EMBL-EBI

Structural Proteomics Automatic

Target SelectionGordon Whamond

EMBL-EBI

Aim: • Provide a resource that facilitates the automatic selection of potential targets for protein structure determination while minimising human interaction with the software (if required).

Input: • Raw amino acid sequence• UniProt accession number• UniProt accession number and a sequence range

Output:• Query sequence showing possible domains• All candidates for structure determination• Recommendation for which sequence to use

Project Overview

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Considerations

• Is there a known structure?

• Are there Classified Structural (CATH, SCOP) Domains?

• Are there Known Sequence (Pfam) Domains?

• Are there Predicted Structural (Gene3D, Superfamily) Domains?

• Do Domain Boundaries Conform to Secondary Structure Restrictions?

• Which Species has a Representative Domain that is the Most Compactly Folded?

• The core implementation needs to be extendible and easily maintainable.

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The software is to be implemented using the Taverna workbench.

This is a tool that can be used to formulate the workflow and implement each of the processes as distributed web services.

Tom Oinn - http://taverna.sourceforge.net/

Taverna

Advantages: • Distributed computing reduces resource requirement.• Easily extendible system• Maintenance issues shifted to external providers

Disadvantages:• Learning curve• Convincing service providers to adopt a standard format• Maintenance issues shifted to external providers

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Taverna

The prototype workflow:

When it is expanded to show all of

the incorporated sub-workflows is

quite complex

Luckily Taverna can provide a top

level view.

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Taverna

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Dealing With DAS

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Taverna

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Process Data

Secondary Structure Elements:(Method not yet chosen)

Sequence Domains:Pfam, Gene3D, Superfamily etc

Protein Folding:RONN, FoldIndex, DisEMBL

Rank Target Selection:Based on loop lengths, folding predictions, etc

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Starting the Process

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Monitoring Progress

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Assess Data

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Review Results

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Extensibility

Java Services

• Straightforward to provide as a web service using Tomcat and Axis

• WSDL (describing the service) can be generated automatically

Legacy Software

• Any command line based tools can be wrapped into a web service using Soaplab

•For example the EMBOSS tools are already available

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Extensibility

Output Format:

To ensure generic service compatibility it helps to define a common

results format. As a result we are using the e-Family service schema

(http://www.efamily.org.uk/)

Current collaborators include:

The Weizmann Institute - FoldIndex

University of Oxford - RONN

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http://www.efamily.org.uk/software/dasclients/spice/

Results Viewers

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Conclusions

Taverna and Web Services:

• Taverna facilitates the provision of complex distributed systems that utilise web services

• This reduces maintenance overheads and keeps technology requirements at a reasonable level

• It is also easily extensible to accommodate new services

Availability:

• Hopefully the core system will be ready by the end of the year

• This will provide the basic workflow for users to customise according to their needs

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Acknowledgments

Thanks to:

Tom Oinn

Andreas Prlic

The RONN and FoldIndex teams

The MSD Group