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

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March 11 2013

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SEURAT-1 “...replacing animal testing”

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OpenTox / ToxBank

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ToxBank

Kohonen, P. et al. MolInf 2013 32(1):47-63.

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Alternative methods …

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Alternative methods …

… computational.

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Alternative methods …

… computational.

“But they don't work, right?”

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How to integrate complementary info?

• Experimental–Cell line–Rat models–Environmetal data– ...

• Computational– “COMP” stuff– “CINF” stuff–Systems biology

Needs: integrate, visualize, analyze.

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Integration platform: Bioclipse

Spjuth, O et al. BMC bioinformatics 2007 8(1):59.

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Hanson, RM. Appl Cryst 2010 43(5):1250-1260.

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Why Bioclipse?

O’Boyle, NM et al. JChemInf 2011 3(1):1-15.

• Open Source eco-system– Jmol, CDK, OPSIN, ...

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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.

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Decision Support (Ola Spjuth)

Spjuth, O. et al. JCIM 2011 51(8):1840-1847.

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OpenTox

Hardy, B. et al. JChemInf 2010 2(1):1-29.Jeliazkova, N et al. JChemInf 2011 3:18.

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Thus: Bioclipse-OpenTox

Willighagen, EL et al. BMC Res Notes 2011 4(1):487.

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Application #1: decision support

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Application #2: descriptor calculation

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Application #3: scripting

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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+.

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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);

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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" ) )}

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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

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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")

));

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OpenTox: running models

models = opentox.listModels(ontologyService);

model = models.get(3); // third model

js.say(

opentox.predictWithModel(

service,

model,

molecules

)

);

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Conclusions & Outlook

• Interactive Toxicity Prediction–Local and

OpenTox services–Scriptable–Mixable–Extensible

• Ontologies–Detail exchange

• Virtual Machine– Inside firewall

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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