Description

Polypharmacology, which studies the interaction of drug with multiple targets, provides a new way to address the issue of high attrition rates arising from lack of efficacy and toxicity, in previous paper (Chen 2009), it demonstrated the usage of pubchem as a source to study polypharmacology through mapping to other biological network. However, it has not been implemented as a tool to serve public and currently the results only limited to small number of examples, which were retrieved and validated by manually literature search. Semantic Web might be useful to automatically find examples and implement it as a tool.

Workflow

polypharmacology_work_flow.JPG

RDF Schema

BioNetworkMappingDiagram.jpg


Drugbank
Kegg

SPARQL query

The following query is a Prolog-like representation
Polypharmacological(Compound, X):- Active(Compound, BioAssay), AssayTarget(Bioassay, Protein), PathwayTarget(Protein, Pathway), DiseaseRelation(Pathway, Disease)
Q:

find all the compounds in assay network targeting at least two of the all proteins targeted by a given drug( ie. quinacrine). explain it
Query1(Compound, ?X) :- Active(?X, BioAssay1), Active(?X, BioAssay2), AssayTarget(Bioassay1, Protein1), AssayTarget(Bioassay2, Protein2), DrugTarget(Drug, Protein1), DrugTarget(Drug, Protein2)

find all the compounds that are active towards the at least two targets that are in a given pathway(i.e mapk pathway)
Query2(Compound, ?X) :- Active(?X, BioAssay1), Active(?X, BioAssay2), AssayTarget(Bioassay1, Target1), AssayTarget(Bioassay2, Target2), PathwayComponent(Pathway, Target1), PathwayComponent(Pathway, Target2), DiseaseCause(Disease, Pathway)


find all the pathways that contains multiple targets, at least two of which are targeted by compounds that are associated with a given side effect (i.e. hepatonecrosis)**
Query2(Compound, ?X) :- Active(?X, BioAssay1), Active(?X, BioAssay2), AssayTarget(Bioassay1, Target1), AssayTarget(Bioassay2, Target2), PathwayComponent(Pathway, Target1), PathwayComponent(Pathway, Target2), DiseaseCause(Disease, Pathway)