Course on Functional Analysis

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1 Course on Functional Analysis ::: An Introduction to Ingenuity Pathway Analysis. Madrid, June 31st, Gonzalo Gómez, PhD. Bioinformatics Unit Structural Biology and Biocomputing program CNIO

2 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

3 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

4 ::: Introduction. Ingenuity Pathways Analysis v5.0 Release Date: 2007/04/16 Customer Support: Integrated approach to Omics analysis :::

5 ::: Introduction.

6 ::: Introduction.

7 ::: Introduction. Answering biological questions :::

8 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

9 ::: Web Accession.

10 ::: Running into IPA. Project Manager Menu.

11 ::: Running into IPA. File > Preferences :::

12 ::: Help and tutorials.

13 ::: Help and tutorials. Help > Tutorials :::

14 ::: IPA Networks Legend. Help >Legend :::

15 ::: IPA Networks Legend. Help >Legend ::: Network Explorer Tags Overlapping Networks Nodes and Edges

16 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

17 ::: Quick start searching a Single Gene. Genes or chemicals Genes/Chemicals associated with Functions/Diseases Genes targeted by Drugs GENES: Affymetrix, Agilent, Affymetrix SNP ID, Applied Biosystems, Code Link, Locus Link, Genbank, HUGO, Illumina, UniGene, RefSeq, Uniprot, etc. DRUGS: Systematic names, IUPAC, CAS, Chemical formula Brand Name.

18 ::: Quick start exploring a Single Gene. Which biological and disease processes are most relevant to my genes of interest? Description GO Annotations Human, Mouse, Rat details Database Information (Gene, RNA, Prot.) Functional roles Mutant Information Modifications and regulation Disease Expression and Localization Physical interactions Literature entries Additional findings

19 ::: Explore and Advanced Search Options. How do I query the Ingenuity Pathways Knowledge Base about specific genes, processes, diseases, drugs, famiies or subcellular locations?

20 ::: Quick start exploring a Single Gene. Description GO Annotations Human, Mouse, Rat details Database Information (Gene, RNA, Prot.) Functional roles Mutant Information Modifications and regulation Disease Expression and Localization Physical interactions Literature entries Additional findings

21 ::: Quick start exploring a Single Gene.

22 ::: Quick start exploring a Single Gene. Interactive gene networks :::

23 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

24 ::: Network Explorer Toolbar.

25 ::: Network Explorer Toolbar.

26 ::: Network Explorer Toolbar. Drawing pathways ::: Also quick access:

27 ::: Exploring a Single Gene. Drawing a pathway :::

28 ::: Network Explorer Toolbar. Building pathways ::: Grow Path explorer (shorstest path) Connect Trim (remove) Highlight Species and tissues highlight Also quick access:

29 ::: Network Explorer Toolbar. Overlaying pathways ::: Expression values Drug Functions and diseases My List Canonical pathway My pathway Ingenuity tox list

30 ::: Network Explorer Toolbar. View options :::

31 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Toolbar 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

32 ::: Exploring Gene Lists. ::: Searching Lists. Gene, drug, AffyID1, Oxal*, CASP*, RefSeq X, cisplatin,

33 ::: Gene Lists. Saving a gene list :::

34 ::: Gene Lists. Stored gene lists :::

35 ::: Gene Lists. Creating pathways with Gene Lists ::: What regulatory effects relationships exists between the genes/proteins in my dataset? Etc.

36 ::: Schedule. 1. Introduction. 2. Running into IPA 3. Quick Search 4. Bar Tools 5. Gene Lists 6. IPA Analysis 7. Sharing Projects

37 ::: Analysis using IPA. Expression data analysis Toxicology analysis Biomarker analysis Metabolomics analysis

38 ::: Types of Analysis.

39 ::: Types of Analysis.

40 ::: Importing data for analysis. - Single observation -.xls datasheet accepted - Up to 18 MB row size limit File format A :::

41 ::: Importing data for analysis. File format B ::: - Multiple observations (up to 10) -.xls datasheet accepted - Up to 18 MB row size limit

42 ::: Sample Analyses. Useful examples to learn how to deal with Ingeunity IPA

43 ::: Core Analysis. Expression Data Analysis. Accession and workflow :::

44 ::: Core Analysis. Expression Data Analysis.

45 ::: Core Analysis. Expression Data Analysis. Core analysis output ::: Results tabs Right-tailed Fisher Exact test

46 ::: Core Analysis. Expression Data Analysis. Some statistics ::: Right-tailed Fisher Exact test 2x2 Contingency Table. α = 0.05 p < 0.05 are considered significant

47 Networks ::: Core Analysis. Lists(Tox) Expression Data Analysis. Results tabs ::: Functions(Bio) Overlapping networks Canonical Pathways Network explorer

48 ::: Networks & Canonical Pathways Which well characterized cell signaling and metabolic pathways are most relevant in my data?

49 ::: Canonical Pathways

50 ::: Core Comparison Analysis. Expression Data Analysis.

51 ::: Core Comparison Analysis. Expression Data Analysis. Core comparison analysis output ::: Which functions and pathways are regulated at different times, doses, or in different tissues in my experiment?

52 ::: IPA-Tox Analysis. Toxicology Analysis.

53 ::: IPA-Tox Analysis. Toxicology Analysis. IPA-Tox List Library :::

54 ::: IPA-Tox Analysis. Toxicology Analysis. IPA-Tox List Library ::: Toxicity lists are lists of genes that are known to be involved in a particular type of toxicity. Manually-curated by Ph.D. Scientists Relevant to drug metabolism Cover oxidative stress response Include panel of P450s, xenobiotic metabolism Relevant to hepatic, renal, and cardiac toxicity and function Contain fibrosis, cardiac hypertrophy and cell death

55 ::: IPA-Tox Analysis. Toxicology Analysis. Does this drug treatment cause any toxic effect?

56 ::: IPA-Tox Analysis. Toxicology Analysis. IPA-Tox analysis output ::: Results tabs

::: IPA-Tox Analysis. Toxicology Analysis. IPA-Tox analysis output ::: Toxicity Functions link expression data to clinical pathology endpoints for mechanistic hypothesis generation.

57 ::: IPA-Tox Analysis. Toxicology Analysis. IPA-Tox analysis output ::: Toxicity Functions link expression data to clinical pathology endpoints for mechanistic hypothesis generation. Categories cover a wide spectrum of well known drug induced injuries and pathologies useful for the drug discovery and development process, such as: Hepatoxicity Steatosis, Necrosis, Fibrosis, and more Cardiotoxicity Cardiomyopathy, cardiac dilation, fibrosis Nephrotoxicity Tubular nephrosis, Phospholipidosis, kidney weight increase, etc.

58 ::: IPA-Tox Comparison Analysis. Toxicology Analysis.

59 ::: IPA-Tox Comparison Analysis. Toxicology Analysis.

60 ::: IPA-Biomarker Analysis. Biomarker Analysis. Are there any potential biomarkers in my samples? What are the unique and common potential biomarkers?