1. RDF based on Integration of Pathway Database and Gene Ontology SNU OOPSLA LAB. 2005 DongHyuk Im

2. Contents  Introduction  Pathway Database  Enzyme Database  Gene Ontology  Related Works  Our Approach  Supporting Function  Data Transformation  Integration of KEGG, Enzyme, Gene Ontology  Querying using SeRQL

3. Pathway?  Most chemical reaction mechanisms are translated from a compound(substrate) to a compound(product) by enzyme acting  Importance  to comparison and analyze pathways in order to understand the process of creating compounds and the evolutive relevance between organisms  Drug Discovery

4. Pathway Map : Glycolysis / GluconeogenesisMap : Aquifex aeolicus

5. Enzyme Database  EC number  Recommended name  Alternative names(if any)  Catalytic activity  Cofactors (if any)  Pointers to the SWISS-PORT entrie(s) that correspond to the enzyme (if any)  Pointers to disease(s) associated with a deficiency of the enzyme (if any)

6. Enzyme Hierarchy [*] [1][2][3] [2.1][2.2][2.3] [2.2.1][2.2.2][2.2.3] [2.2.2.1][2.2.2.2][2.2.2.3]  Four levels  EC number  Ex) 1.1.1.1 is a member of the top level group [1]  The leftmost number identifies the highest level  [2.4.2.3] – [2.4.2.4](sibling) : similar reactions in pathway

7. Gene Ontology

8. KEGG

9.  To computerize all aspects of cellular functions in terms of the pathway of interacting molecules or genes  To maintain gene catalogs for all organisms and link each gene product to a pathway component  To organize a database of all chemical compounds in the cell and link each compound to a pathway component  To develop computational technologies for pathway comparison, reconstruction, and analysis

10. Why RDF Integration?  Pathway data model : DAG  RDF is a good model for representing pathway  RDF data model : DAG  Need integration of multiple knowledge sources available from internet : one of the major problems in biologists  RDF is a good model for same standard  Enzyme, GO : hierarchy structure  RDF is a good model for representing hierarchy structure  GO annotation is important  Enzymes(proteins) in certain pathway need GO annotation

11. Related Works  KEGG: Kyoto Encyclopedia of Genes and Genomes, 1999, Nucleic Acids Res.  YeastHub: a semantic web case for integrating data in the life science domain, 2005, Bioinformatics  LIGAND: database of chemical compounds and reactions in biological pathways, 2002, Nucleic Acids Res.  Gene Ontology: tool for the unification biology, the Gene Ontology Consortium, 2000, Nature Genetics.

12. Our System’s Supporting  KEGG  Search compound  Path prediction  Search Enzyme  Our system’s function to add  Integration Query (pathway+enzyme+GO)  Relaxation Query using GO hierarchy  Searching pathway using enzyme information

13. Search Compounds Compound : C00668 target

14. Pathway Prediction Tool compound Relaxation query using enzyme hierarchy

15. Search Enzyme Enzyme : 5.3.1.9

16. From Pathway to Gene Ontology Select enzyme

17. Data Translation for Integration KGML Data XSLT KEGG RDF Data Enzyme RDF Data GO RDF Data GENOS Storage Adding GO ID XSLT : http://www.w3.org/2005/02/13-KEGG/

18. KEGG RDF Data(1/2) <Rectangle k:name="aldH1" k:fgcolor="#000000" k:bgcolor="#BFFFBF" k:x="170" k:y="1018" k:width="45" k:height="17"/> <Rectangle k:name="1.2.1.5" k:fgcolor="#000000" k:bgcolor="#FFFFFF" k:x="170" k:y="1039" k:width="45" k:height="17"/> <Circle k:name="C00033" k:fgcolor="#000000" k:bgcolor="#FFFFFF" k:x="102" k:y="971" k:width="8" k:height="8"/> Gene entry Enzyme entry Compound entry No information

19. KEGG RDF Data(2/2) Relation Reaction

20. How to Process KEGG Pathway  Problem  GENOS(Sesame) does not support multiple graph  KEGG data consists of multiple documents  Ex) map00010.rdf, aae00010.rdf …  Solution  Using namespace, we can distinguish maps  When Storing pathway data, pathway’s map name is added as a namespace in resource table of GENOS

21. Processing Pathway Data …. <Rectangle k:name="aldH1" k:fgcolor="#000000" k:bgcolor="#BFFFBF" k:x="170" k:y="1018" k:width="45" k:height="17"/> conflict IDNameSpaceLocalname 1…… 2…Glycolysis/… 3aae#00010_1 4…aq_186 5… 6aae#00020_1 7 8map#00010_1 9…. resources table of GENOS SubjectPredicateObject ……… 3…… 6…… 8…… ……… triples table of GENOS

22. Integrating Databases Enzyme number GO ID

23. Relaxation Querying using SeRQL E1.* C1 C2 E1 SELECT C1,C2 FROM Path_EXP WHERE E1 LIKE “1.*" Dewey order Ex. 1.1 and 1.2 are childrens of 1 use Prefix SeRQL subclassof

24. Considering Performance aae:aq_018path:aae03010 aae:aq_020path:aae03010 aae:aq_021path:aae00400 …. eco:b1236path:eco00052 eco:b1236path:eco00500 eco:b1236path:eco00520 …. KEGG : Pathway List GenesMap using genes_index

25. Schedule  Implementation (~11/30)  Integrated Databases  Query Processor for pathway  Simple UI (Web :JSP)  Complete Paper (~12/10)