introduce a semantic framework for studying systems chemical biology / systems pharmacology, in which three major projects (Chem2Bio2RDF, Chem2Bio2OWL, SLAP (semantic link association prediction) are covered.

1. From Data Integration to Data mining in Semantic Web systems chemical biology as a case study Bin Chen School of Informatics and Computing Indiana University at Bloomington Lecture for S636 Nov 17, 2011

6. SPARQL RDF Ontology Algorithm and tools Applications Experimental Data Text mining Data Chem2Bio2RDF Chem2Bio2OWL Path finding; Association search; Association ranking and prediction Polypharmacology; drug side effect Architecture of Semantic Systems Chemical Biology

9. Use RDF to Integrate Data http://chem2bio2rdf.org/drugbank/DB01076 name company lipitor Pfizer http://chem2bio2rdf.org/drugbank/DB01076 Molecular_Weight formula 558.6398 C33H35FN2O5 Database 1 Database 2 Same URI, merged!

10. Use RDF to Link Data http://chem2bio2rdf.org/drugbank/DB01076 sameAs http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB01076 http://chem2bio2rdf.org/pubchem/resource/pubchem_compound/60823 cid

11. uniprot Bio2RDF Others LODD Chem2Bio2RDF Virtuoso Triple store SPARQL ENDPOINTS Dereferenable URI Browsing PlotViz: Visualization Cytoscape Plugin Linked Path Generation and Ranking Third party tools

12. Workflow for RDF conversion XML CSV DB TXT Relational DB D2R Mapping D2R server Dumping Virtuoso Triple Store Scripts Ontology Publishing External Sources Download Local copy … Chen B,et al. Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data. BMC Bioinformatics. 2010

13. # Table c2b2r_DrugBankDrug map:c2b2r_DrugBankDrug a d2rq:ClassMap; d2rq:dataStorage map:database; d2rq:uriPattern "drugbank_drug/@@c2b2r_DrugBankDrug.DBID|urlify@@"; d2rq:class drugbank:DrugBankDrug; d2rq:classDefinitionLabel "c2b2r_DrugBankDrug"; . map:c2b2r_DrugBankDrug__label a d2rq:PropertyBridge; d2rq:belongsToClassMap map:c2b2r_DrugBankDrug; d2rq:property rdfs:label; d2rq:pattern "@@c2b2r_DrugBankDrug.Generic_Name@@"; . map:c2b2r_DrugBankDrug_DBID a d2rq:PropertyBridge; d2rq:belongsToClassMap map:c2b2r_DrugBankDrug; d2rq:property drugbank:DBID; d2rq:propertyDefinitionLabel "c2b2r_DrugBankDrug DBID"; d2rq:column "c2b2r_DrugBankDrug.DBID"; Table D2R mapping RDF Exhibit link

14. Node represents each database colored by its RDF vender; Directed edge shows the linkage from one dataset to another dataset, colored by the linkage type. E.g,., the type compound includes CID, CAS, ChEBI, DBID and so on. The size of nodes and the width of edges are dependent on the # of triples and # of linkages respectively. Chem2Bio2RDF Datasets http://chem2bio2rdf.org Chem2Bio2RDF data Other data venders compound protein/gene chemogenomics literature others

15. http://linkeddata.org

16. uniprot Bio2RDF Others LODD Chem2Bio2RDF Virtuoso Triple store SPARQL ENDPOINTS Dereferenable URI Browsing PlotViz: Visualization Cytoscape Plugin Linked Path Generation and Ranking Third party tools

18. Implement cheminformatics and bioinformatics tools into SPARQL ARQ Function Extension SPARQL Chemistry Development Kits BioJAVA Web Services PREFIX drugbank: < http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/ > PREFIX f: <java:org.bio2chem2rdf.arq.> SELECT ?x ?s WHERE { ?x drugbank:smilesStringCanonical ?s FILTER ( f:tanimoto( 'NS(=O)(=O)C1=CC(=C(Cl)C(Cl)=C1)S(N)(=O)=O', ?s, 'MACCS') > 0.9 ) } f:tanimoto is used for compound similarity search

20. link

22. Node represents each database colored by its RDF vender; Directed edge shows the linkage from one dataset to another dataset, colored by the linkage type. E.g,., the type compound includes CID, CAS, ChEBI, DBID and so on. The size of nodes and the width of edges are dependent on the # of triples and # of linkages respectively. Chem2Bio2RDF Datasets http://chem2bio2rdf.org Chem2Bio2RDF data Other data venders compound protein/gene chemogenomics literature others

23. Ontology workflow

28. Chem2Bio2OWL

34. Two objects are similar if they are related to similar objects Coauthorship Same Target

35. Two objects are related if they share same objects or their related objects are related Compound 1 Protein 2 Protein 1 Compound 1 Protein 2 Protein 1 Compound 2 Computer Science Person2 Person 1 Computer Science Person2 paper1 paper2 advisor major publish cite conference

36. Cmpd1 Protein 1 Protein 2 Cmpd 2 Cmpd 1 Cmpd 2 Protein 1 Neighbor Chemogenomics Chemogenomics Chemogenomics Chemogenomics Protein 2 Cmpd1 Protein 1 Chemogenomics hasGO hasGO Protein 2 Cmpd1 Protein 1 Chemogenomics PPI GO:0001 Sample patterns Cmpd1 Protein 1 Cmpd 2 Chemogenomics hypertension Side effect Side effect Cmpd1 Protein 1 Cmpd 2 Chemogenomics Substructure substructure substructure

37. Target 2 Compound1 Compound 2 Compound 3 Target 3 GO:00001 hasGO hasGO chemogenomics chemogenomics chemogenomics chemogenomics chemogenomics neighbor Side Effect 1 hasSideEffect hasSideEffect Gene Family 1 hasGeneFamily hasGeneFamily Target 1 chemogenomics Target 4 chemogenomics proteinProteinInteraction Association depends on its neighborhood

39. Statistical Model Convert the question to a path surfing problem Gene i Gene j PPI PPI PPI hasGO hasGO hasPathway chemogenomics P(i j) =1/3

40. Protein 2 Cmpd1 (s) Protein 1 (t) e1 e2

42. Statistical Model 3. Nodes association estimation Raw score of random pairs fit to normal distribution!

43. Direct: drug target pairs with IC50<30um Indirect: drug target pairs with no interaction Random: random pairs

45. SLAP interface

47. Thanks!