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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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slide1

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
Iterative Signature Algorithm
  • Unsupervised large-scale data analysis tool
  • Modularizes the expression matrix
  • Reduction of complexity
  • Allows for easy data integration
  • Interactive webtool
modular analysis
Modular Analysis
  • A block of the reordered expression matrix
  • Genes and samples have scores
  • Captures differential co-expression

Transcription Module

slide6
Gábor Csárdi and Sven Bergmann

Computational Biology Group,

Department of Medical Genetics,

University of Lausanne,

Switzerland

Modular Analysis of Multi-tissue Gene Expression Data
the data set
The Data Set
  • Coming from WP2, Frans Schuit\'s group.
  • C57bl6 mice, plus 7 S/A islet samples
  • 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.
  • 3-5 samples/tissue, 89 altogether
  • 19 islet samples, 8 on high fat diet
  • After filtering based on variance: 14,540 of 45,101 probesets left on the mouse4302 array
batch and tissue effects
Batch and Tissue Effects

Pituary gland

Islets

slide9

Spearman Rank correlation between 75 Affy mouse 430 2.0 arrays

TISSUE (n arrays)‏

High Fat Diet (5)‏

1

Islets

2

Standard Diet (4)‏

3

Pancreatic acini (3)‏

4

Adrenal (3)‏

5

Brain (3)‏

6

ES cells (3)‏

7

Adipose tissue (3)‏

8

Eye (3)‏

9

Heart (3)‏

10

Small intestine (3)‏

11

Hypothalamus (3)‏

12

Liver (3)‏

13

Lung(3)‏

14

Kidney (3)‏

15

Parotis gland (3)‏

16

Spleen (3)‏

17

Seminal vesicles (3)‏

18

Testis (3)‏

19

Thymus (3)‏

20

Diafragm (3)‏

21

Skeletal muscle (4)‏

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
Very preliminaryModular Analysis Results
  • 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
Pancreas-Specific Modules(Islets + contaminating exocrine cells)‏
  • Example: #49, 35 probes, 27 Entrez genes, 43 conditions, 19 islet samples with positive scores
  • Many pancreas related genes
pancreas specific modules
Pancreas-Specific Modules
  • Genes: Gcg, Iapp, Abcc8, Scn9a, Prss2, Pnlip, Ela3, Rab37, Cuzd1, Pnliprp2, Clps, Rnase1, Asb6, Ctrb1, BC039632, B830017H08Rik, A930021C24Rik, 2210010C04Rik, 1810049H19Rik
pancreas specific modules1
Pancreas-specific Modules
  • Module #49
  • Differentiates between islets and other tissues
islet specific go enrichment
Islet specific GO enrichment

P-value # Category

5.03e-7 49 digestion

1.25e-12 10 extracellular region

3.18e-5 20 mitochondrion

1.44e-4 25 proton-transporting ATP synthase

complex, catalytic core F(1)‏

1.04e-6 64 serine-type endopeptidase activity1.49e-4 151 endopeptidase activity

3.33e-4 16 structural constituent of ribosome

islet specific kegg enrichment
Islet specific KEGG enrichment

P-value # Category

4.37e-6 16 Ribosome

3.26e-4 155 Oxidative phosphorylation

islet specific mirnas
Islet specific miRNAs

P-value # Category

6.65e-3 892 miR-30 family

high fat diet islets
High Fat Diet Islets
  • Running ISA on the 19 islet samples only
  • Only 8,288 probesets after filtering
  • Module #41 differentiates between HF/LF diets best:

http://www2.unil.ch/cbg/Eurodia/isa5-html/maintable.html

high fat diet islets1
High Fat Diet Islets
  • 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 islets2
High Fat Diet Islets
  • Module #41
  • 58 probes, 45 Entrez genes
  • Two outliers
acknowledgements
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

KU Leuven:

Leentje van Lommel

Frans Schuit

Thanks to EuroDia!

http://serverdgm.unil.ch/bergmann

high fat diet islets3
High Fat Diet Islets
  • Serine-type endopeptidase activity, GO molecular function category
high fat diet islets4
High Fat Diet Islets
  • Intersection of module #41 and “Serine-type endopeptidase activity”, GO molecular function category
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