Chemical ontologies: what are they, what are they for, and what are the challenges

EBI is an Outstation of the European Molecular Biology Laboratory.

Chemical Ontologies

What are they?What are they for?What are the challenges?

Janna Hastings, EBI Chemoinformatics and Metabolism

6th German Conference on Chemoinformatics, Goslar, 8 November 2010

Problem

How do we find the informationwe need?

Data deluge

Multiple databases, heterogeneous data

Ambiguity, multiple synonyms

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Data lost in

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Intelligent systems

The answer is42

I’ll show you why

Logical inference

All men are mortal

Socrates is a man

Therefore, Socrates is mortal

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finding the implications of what you know

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Community terminological standardisation

Dictionary: synonyms, definitions

Hierarchical organisation

Logical model allowing computer inferences beyond what is explicitly encoded

Knowledge-based applications

Ontologies to filter and organise data

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The Web Ontology Language (OWL)

Hierarchicalorganisation

SynonymsCross-references

Logicaldefinitions

Can be re-used inmultiple applications

root

leaves

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ChEBI Ontology

Chemical entity Role

catecholamines

Biological role

Application

hormone

vasodilator agent

(R)-adrenaline

CHEMINF Ontology

DescriptorSoftware library

ACD Labs

logP

-.539-2.369

logD

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Chemical entity

carboxylic acid

acetylsalicylic acid(aspirin)

chlorfenvinfos

organophosphorouscompound

aldehyde

organic molecular entity

inorganic molecular entity

pyridoxal(vitamin B6)

sodium chloride

Molecular entity

Group hydroxy group

Chemical substance

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Role

analgesic

acetylsalicylic acid(aspirin) chlorfenvinfos

insecticide

vitamin

pyridoxal(vitamin B6)

Biological role Application

drug

pesticide

Chemical role

acid

sulfuric acid

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Chemical information entity

DescriptorSoftware library

CDK

logP

OpenBabel

Algorithm

MolecularDescriptor

implements calculates

SubstanceDescriptor

atom count

boiling point

melting pointlargest chain

fused cycles

Hueckel’saromaticity

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Chemical database Bioactivity

databaseBioactivity database Metabolism

databaseMetabolism database

Pathway database

LiteratureLiterature

Chemical entities

Roles

Properties

Unified browsing and querying

Disentangling hierarchies

Disambiguating terminology

Ontology representation in a complex domain

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Sounds great, but...

What are the challenges?

Chemicals and roles

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de Matos, P. et al: Chemical Entities of Biological Interest: an update. NAR Database issue 2010

vitamin

hormone

neurotransmitter

CNS stimulant

carboxylic acid

peptide

trimethylxanthine

polycyclic cage

has role

Chemicals and structures

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J. Hastings, C. Batchelor, C. Steinbeck, S. Schulz: What are chemical structures and their relations? FOIS 2010

chemical entity

molecule

chemical graph

molecular structure

has attribute

What is the structure of Vancomycin?

Representing complex structures

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Chemical classes can be defined by

parts of structures

and/or properties of structures

carboxylic acid

cyclic molecule

if molecule has part some carboxy group

if molecule has property cyclic, i.e. a self-connectedcyclic path exists through the molecule’s atoms

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Pre-compute and assert all parts and properties

Represent atoms and bonds in ontology

Integration of chemoinformatics and ontology toolsIntegration of chemoinformatics and ontology tools

J. Hastings et al.: Representing chemicals using OWL, description graphs and rules. OWLED 2010

Purpose and mode of action

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epinastine

application

antiallergic drug

is a

biological role

histamine antagonist

is a

has rolehas role

C. Batchelor, J. Hastings, C. Steinbeck: Ontological dependence, dispositions and institutional reality in chemistry. FOIS 2010

Single molecule

Independent ofintent

Bulk quantity of molecules

Depends on human intent(e.g. license, prescription)

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Conditions in bioactivity models

Consider aspirin as treatment for a headache

Too few individual molecules will have no effect

Too many tablets will have unpleasant additional effects

Image credit: tell.fll.purdue.edu

J. Hastings, C. Steinbeck, L. Jansen, S. Schulz: Substance concentrations as conditions for the realization of dispositions. ISMB Bio-Ontologies SIG 2010

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Christoph Steinbeck

Paula de Matos

Marcus Ennis

Steve Turner

Adriano Dekker

Kenneth Haug

Rafael Alcántara Martin

Zara Josephs

Pablo Moreno

Kalai Jayaseelan

Mark Rijnbeek

Nico Adams

Colin Batchelor, RSC

Stefan Schulz, Freiburg

Egon Willighagen, Uppsala

Michel Dumontier, Carleton

Leonid Chepelev, Carleton