Transcript Association of variations in I kappa B

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
In silico experiments in bioinformatics
Bioinformatics analyses - in silico experiments - workflows
Resources/Services
Genscan
EMBL
BLAST
Clustal-W
Example workflow: Investigate the evolutionary relationships between proteins
Query
Protein
sequences
Clustal-W
Multiple
sequence
alignment
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
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
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
In silico experiments
in Graves’ disease
•
Microarray data analysis
•
Gene annotation
pipeline
•
Design of genotype
assays for SNP
variations
Classical approach to the
bioinformatics of Graves’ disease
Data Analysis - Microarray
Study Annotations for many different Genes
Import microarray data to Affymetrix
data Mining Tool, Run Analyses and
select
Select Gene and Visually examine SNPS
lying within
Experiment Design to test Hypotheses
Find restriction sites and design primers by eye for
genotyping experiments
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
Modelling in silico experiments as workflows
•
•
Annotation Pipeline
Semantic, syntactic
and format typing of
data in workflow
Data has to be
filtered, transformed,
parsed for
consumption by
services
Query
GO
MEDLINE KEGG SwissProt InterPro
PDB
Blast
HGBASE
Results: Differential expression and
variations of the I kappa B-epsilon gene
Figure 2. Results of real-time RT-PCR NFKBIE
expression levels between GD patients and controls
Normalised NFKBIE expression
8
6
4
2
n=30
3’ UTR SNP – 3948 C/A
0
Controls
Graves’
disease
Mean NFKBIE expression levels • Controls: 1.60 +/- 0.11 (SEM)
• GD:
2.22 +/- 0.20 (SEM)
• P=0.0047 (T-test)
- Mnl restriction site
- χ2 = 9.1, p = 0.0025, Odds Ratio = 1.4
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
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