ChEBI

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ChEBI
Kirill Degtyarenko, EMBL-EBI / EPO
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The team

• Rafael Alcántara
• Michael Ashburner
• Volker Ast
• Michael Darsow
• Paula de Matos
• Marcus Ennis
• Janna Hastings
• Alan McNaught
• Inma Spiteri
• Christoph Steinbeck
• Martin Zbinden

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ChEBI What is it?
Chemical Entities of Biological Interest an
EBI database/dictionary of biochemical compounds
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What are the biochemical compounds?
Can be defined as consisting of molecules not
directly encoded by the genome ... that are
either the products of nature or are synthetic
products used ... to intervene in the processes
of living organisms Michael Ashburner
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Molecular entity
Any constitutionally or isotopically distinct
atom, molecule, ion, ion pair, radical, radical
ion, complex, conformer etc., identifiable as a
separately distinguishable entity IUPAC Gold
Book
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In fact, ChEBI contains

• Molecular entities
• trans-vaccenic acid
• Groups
• trans-vaccenoyl group
• Classes
• fatty acids

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Small molecules?

• Yes, but big molecules as well!
• alumina
• amylose
• metaborate
• poly(vinyl alcohol)

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Current status (17.12.08)
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1-D ChEBI

• Numeric ID
• Carefully checked terminology
• Unambiguous ChEBI name
• IUPAC names
• Cross-references to free resources

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Unambiguous ChEBI name

• CHEBI28918
• L-adrenaline
• not just adrenaline

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Systematic Name (IUPAC)
2-3-(trifluoromethyl)phenylaminobenzoic acid
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Common Name

• flufenamic acid (INN English)
• acide flufénamique (INN French)
• ácido flufenámico (INN Spanish)
• acidum flufenamicum (INN Latin)
• Flufenaminsäure (German)

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The Unpronounceables
CHEBI48935 (E)-roxithromycin
IUPAC name (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,1
4R)-4-(2,6-dideoxy-3-C-methyl-3-O-methyl-a-L-ribo-
hexopyranosyloxy)-14-ethyl-7,12,13-trihydroxy-10-
(2-methoxyethoxy)methoxyimino-6-3,4,6-trideoxy
-3-(dimethylamino)-ß-D-xylo-hexopyranosyloxy-3,5,
7,9,11,13-hexamethyloxacyclotetradecan-2-one
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What is the common name of roxithromycin?
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Roxithromycin (2)
CHEBI48844 roxithromycin
(E)-roxithromycin
(Z)-roxithromycin
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What is thiamine?
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Need for 2-D

• Better to see the face than to hear the name
  (Zen proverb)
• Structures and identifiers based on structures
  offer new ways of crosslinking to other databases
• Structure search

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Connection table
ChEBI 9 10 0 0 0 0 999 V2000
11.8219 -7.2713 0.0000 C 0 0 0 0 0 0
0 0 0 0 0 0 11.8219 -8.0922 0.0000 C
0 0 0 0 0 0 0 0 0 0 0 0 12.6074
-7.0165 0.0000 N 0 0 0 0 0 0 0 0 0
0 0 0 11.1072 -6.8574 0.0000 C 0 0
0 0 0 0 0 0 0 0 0 0 12.6039 -8.3505
0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
11.1072 -8.5027 0.0000 N 0 0 0 0 0
0 0 0 0 0 0 0 13.0886 -7.6818
0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
10.3923 -7.2713 0.0000 N 0 0 0 0 0 0
0 0 0 0 0 0 10.3888 -8.0922 0.0000 C
0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0
0 0 0 1 3 1 0 0 0 0 1 4 1 0 0 0
0 2 5 1 0 0 0 0 2 6 1 0 0 0 0
3 7 1 0 0 0 0 4 8 2 0 0 0 0 6 9
2 0 0 0 0 5 7 2 0 0 0 0 8 9 1 0
0 0 0 M END
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2-D ChEBI

• One or more 2-D (or 3-D) connection tables
• One is default
• Autogenerated images (PNG)
• Default diagrams should be unambiguous

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The Fine Art of chemical drawing
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Linear forms of monosaccharides
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Pyranose forms of monosaccharides
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Fused systems
(R)-camphor
ambiguous
unambiguous
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Square planar geometry
cisplatin
transplatin
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From 2-D back to 1-D

• SMILES
• InChI

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SMILES (1)

