Pathway Informatics 6 th July, 2015 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information...

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

Transcript of Pathway Informatics 6 th July, 2015 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information...

Pathway Informatics6th July, 2015

Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServicesHealth Sciences Library SystemUniversity of [email protected]

Biological Pathway Map

http://www.hsls.pitt.edu/molbio

Pathway Informatics

L i s t o f G e n e s

Protein-Protein Interaction Database

P a t h w a y M a p

http://www.hsls.pitt.edu/molbio

Biological Interaction Network

Name Time 0 Time 15 mins Time 1 hr Time 5 hrIL6 35.45% 36.46% 95.34% 13.91%PDGFRA 32.42% 45.43% 30.99% 56.62%DCN 21.42% 1.29% 33.13% 41.40%ZFP36L1 48.17% 47.56% 84.31% 6.72%DEGS 46.41% 90.30% 52.14% 31.61%GNB2 42.37% 98.25% 25.28% 53.26%ATRN 93.42% 75.90% 1.56% 82.61%PDK4 88.18% 38.03% 95.95% 5.78%MAPK1 20.88% 64.99% 43.18% 52.77%THBS1 99.61% 54.35% 85.28% 85.69%CD68 9.35% 44.81% 69.03% 64.88%DIAPH2 54.16% 34.47% 63.26% 33.46%Sep6 30.12% 48.83% 28.57% 76.28%BFAR 10.18% 7.65% 60.30% 42.66%CCRK 79.03% 19.54% 96.15% 88.79%MT1E 49.07% 23.60% 93.13% 15.83%

Biological Table

B-factor, properdinAPEX nuclease (multifunctional DNA repair enzyme) 1ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)proliferating cell nuclear antigenheterogeneous nuclear ribonucleoprotein A1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)three prime repair exonuclease 2ligase I, DNA, ATP-dependentflap structure-specific endonuclease 1cyclin A2cyclin-dependent kinase inhibitor 1A (P21)checkpoint kinase 1 homolog (S. pombe)replication protein A1, 70kDaWerner syndromeexonuclease 1uracil-DNA glycosylase 2

Gene List

Gene list to pathways

http://www.hsls.pitt.edu/molbio

Topics

D a t a b a s e s

B i o l o g i c a l P a t h w a y M a p s

P r o t e i n - P r o t e i n I n t e r a c t i o n

H i g h - t h r o u g h p u t g e n e e x p r e s s i o n ( M i c r o a r r a y ) D a t a b a s e

http://www.hsls.pitt.edu/molbio

Topics

Software

Create a gene list: Geo2R, NextBio

Pathway Analysis : NIH DAVID, Ingenuity IPA, Metacore,

http://www.hsls.pitt.edu/molbio

Pathway Databases

http://www.hsls.pitt.edu/molbio

Biological Pathways

Metabolic Signaling

http://www.hsls.pitt.edu/molbio

Databases-Pathways

NCBI Biosystems KEGG http://www.ncbi.nlm.nih.gov/biosystems

Pathway Commons: http://www.pathwaycommons.org/pc/

YFG – Sigma Aldrich: Your Favorite Gene

Millipore Pathways: http://www.millipore.com/pathways/pw/pathways

Applied BioSystems: http://www5.appliedbiosystems.com/tools/pathway/

http://www.hsls.pitt.edu/molbio

PPI Databases

http://www.hsls.pitt.edu/molbio

What proteins interact with my favorite protein?

http://www.hsls.pitt.edu/molbio

PPI Databases

BioGRID STRING

http://www.hsls.pitt.edu/molbio

Link to the video tutorial:http://media.hsls.pitt.edu/media/molbiovideos/ppi.swf

Resources

BioGrid: http://thebiogrid.org/

STRING: http://string-db.org/

- Retrieve interacting partners of a protein of your interest

-What proteins interact with human EGFR?

-

BioGrid

http://www.hsls.pitt.edu/molbio

BioGrid Search Result Page

http://www.hsls.pitt.edu/molbio

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

http://www.hsls.pitt.edu/molbio

STRING

http://www.hsls.pitt.edu/molbio

Gene Lists

http://www.hsls.pitt.edu/molbio

Gene Lists

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

http://www.hsls.pitt.edu/molbio

Gene Expression Databases

NCBI• Gene Expression Omnibus (GEO)

