1. Overview of Genevestigator

2. Content Introduction Tools Additional tips Metaprofile analysis
Biomarker search
RefGenes
Clustering analysis
Additional tips

3. Concept of Genevestigator
Tissue type 1
Tissue type 2
Tissue type 3
Tissue type 4 …
Tissue type 200 …
Thousands of microarray
experiments world-wide
Curation of data and annotation
Model of a summarized
output
Curation: normalization and annotation of
- Anatomy
- Development
- Stimulus and Mutation
Establishment of the
Genevestigator
Database

4. Curation: quality control of microarray data
Unprocessed probe intensity
RNA degradation plots
Probe-level analysis (RLE, NUSE)
Border element analysis
Array-array correlation plots

5. Overview of the Genevestigator System
Database and Application Server Cluster
Website
Java Client Application

6. GENEVESTIGATOR
Tools

7. Genevestigator CLASSIC tool: Meta Profile Analysis

8. Meta Profile Analysis: analytical approach
genes
Anatomy
[space]
Development
[time]
Stimulus /
Mutation
[response]
which conditions?

9. Meta-Profile Analysis
1. Chose an organism
2. Enter the genes you wish to work with

10. Meta-Profile Analysis
View and interpret the results across:
Anatomical categories (Anatomy tab)
Developmental stages (Development tab)
Chemicals, diseases, treatments, etc. (Stimulus tab)
Genetic modifications (Mutation tab)
Tumor types (Neoplasm tab)

11. Meta-Profile Analysis: Anatomy tool
Looks at how genes are expressed in different tissues
Mean and standard deviation
Anatomy categories as a tree (ontology); expand / collapse
Number of arrays per category is indicated
Looks at how genes are expressed in different tissues
Mean and standard deviation
Anatomy categories as a tree (ontology); expland / collapse
Number of arrays per category is indicated
Anatomical expression profile of ß-Actin in the mouse

12. Meta-Profile Analysis: Development tool
Looks at how genes are expressed during the life cycle of an organism
Example for human
Example for mouse / rat
Expression profile of BDNF across the
human development

13. Meta-Profile Analysis: Stimulus and Mutation tools
Most upregulating conditions
List (or tree)
of various
conditions
Spots indicate the
responses of selected
gene(s) to the list of conditions
Most downregulating conditions

14. Meta-Profile Analysis: Neoplasm tool
Looks at how genes are expressed in different tumors
Mean and standard error
Tumors ordered as a tree (ontology); expand / collapse
Number of arrays per category is indicated
Looks at how genes are expressed in different tissues
Mean and standard deviation
Anatomy categories as a tree (ontology); expand / collapse
Number of arrays per category is indicated
Expression profile of NPY1 receptor across human tumors

15. Genevestigator ADVANCED Tools

16. Biomarker search: analytical approach
conditions
which genes?
Anatomy
[space]
Development
[time]
Stimulus /
Mutation
[response]

17. Biomarker search 1. Chose an organism
2. Chose conditions and run analysis
3. Save target genes for further analysis

18. Biomarker Search
Identify genes that exhibit specific expression characteristics
Anatomy
Development
Stimulus / Mutation

19. Biomarker Search in Genevestigator
target condition
condition 1
condition 2
condition 3
condition 4
condition 5
condition 6
condition 7
condition 8
condition 9
condition 10
condition 11
condition 12
condition 13
condition 14
condition 15
condition 16
condition 17
condition 18
condition 19
condition 20
condition 21
condition 22
condition 23
condition 24
condition 25
condition 26
condition 27
condition 28
condition 29
condition 30
condition 31
condition 32
condition 33
condition 34
condition 35
condition 36
condition 37
condition 38
condition 39
condition 40
condition 41
condition 42
condition 43
condition 44
condition 45
condition 46
condition 47
condition 48
condition 49
condition 50
condition 51
condition 52
condition 53
condition 54
condition 55
condition 56
condition 57
condition 58
condition 59
condition 60
condition 61
condition 62
condition 63
condition 64
condition 65
condition 66
condition 67
condition 68
condition 69
condition 70
condition 71
condition 72
condition 73
condition 74
condition 75
gene 3
gene 5
gene 7
gene 13
gene 17
gene 10
gene 2
gene 15
gene 9
gene 12
gene 4
gene 11
gene 16
gene 1
Imagine extending this to a much wider set of conditions…
you may find other conditions to which the set of genes respond
gene 6
gene 8
gene 14
other conditions to which the genes are responding

20. Biomarker Search in Genevestigator
Example: human genes responsive to Actinomycin-D
target condition(s)
Actinomycin-D
vMyb
Oncolytic herpes
simplex virus
Propiconazole
Sapphyrin
Echinomycin
Cell cycle inhibition
co-inducing conditions
Chemical: ARC

21. RefGenes – find the best housekeeping genes
Validation experiment
on mouse liver
geNorm selection of the most
stable reference genes within
this experiment
Dataset: 197 arrays from mouse liver

22. Clustering Analysis
Goal: to identify groups of genes that have similar expression characteristics
Tools:
Hierarchical clustering (with leaf ordering)
Biclustering (BiMax algorithm)

23. Hierarchical clustering
Cluster sets of genes expressed at different stages of plant development
HC using leaf ordering algorithm

24. Biclustering
Search for biclusters in a list of 64 genes responsive to myocardial infarction
One of many possible biclusters
Development profile of these 7 genes

25. GENEVESTIGATOR
Useful features

26. Useful features - tooltips
Tooltips (mouse-over) provide detailed information about
a treatment, a spot, or an experiment.

27. Focus function Focus on an array selection Focus on a gene selection
tools will compile results from this combination of data
allows to easily jump from one selection of genes or arrays to another selection
Note: be sure that genes and organism/arrays are compatible!
(e.g. you cannot look at mouse genes in a selection of rat arrays…) 27

28. Exporting figures scale export image Save export image in: PNG JPEG
EPS

29. Exporting data Export content: Mean value Standard error values
Export format:
tab-delimited (TXT) or
comma-separated (CSV)

30. Saving workspaces Saves content of selections:
selections of experiments and arrays
selections of genes
status of checkboxes
Benefits:
allows to share results between colleagues
allows to continue your research at a later stage without losing the context

31. GENEVESTIGATOR
End of presentation