Overview of Genevestigator

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

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

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

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

GENEVESTIGATOR Tools

Genevestigator CLASSIC tool: Meta Profile Analysis

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

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

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)

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

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

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

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

Genevestigator ADVANCED Tools

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

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

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

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

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

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

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

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

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

GENEVESTIGATOR Useful features

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

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

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

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

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

GENEVESTIGATOR End of presentation