Inaugural meeting
Edinburgh 1-3 October
1-3 October
Wednesday 1/10
• 14.00-15.00 System-wide Genetical Genomics:
Tutorial by Prof. Ritsert Jansen, Groningen
University, The Netherlands
• 15.00-15.30 coffee
• 15.30-16.00 eQTL in practise: Regulatory networks
underlying barley interaction with rust fungi. Dr.
Arnis Druka, SCRI, Dundee
• 16.00-17.30 software presentations:
–
–
–
–
–
–
GG_design (Groningen, TBC)
ONDEX (Chris Rawlings, Rothamsted Research)
GridQTL (DJ de Koning, Edinburgh University)
BioLayout (Tom Freeman, Edinburgh University)
TBC (David Wild, Warwick University)
Software introduced in 10 minutes each. Followed by
informal mixer with drinks
1-3 October
Thursday 2/10
• 09.00-10.00 Dirk Husmeier, BIOSS. Tutorial
on recent machine learning and statistical
methods for reconstructing regulatory
networks from postgenomic data
• 10.00-10.30 coffee
• 10.30-12.00: Presentations from participants,
drawn from conference abstracts
- Oliver Stegle, University of Cambridge
- Alex Lam, Edinburgh University
- Reinhart Gutkhe, Hans-Knöll-Institut, Jena,
Germany
1-3 October
Thursday 2/10
• 13.30-13.45 Welcome and introduction to meeting
• 13.45-15.00 Professor Vivian Cheung (University of
Pennsylvania) Keynote: Genetics of Variation in
Human Gene Expression
• 15.00-15.30 Coffee + posters
• 15.30-17.30 Genetic dissection in action
– 15.30-16.15 Dr. Gerald de Haan (University of Groningen):
Using genetical genomics for Stem Cell Research
– 16.15-17.00 Professor Jonathan Flint (Wellcome Trust
Centre for Human Genetics): the genetic basis of
psychiatric disorders
• 17.00-17.30 ‘elevator pitch’ for first ten posters
followed by posters and drinks
1-3 October
Thursday Evening
• Conference dinner 19.30
Tempus bar
25 George Street, Edinburgh, EH2 2PA
0131 240 7197
Friday 3/10
• 09.00-10.30 Modelling Networks
– 09.00-09.45 Prof. David Wild (Warwick University)
Network Inference - Decoding the Strategy of the Genes
– 09.45-10.30 Prof. Michael Stumpf (Imperial College)
Bayesian methods for reverse engineering of biological
networks
• 10.30-11.00 coffee and posters
– 11.00- 11.10 Introducing the StoMP MATSYB network:
partner network of GeneSys by Dr. Rosalind Allen,
University of Edinburgh
– 11.10-11.40 Prof. Barry Wanner, Purdue University
• 11.40-12.30 Elevator pitch for remaining posters
1-3 October
Friday 3/10
• 13.30-15.00 Exploiting the public domain
– 13.30-14.15 Dr. Enrico Petretto (Imperial College) eQTLs
and reverse engineering approaches in the rat:
exploiting multiple tissues
– 14.15-15.00 Professor Robert Williams (University of
Tennessee Health Science Center) Systems genetics of
brain function and disease using the GeneNetwork
platform
• 15.00-15.30 coffee & posters
• 15.30-16.30 “Ask the Experts”: panel discussion
with speakers
• 16.30 Closure
1-3 October
Coordinators
Chris Rawlings, Tim Aitman, Dirk Husmeier,
John Whittaker, Robbie Waugh, Arnis
Druka, Chris Haley & DJ de Koning
www.genesys.ac.uk
1-3 October
Main Goal
Integration between genetics,
bioinformatics and mathematics
to facilitate the reverseengineering of regulatory
networks using genetic mapping
data and high throughput data,
such as transcriptomics
1-3 October
Breadth and depth of the
network
• ‘higher’ organisms including crops,
rodents, livestock and humans
• Dissection of complex traits via
genetic mapping, supplemented by
functional data
• Reverse engineering of underlying
networks
1-3 October
Genetic mapping (on its own)
X
25
Evidence for QTL
• Gene Identification by
(QTL) mapping
• Map to every
increasing resolution
to reach nucleotide
• Some success for
major genes but
difficult and expensive
• May not be possible
• Recombinations
not available
• Populations too
small
20
15
10
5
0
0
10
20
30
Chrom osom e
1-3 October
40
50
Gene networks from microarrays
Nodes = genes; Edges = (Cor)relations
Reverse Engineering: learn the network structure
from ‘omics data
1-3 October
Gene interventions
1-3 October
Problem: Statistical significance of the
networks
• Complex models: Transcript levels of
hundreds of genes.
