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An Innovative Medicines Initiative to Build a Semantics-Based Open Pharmacology Space for Drug Discovery Twitter: @Open_Phacts Prof Carole Goble FREng FBCS www.openphacts.org BioITWorldExpoEurope – Oct 13 2011
Why is it so hard to…. What’s the structure? Are they in our file? Whats similar? Whats the target? Pharmacology data? Known Pathways? Working On Now? Connections to disease? Expressed in right cell type? Competitors? IP?
Syntactic Normalisation Semantic Normalisation KEGG URI CheBI URI BRENDA URI Open Data Linked Data Linked Knowledge OPS in RDF “ triples” Annotated OPS with ontologies
Developers (Builders) End users (Drivers) A use case driven approach Prioritised research questions Prioritised data sources Target dossiers about targets, incorporating related information on sequences, structures, pathways, diseases and small molecules Chem/bio space navigator of sets of pharmacologically annotated small molecules, by chemical substructures, pharmacophores, biological activities Polypharmacology browser map coverage of the chemo-biological space for polypharmacological profiling of small molecules Exemplars
Developers (Builders) End users (Drivers) A use case driven approach Target validation work-bench: in silico target validation studies Fusion/aggregation of data from different domains to improve predictions of drug-transporter interactions Combination of physicochemical data & data from transporter interaction for prediction of blood-brain barrier permeation and tissue distribution Prioritised research questions Prioritised data sources Bench mark Pilots
Chemspider for cross check of chemistry Wombat as show case for integration of commerical db Science-Driven Data set selection Database Webpage Available for No of Ligands Ligands TP Search http://18.104.22.168/tp-search/index.html Human, Mouse, Rat, Rabbit, Pig >5,000 Inhibitor, substrate, inducers ChEMBL https://www.ebi.ac.uk/chembldb/ Human, Mouse, Rat ~ 5,000 Inhibitor, substrate, inducers PharmGKB http://www.pharmgkb.org Human NA NA DrugBank http://www.drugbank.ca/ Human NA NA HMTDSEngine http://digibench.net/ Human NA NA PubchemBioassay http://www.ncbi.nlm.nih.gov/sites/entrez Human 194,393 ABCB1, G2 Inhibitors, others NCI Database http://dtp.nci.nih.gov/ Human ~ 30,000 Substrates/Collatral sensitivity CancerResource http://bioinf-data.charite.de/cancerresource/index.php?site=home Human NA Ligands
Does it provide an adequate answer to the questions 15 and 30?
Demo for users (drive group) to recalibrate build tasks in order to better respond to user requirements
rdf mapping id mapping concept mapping interface data Sources triple store chemical resolution Chem2Bio2RDF text mining
GUI - User suggestions for workflow Select question (“template” from category) Fill in template variables Via “relation browser” and add filters (IC50 value, dates etc) View results, filter and export dataset Select relevant data sources Execute search Modify query (change concepts and attributes) www.openphacts.org
LSP4All (Lundbeck) Generic Interface search by enzyme family Q15: All oxidoreductase inhibitors active <100nMolars in both human & mouse Credit: Sune Askjær / Claus Stie Kallesøe (Lundbeck) Pharmacological data Exact and structure search Navigate from compounds to targets