RDF Workshop. ChEMBL Examples and Tutorial. Mark Davies. ChEMBL Group, Technical Lead 30/04/2014

Transcription

1 RDF Workshop ChEMBL Examples and Tutorial Mark Davies ChEMBL Group, Technical Lead 30/04/2014

2 Query 1 Find All Small Molecules PREFIX cco: < SELECT?molecule WHERE {?molecule a cco:smallmolecule. }

3 Query 2 - Find all FDA Approved Drugs PREFIX cco: < SELECT?molecule WHERE {?molecule a cco:smallmolecule.?molecule cco:highestdevelopmentphase?phase. FILTER(?phase = 4 ) }

4 Query 3 Find GPCR Bioactivity Data Find all molecules which bind GPCRs PREFIX cco: < PREFIX cpc: < SELECT?molecule?activity?assay?target WHERE {?molecule a cco:smallmolecule.?smol cco:hasactivity?activity.?activity cco:hasassay?assay.?assay cco:hastarget?target.?target cco:hasproteinclassification cpc:chembl_pc_1020. }

5 ChEMBL Protein Classification

6 Query 4 Find Secreted Proteins PREFIX rdfs: < PREFIX cco: < PREFIX sio: < PREFIX skos: < SELECT?uniprot?target?target_name?target_type WHERE { {# Select targets - In this example Secreted Proteins(CHEMBL_PC_3) < cco:hastargetdescendant?target.?target rdfs:label?target_name ; cco:hastargetcomponent?target_component ; cco:organismname?organism ; cco:targettype?target_type.?target_component skos:exactmatch?uniprot.?uniprot a cco:uniprotref. } }

7 Query 5 Secreted Protein Approved Drugs PREFIX rdfs: < PREFIX cco: < PREFIX sio: < PREFIX skos: < SELECT?uniprot?target?target_name?target_type (count(distinct?molecule) as?drug_binding_count) WHERE { {# Select approved drug molecules which bind targets?target cco:hasassay?assay.?assay cco:hasactivity?activity.?activity cco:hasmolecule?molecule ; cco:pchembl?molecule_pchembl.?molecule cco:highestdevelopmentphase?molecule_phase. FILTER(?molecule_pchembl > 6 ) FILTER(?molecule_phase = 4 ) } {# Select some targets - In this example GPCRs (CHEMBL_PC_1020) < cco:hastargetdescendant?target.?target rdfs:label?target_name ; cco:hastargetcomponent?target_component ; cco:organismname?organism ; cco:targettype?target_type.?target_component skos:exactmatch?uniprot.?uniprot a cco:uniprotref. } } group by?uniprot?target?target_name?target_type order by desc(count(distinct?molecule))

8 Query 6 - Secreted Protein Drug-Like Mols PREFIX rdfs: < PREFIX cco: < PREFIX sio: < PREFIX skos: < SELECT?uniprot?target?target_name?target_type (count(distinct?molecule) as?drug_binding_count) WHERE { {# Select approved drug molecules which bind targets?target cco:hasassay?assay.?assay cco:hasactivity?activity.?activity cco:hasmolecule?molecule ; cco:pchembl?molecule_pchembl.?molecule cco:highestdevelopmentphase?molecule_phase. FILTER(?molecule_pchembl > 6 ) FILTER(?molecule_phase = 4 ) } {# Select some targets - In this example secreted molecules (CHEMBL_PC_3) < cco:hastargetdescendant?target.?target rdfs:label?target_name ; cco:hastargetcomponent?target_component ; cco:organismname?organism ; cco:targettype?target_type.?target_component skos:exactmatch?uniprot.?uniprot a cco:uniprotref. } } group by?uniprot?target?target_name?target_type order by desc(count(distinct?molecule))