• Sparse data: Typically a few dozen
samples.
1-3 October
traits
Comparative Cereal Crop
Genetics/Genomics
Integrated QTLs
orthologous
markers
physical
map &
sequence
wheat
barley
lolium
genetics data
Brachypodium
ESTs
Rice
Transcriptomics
Arabidopsis
Annotated
Probe sets
1-3 October
Candidate Gene Prioritisation
model(s)
e.g. Arabidopsis
Brachypodium
Crops
Willow
Wheat
pathways
Linked
References
QTL Map
Orthologous
Markers
Incomplete
genome
Physical
map
Expression Patterns
Genes
Ontologies
Complete
genome
List of candidate genes linked to biological processes
Genetical Genomics
X
50
+
50
Test Statistic
40
30
20
10
0
0
50
100
150 cM
40
Test Statistic
Disease
challenge on
experimental
population
30
20
10
0
0
50
100
150 cM
• QTL study AND gene expression
study in experimental population
• Is QTL also an eQTL?
– Cis and trans effects
• Additional eQTL
QTL and eQTL Information
Cis-acting eQTL
eQTL G1
TRAIT QTL
GENE 1
1-3 October
eQTL: cis-acting
• eQTL: Genome region that affects the
expression level of one or more genes
(in a given tissue at a given time)
• Cis-acting: the location of the eQTL
coincides with the gene that is
affected
• This suggests a polymorphism within
the gene, affecting expression levels.
1-3 October
QTL and eQTL Information
Trans-acting eQTL
eQTL G2
TRAIT QTL
GENE 2
1-3 October
eQTL: trans-acting
• Trans-acting: the
location of the eQTL is
different from that of
the gene that is affected
• Some trans-acting
eQTL affect many
genes
• This suggests ‘hubs’ of
gene regulation
1-3 October
Promise of eQTL
• Reconstruct genetic pathways
• Combine:
– Position of genes, Position of eQTL
– Pleiotropic and Epistatic action of eQTL
• Pathways relating eQTL and trait QTL
Jansen & Nap, 2001 TIG 17:388-391
Challenges
• eQTL studies combine all the challenges from
microarrays AND QTL studies!!
• Biological
– Appropriate tissue, timing, environment
• Technical
– Cost
– Appropriate array technology
– Measurement error, biases, data extraction
• Computational
– Analysis of thousands of traits
– Controlling the error rate
• Inferential
– From eQTL to gene network
Network inference in Genetical
Genomics
• Genetical genomics provides a
potential causal starting point
• Co-location of functional and eQTL
can provide local candidate genes
• Epistatic interactions can be
modelled directly
• Requires integration between various
disciplines
1-3 October
Delivery
• 3 annual meetings
• Interactive workshop followed by full
blown conference
• First meeting 1-3 October 2008
– NESC Edinburgh
– 1-2: Workshop (n~50)
– 2-3: Conference (n~100)
1-3 October
Inaugural meeting
• 1-3 October NESC Edinburgh
• Free registration at:
http://www.nesc.ac.uk/esi/events/868/
• Speakers include:
Vivian Cheung, Ritsert Jansen, Gerald de
Haan, Michael Stumpf, Jonathan Flint,
Rob Williams, David Wild, Dirk Husmeier
Full preliminary programme on flyers
1-3 October
Sister Network: STOMP
• Cross-present at meetings
• Sponsor visits between network
partners
• Linking websites
• Exchange expertise
1-3 October
Coordinators
Chris Rawlings, Tim Aitman, Dirk Husmeier,
John Whittaker, Robbie Waugh, Arnis
Druka, Chris Haley & DJ de Koning
www.genesys.ac.uk