1. Merging Curated and in silico Interaction Data in Network Analysis

2. without prior knowledge
Overview
Curated Networks
Problem
in silico
Outlook
without prior knowledge

3. Introduction

4. Integration across Studies
By group
By platform 4
Integration across Studies

5. Integration by Normalization

6. Integration by Ranking
Gene
Exp1
Exp2
Rank
SIL
2.3
COL
3.2
CEAC
NOV
2.2
3.0
NID
2.1
2.7 …
PROM
TUBA1
1.6
1.5
FEL
1.4
Gene
Exp1
Exp2
SIL
2.3
COL
3.2
NOV
2.2
CEAC
3.0
2.1
NID
2.7
PROM
TUBA1
1.6
1.5
FEL
1.4
Integration by Ranking

7. Using Gene Set Enrichment Analysis

8. Overlap of significant genes
Gene fold change in list A B C D
Gene 2
1.3
1.5
Gene 17
2.2 2
0.4
Gene 22
-1.9 -5
Gene 3
0.5
-2.4
-0.5 -2
List B
List C
Gene 3
List D
Overlap of significant genes

9. Overlap of significant gene function
List B
List C
Regulation of B-cell mediated immunity
Gene 3
List D
Overlap of significant gene function

10. Overlap of significant genes
Gene fold change in list A B C D
Gene 2
1.3
1.5
Gene 17
2.2 2
0.4
Gene 22
-1.9 -5
Gene 3
0.5
-2.4
-0.5 -2
Gene 3
Gene 17
Gene 2
Gene 22
Overlap of significant genes

11. Example gene sets Function: Gene Ontology, KEGG Pathways, ...
Localization: X-Chromosome
Regulation: Targets of FOXP3
...

12. Genomica: defining gene sets

13. Gene sets to experiments

14. Enriched gene sets

15. Enriched gene sets

16. Grouping to modules 16

17. Defining conditions 17

18. Modules to conditions 18

19. Integration via Networks

20. Leishmania

21. Filtering (by integration)
Analysis Workflow
Up/down-regulated genes, proteinsSignificance analysisFunctional annotation
Trem
Lipids
Unfolded Protein Response
Oxidative Stress
Arginin
Iron
Filtering (by integration)

22. Intersection Proteins
Pathway
Intersection Proteins
Genes
Functional Selection 22

23. Protein Interactions: Intersection

24. Finding ‘Fringe’ Proteins
Intersection Proteins
Finding ‘Fringe’ Proteins 24

25. Intersection Proteins
Fringe Proteins
Intersection Proteins
Trem and other pathways
Trem (other)
Trem ‘Fringe’
Non-Trem

26. Unfolded Protein Response
Trem
Iron
Arginin
Lipids
Oxidative Stress
Unfolded Protein Response
Repeat for all Categories

27. Unfolded Protein Response
Trem
Iron
Arginin
Lipids
Oxidative Stress
Unfolded Protein Response
Add Fringe Interactions

28. Interactions Captured
Intersection
Intersection & Fringe
Fringe (within pathway)
Fringe & Fringe (different pathways) 28

29. Combined Representation
Trem
Arg
Iron
Oxidative Stress
Lipids
Unfolded Protein Response
Combined Representation

30. Add Expression Time Series
0/3/6/12/24h after infection
Identify active Subnetworks

31. Oxidative Stress and Lipid Pathway
Lipids
Oxidative Stress and Lipid Pathway

32. Experimental validation
Oxidative Stress Response linked to alternative Lipid Pathway