‘basic’ IPA training session

Stéphane Plaisance

Training (Leuven-Gasthuisberg) April-02, 2010

Technology focus on Bioinformatics

Proprietary and Confidential

IPA Training

Carmela Jaravata, M.A., Ph.D.March 23, 2010

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TOP ➪ DOWN knowledge ➪ experiment

Proprietary and Confidential 4

The ChallengeGain Rapid Understanding of Experimental Systems

Experimental Platforms

FAS VEGFA bevacizumabMolecules

AngiogenesisApoptosisCellular

Processes

CancerDisease Processes

Guide in vivo/in vitro assays

Search for genes implicated in disease

Identify related cellular processes/pathways

Generate hypothesis

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BOTTOM ➪ UP results ➪ knowledgeProprietary and Confidential 5

The ChallengeIntegrate, Interpret, and Gain Therapeutic Insight from

Experimental Data

Experimental Platforms

FAS VEGFA bevacizumabMolecules

AngiogenesisApoptosisCellular

Processes

CancerDisease Processes

Disease/physiological response

Overlapping cellular processes/pathways

Molecular Interactions

Molecular Perturbation

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!"#$%&'

Proprietary and Confidential 6

The Solution: Ingenuity

All Ingenuity Solutions are powered by the Ingenuity Knowledge Base

Ingenuity Labs

IPA

Ingenuity Knowledge BaseContent Ontology

Content Offerings

and Services

!"#$%&'

Proprietary and Confidential 6

The Solution: Ingenuity

All Ingenuity Solutions are powered by the Ingenuity Knowledge Base

Ingenuity Labs

IPA

Ingenuity Knowledge BaseContent Ontology

Content Offerings

and Services

>2.6 million findings manually extracted from full textExtensive libraries of metabolic and signaling pathwaysChemical and drug informationScalable best-in-class content acquisition processes

>960,000 biological objects and processes in 12 major branchesRobust, up-to-date synonym libraryOntology = Knowledge infrastructure tools and processes for structuring biological and chemical knowledge

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Ingenuity Content

Expert Extraction: Full text from top journalsCoverage of >700 journals, plus review articles and textbooksIngenuity®Expert Findings and Ingenuity® Expert Assist Findings

Import Annotations, Findings:OMIM, GO, Entrez GeneTissue and Fluid Expression / LocationMolecular Interactions (e.g. BIND, DIP, TarBase)

Internally curated knowledge:Signaling & Metabolic PathwaysDrug / Target / Disease relationshipsToxicity Lists

All findings are structured for computation & updated regularly

!"#$%&'

Proprietary and Confidential 8

Ingenuity ContentExpert Extraction: Full text from top journals

Coverage of >700 journals, plus review articles and textbooksIngenuity® Expert Findings and Ingenuity®

ExpertAssist FindingsImport Annotations, Findings:

OMIM, GO, Entrez GeneTissue and Fluid Expression LocationMolecular Interactions (e.g. BIND, DIP, TarBase)

Internally curated knowledge:Signaling & Metabolic PathwaysDrug/Target/Disease relationshipsToxicity Lists

All findings are structured for computation and updated regularly

American J. PathologyArteriosclerosis, Thrombosis and Vascular BiologyBiochemistryBloodCancer ResearchCellCurrent BiologyDevelopmentEMBOEuropean J. of ImmunologyFASEB JournalGenes and DevelopmentHypertensionImmunityJ. Biological ChemistryJ. Cell BiologyJ. Experimental MedicineJ. ImmunologyJ. Lipid ResearchJ. National Cancer InstituteJ. NeuroscienceMolecular and Cellular BiologyMolecular Biology of the CellMolecular CellNatureNature Cell BiologyNature GeneticsNature MedicineNeuronOncogeneProc. National Acad. Sciences USAScience

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What do you need to use IPA ?

access and DATA

basic tools to manipulate the data

graphic support to make networks

statistics to find significance and overlay knowledge

YOUR brain to ask the right questions

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access IPA

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https://analysis.ingenuity.com/pa/!"#$%&'

Proprietary and Confidential 19

Logging Into IPA

login with email_address (*)

(*) back in your lab: ask your BITS-committee member for login credentials

java applet =>

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the IPA user-interface

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a simpleapplicationinterface

<must read>

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➷

➷

➷

Today’s focus (➷)

❷

❸!

❶

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❷ ❸❶

search for molecules, diseases, pathways

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ExercisesSearch for an affymetrix probe (210512_s_at), a gene symbol (VEGFA), a genbank accession (NM_001025366) ...

