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Chemoinformatics and Metabolism

Chemoinformatics and Metabolism. Paula de Matos. Chemoinformatics and Metabolism Group Research. Indexing, searching and dissemination of chemical information. Natural Products and Metabolomics. Cheminformatics Algorithms and Toolkits. Chemical Entities of Biological Interest.

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Chemoinformatics and Metabolism

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  1. Chemoinformatics and Metabolism Paula de Matos

  2. Chemoinformatics and Metabolism Group Research Indexing, searching and dissemination of chemical information Natural Products and Metabolomics Cheminformatics Algorithms and Toolkits

  3. Chemical Entities of Biological Interest • A database containing a freely available, manually annotated dictionary of molecular entities focused on ‘small’ chemical compounds. • Provides a method to navigate the chemical space via an ontology • ChEBI aims to provide a central, definitive reference of chemical nomenclature. Dictionary

  4. http://www.ebi.ac.uk/chebi Dictionary Resource for Nomenclature

  5. What does ChEBI cover? • Mostly small entities • Big entities too like • alumina • amylose • metaborate • Excludes proteins and nucleic acids 5

  6. ChEBI Web Services • Programmatic access to a ChEBI entry • SOAP based Java implementation • Clients currently available in Java and perl • Four methods with which to access data • getLiteEntity • getCompleteEntity • getOntologyParents • getOntologyChildren • Documented at http://www.ebi.ac.uk/chebi/webServices.do.

  7. ChEBI Status

  8. ChEBI further info • http://www.ebi.ac.uk/chebi • Mailing lists: • chebi-help@ebi.ac.uk • chebi-announce@lists.sourceforge.net • chebi-ontology@lists.sourceforge.net • Submitting data • http://www.ebi.ac.uk/chebi/submissions

  9. The Chemistry Development Kit (CDK): An Open Source Java-Library for Structural Chemo- and Bioinformatics • >90.000 Lines of Code, >900 Classes, > 9000 Methods • Library Generation • Virtual Screening • Molecular Property Prediction • Visualization http://cdk.sourceforge.net (1) Steinbeck, C.; Hoppe, C.; Kuhn, S.; Guha, R.; Willighagen, E. L. Current Pharmaceutical Design 2006, 12, 2111-2120. (2) Steinbeck<, C.; Han, Y. Q.; Kuhn, S.; Horlacher, O.; Luttmann, E., Willighagen, E. Journal of Chemical Information and Computer Sciences 2003, 43, 493-500.

  10. The Chemistry Development Kit (CDK) Visualization Input/Output • I/O (CML, MDL Molfile, SDF, PDB) • SMILES • InChI • Structure-Diagram-Layout (SDG) • 2D Rendering • 3D Rendering Library Enumeration Modelling • Deterministic Isomer generator • Stochastic Structure Generators via • Simulated Annealing • Genetic Algorithms • 3D Model-Builder • Atom-Typing • Force-Field • Representation of Biomolecular Structures Chemical Graphs Properties • Isomorphism detection • Maximum-Common-Substructure Searches • SMARTS- and Substructure searches • Ring searches • Aromaticity detection • Fingerprinting • > 70 QSAR-Descriptors • QSAR model building

  11. Example: Structure Diagram Generation

  12. Example: Fingerprinting IMolecule superstructure = MoleculeFactory.makeIndole(); IMolecule substructure = MoleculeFactory.makePyrrole(); Fingerprinter fingerprinter = new Fingerprinter(); BitSet superBS = fingerprinter.getFingerprint(superstructure); BitSet subBS = fingerprinter.getFingerprint(substructure); boolean isSubset = FingerprinterTool.isSubset(superBS, subBS); Bitscreen coding for structural features 0 0 1 1 0 1 0 0 1 0 Hetero-aryl -COOH Alky O-Alkyl -NH2

  13. CDK in numbers • 67 registered developers on SF • 86 people subscribed to cdk-devel list • 111 people subscribed to cdk-user list

  14. CDK in numbers 80,966 downloads since 2001

  15. CDK in numbers CDK article (2003) cited 68 times

  16. CDK info • Project home page: • http://cdk.sourceforge.net/ • Mailing list: • cdk-user@lists.sourceforge.net • cdk-devel@lists.sourceforge.net • Documentation • http://pele.farmbio.uu.se/nightly/

  17. OrChem • Oracle chemistry plug-in using the Chemistry Development Kit (CDK) providing substructure and similarity searches for chemical graphs. • OrChem is suitable for Oracle 11G and onwards • Not an Oracle data cartridge - it doesn't need Oracle's extensibility architecture because its Java components run as Java stored procedures inside the Oracle standard JVM (Aurora).

  18. Problem • Chemical substructure or similarity searching is computationally expensive especially on a large dataset?

  19. OrChem database structure

  20. Example OrChem Queries • Similarity search • select * from table( orchem_simsearch.search( 'OC4=C(C(=C3OC(C)(COC=1C=CC(=CC=1)CC2C(=O)NC(=O)S2)CCC3=C4C)C)C','SMILES',0.8,null,'N') ) ; • Substructure search • select orchem_subsearch.search(molfile,'MOL',50,'Y') from compounds where molregno=12345;

  21. Fingerprint distribution

  22. Parallel vs. Non parallel Performance of substructure search on 3.5 million compounds

  23. Substructure benchmarking Performance of substructure search on 3.5 million compounds

  24. Similarity Benchmarking

  25. OrChem info • http://orchem.sourceforge.net/ • Mailing list: • orchem-devel@lists.sourceforge.net

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