Cheminformatics and Metabolism

Chemical resources (structure, bioactivity and metabolomics): ChEBI, MetaboLights and the Enzyme Portal

SME Bioinformatics Forum, Barcelona 8-9 October 2012

Pablo Conesa

EBI is an Outstation of the European Molecular Biology Laboratory. Overview

• ChEBI

Enzyme • Enzyme Portal Portal

• MetaboLights

2 29.10.2012 ChEBI – Chemical Entities of Biological Interest ChEBI dictionary of „small‟

EBI is an Outstation of the European Molecular Biology Laboratory. What is ChEBI?

• Chemical Entities of Biological Interest • Freely available • Focused on „small‟ chemical entities (no or nucleic acids) • Illustrated dictionary of chemical nomenclature • High quality, manually annotated database • Provides chemical ontology

Access ChEBI at http://www.ebi.ac.uk/chebi/

4 29.10.2012 ChEBI – Chemical Entities of Biological Interest Chemicals - ChEBI

Nomenclature Ontology metabolite 1,3,7-trimethylxanthine CNS stimulant methyltheobromine trimethylxanthines

Chemical data Database Xrefs Formula: C8H10N4O2 MSDchem: CFF Charge: 0 KEGG DRUG: D00528 Mass: 194.19

Chemical Informatics Visualisation InChI=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 Small annotations

• Often appear as free text in biological databases, in which they are not the core data • Are frequently referred to by common names which may be chemically ambiguous • eg. = (S)-adrenaline ? (R)-adrenaline ?

• May be referred to by several different names • , acetaminophen, 4-acetamidophenol, N-(4-hydroxyphenyl)acetamide, …

ChEBI home page

13 29.10.2012 ChEBI – Chemical Entities of Biological Interest ChEBI entries contain

• A unique, unambiguous, recommended ChEBI name and an associated stable unique identifier • An illustration where appropriate (compounds and groups, but generally not classes) • A definition where appropriate (mostly classes) • A collection of synonyms, including the IUPAC recommended name for the entity where appropriate • A collection of cross-references to other databases

• Links to the ChEBI ontology

14 29.10.2012 ChEBI – Chemical Entities of Biological Interest ChEBI entry view

15 29.10.2012 ChEBI – Chemical Entities of Biological Interest Automatic Cross-references

16 29.10.2012 ChEBI – Chemical Entities of Biological Interest Chemical Structures

• Chemical structure may be interactively explored using MarvinView applet

• Available in formats • Image • Molfile • InChI and InChIKey • SMILES

17 29.10.2012 ChEBI – Chemical Entities of Biological Interest How is ChEBI maintained?

• Automatic loading of preliminary data

• Automatic loading of data annotated elsewhere

• Manual annotation

• User requests via Submission Tool

• Public release: First Monday of every month.

18 29.10.2012 ChEBI – Chemical Entities of Biological Interest For more information

• Email: [email protected]

• SourceForge: https://sourceforge.net/projects/chebi/

• User Manual: http://www.ebi.ac.uk/chebi/userManualForward.do

• RSS Feed

19 29.10.2012 ChEBI – Chemical Entities of Biological Interest The EBI Enzyme Portal Your portal to enzyme-related information at the EBI

EBI is an Outstation of the European Molecular Biology Laboratory. The Enzyme Portal integrates EBI’s enzyme resources into a single access point

MACiE ChEMBL

Enzyme Portal

InterPro Enzyme Portal home page Enzyme Portal Results Page Enzyme Portal Entry Summary Enzyme Portal Structure Enzyme Portal Reactions/Pathways Enzyme Portal Small Molecules Enzyme Portal Small Molecules Enzyme Portal Diseases Enzyme Portal Literature Online training – Quick Tour

• http://www.ebi.ac.uk/training/online/course/enzyme-portal- quick-tour

34 29.10.2012 ChEBI – Chemical Entities of Biological Interest MetaboLights a repository for metabolomics experiments and derived information

EBI is an Outstation of the European Molecular Biology Laboratory. MetaboLights - Goal

Create the first open cross-species, cross- platform metabolomics repository

http://www.ebi.ac.uk/metabolights (metabolights.org, metabolights.eu) 29 October 2012 36 29 October 2012 MetaboLights – Main components

• Data Submission✔ • ISA creator • Online data deposition

• Repository ✔ • Complete metabolomics experiments/studies • Sharing Experiments

• Reference Layer • Metabolite identification • Curated

37 29/10/2012 MetaboLights – Data Submission Channels

• ISAcreator

• Bulk submission pipeline

38 29/10/2012 ISAcreator

Nature Genetics doi:10.1038/ng.1054 Susanna-Assunta Sansone,…... Haug, Neumann, de Matos, Griffin, Steinbeck, ….. and Hide

39 29 October 2012 ISAcreator - Study

42 29 October 2012 ISAcreator - Assays

43 29/10/2012 ISAcreator - Metabolite Identification plugin

29 October 2012 44 MetaboLights – Repository Website

http://www.ebi.ac.uk/metabolights (metabolights.org, metabolights.eu)

45 29 October 2012 MetaboLights – Private data

46 29 October 2012 MetaboLights – Study Details

47 29 October 2012 MetaboLights - Search

48 29 October 2012 MetaboLights – Download page

49 29/10/2012 MetaboLights - Curation

Nomenclature Species Tissues GC Disease NMR MS Crossrefs Organs Structure LC Cell Types Identifier Pathways

Reference Reference Reference Spectroscopy Chemistry Biology

Publication

Experimental Repository MetaboLights

50 29 October 2012 MetaboLights – The way forward

• Standards, MSI compliance • Filling a gap, “First of a kind” • Journals • Stable identifiers • High demand • High quality curated data • Listening to our users • Open Data Access

51 29/10/2012 Thank you

Any questions?

EBI is an Outstation of the European Molecular Biology Laboratory.