Upload
egon-willighagen
View
104
Download
0
Embed Size (px)
DESCRIPTION
Bioclipse-OpenTox is a platform developed for the interactive prediction of toxicity-related properties or organic molecules. Integrating two independent projects, it enables toxicity prediction based on the analysis of chemical structures, and visualization the substructure contributions to the toxicity prediction. OpenTox is a semantic web framework, based on web services, which supports open data exchange and toxicology model building and validation. Bioclipse is used to provide user-friendly solution for graphical interaction and visualisations, as well as scripting for workflow needs. It was recently extended to dynamically discover computational algorithms exposed via the OpenTox servers, acting as a registry of available computational toxicology services on the OpenTox network. We further show how predictions from multiple services can be simultaneously evaluated while editing substructures new compounds.
Citation preview
Department of Bioinformatics - BiGCaT 1
Bioclipse-OpenTox:Interactive PredictiveToxicology
Egon Willighagen, @egonwillighagenDept. of Bioinformatics - BiGCaT - Maastricht University
orcid.org/0000-0001-7542-0286
ACS New Orleans, 9 April 2013, #ACSNola #DrugDisco
Department of Bioinformatics - BiGCaT 2
March 11 2013
Department of Bioinformatics - BiGCaT 3
SEURAT-1 “...replacing animal testing”
Department of Bioinformatics - BiGCaT 4
OpenTox / ToxBank
Department of Bioinformatics - BiGCaT 5
ToxBank
Kohonen, P. et al. MolInf 2013 32(1):47-63.
Department of Bioinformatics - BiGCaT 6
Alternative methods …
Department of Bioinformatics - BiGCaT 7
Alternative methods …
… computational.
Department of Bioinformatics - BiGCaT 8
Alternative methods …
… computational.
“But they don't work, right?”
Department of Bioinformatics - BiGCaT 9
How to integrate complementary info?
• Experimental–Cell line–Rat models–Environmetal data– ...
• Computational– “COMP” stuff– “CINF” stuff–Systems biology
Needs: integrate, visualize, analyze.
Department of Bioinformatics - BiGCaT 10
Integration platform: Bioclipse
Spjuth, O et al. BMC bioinformatics 2007 8(1):59.
Department of Bioinformatics - BiGCaT 11
Hanson, RM. Appl Cryst 2010 43(5):1250-1260.
Department of Bioinformatics - BiGCaT 12
Why Bioclipse?
O’Boyle, NM et al. JChemInf 2011 3(1):1-15.
• Open Source eco-system– Jmol, CDK, OPSIN, ...
Department of Bioinformatics - BiGCaT 13
Many extensions...
Core bioclipse: latex, ui, bioclipse, xml, js, balloon, cdk, rdf, inchi, cml, moltable, jcp, jcpprops
Additional libraries: bridgedb, metfrag, metware, joelib, oscar, opsin, r, pellet, specmol, spectrum, bibtex, owl, ds, qsar, ambit, structuredb
Online services: cir, opentox, google, gist, myexperiment, sadi, pubchem, pubmed, nmrshiftdb, twitter
… and more.
Department of Bioinformatics - BiGCaT 14
Decision Support (Ola Spjuth)
Spjuth, O. et al. JCIM 2011 51(8):1840-1847.
Department of Bioinformatics - BiGCaT 15
OpenTox
Hardy, B. et al. JChemInf 2010 2(1):1-29.Jeliazkova, N et al. JChemInf 2011 3:18.
Department of Bioinformatics - BiGCaT 16
Thus: Bioclipse-OpenTox
Willighagen, EL et al. BMC Res Notes 2011 4(1):487.
Department of Bioinformatics - BiGCaT 17
Application #1: decision support
Department of Bioinformatics - BiGCaT 18
Application #2: descriptor calculation
Department of Bioinformatics - BiGCaT 19
Application #3: scripting
Department of Bioinformatics - BiGCaT 20
Managers: the vital organs of Bioclipse
Some theory● Make sure that things happen● They provide all domain-related functionality● All Bioclipse GUI is using managers in the background● Takes care of threading (background processes)● They are plugged into the system● Bioclipse dynamically discovers managers when booted● Extend the JavaScript Console (also Groovy)Spjuth, O., Alvarsson, J., Berg, A., Eklund, M., Kuhn, S., Mäsak, C., Torrance, G., Wagener, J., Willighagen, E. L., Steinbeck, C., Wikberg, J. E., Dec. 2009. Bioclipse 2: A scriptable integration platform for the life sciences. BMC Bioinformatics 10 (1), 397+.
Department of Bioinformatics - BiGCaT 21
Managers can be combined ...var alkanesIUPACNames = ["methane", "ethane", "propane", "butane"];
var alkanes = cdk.createMoleculeList()for (var i=0; i<alkanesIUPACNames.length; i++) { js.say("Adding: " + alkanesIUPACNames[i]); alkanes.add( opsin.parseIUPACName(alkanesIUPACNames[i]) );}
var filename = "/OpenTox/alkanes.sdf";cdk.saveSDFile(filename, alkanes);ui.open(filename);
Department of Bioinformatics - BiGCaT 22
OpenTox: downloading data sets
var service = "http://apps.ideaconsult.net:8080/ambit2/";
var datasets = opentox.listDataSets(service);for (set=0; set<5; set++) { var dataset = datasets.get(set); js.say("Downloading set: " + dataset); ui.open( opentox.downloadDataSetAsMDLSDfile( service, dataset, "/OpenTox/ambit/" + set + ".sdf" ) )}
Department of Bioinformatics - BiGCaT 23
OpenTox: authentication
opentox.getToken(); // return a null
// log in on the OpenTox networkopentox.login("user", "password")
opentox.getToken(); // returns the active token
// log out againopentox.logout()
opentox.getToken(); // return again
Department of Bioinformatics - BiGCaT 24
OpenTox: XLogP calculationmolecules = cdk.createMoleculeList();
molecules.add(cdk.fromSMILES("COC"));
molecules.add(cdk.fromSMILES("CNC"));
js.say(opentox.calculateDescriptor(service, descriptor, molecules));
js.say(opentox.calculateDescriptor(
service, descriptor,
cdk.fromSMILES("CCC")
));
Department of Bioinformatics - BiGCaT 25
OpenTox: running models
models = opentox.listModels(ontologyService);
model = models.get(3); // third model
js.say(
opentox.predictWithModel(
service,
model,
molecules
)
);
Department of Bioinformatics - BiGCaT 26
Conclusions & Outlook
• Interactive Toxicity Prediction–Local and
OpenTox services–Scriptable–Mixable–Extensible
• Ontologies–Detail exchange
• Virtual Machine– Inside firewall
Department of Bioinformatics - BiGCaT 27
Acknowledgements
• Uppsala University–Ola Spjuth
• Karolinska Institutet–Roland Grafström
• IdeaConsult Ltd.–Nina Jeliazkova
• DouglasConnect–Barry Hardy–Roman Affentranger
• http://bioclipse.net
Mentioned EU projects• http://opentox.org• http://toxbank.net• http://dixa-fp7.eu