Pathway Informatics 6 th July, 2015 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information Services Health Sciences Library System University of Pittsburgh

Biological Pathway Map

Pathway Informatics List of Genes Protein-Protein Interaction Database Pathway Map

Biological Interaction Network Biological Table Gene List Gene list to pathways

Topics Databases Biological Pathway Maps Protein-Protein Interaction High-throughput gene expression (Microarray) Database

Topics Software  Create a gene list: Geo2R, NextBio  Pathway Analysis : NIH DAVID, Ingenuity IPA, Metacore,

Pathway Databases

Biological Pathways Metabolic Signaling

Biological Pathway Databases KEGG Ingenuity IPA GeneGo Metacore Millipore Pathways (Metacore) Sigma Your Favorite Genes (IPA) Life Technologies GeneAssist Pathway Commons

Databases-Pathways NCBI Biosystems  KEGG  Pathway Commons: YFG – Sigma Aldrich: Your Favorite Gene Your Favorite Gene Millipore Pathways: Applied BioSystems:

PPI Databases

What proteins interact with my favorite protein?

PPI Databases BioGRID STRING

Link to the video tutorial: Resources BioGrid: STRING: Retrieve interacting partners of a protein of your interest - What proteins interact with human EGFR? -

BioGrid

BioGrid Search Result Page

STRING - Known and Predicted Protein- Protein Interactions  An ultimate resource for finding both predicted and experimental verified PPI  Not limited to human, mouse and rat  Developed at CPR, EMBL, SIB, KU, TUD and UZH CPREMBLSIBKUTUDUZH

STRING

Gene Lists

Gene Lists Microarrays Protein arrays CHIP-chip SNP arrays RNA Seq Literature Search

Gene Expression Databases NCBI Gene Expression Omnibus (GEO) EBI ArrayExpress

Gene Expression Database

Use of GEO Data 

Generate a gene list

Pathway Analysis Control A549 cell + Ethanol (25  mol/L) 48 hr Treated A549 cell + Resveratrol (25  mol/L) 48 hr

Retrieve Gene Expression data NCBI GEO EBI ArrayExpress NextBio Research

Gene Expression Database

Searching GEO

Searching GEO

Searching GEO

GEO2R

GEO2R – Experiment to Gene List

GEO2R – Experiment to Gene List

GEO2R – Experiment to Gene List

NextBio Registration

NextBio

NextBio

NextBio

NextBio Search

NextBio GeneList

Gene Expression Atlas

Array Express

Literature to GeneList GEOGeo2RNextBioGene List

Gene Lists to Biology

Suggested Reading

GO Consortium

GO Annotation Cellular Component Biological Process Molecular Function

Copyright restrictions may apply. Khatri, P. et al. Bioinformatics : ; doi: /bioinformatics/bti565 Levels of abstraction Gene Ontology (GO)

Copyright restrictions may apply. Khatri, P. et al. Bioinformatics : ; doi: /bioinformatics/bti565 Evolution history of GO-based functional analysis software Development of gene ontology based tools

Biological Table Biological List Gene list to Biology Functions Pathways Interaction Networks

Discovery Step: Pathway Analysis Ingenuity IPA DAVIDMetacore Gene List

Pathway Analysis Software NLP Driven PathwayArchitectPathwayStudio Human Curated Ingenuity IPA GeneGO’s Metacore Biobase Explain “ Axin binds beta-catenin, GSK-3beta and APC.” Extracted Facts: Axin - beta-catenininteraction: Binding Axin - GSK-3betainteraction: Binding Axin - APCinteraction: Binding

DAVID Bioinformatics Resources

DAVID Tools Functional Annotation  Clustering Chart – Term centric Table – Gene centric

DAVID

NIH DAVID

Ingenuity IPA

IPA

IPA Function

IPA Pathways

IPA Pathway

IPS Upstream Regulator

IPA Mechanistic Network

IPA Networks

IPA

GeneGo: Metacore

Pathway Analysis: GeneGo Metacore

Metacore: Analyze Network (receptors) p53 C-Myc

Metacore: Transcription Regulation

Cytoscape

Hands-on Exercise Use NIH DAVID to uncover enriched pathways associated with the “gene list – 1”

Thank you! Any questions? Ansuman Chattopadhyay