
• Links to graphical versions! (All drawn, just
awaiting uploading.)
• More SMIRKS strings!
Using ontologies in text mining
• To provide a controlled vocabulary of terms found in text and a common identifier.
• This identifier hopefully is a resolvable HTTP URI, for example, for chemical compounds http://purl.obolibrary.org/obo/CHEBI_36063 ) and to methods terminology
Ontologies as synonym sets for text-mining
• We have text-mined the whole 21st century
RSC archive with a myriad of ontologies.
Results are on the publishing platform
• We have looked for correlations between
molecules and ontology terms.
• Two examples follow…
Co-occurrences with ?
alcohols (CHEBI:30879) solvents (CHEBI:46787)
coproporphyrins (CHEBI:23388) 3D DOSY-TOCSY
(CHMO:0001950) lipase activity (GO:0016298) solvolysis
(MOP:0000620) wood (ENVO:00002040) aliphatic alcohol
(CHEBI:2571) Raman circular dichroism spectroscopy
(CHMO:0001160) propoxy group (CHEBI:46881) steam
reforming (CHMO:0001450) hydrogenation (MOP:0000589)
aqueous-phase reforming (CHMO:0001444) sonication
(CHMO:0001707)
Co-occurrences with ?
reducing agent (CHEBI:63247) ascorbic acid (CHEBI:22652)
antioxidant (CHEBI:22586) reduction (MOP:0000569) electrode
(CHMO:0002344) ascorbate (CHEBI:22651) modified residue
(SO:0001089) phosphate buffer (CHMO:0001734) oxidation
(MOP:0000568) nafion polymer (CHEBI:61428) vitamin C
(CHEBI:21241) antioxidant activity (GO:0016209) atom-transfer
radical polymerisation (MOP:0000684) detection of glucose
(GO:0051594) reducing agent (CHEBI:63247) glucose
(CHEBI:17234) graphene (CHEBI:36973)
Projects and Ontologies
• 3-year Innovative Medicines Initiative project
• Integrating chemistry and biology data using semantic web technologies
• Open source code, open data and open standards
• Academics, Pharmas, Publishers…• To put medicines in the pipeline…
The Open PHACTS community ecosystem
Our RDF schema
Two dozen calculated properties >106 molecules•CHEMINF ontology for cheminformatics•QUDT for units and numeric values•ChemSpider IDs for molecules
Calculation
connection table
has_input
benzeneis_about
calculated log Phas_output
dimensionless
has_unit 2.177has_value
0.234has standard
uncertainty
RSC data in Open PHACTS
1. Molecule synonyms and identifiers
2. Linksets between ChEBI, ChEMBL, DrugBank
and OPS identifiers
3. Molecule–molecule relations (“parent–child”) of
interest for drug discovery
4. Calculated physicochemical properties for
compounds (both molecular and macroscopic)
Synonyms and identifiers
Newly added to the CHEMINF ontology:
•Validated ChemSpider synonyms•Unvalidated ChemSpider synonyms•Validated database identifiers•Unvalidated database identifiers •InChI, InChIKey, SMILES •Preferred ChemSpider name
Physicochemical properties
log P log D (at pH 5.5, at pH 7.4) bioconcentration factor KOC (at pH 5.5, at pH 7.4) index of refraction polar surface area molar refractivity molar volume polarizability surface tension density at STP flash point at 1 atm boiling point at 1 atm enthalpy of vaporization at STP vapour pressure at STP
It is actually more complicated..
benzene’s connection table
OPSbenzene
calculation result
QUDTdimensionless
quantity
“2.17”^^xsd:float
IAOis about
OBIhas specified
output
OBIhas specified
input
QUDThas value
QUDThas standard uncertainty
QUDThas unit
CHEMINFcalculated log P
rdf:type
CHEMINFconnection table
rdf:type
“0.234”^^xsd:float
calculation process
CHEMINFexecution of ACD/Labs
PhysChem software library version 12.01
rdf:type
What’s built on top of this?
Chemistry Data to manage…
• Compounds
• Reactions
• Spectra
• Crystals (in development)
• Materials
• Assays
• Algorithms
• …
Future Work
• Extending use of ontologies across all of our work on databases and as an underpinning to the Chemical Data Repository
• Adding ontologies to other grant-based projects such as PharmaSea
• Continued collaborations with University of Southampton on Labtrove for Chemistry
• RSC collaboration with Dr Stuart Chalk (UNF) on data standards and ontologies
• Working with CHAS on hazard/safety data
Thank you
•Email: [email protected]•ORCID: 0000-0002-2668-4821 •Twitter: @ChemConnector•Personal Blog: www.chemconnector.com •SLIDES: www.slideshare.net/AntonyWilliams