chem2bio2rdf portal
TRANSCRIPT
CHEM2BIO2RDF: A LINKED OPEN DATA PORTAL FOR SYSTEMS CHEMICAL BIOLOGY
Bin Chen, Ying Ding, Huijun Wang, David Wild, Xiao Dong, Yuyin Sun, Qian Zhu, Madhuvanthi Sankaranarayanan
Indiana University at Bloomington
Chemical Biology Systems Phenotype
interacting mapping
CompoundDrug
ProteinGene
PPIMetabolic PathwayGene Regulatory
DiseaseSide effectToxicity
Chemogenomics
What’s Systems Chemical Biology
All the public data are scattered around the web…
MATADOR
Bio2RDF
(biological data)
LODD
(Drug/Chemical Data)
Chem2Bio2RDF
(chemogenomics---how chemical interact with biological data)
Linked Open Data (LOD)
Bio2RDF LODD Linked Life Data Chem2Bio2RDF
Workflow for RDF conversion
XML
CSV
DB
TXT
Relational DB
D2R Mapping
D2R server
Dumping VirtuosoTriple Store
Scripts
Ontology
Publishing
External Sources
DownloadLocal copy
…
We are focusing on how chemical interacts with biological data
MATADOR
12 databases 204, 981 compounds 17, 930 genes 646, 608 associations
Caveat: Not all binding data!
Literature based Systems Chemical Biology
Covering 1865-200918,502,916 PubMed/Medline literature records!
Workflow for conversion PubMed/Medline data
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
Over 110 million triples!
Chem2Bio2RDF data
Other data venders
compoundprotein/genechemogenomicsliteratureothers
uniprot
Bio2RDF
Others
LODD
Chem2Bio2RDF
VirtuosoTriple store
SPARQL ENDPOINTS
Dereferenable URI
Browsing
PlotViz: Visualization
Cytoscape Plugin
Linked Path Generation and Ranking
Third party tools
(Dereferenable URI)http://chem2bio2rdf.org/medline/resource/medline/15722552
Link to Bio2RDF disease
Link to Chem2Bio2RDF Gene
Link to PubMed website
Link to Chem2Bio2RDF pathway
Link to Chem2Bio2RDF side effect
Facet browsers using Exhibit
http://chem2bio2rdf.org/exhibit/drugbank.html
Search Chem2Bio2RDF
Search engine results
SPARQL results Cytoscape plugin
Answer scientific questions
Give me all information about this compound Give me all information about this target Find chemical associated genes Find gene associated chemicals Find disease associated chemicals Find side effect associated chemicals Find all the drug-like compounds in PubChem BioAssay that
share at least two targets with a drug in DrugBank Link KEGG / Reactome Pathways and PubChem to identify
potential multiple pathway inhibitors for MAPK
More in http://chem2bio2rdf.wikispaces.com/multiple+sources
CASE study: Adverse drug reaction
1. Scientific Question
Drugs that cause similar adverse side effects often have totally different chemical structures
Cholestasis, Bile salt transporters in liver
2. hypothesis
drug targets might function in the same pathway
3. Methods
SPARQL
find KEGG pathways containing at least two of the targets associated with a given side effect (i.e. hepatomegaly)
PREFIX chem2bio: <http://localhost:2020/vocab/resource/>SELECT ?pathway_id (count(?pathway_id) as ?count)WHERE {?compound chem2bio:sider_side_effect ?side_effect . ?compound chem2bio:sider_cid ?dbid . ?targetid chem2bio: DrugBankTarget_dbid ?dbid . ?targetid chem2bio: DrugBankTarget_swissport_id ?UniProt_id . ?pathwayidchem2bio:KEGG_pathway _gene_keggid ?UniProt_id . ?pathwayid chem2bio:KEGG_pathway _pathway_id ?pathway_id . FILTER regex(?side_effect,\"hepatomegaly\",\"i\") . } GROUP BY ?pathway_id ORDER BY ?count DESC;
Path finding and visualization
HepatitisHepatic Necrosis
Hepatomegaly
VEGF signaling pathway
Calcium signaling pathway
Gap Junction
Arachidonicacid
metabolism
Neuroactiveligand-receptor
interactionPathways in
cancerSmall cell
lung cancer
HTR2AHRH1GABRA
1PTGS1 DRD2
ADRA1A
HTR1A ADRA1BGRIA1 ADRB1GLRA
1DRD1PTGS2
Olanzapine
Ziprasidone ClozapineIsofluraneDoxazosin RisperidoneDrug
Target
Pathway
Side Effect
hepatomegaly & Gap Junction?
4. results
PREFIX medline: <http://chem2bio2rdf.org/medline/resource/>PREFIX kegg: <http://chem2bio2rdf.org/kegg/resource/>PREFIX sider: <http://chem2bio2rdf.org/sider/resource/>
select *from <http://chem2bio2rdf.org/medline>from <http://chem2bio2rdf.org/kegg>from <http://chem2bio2rdf.org/sider>
where{?kegg_id kegg:Pathway_name ?pathway_name . FILTER regex(?pathway_name,"gap junction","i") .?pmid medline:pathway ?kegg_id .?pmid medline:side_effect ?sider .?sider sider:side_effect ?side_effect . FILTER regex(?side_effect,"Hepatomegaly","i") .}
Retrieve literatures talking about hepatomegaly & Gap Junction
Literature based validation
5. validation
Summary
Chem2Bio2RDF portal attempts to collect and link all public data related to Systems Chemical Biology
Chem2Bio2RDF offer various tools to browse, search and explore the data source
Case studies demonstrate that it could serve as an useful portal in drug discovery
THANKS!