SABIO-RK Making Reaction Kinetics Data

Accessible

Martin GolebiewskiEML Research, Heidelberg, Germany

Biochemical Pathways

Enzyme Kinetics

Calculation of reaction rates:

SKSV

vm

m

Kinetic Law:

Kinetic Parameters:

Vm = Maximum velocity

Km = Michaelis Constant

e.g. Michaelis-Menten Kinetics

Kinetic Data: Database Resources

BRENDA

http://www.brenda.uni-koeln.de/

Comprehensive list of kinetic parameters based on literature information

UniProt Knowledgebase/Swiss-Prot

http://www.expasy.org/

Represents kinetic parameters in comment lines of proteins (new feature)

BioModels Database

http://www.ebi.ac.uk/biomodels/

Stores published mathematical models of biological interests

Why Another Kinetics Database ?

• Kinetic parameter values depend on environmental conditions (temperature, pH, concentrations, experimental assay, etc.)

• Parameters only interpretable with their corresponding kinetic laws

• None of the databases links experimental kinetic parameter data for single reactions to complete sets of information comprising- Kinetic Law for the reaction rate- Environmental conditions- Concentrations of reactants and modifiers- Data source (original publication)- Organism, tissue and cellular location

• Kinetic Data must be easily accessible and interchangeable

We need an accessible database that merges this informationfor published kinetic data

SABIO-RK: Database populationSABIO-RK describes Reaction Kinetics and is an extension of SABIO (System for the Analysis of Biochemical Pathways)

SABIO

Pathways

Reaction

Enzymes

Reactants

Organisms

Extraction

KEGG

UniProt

Other DBs

SABIO-RK

Concentrations

Kinetic Law

Environment

Reactants

Parameters

KineticData(publ.)

KineticData(publ.)

Pub

Pub

SABIO-RK: Database populationWorkflow

Kinetic data manually extracted from literature by students

Intermediate SQL databaseInputinterface

Curators verify andcomplete the data andcheck it for consistency

Data structuring

Integration into a relational database (Oracle)

SABIO-RK / SABIO

Information to unify the data

SABIO-RK: Database population Curation Problems

• Information missing in publications about assay proceedings,experimental conditions or complete reactions (with all reactants)

• Synonymic or aberrant notations of compounds and enzymes:- different nomenclature systems used- commonly used trivial names vs. systematic names- functional classification of enzymes vs. physical enzyme proteins (e.g. only 1 EC-class for hundreds of protein kinases)

• Multiplicity of parameter units:- mass or molar concentrations (mg/ml vs. mmol/l)- different systems (e.g. katal, unit or mol/min for enzymatic activity)- enzyme activities can be specific (unit/mg) or absolute (unit)- different scales (e.g. M, mM, µM, nM)

SABIO-RK: Database population Statistics

• 20 students extracting kinetic data from literature

• 3 curators verifying and inserting data into SABIO-RK

• 735 publications entered by students (7180 entries for 1900 reactions)

• Integrated in SABIO-RK:

~ 4500 Entries (38% with kinetic law equation)

~ 1000 Different reactions (in 170 organisms)

~ 300 Different enzymes (EC classes)

~ 11300 Kinetic parameters: 4014 Km and similar3666 kcat and Vmax852 Ki (inhibitor

constants)

SABIO-RK

SABIO-RK: User interface

• Web-accessible and freely available for academic users

• Users can query SABIO-RK by specifying- reactants, enzymes and/or pathways- organisms, tissues and cellular locations- experimental conditions (pH, temperature)

• Links to other databases:- SwissProt (for protein information about enzymes)- PubMed (to refer to original publication)

• System supports export of the selected kinetic data in SBML(Systems Biology Mark-up Language) format

SABIO-RK: SBML output

Aldolase reaction

Glycolysis reactions

SABIO-RK: Future Perspectives

• Extension of search functions in the user interfacee.g. find pathway from one compound to another

• Expansion of the data export functions in the user interfaceInformation very limited that can be exported in SBML format

• Description of the detailed mechanism of the reactionse.g. elementary steps with corresponding rate constants

• Annotation to other hierarchy levels (building ontologies)e.g. integration of classification tools for chemical compounds

• Annotation to other databases and usage of controlled vocabularye.g. BioModels, ChEBI, KEGG, UniProt/SwissProt

SABIO-RK: Future Perspectives

• (Semi-)Automatic extraction of kinetic data by text mining tools

Problems:- Publications containing kinetic data have to be identified- Most of kinetic data found in tables, graphs or figures- Reaction formulas and kinetic law equations are mainly pictures- Automatic annotation of compounds, parameters, etc. is difficult

Manual data extraction might help to find rules for text mining.

• SABIO-RK as platform for experimental kinetic data

- Scientists producing the data can directly enter it into SABIO-RK- All the needed information can be given by the experimenters- No data lost or questionable because of missing information

Summary• SABIO-RK is a web-accessible database containing biochemical

reaction kinetics data for systems biologists and experimenters

• Merges general reaction information retrieved from otherdatabases and kinetic data manually extracted from literature

• High degree of interrelation (all necessary information is linked)

• Type of kinetics, modes of inhibition or activation and corresponding equations are shown with their parameters, measured values and experimental conditions

• Kinetic data can be exported in SBML file format

• http://sabio.villa-bosch.de/SABIORK

Acknowledgements

Scientific Databases and Visualization Group:• Renate Kania and Ulrike Wittig (database curators)• Andreas Weidemann (programming: input interface, SQL database)• Olga Krebs (database administration)• Saqib Mir (programming: user interface, web-services)• Isabel Rojas (programming and trying to organize all this)• all our students entering the data

For helpful discussions:• Ursula Kummer, Sven Sahle, Ralph Gauges (BCB-Group)• Rebecca Wade and Matthias Stein (MCM-Group)

Thank you !