TIP: use the simple SEARCH

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ExercisesSearch for an affymetrix probe (210512_s_at), a gene symbol (VEGFA), a genebank accession (NM_001025366)

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!"#$%&'

Proprietary and Confidential 6

The Solution: Ingenuity

All Ingenuity Solutions are powered by the Ingenuity Knowledge Base

Ingenuity Labs

IPA

Ingenuity Knowledge BaseContent Ontology

Content Offerings

and Services

IPAsupport for

manySynonyms

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auto-complete while typing

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❸

❶

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Molecule Types

SubCellularlocation

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ExercisesSearch peptidases found in the nucleus and implicated in Parkinson’s disease

TIP: use SEARCH / Functions and diseases (! bold)

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-Pathways & Networks-

let’s build, explore & annotate

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-easy-

get the FULL neighbor for your favorite gene

in 3 mouse clicks

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search your gene by nameright-click and add to new pathwaydouble-click the gene-nodeclick on ‘Neighborhood Explorer’

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Exercisestry this with YOUR favorite gene

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what next ?

turn it into a ‘hairy-ball’ extract useful information

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-lists-

your best friend to move data from one part to

another

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from anything you can create alist

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from a listexport to excel

create a pathwaysrun an analysis

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ExercisesCreate a list of Alzheimer disease markers

TIP: use SEARCH / Functions and diseases

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ExercisesCreate a list of Alzheimer disease markers

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-the ‘compare’ tool-

find common and unique molecules

liste Z

process Y

disease X

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support for all data types

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ExercisesSearch molecules common to the Parkinson signaling pathway and your list of Alzheimer disease markers

TIP: use COMPARE / custom canonical pathways & SEARCH

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ExercisesSearch molecules common to the Parkinson’s signaling pathway and a list of Alzheimer disease markers

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-Build & Overlay-

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two main tool-boxes

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ExercisesSearch for the following genes in IPA and add them to a pathway:A2M, APOE, APP, HFE, HFE2, LRP1, PSEN1, PSEN2, SLC40A1, TF, TRF2

TIP: use advanced search and set the identifier type

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ExercisesSearch for the following genes in IPA and add them to a pathway:A2M, APOE, APP, HFE, HFE2, LRP1, PSEN1, PSEN2, SLC40A1, TF, TRF2

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ExercisesWhat are the connections between these molecules that occur in nervous system tissues and CNS cell lines (with the relaxed filter)?

TIP: use BUILD / Connect and specific filters

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ExercisesWhat are the connections between these molecules that occur in nervous system tissues and CNS cell lines (with the relaxed filter)?

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ExercisesSelect a gene that does not have any molecular connections. What are the first 5 genes that are directly upstream of this molecule?

TIP: use BUILD / Grow (pay attention to bold)

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ExercisesSelect a gene that does not have any molecular connections. What are the first 5 genes that are directly upstream of this molecule?

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second main tool-box

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ExercisesWhat Functions are all the molecules on this pathway involved in?

TIP: use OVERLAY (! bold)

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ExercisesWhat Functions are all the molecules on this pathway involved in?

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ExercisesAre these molecules involved in any Canonical Pathways?

TIP: change OVERLAY-type

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ExercisesAre these molecules involved in any Canonical Pathways?

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ExercisesWithin what sub-cellular locations are the active forms of these molecules present?

TIP: change visual mode

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ExercisesWithin what sub-cellular locations are the active forms of these molecules present?

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importing a gene or a gene-listinto IPA

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from Genevestigatorfrom a publicationfrom any gene-setfrom your own data...

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importing more data into IPA

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Exercisesupload ‘Prostate Disease’ data provided on the memory-stick

TIP:

only one column as gene identifierone or more column(s) as data (observation)

(! pick the correct data type)

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choosing the correct data-type is crucial

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-core analysis-

what is over-represented in my data?

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Exercisesprepare a core analysis with the uploaded ‘Prostate Disease’ data

using only Ingenuity Expert Findings

with at least 2-fold change in expression

only considering down-regulated genes

TIP: explore what is behind each pop-up (use refresh)

how many genes pass the filters?

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Exercises

n=15561

hit the run button and have a break

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quick overview63

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the BITS team

http://www.bits.vib.be ( wiki )http://sites.google.com/site/dmbits/

Joachim Jacob & Stéphane Plaisance

VIB-HQ - Rijvisschestraat 120, B-9052 Zwijnaarde (Gent) tel: 09.244.66.11 - email: BITS@vib.be

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Questions

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