• Simplified Molecular Input Line Entry
  Specification
• Developed by David Weininger in 1988
• Extended by others (e.g. Daylight)
• String of standard ASCII characters
• A number of valid SMILES can be produced for the
  same molecule

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SMILES (2)

• N1CNC2C1CNCN2
• c1ncc2ncnc2n1
• C1N\CN/C\2N/CN\C1/2
• c1ncnc2/NC\Nc12
• n1cc2c(nc1)ncn2
• Hc1nc(H)c2n(H)c(H)nc2n1

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InChI (1)

• IUPAC International Chemical Identifier or InChI
• Open source
• Developed by Stein, Heller, Tchekhovskoi and
  McNaught
• Used by NIST, PubChem, CML and ChEBI

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InChI (2)
InChI1/C5H4N4/c1-4-5(8-2-6-1)9-3-7-4/h1-3H,(H,6,7
,8,9)/f/h7H
InChIKeyKDCGOANMDULRCW-QDQILVOLCG
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Limitations (1)

• Stereochemistry other than sp3 tetrahedral and
  sp2 trigonal planar
• Polymers
• Conformers
• Radicals/different spin state
• Topological isomers
• Mixtures
• Markush structures

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Limitations (2)
cisplatin
transplatin
InChI1/2ClH.2H3N.Pt/h21H21H3/q2/p-2
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3-D ChEBI
cisplatin
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Uncertainty and ambiguity in chemistry

• Compositional uncertainty
• Positional uncertainty
• Configurational uncertainty
• Conformational uncertainty

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Compositional uncertainty

• Examples
• an alkali metal cation
• vanadate(V) anion
• 2Hethanol

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Positional uncertainty

• Examples
• L-bromohistidine residue
• pteroic acid (several tautomers)

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Configurational uncertainty

• Examples
• androstane
• rel-(2R,3R)-2-amino-3-methylpentanoic acid
• tetradec-11-enoic acid

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Conformational uncertainty

• Examples
• cyclohexane chair, boat, twist
• protein secondary structure ?, ?, ?

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ChEBI ontology

• Molecular structure ontology
• Subatomic particle ontology
• Role ontology
• Biological role
• Application

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L-adrenaline

• Molecular structure ontology
• catecholamines
• Biological role
• hormone
• Application
• antiglaucoma
• bronchodilator
• cardiostimulant

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The family relations
L-cystein-S-yl
L-cysteine()
L-cysteine zwitterion
cysteine
D-cysteine
L-cysteino
L-cysteine
L-cysteinium
L-cysteinyl
L-cysteinate(1)
L-cysteine residue
L-cysteinate(2)
L-cysteinate residue
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Relationships in ChEBI
? Is A generic
? Has Part generic
? Is Conjugate Acid Of specific
? Is Conjugate Base Of specific
? Is Enantiomer Of specific
? Is Tautomer Of specific
R Is Substituent Group From specific
H Has Parent Hydride specific
F Has Functional Parent specific
? Has Role generic?
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Is A relationship
?
L-cysteine
cysteine
is a
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Is Enantiomer Of
?
L-cysteine
D-cysteine
is enantiomer of
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Has Part
has part
?
L-cysteinium
L-cysteine hydrochloride
is part of
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Is Conjugate Acid Of
L-cysteinium
L-cysteinate(2)
L-cysteine
L-cysteinate(1)
is conjugate acid of
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Is Conjugate Base Of
L-cysteinium
L-cysteinate(2)
L-cysteine
L-cysteinate(1)
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Acid/base relationships
L-cysteinium
L-cysteinate(2)
?
?
L-cysteine
L-cysteinate(1)
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Is Tautomer Of
L-cysteine
L-cysteine zwitterion
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Is Tautomer Of
1H-pyrrole
3H-pyrrole
2H-pyrrole
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Has Parent Hydride
is parent hydride of
H
salutaridinol
has parent hydride
morphinan
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Has Functional Parent
is functional parent of
F
7-O-acetylsalutaridinol
has functional parent
salutaridinol
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Is Substituent Group From
L-cysteine


L-cysteinyl
L-cysteino


L-cysteine residue
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The family relations
L-cysteine()
L-cysteinium
L-cystein-S-yl
cysteine
L-cysteine zwitterion
L-cysteine
D-cysteine
L-cysteino
L-cysteinyl
L-cysteinate(1)
L-cysteine residue
L-cysteinate(2)
L-cysteinate residue
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Ontology of L-cysteine
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Ontology of L-cysteine (1)
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Ontology of L-cysteine (2)
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Thank you