Transcript IPA 8.5 - Bioinformatics Unit

Course on Functional Analysis
::: An Introduction to Ingenuity Pathway Analysis.
Madrid, Feb 16th, 2010.
Gonzalo Gómez, PhD.
[email protected]
Bioinformatics Unit
Structural Biology and Biocomputing program
CNIO
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Introduction.
Ingenuity Pathways Analysis (IPA)
Ingenuity Pathways Analysis v8.5
Release Date: Feb 2010
Customer Support: [email protected]
http://www.ingenuity.com/products/pathways_analysis.html
Integrated approach to “Omics” analysis :::
::: Introduction.
Ingenuity Pathways Analysis (IPA)
::: Introduction.
Ingenuity Pathways Analysis (IPA)
::: Introduction.
Ingenuity Pathways Analysis (IPA)
Types of analysis :::
::: Introduction.
Ingenuity Pathways Analysis (IPA)
Answering biological questions :::
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Web Accession.
Ingenuity Pathways Analysis (IPA)
https://analysis.ingenuity.com/pa/
::: Running into IPA.
Ingenuity Pathways Analysis (IPA)
Project
Manager
Menu.
::: Running into IPA.
Ingenuity Pathways Analysis (IPA)
File > Preferences :
::: Help and tutorials.
Ingenuity Pathways Analysis (IPA)
::: Help and tutorials.
Ingenuity Pathways Analysis (IPA)
Help > Tutorials ::
::: IPA Networks Legend.
Ingenuity Pathways Analysis (IPA)
Help >Legend :
::: IPA Networks Legend.
Ingenuity Pathways Analysis (IPA)
Network Explorer Tags
Help >Legend :
Overlapping Networks
Nodes and Edges
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Quick start searching a Single Gene.
Ingenuity Pathways Analysis (IPA)
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.
::: Quick start exploring a Single Gene.
Ingenuity Pathways Analysis (IPA)
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…
::: Explore and Advanced Search Options.
Ingenuity Pathways Analysis (IPA)
How do I query the Ingenuity Pathways Knowledge Base about specific
genes, processes, diseases, drugs, famiies or subcellular locations?
::: Quick start exploring a Single Gene.
Ingenuity Pathways Analysis (IPA)
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…
::: Quick start exploring a Single Gene.
Ingenuity Pathways Analysis (IPA)
::: Quick start exploring a Single Gene.
Ingenuity Pathways Analysis (IPA)
Interactive gene networks
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
::: Exploring a Single Gene.
Ingenuity Pathways Analysis (IPA)
Building a pathway :
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
Building pathways
Grow
Path explorer (shorstest path)
Connect
Trim (remove)
Keep (filter)
Add Molecule/Relationship
Also…quick access:
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
Building pathways :
Add molecule relationship
Also…quick access:
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
Expression values
Drug
Functions and diseases
My List
Canonical pathway
My pathway
Ingenuity tox list
Highlight
Overlaying pathways
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
Designing pathways ::
::: Network Explorer Toolbar.
Ingenuity Pathways Analysis (IPA)
View options ::
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Toolbar
Gene Lists
IPA Analysis
Sharing Projects
::: Exploring Gene Lists.
Ingenuity Pathways Analysis (IPA)
::: Searching Lists
Gene,
drug,
AffyID1,
Oxal*,
CASP*,
RefSeq X,
cisplatin,
…
::: Gene Lists.
Ingenuity Pathways Analysis (IPA)
Saving a gene list :
::: Gene Lists.
Ingenuity Pathways Analysis (IPA)
Stored gene lists :
::: Gene Lists.
Ingenuity Pathways Analysis (IPA)
What regulatory effects relationships exists
between the genes/proteins in my dataset?
Creating pathways with Gene Lists
Etc.
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Bar Tools
Gene Lists
IPA Analysis
Sharing Projects
::: Analysis using IPA.
Ingenuity Pathways Analysis (IPA)
Expression data analysis
Toxicology analysis
Biomarker analysis
Metabolomics analysis
::: Types of Analysis.
Ingenuity Pathways Analysis (IPA)
Core Analysis:
Core Analysis allows you to interpret datasets in the context of biological processes, pathways and molecular networks.
Core Comparison Analysis:
Core Comparison allows you to analyze changes in biological states across time and dosages. First run a core analysis on your multiple datasets
that represent multiple timepoints or dosage treatments and use core Comparison Analysis to understand which biological processes and/or diseases
are relevant to each timepoint or dose.
Tox Analysis:
The tox solution allows you to assess toxicity and safety of compounds of interest early in the development process and rapidly understand
the relevant toxicity phenotypes and clinical pathology endpoints associated with a dataset.
Tox Comparison Analysis:
Allows you to analyze changes in relevant toxicity phenotypes and clinical pathology endpointsacross time and dosages.
First run a Tox Analysis on your multiple datasets that represent multiple timepoints or dosage treatments, use Tox Comparison Analysis to understand
which tox functions and/or pathways are relevant to each timepoint or dose.
