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!