Building a flexible infrastructure with Bioclipse, open source, and federated

cloud services

1 Dept. Pharmaceutical Biosciences, Uppsala University, Sweden2 Global Safety Assessment, AstraZeneca R&D, Sweden

Ola Spjuth1 and Lars Carlsson2

Contents

• The Bioclipse Workbench

• Federated cloud services (XMPP)

• Global Safety Assessment at AstraZeneca• Decision support for drug safety assessment

• Site-of-metabolism prediction

• Interpretable QSAR models

• Molecular optimization

Bioclipse • A versatile workbench for the life sciences• Open source, Java, builds on Eclipse

(www.eclipse.org)• Extensible architecture - everything is a

plugin• Use open standards if available

Spjuth O, Helmus T, Willighagen EL, Kuhn S, Eklund M, Wagener J, Murray-Rust P, Steinbeck C, Wikberg JES.Bioclipse: an open source workbench for chemo- and bioinformatics.BMC Bioinformatics 2007, 8:59.

O. Spjuth, J. Alvarsson, A. Berg, M. Eklund, S. Kuhn, C. Mäsak, G. Torrance, J. Wagener, E. L. Willighagen, C. Steinbeck, and J. E. S. Wikberg.Bioclipse 2: A scriptable integration platform for the life sciences.Submitted, 2009.

What is a Rich Client?• An application that uses the windowing and

GUI features of the operating system• Responsive UI

• Portable

• Offline operations

• Servers on demand

• Drag & drop

• Integration with platform (files, printer etc)

• Provisioning system

• Much, much, more…

Bioclipse features

• Many plugins for the life sciences• e.g. 2D editor, 3D interactive visualization, sequence editors...

• Bioclipse 2.0: All functionality available from

Bioclipse Scripting Language • Cheminformatics framework: The Chemistry

Development Kit (CDK) - http://cdk.sourceforge.net

• Can utilize existing Eclipse plugins• Reporting tools• Workflows (Knime)• Customize for user needs

Component-based architecture

Bioclipse

Proteochemometrics

2D

3DData analysis

Spectra

Molecular dynamics

Bioclipse

• Use the well-established, mature Eclipse architecture in the life sciences

Other Eclipse-applications: Maestro – NASA Space Mission Management

Other Eclipse-applications:

Dutch railways

XMPP services: Background

A Web service is a way to provide interoperable online functionality

The problem:• Current Web service technologies (e.g.

SOAP and REST)• are synchronous• do not have service discovery built-in• require documents describing the services

XMPP architecture

Wagener J, Spjuth O, Willighagen EL, Wikberg JES.

XMPP for cloud computing in bioinformatics supporting discovery and invocation of asynchronous Web services.

BMC Bioinformatics 2009, 10:2799

Some mid-pres conclusions

• Rich clients are useful• High-end visualizations, work offline, networked

resources on demand

• Bioclipse• An extensible workbench (Rich Client) for the life

sciences

• XMPP + IO-Data• Provides federated, asynchronous, discoverable

cloud services• Ideal for long-running jobs

Bioclipse and Drug Discovery

Meets computational and reporting demands at various stages in the drug-discovery process

DISCOVERY DEVELOPMENT

LI FTIMLO CD

Batch/scripting Tailored plugins

Rich content

Global Safety Assessment, AstraZeneca R&D

The objective of the group at AZ is to provide state-of-the-art tools to facilitate decision making in the drug-discovery process The main focus is on predictive toxicology

Ames Risk AssessmentSystem

• Fully Automated QSAR

• Full Read-Across

• QSAR Interpretation

• Structural Warnings

Bioclipse Software Demonstration

• Batch/scripting (Virtual Screening)• Decision Support (paper submitted to

JCIM, co-authors Ernst Ahlberg Helgee and Dr. Scott Boyer)

• Molecular Optimization (paper submitted to JCIM, co-authors Ernst Ahlberg Helgee and Dr. Scott Boyer)

• MetaPrint2D (paper to be submitted, co-authors Sam Adams, Prof. Robert C. Glen and Dr. Scott Boyer)

Live Demo

Bioclipse Achievements

In 2 years:

• > 29.000 downloads

•>30 contributors - Uppsala, Cambridge, Cologne, Scripps, EBI, Munich, NIH ...

• Bioclipse 2.0 released!

Jury’s

Special

Prize

Genetta Soft AB

Professional consultancy services for Bioclipse• Custom-tailored releases• Develop and integrate custom functionality• Support, documentation, education

www.genettasoft.com

AcknowledgementsDept. Pharmaceutical Biosciences, Uppsala University, Sweden

Prof. Jarl E. S. Wikberg

Dr. Egon Willighagen

Martin Eklund

Jonathan Alvarsson

Carl Mäsak

Eskil Anderssen

Annsofi Andersson

Arvid Berg

Bjarni Juliusson

Unilever Centre for Molecular Informatics, Univ. Cambridge, UK

Prof. Peter Murray-Rust

Prof. Robert Glen

Samuel Adams

Linnaeus Centre for Bioinformatics, Uppsala, Sweden

Dr. Erik Bongcam-Rudloff

Sofia Burvall

European Bioinformatics Institute, Hinxton, UK

Dr. Christoph Steinbeck

Stefan Kuhn

Dr. Gilleain Torrence

Cologne University Bioinformatics Centre (CUBIC), Germany

Dr. Tobias Helmus

Miguel Rojas

Thomas Kuhn

Dept Clinical Pharmacology, Uppsala University, Sweden

Prof. Rolf Larsson

Dr. Claes Andersson

Hanna Göransson

Ludwig-Maximilians-Universität, Munich, Germany

Dr. Johannes Wagener

Dept. Pharmaceutical Biosciences, Uppsala University, Sweden

Prof. Johan Åqvist

Dr. Martin Nervall

Göran Wallin

Global Safety Assessment, AstraZeneca, Mölndal Sweden

Dr. Scott Boyer

Ernst Ahlberg Helgee

Van Drie Research LLC, MA, US

Dr. John Van Drie

Indiana University, IN, USA

Dr. Rajarshi Guha

Others

Dr. Jerome Pansanel

… and all others for contributing code, feature requests, bug reports, proposals, and comments!

Thank you!

Supporting slides

Bioclipse Decision Support:

Safety assessment

Near-real time predictions

Bioclipse Decision Support:

Interpretation of models

Interpret results graphically

Bioclipse Decision Support:

Optimize problematic regions

Optimization invokes an XMPP service (long-running job)

Bioclipse Decision Support:

Inspect optimized structures

Upon completion, results are opened for inspection

Bioclipse Decision Support:

Multiple Molecules

Batch processing with overview

Bioclipse Decision Support:

Report generation

Integrated report generation (export to Excel, Word, ppt, pdf, etc)

MetaPrint2D:Site-of-metabolism prediction

L. Carlsson, O. Spjuth, S. Adams, R. C. Glen, and S. Boyer. Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using metaprint2d and bioclipse.Manuscript in preparation.

MetaPrint2D:Site-of-metabolism prediction

Predict multiple structures

L. Carlsson, O. Spjuth, S. Adams, R. C. Glen, and S. Boyer. Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using metaprint2d and bioclipse.Manuscript in preparation.

Standardized QSAR in Bioclipse

O. Spjuth, E. L. Willighagen, R. Guha, and J. E. S. Wikberg.Towards interoperable and reproducible QSAR analyses: Exchange of data sets. Manuscript in preparation.