Download Lund_v3

WP8:
Computational analysis of
beta-cell modular organization
EuroDia Meeting
Lund, 23-25 February 2009
Sven Bergmann
Department of Medical Genetics, UNIL &
Swiss Institute of Bioinformatics
http://serverdgm.unil.ch/bergmann
Iterative Signature Algorithm
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Unsupervised largescale data analysis tool
Modularizes the
expression matrix
Reduction of complexity
Allows for easy
data integration
Interactive webtool
Modular Analysis
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Transcription Module
A block of the
reordered
expression matrix
Genes and
samples have
scores
Captures
differential coexpression
Non-modular Analysis
Modular Analysis
Modular Analysis of Multi-tissue
Gene Expression Data
Gábor Csárdi and Sven Bergmann
Computational Biology Group,
Department of Medical Genetics,
University of Lausanne,
Switzerland
The Data Set
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Coming from WP2, Frans Schuit's group.
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C57bl6 mice, plus 7 S/A islet samples
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23 different tissues: adrenal gland, bone marrow, brain,
diaphragma, ES cells, eye, fat, fetal, gastrocnemius muscle,
heart, islet, kidney, liver, lung, ovary, parotis gland, pituitary
gland, placenta, seminal vesicles, small intestine, spleen, testis,
thymus.
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3-5 samples/tissue, 89 altogether
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19 islet samples, 8 on high fat diet
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After filtering based on variance: 14,540 of
45,101 probesets left on the mouse4302 array
Batch and Tissue Effects
Pituary gland
Islets
Spearman Rank correlation between 75 Affy mouse 430 2.0 arrays
TISSUE (n arrays)
High Fat Diet (5)
Islets
Standard Diet (4)
1
Pancreatic acini (3)
Adrenal (3)
Brain (3)
ES cells (3)
Adipose tissue (3)
Eye (3)
Heart (3)
Small intestine (3)
Hypothalamus (3)
Liver (3)
Lung(3)
Kidney (3)
Parotis gland (3)
Spleen (3)
Seminal vesicles (3)
Testis (3)
Thymus (3)
Diafragm (3)
Skeletal muscle (4)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
2
Pituitary gland (5) 22
Bone marrow (4) 23
1
2
3
4 5
6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
23
Very preliminary
Modular Analysis Results
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977 transcription modules were identified
High enrichment by tissues, GO categories,
KEGG pathways and transcription factors
Condition
plots
Show tissue
specific
modules
http://www2.unil.ch/cbg/Eurodia/isa3-html/maintable.html
Pancreas-Specific Modules
(Islets + contaminating exocrine cells)
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Example: #49, 35 probes, 27 Entrez genes, 43
conditions, 19 islet samples with positive scores
Many pancreas related genes
Pancreas-Specific Modules
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Genes: Gcg, Iapp, Abcc8, Scn9a, Prss2, Pnlip,
Ela3, Rab37, Cuzd1, Pnliprp2, Clps, Rnase1,
Asb6, Ctrb1,
BC039632, B830017H08Rik, A930021C24Rik,
2210010C04Rik, 1810049H19Rik
Pancreas-specific Modules
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Module #49
Differentiates
between islets
and other
tissues
Islet specific GO enrichment
P-value
5.03e-7
#
49
Category
digestion
1.25e-12
3.18e-5
1.44e-4
10
20
25
1.04e-6
1.49e-4
64 serine-type endopeptidase activity
151 endopeptidase activity
3.33e-4
16
extracellular region
mitochondrion
proton-transporting ATP synthase
complex, catalytic core F(1)
structural constituent of ribosome
Islet specific KEGG enrichment
P-value
4.37e-6
3.26e-4
#
Category
16 Ribosome
155 Oxidative phosphorylation
Islet specific miRNAs
P-value
6.65e-3
#
Category
892 miR-30 family
Islets-only Analysis
High Fat Diet Islets
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Running ISA on the 19 islet samples only
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Only 8,288 probesets after filtering
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Module #41 differentiates between HF/LF diets
best:
http://www2.unil.ch/cbg/Eurodia/isa5-html/maintable.html
High Fat Diet Islets
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Condition scores
significantly differ,
p-value: 8.5*10-3
Significantly enriched
for serine-type
endopeptidase activity,
p-value: 3*10-12
Enriched for regulation
by Trypsin GTF,
p-value: 3*10-14
High Fat Diet Islets
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Module #41
58 probes, 45
Entrez genes
Two outliers
Acknowledgements
UNIL CBG:
Zoltán Kutalik
Micha Hersch
Aitana Morton
Diana Marek
Barbara Piasecka
Bastian Peter
Karen Kapur
Alain Sewer
Toby Johnson
Armand Valsessia
Gabor Csardi
Sascha Dalessi
Thanks to EuroDia!
KU Leuven:
Leentje van
Lommel
Frans Schuit
http://serverdgm.unil.ch/bergmann
High Fat Diet Islets
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Serine-type
endopeptidase
activity, GO
molecular
function
category
High Fat Diet Islets
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Intersection of
module #41
and “Serinetype
endopeptidase
activity”, GO
molecular
function
category