EBI• ArrayExpress

http://www.hsls.pitt.edu/molbio

Gene Expression Database

http://www.hsls.pitt.edu/molbio

Use of GEO Data

http://goo.gl/yD2hR

http://www.hsls.pitt.edu/molbio

Generate a gene list

http://www.hsls.pitt.edu/molbio

Pathway Analysis

Control A549 cell

+

Ethanol (25mmol/L) 48 hr

TreatedA549 cell

+

Resveratrol (25mmol/L) 48 hr

http://www.hsls.pitt.edu/molbio

Retrieve Gene Expression data

NCBI GEO EBI ArrayExpress NextBio Research

http://www.hsls.pitt.edu/molbio

Gene Expression Database

http://www.hsls.pitt.edu/molbio

Searching GEO

http://www.hsls.pitt.edu/molbio

Searching GEO

http://www.hsls.pitt.edu/molbio

Searching GEO

http://www.hsls.pitt.edu/molbio

GEO2R

http://www.hsls.pitt.edu/molbio

GEO2R – Experiment to Gene List

http://www.hsls.pitt.edu/molbio

GEO2R – Experiment to Gene List

http://www.hsls.pitt.edu/molbio

GEO2R – Experiment to Gene List

http://www.hsls.pitt.edu/molbio

NextBio Registration

https://www.nextbio.com/b/register/register.nb

http://www.hsls.pitt.edu/molbio

NextBio

http://www.hsls.pitt.edu/molbio

NextBio

http://www.hsls.pitt.edu/molbio

NextBio

http://www.hsls.pitt.edu/molbio

NextBio Search

http://www.hsls.pitt.edu/molbio

NextBio GeneList

http://www.hsls.pitt.edu/molbio

Gene Expression Atlas

http://www.ebi.ac.uk/gxa/

http://www.hsls.pitt.edu/molbio

Array Express

http://www.hsls.pitt.edu/guides/genetics

Literature to GeneList

GEO

Geo2R NextBio

Gene List

http://www.hsls.pitt.edu/molbio

Gene Lists to Biology

http://www.hsls.pitt.edu/molbio

Suggested Reading

http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002820

http://www.hsls.pitt.edu/molbio

GO Consortium

http://www.hsls.pitt.edu/molbio

GO Annotation

Cellular Component

Biological Process

Molecular Function

http://www.hsls.pitt.edu/molbio

Copyright restrictions may apply.

Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565

Levels of abstraction

Gene Ontology (GO)

Copyright restrictions may apply.

Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565

Evolution history of GO-based functional analysis software

Development of gene ontology based tools

Name Time 0 Time 15 mins Time 1 hr Time 5 hrIL6 35.45% 36.46% 95.34% 13.91%PDGFRA 32.42% 45.43% 30.99% 56.62%DCN 21.42% 1.29% 33.13% 41.40%ZFP36L1 48.17% 47.56% 84.31% 6.72%DEGS 46.41% 90.30% 52.14% 31.61%GNB2 42.37% 98.25% 25.28% 53.26%ATRN 93.42% 75.90% 1.56% 82.61%PDK4 88.18% 38.03% 95.95% 5.78%MAPK1 20.88% 64.99% 43.18% 52.77%THBS1 99.61% 54.35% 85.28% 85.69%CD68 9.35% 44.81% 69.03% 64.88%DIAPH2 54.16% 34.47% 63.26% 33.46%Sep6 30.12% 48.83% 28.57% 76.28%BFAR 10.18% 7.65% 60.30% 42.66%CCRK 79.03% 19.54% 96.15% 88.79%MT1E 49.07% 23.60% 93.13% 15.83%

Biological Table

B-factor, properdinAPEX nuclease (multifunctional DNA repair enzyme) 1ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)proliferating cell nuclear antigenheterogeneous nuclear ribonucleoprotein A1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)three prime repair exonuclease 2ligase I, DNA, ATP-dependentflap structure-specific endonuclease 1cyclin A2cyclin-dependent kinase inhibitor 1A (P21)checkpoint kinase 1 homolog (S. pombe)replication protein A1, 70kDaWerner syndromeexonuclease 1uracil-DNA glycosylase 2

Biological List

Gene list to Biology

Functions

Pathways

Interaction Networks

http://www.hsls.pitt.edu/molbio

Discovery Step: Pathway Analysis

Ingenuity IPA

DAVID

MetacoreGene List

http://www.hsls.pitt.edu/molbio

Pathway Analysis Software

NLP DrivenPathwayArchitectPathwayStudio

Human CuratedIngenuity IPAGeneGO’s MetacoreBiobase Explain

“ Axin binds beta-catenin, GSK-3beta and APC.”

Extracted Facts:Axin - beta-catenin interaction: BindingAxin - GSK-3beta interaction: BindingAxin - APC interaction: Binding

http://www.hsls.pitt.edu/molbio

DAVID Bioinformatics Resources 

http://www.hsls.pitt.edu/molbio

DAVID Tools

Functional Annotation Clustering

Chart – Term centric Table – Gene centric

http://www.hsls.pitt.edu/molbio

DAVID

http://www.nature.com/nprot/journal/v4/n1/fig_tab/nprot.2008.211_T1.html

http://www.hsls.pitt.edu/guides/genetics

NIH DAVID

http://www.hsls.pitt.edu/molbio

Ingenuity IPA

http://www.hsls.pitt.edu/molbio

IPA

IPA

IPA

IPA Function

IPA Function

IPA Pathways

IPA Pathway

IPS Upstream Regulator

IPA Mechanistic Network

IPA Networks

IPA Networks

IPA

GeneGo: Metacore

http://www.hsls.pitt.edu/guides/genetics

Pathway Analysis: GeneGo Metacore

http://www.hsls.pitt.edu/guides/genetics

Metacore: Analyze Network (receptors)

p53C-Myc

Metacore: Transcription Regulation

http://www.hsls.pitt.edu/guides/genetics

Cytoscape

http://www.hsls.pitt.edu/molbio

Hands-on Exercise

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

http://www.hsls.pitt.edu/molbio

Thank you!Any questions?

Ansuman [email protected]

http://www.hsls.pitt.edu/molbio