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ChEBI and SABIO-RK: Association of chemical compound information and reaction kinetics data

ChEBI and SABIO-RK: Association of chemical compound information and reaction kinetics data Ulrike Wittig Scientific Databases and Visualization Group EML Research, Heidelberg. Modifier. Activator. Substrates. Inhibitor. Products. Enzyme. Biochemical reaction. Reaction kinetics.

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ChEBI and SABIO-RK: Association of chemical compound information and reaction kinetics data

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  1. ChEBI and SABIO-RK: Association of chemical compound information and reaction kinetics data Ulrike Wittig Scientific Databases and Visualization Group EML Research, Heidelberg

  2. Modifier Activator Substrates Inhibitor Products Enzyme Biochemical reaction

  3. Reaction kinetics Vmax maximal enzyme velocity KM Michaelis-Menten constant (k2+k-1)/k1

  4. Reaction kinetics • 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

  5. SABIO-RK SABIO-RK describes Reaction Kinetics and is an extension of SABIO (System for the Analysis of Biochemical Pathways) SABIO Enzymes Organisms Reaction Reactants Pathways SABIO-RK Concentrations Reactants Kinetic Law Environment Parameters

  6. Data flow • 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

  7. Automatic input(XML based) Generation of experimental data Storage of kinetic data (e.g. Km, Vmax) SABIO-RK Database of experimental raw data Link to original data Data access Collaboration with Douglas Kell, Neil Swainston (Manchester Center for Integrative Systems Biology)

  8. Manual data input • Kinetic data from publications • Tables, Formula, Graphs, Pictures • Some assay conditions or methods descriptiononly 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

  9. Input interface

  10. 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

  11. Curation of chemical compounds  Search for multiple entries for identical compounds • KEGG IDs: C00201, C03802 • SABIO-RK ID: 1674 • ChEBI IDs: 37413, 37076

  12. KEGG IDs: C00677, C04283 • SABIO-RK ID: 1690 • ChEBI IDs: 16381, 16516

  13. 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 names Analysis of compound names and generation of SMILES string • Generation of chemical structure based on SMILES string • Classification of chemical compounds

  14. 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

  15. Analysis of compound names

  16. Classification of compounds • Generation ofstructural formula, totalsformula and molecular weight based on SMILES string • Rules forcompound 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

  17. Access to SABIO-RK Web-based user interfacefor 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)

  18. 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

  19. Links to external databases • Cellular location • Gene Ontology • Protein • UniProt • Literature source • PubMed • Compound • KEGG • PubChem • ChEBI • Enzyme • KEGG • ExPASy Enzyme • IntEnz • IUBMB • Reactome

  20. Annotations in SBML

  21. ChEBI links to SABIO-RK

  22. SABIO-RK links to ChEBI

  23. 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.)

  24. Future Perspectives • 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

  25. SABIO-RK team Renate Kania Olga Krebs Andreas Weidemann Saqib Mir Henriette Engelken Martin Golebiewski Ulrike Wittig Isabel Rojas Financial support: SABIO-RK is member of:

  26. http://sabio.villa-bosch.de/SABIORK

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