Association of variations in I kappa B-epsilon with Graves' disease using classical and myGrid methodologies

1
Association of variations in I kappa B-epsilon
with Graves' disease using classical and myGrid
methodologies

• Peter Li
• School of Computing Science
• University of Newcastle upon Tyne

2
In silico experiments in bioinformatics
Bioinformatics analyses - in silico experiments
- workflows
Resources/Services
BLAST
Example workflow Investigate the evolutionary
relationships between proteins
Multiple sequence alignment
Protein sequences
Query
3
Issues in bioinformatics

• Difficult to perform bioinformatics analyses

Large amounts of distributed data in different
databases Highly heterogeneous Lack of
standards Many applications Different
algorithms, implementations Lack of programmatic
access
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e-Science and myGrid

• e-Science for in silico experiments
• Potential solution to problems in bioinformatics
• Using the Grid as a framework
• Bioinformatics resources deployed as Web Services
• myGrid
• Development of middleware to support the
  performance of in silico experiments in biology
• Investigated the use of myGrid workflow
  technology in the genetic analysis of Graves
  disease

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Graves disease

• Autoimmune thyroid disease
• Lymphocytes attack thyroid gland cells causing
  hyperthyroidism
• An inherited disorder
• Complex genetic basis
• Symptoms
• Increased pulse rate, sweating, heat intolerance
• goitre, exophthalmos

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In silico experiments in Graves disease

• Microarray data analysis
• Gene annotation pipeline
• Design of genotype assays for SNP variations

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Classical approach to the bioinformatics of
Graves disease
Study Annotations for many different Genes
Data Analysis - Microarray Import microarray
data to Affymetrix data Mining Tool, Run Analyses
and select
Experiment Design to test Hypotheses Find
restriction sites and design primers by eye for
genotyping experiments
Select Gene and Visually examine SNPS lying within
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Taverna workflow system

• Used to compose and enact in silico experiments
  in myGrid
• Freefluo enactor
• Scufl language
• Workbench GUI
• Service browser
• Model explorer for workflow composition
• Graphical view of workflow
• Free and open source

http//taverna.sf.net
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Modelling in silico experiments as workflows

• Semantic, syntactic and format typing of data in
  workflow
• Data has to be filtered, transformed, parsed for
  consumption by services

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Results Differential expression and variations
of the I kappa B-epsilon gene
3 UTR SNP 3948 C/A
n30

• Mean NFKBIE expression levels -
• Controls 1.60 /- 0.11 (SEM)
• GD 2.22 /- 0.20 (SEM)
• P0.0047 (T-test)

- Mnl restriction site - ?2 9.1, p 0.0025,
Odds Ratio 1.4
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Comparison between conventional bioinformatics
and Taverna workflow approaches

• Advantages
• Graphical composition of experiments
• Automation and speed
• Management of workflow information
• Share and reuse workflows for other diseases
• Issues
• Initial cost of learning/activation energy
• Lack of Web Service interface to required
  resources

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Acknowledgements

• Institute of Human Genetics
• Simon Pearce and Claire Jennings
• School of Computing Science
• Anil Wipat, Matthew Pocock and Keith Hayward
• European Bioinformatics Institute
• Tom Oinn