Pathway Informatics 6 th July, 2015 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information...
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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
Biological Pathway Databases KEGG Ingenuity IPA GeneGo Metacore
Millipore Pathways (Metacore) Sigma Your Favorite Genes (IPA) Life Technologies GeneAssist
Pathway Commons
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
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
Pathway Analysis: GeneGo Metacore
http://www.hsls.pitt.edu/guides/genetics
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