::: Types of Analysis.
Ingenuity Pathways Analysis (IPA)
Biomarker Filter:
The biomarker analysis solution allows you to identify and prioritize the most relevant and promising molecular biomarker candidates
from datasets from nearly any step of the drug discovery process or any type of disease research. Use the Biomarker Filter to prioritize molecular biomarker
candidates based on contextual information such as mechanistic connection to diseases, detection in bodily fluids. Then, use the Biomarker Comparison
Analysis to identify biomarker candidates that discriminate between or are common to a disease state and/or drug response.
Biomarker Comparison Analysis:
To identify biomarker candidates that discriminate between or are common to a disease state and/or drug response.
First run the Biomarker Filter to prioritize molecular biomarker candidates based on contextual information such as mechanistic connection to diseases,
detection in bodily fluids, and use the Biomarker Comparison Analysis to identify biomarker candidates that discriminate between multiple samples.
Metabolomics Analysis:
The metabolomics analysis solution allows you to gain biological insight into cell physiology and metabolism from metabolite (endogenous chemicals)data.
If you have multiple time points or dosage treatments, use Comparison Analysis to understand which biological processes and/or diseases are relevant to
each time point or dose.
Metabolomics Comparison Analysis: Comparison Core/ Metabolomics Analysis allows you to compare multiple experimental conditions in the context
of biological processes, pathways and molecular networks
::: Importing data for analysis.
Ingenuity Pathways Analysis (IPA)
File format A :::
- Single observation
- .xls datasheet accepted
- Up to 18 MB
- 50000 row size limit
::: Importing data for analysis.
Ingenuity Pathways Analysis 7.1 (IPA)
File format B :::
- Multiple observations (up to 10)
- .xls datasheet accepted
- Up to 18 MB
- 50000 row size limit
::: Sample Analyses.
Ingenuity Pathways Analysis (IPA)
Useful examples to learn how to deal
with Ingenuity IPA…
::: Core Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Accession and workflow
Core Analysis:
Core Analysis allows you to interpret datasets in the context of biological processes, pathways and molecular networks.
::: Core Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
::: Core Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Core analysis output :
Results
tabs
Right-tailed
Fisher Exact test
::: Core Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Some statistics ::
Right-tailed
Fisher Exact test
2x2 Contingency Table.
 = 0.05
p < 0.05 + FDR are considered significant
::: Core Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Networks
Results tabs ::
Lists(Tox)
Functions(Bio)
Canonical Pathways
Overlapping networks
Network explorer
::: Networks & Canonical Pathways
Ingenuity Pathways Analysis (IPA)
Which well characterized cell signaling and metabolic
pathways are most relevant in my data?
::: Canonical Pathways
Ingenuity Pathways Analysis (IPA)
::: Core Comparison Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Core Comparison Analysis:
Core Comparison allows you to analyze changes in biological states across time and dosages. First run a core analysis on your multiple datasets
that represent multiple timepoints or dosage treatments and use core Comparison Analysis to understand which biological processes and/or diseases
are relevant to each timepoint or dose.
::: Core Comparison Analysis.
Expression Data Analysis.
Ingenuity Pathways Analysis (IPA)
Core comparison analysis outpu
Which functions and pathways are regulated
at different times, doses, or in different tissues
in my experiment?
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
Tox Analysis:
The tox solution allows you to assess toxicity and safety of compounds of interest early in the development process and rapidly understand
the relevant toxicity phenotypes and clinical pathology endpoints associated with a dataset.
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
IPA-Tox List Library
:::
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
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
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
Does this drug treatment
cause any toxic effect?
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
IPA-Tox analysis output :
Results
tabs
::: IPA-Tox Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
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.
::: IPA-Tox Comparison Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Tox Comparison Analysis.
Toxicology Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Biomarker Analysis.
Biomarker Analysis.
Ingenuity Pathways Analysis (IPA)
Are there any potential biomarkers in my samples?
What are the unique and common potential biomarkers?
::: IPA-Biomarker Analysis.
Biomarker Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Biomarker Comparison Analysis.
Biomarker Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Biomarker Comparison Analysis.
Biomarker Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Biomarker Comparison Analysis.
Biomarker Analysis.
Ingenuity Pathways Analysis (IPA)
::: IPA-Metabolomics Analysis.
Metabolomics Analysis
Ingenuity Pathways Analysis (IPA)
::: IPA-Metabolomics Comparison Analysis.
Metabolomics Analysis
Ingenuity Pathways Analysis (IPA)
::: Schedule.
1.
2.
3.
4.
5.
6.
7.
Introduction.
Running into IPA
Quick Search
Bar Tools
Gene Lists
IPA Analysis
Sharing Projects
::: Sharing Projects.
Ingenuity Pathways Analysis (IPA)
File > Share > Invitations Manager
Accept or decline invitations…
::: Sharing Projects.
Ingenuity Pathways Analysis (IPA)
Inviting to share projects…
File > Share > Share Manage
Thanks !
[email protected]