Pipeline for automated structure-based classification in the ChEBI ontology
15
Pipeline for automated structure-based classification in the ChEBI ontology Janna Hastings Coordinator, Cheminformatics and Metabolism www.ebi.ac.uk/chebi ACS Symposium on Chemical Ontologies, Taxonomies and Schemas. Dallas, 16 March 2014
-
Upload
janna-hastings -
Category
Technology
-
view
446 -
download
0
description
Presented at the ACS in Dallas: ChEBI is a database and ontology of chemical entities of biological interest, organised into a structure-based and role-based classification hierarchy. Each entry is extensively annotated with a name, definition and synonyms, other metadata such as cross-references, and chemical structure information where appropriate. In addition to the classification hierarchy, the ontology also contains diverse chemical and ontological relationships. While ChEBI is primarily manually maintained, recent developments have focused on improvements in curation through partial automation of common tasks. We will describe a pipeline we have developed for structure-based classification of chemicals into the ChEBI structural classification. The pipeline connects class-level structural knowledge encoded in Web Ontology Language (OWL) axioms as an extension to the ontology, and structural information specified in standard MOLfiles. We make use of the Chemistry Development Kit, the OWL API and the OWLTools library. Harnessing the pipeline, we are able to suggest the best structural classes for the classification of novel structures within the ChEBI ontology.
Transcript of Pipeline for automated structure-based classification in the ChEBI ontology
Pipeline for automated structure-based classification in the ChEBI ontology
Pipeline for automated structure-based classification in the ChEBI ontology
Janna Hastings
Coordinator, Cheminformatics and Metabolism
www.ebi.ac.uk/chebi
ACS Symposium on Chemical Ontologies, Taxonomies and Schemas. Dallas, 16 March 2014
Chemical Entities of Biological Interest
Freely available online, available
for download in full
Freely available online, available
for download in full
Low molecular weight, i.e. no proteins
Low molecular weight, i.e. no proteins
Definitions, relationships,
hierarchy
Definitions, relationships,
hierarchy
E.g. metabolites,
drugs, pesticides
E.g. metabolites,
drugs, pesticides
38,215 entries last release
38,215 entries last release
What does ChEBI provide?
Chemical structures and visualisations
caffeine1,3,7-trimethylxanthine methyltheobromine
Names and synonyms
Formula: C8H10N4O2Charge: 0 Mass: 194.19
Chemical data
metaboliteCNS stimulanttrimethylxanthines
Ontology – classifications
MSDchem: CFFKEGG DRUG: D00528PubMed citations
Links to more information
Chemical InformaticsInChI=1/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
SMILES CN1C(=O)N(C)c2ncn(C)c2C1=O
Example ChEBI entry page
Example entry page (continued)
Example entry page (continued)
Structure-based classification in ChEBI
Challenges with manual classification
• May be incomplete
• May be inconsistent
• Difficult to maintain (even with extensive use of computationally expensive automatic validations)
• Blocks automatic loading of otherwise high-quality externally annotated chemical data into ChEBI (as no classification available)
SOCO (SMARTS, OWL) Leonid Chepelev, Michel Dumontier, collaborators• Given a training set of classified molecules,
examine structures for consensus features across all (using fragmentation and feature detection)
• Capture features hierarchically
• Use OWL to classify
Chepelev et al. BMC Bioinformatics 2012 13:3 doi:10.1186/1471-2105-13-3
Limitations of SOCO
• No support for negation
• Only “min” (at least) counting supported, not max or exact. Thus, dicarboxylic acid is_a monocarboxylic acid (Every two-legged human is also a one-legged human in the sense that they have at least one leg…)
• SMARTS is powerful – but not very human-readable. ChEBI is for human biologist and chemist consumption. E.g. SMARTS for the class of aliphatic amines: [$([NH2][CX4]),$([NH]([CX4])[CX4]),$[NX3]([CX4])([CX4])[CX4])]
Can we do better at making definitions accessible?
A new pipeline for automated structure-based ontology classification in ChEBI
Definitions (OWL)
ChEBI structures
OWL Parser => logical
cheminformatics definitions
OWL Parser => logical
cheminformatics definitions
Novelstructure
Candidateclasses
RankingRankingBest classes: save is_a relations
MatchingMatching
Human-readable definitions, mapped to structures in ChEBI knowledgebase
thiadiazoles:molecular_entity and has_part some ( 1,2,3-thiadiazole or 1,2,4-thiadiazole or 1,2,5-thiadiazole or 1,3,4-thiadiazole )
diterpenoid: organic_molecular_entity and has_part exactly 2 terpenoid
organic ion: organic_molecular_entity and ( has_charge some int[>0] or has_charge some int[<0] )monocyclic compound: molecular_entity and has_cycles value "1"^^int
Logical operatorsLogical operators
Counts (min, max and exact)
Counts (min, max and exact)
PropertiesProperties
PartsParts
Planned integration into ChEBI tools
• ChEBI internal data loader and bulk submissions
• ChEBI online submission tool
Pre-population of matched
classes
Pre-population of matched
classes
Acknowledgements – Thanks!
ChEBI team:
Christoph SteinbeckGareth OwenAdriano DekkerNamrata KaleSteve TurnerVenkatesh Muthukrishnan
Collaborators:
Colin Batchelor, RSCLian Duan, ETHLeonid Chepelev, OttawaMichel Dumontier, StanfordDespoina Magka, OxfordIlinca Tudose and John May, EBI
Funding:
BBSRC “Continued development of ChEBI towards better usability for the systems biology and metabolic modelling communities” BB/K019783/1
Questions?
Thank you for listening!Thank you for listening!
ACS Symposium on Chemical Ontologies, Taxonomies and Schemas. Dallas, 16 March 2014
