chebi and sabio-rk: association of chemical compound information and reaction kinetics data ulrike...
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ChEBI and SABIO-RK: Association of chemical compound
information and reaction kinetics data
Ulrike Wittig Scientific Databases and Visualization Group
EML Research, Heidelberg
Substrates
Products
Enzyme
Activator
Inhibitor
Modifier
Biochemical reaction
Reaction kinetics
Vmax maximal enzyme velocity
KM Michaelis-Menten constant (k2+k-1)/k1
• Essential for simulations of biochemical reactions /pathways (not only parameter values but also rate law equations)
• Dependency on environmental conditions
• Dependency on biological location (organism, tissue, cellular location)
• Data must be easily accessible and interchangeable
Collection and standardization of reaction kinetics data Links to biochemical, environmental and experimental context Links to corresponding data of external resources Complex search and export functions
Reaction kinetics
SABIO-RK
SABIO-RK describes Reaction Kinetics and is an extension of SABIO (System for the Analysis of Biochemical Pathways)
SABIO
Pathways
Reaction
Enzymes
Reactants
Organisms
SABIO-RK
Concentrations
Kinetic Law
Environment
Reactants
Parameters
• Automatic extraction of information from other databases (e.g. KEGG)
• Kinetic data manually extracted from literature
• Kinetic data directly obtained from laboratory experiments
• Manual curation, assisted by semi-automatic tools for standardization (unification, structuring, normalization, annotation)
• Access through a web-based user interface
• Access through web-services
• Export in SBML (Systems Biology Markup Language) format
Data flow
Automatic input(XML based)
SABIO-RKDatabase ofexperimental
raw data
Storage of kinetic data(e.g. Km, Vmax)
Link to original data
Data access
Generation of experimental data
Collaboration with Douglas Kell, Neil Swainston(Manchester Center for Integrative Systems Biology)
Manual data input
• Kinetic data from publications
• Tables, Formula, Graphs, Pictures
• Some assay conditions or methods description only noted as reference
• No controlled vocabulary in the literature (different names of compounds, enzymes etc.)
• Missing or incomplete information
-Incomplete reactions (e.g. products not mentioned)
-Missing organism specification
-Isoenzyme not specified (old papers)
Web-based input interface
Input interface
Curation
• Data first inserted in an intermediate database
• Curation process (search for errors and inconsistencies)– Manually by biological experts– Semi-automatically by consistency checks– Standardization– Unification– Annotation to controlled vocabularies and external databases
• Transfer data from intermediate to public SABIO-RK database
Curation of chemical compounds Search for multiple entries for identical compounds
– KEGG IDs: C00201, C03802
– SABIO-RK ID: 1674
– ChEBI IDs: 37413, 37076
– KEGG IDs: C00677, C04283
– SABIO-RK ID: 1690
– ChEBI IDs: 16381, 16516
Identification of identical chemical compounds
Goal:
Linking different databases by names of chemical compounds(e.g. ChEBI, KEGG, PubChem)
Methods developed to support curation:
Normalization of compound namesAnalysis of compound names and generation of SMILES stringGeneration of chemical structure based on SMILES stringClassification of chemical compounds
Normalization of compound names
Examples of normalization rules:
-Lowercase letters only-Normalize different types of brackets to one type-Remove spaces-Replace ‘-p’ at end of name by ‘-phosphate’-Replace all suffixes ‘-phosphate’ by prefixes ‘phospho-’-Replace ‘ate’ followed by a delimiting character by ‘ic acid’ (acid-base pairs)-Three-letter amino acid code get replaced by full amino acid names -Prefixes of Chemical Compound names are normalised by sorting them: 2-propanone-1-amino-3-(phosphono… 1-amino-2-propanone-3-(phosphono…
-Identification of synonymous parts in different names …valpro... ...2-propylpentano...
Generation of lists of normalized compound names for different databases (e.g. SABIO-RK, ChEBI, KEGG, PubChem)
Matching the lists from different databases to find synonyms of chemical compounds
Analysis of compound names
Classification of compounds
- Generation of structural formula, totals formula and molecular weight based on SMILES string
- Rules for compound classifications
- Graph and sub-graph search for functional groups
- Classification using different criteria, for example D-Glucose is a:
-Aldose (functional group aldehyde)-Hexose (number of C-Atoms = 6)
SABIO-RK search for general compounds and all sub-classes
Access to SABIO-RK
Web-based user interface
for browsing and searching the data manually
Web services (API access)
can be automatically called by external tools, e.g. by other databases or simulation programs for biochemical network models
(http://sabio.villa-bosch.de/SABIORK/webservice.jsp)
SABIO-RK web interface
• Web access to search for general reaction information, kinetic laws, kinetic parameters, experimental conditions etc.
• Colour-coded representation of results
– Kinetic data available matching search criteria
– Kinetic data available but not matching search criteria
– No kinetic data available
• Export of kinetic data in SBML (Systems Biology Mark-up Language)
• Annotations to external databases, ontologies and controlled vocabularies
Links to external databases• Cellular location
– Gene Ontology
• Protein– UniProt
• Literature source– PubMed
• Compound– KEGG– PubChem – ChEBI
• Enzyme– KEGG– ExPASy Enzyme– IntEnz– IUBMB– Reactome
Annotations in SBML
ChEBI links to SABIO-RK
SABIO-RK links to ChEBI
SABIO-RK Summary
curated data based on literature information (ca. 2000 papers with >25000 entries)
offers a platform for kinetic data storage and exchange
free available for academic use
uses existing standard data formats, controlled vocabularies and ontologies
links to original data sources (literature, databases etc.)
• Kinetic information about reaction mechanism– separate reactions for intermediate steps
• Kinetic data for signaling reactions
• Information about in vivo metabolite concentrations
• SABIO-RK as platform for experimental kinetic data– scientists producing the data can directly enter it into SABIO-RK
• Extention of web interface (less reaction oriented)– search for inhibitors/ activators (drugs) etc.– search for enzymes
Future Perspectives
Financial support:
Renate KaniaOlga KrebsAndreas WeidemannSaqib MirHenriette EngelkenMartin GolebiewskiUlrike WittigIsabel Rojas
SABIO-RK is member of:
SABIO-RK team
http://sabio.villa-bosch.de/SABIORK