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

Pathway Informatics6th July, 2015

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

mailto:[email protected]

Biological Pathway Map

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

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




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




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




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


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




http://www.sigmaaldrich.com/life-science.html

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


http://www.pathwaycommons.org/about/



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.ncbi.nlm.nih.gov/biosystems

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

http://www.sigmaaldrich.com/life-science/your-favorite-gene-search.html






PPI Databases




What proteins interact with my favorite protein?




PPI Databases

BioGRID STRING




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?

-

http://media.hsls.pitt.edu/media/molbiovideos/ppi.swf

http://thebiogrid.org/

http://string-db.org/

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


http://www.cpr.ku.dk/

http://www.embl.org/

http://www.isb-sib.ch/

http://healthsciences.ku.dk/

http://www.biotec.tu-dresden.de/

http://www.uzh.ch/



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

http://goo.gl/yD2hR


http://goo.gl/yD2hR



Generate a gene list




Pathway Analysis

Control A549 cell

+

Ethanol (25mmol/L) 48 hr

TreatedA549 cell

+

Resveratrol (25mmol/L) 48 hr




Retrieve Gene Expression data

NCBI GEO EBI ArrayExpress NextBio Research




Gene Expression Database




Searching GEO




GEO2R




GEO2R – Experiment to Gene List




NextBio Registration

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


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



NextBio




NextBio Search




NextBio GeneList




Gene Expression Atlas

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


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



Array Express

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


Literature to GeneList

GEO

Geo2R NextBio

Gene List




Gene Lists to Biology




Suggested Reading

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


http://www.ploscollections.org/article/info:doi/10.1371/journal.pcbi.1002820



GO Consortium




GO Annotation

Cellular Component

Biological Process

Molecular Function




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




Discovery Step: Pathway Analysis

Ingenuity IPA

DAVID

MetacoreGene List




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




DAVID Bioinformatics Resources




DAVID Tools

Functional Annotation Clustering

Chart – Term centric Table – Gene centric




DAVID

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


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


NIH DAVID




Ingenuity IPA




IPA Function

IPA Pathways

IPA Pathway

IPS Upstream Regulator

IPA Mechanistic Network

IPA Networks

GeneGo: Metacore



Pathway Analysis: GeneGo Metacore



Metacore: Analyze Network (receptors)

p53C-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 [email protected]


mailto:[email protected]