9 Reactome Pathways - Apoptosis TNF Signaling =

10 Query 7 Reactome Proteins Running a federated query against Reactome SPARQL endpoint PREFIX dc: < PREFIX biopax3: < PREFIX rdfs: < PREFIX foaf: < PREFIX owl: < PREFIX xsd: < PREFIX rdf: < PREFIX skos: < PREFIX dcterms: < SELECT DISTINCT?pathwayname?uniprot WHERE # Pull back proteins from Reactome Endpoint involved in TNF Signaling (REACT_1432.5) { SERVICE < { { < rdf:type biopax3:pathway ; biopax3:pathwaycomponent?reaction ; biopax3:displayname?pathwayname.?reaction rdf:type biopax3:biochemicalreaction { {?reaction?rel?protein } UNION {?reaction?rel?complex.?complex rdf:type biopax3:complex.?complex?comp?protein } }?protein rdf:type biopax3:protein.?protein biopax3:entityreference?uniprot } } }

11 Query 8 - Reactome Proteins + Drug-Like Mols PREFIX rdfs: < PREFIX cco: < PREFIX sio: < PREFIX skos: < PREFIX biopax3: < SELECT?pathwayname?uniprot?target?target_name?molecule { {# ChEMBL Block 1?molecule cco:highestdevelopmentphase?molecule_phase.?activity cco:hasmolecule?molecule.?activity cco:pchembl?pchembl.?assay cco:hasactivity?activity. } # Pull back proteins from Reactome Endpoint involved in TNF Signaling (REACT_1432.5) SERVICE < { { < a biopax3:pathway ; biopax3:pathwaycomponent?reaction ; biopax3:displayname?pathwayname.?reaction a biopax3:biochemicalreaction { {?reaction?rel?protein } UNION {?reaction?rel?complex.?complex a biopax3:complex.?complex?comp?protein } }?protein a biopax3:protein.?protein biopax3:entityreference?uniprot } } {# ChEMBL Block 2?target_component skos:exactmatch?uniprot.?target_component cco:hastarget?target.?target cco:hasassay?assay ; rdfs:label?target_name. } # Work around to get RO5 Value BIND(IRI(CONCAT(?molecule,'#num_ro5_violations')) AS?ro5_violations_iri)?ro5_violations_iri sio:sio_000300?ro5_violations_value. FILTER(?molecule_phase < 4 ) FILTER(?pChembl > 6 ) FILTER(?ro5_violations_value = 0 ) }

12 Revisiting Reactome Identifying the proteins in the pathway shown which interact with drug-like molecules Caspase-8 34 TNF-alpha 12 TNF-R1 7 RIPK1

13 Query 9 Select the Caspase-8 Molecules PREFIX rdfs: < PREFIX cco: < PREFIX sio: < PREFIX skos: < PREFIX biopax3: < SELECT DISTINCT?molecule?molecule_name { {?molecule cco:highestdevelopmentphase?molecule_phase ; sio:sio_000008?molecule_ro5 ; rdfs:label?molecule_name.?molecule_ro5 a sio:cheminf_ ; sio:sio_000300?molecule_ro5_val.?activity cco:hasmolecule?molecule.?activity cco:pchembl?pchembl.?assay cco:hasactivity?activity. < cco:hasassay?assay ; } FILTER(?molecule_phase < 4 ) FILTER(?pChembl > 6 ) FILTER(?molecule_ro5_val = 0 ) }

14 Questions 1. How many Assays are in ChEMBL_18 RDF? (Hint: use type Assay) 2. How many Activities are in ChEMBL_18 RDF? (Hint: use type Activity) 3. How many human kinase targets are there in ChEMBL_18 RDF? (Hint: Look under Enzyme classification to find Kinases)

15 Questions 4. Find all drug-like molecules in the ChEMBL_18 RDF? How many molecules have been returned? Explain your search criteria? 5. Choose a protein target which is bound by a molecule from list above and find the following information: Protein name Protein classification Organism name

16 Answers Using Rule of Five violations equal zero 5. Selected ChEMBL Molecule CHEMBL22 and an example query could be: Click on target link to get Protein Classification details