Pathway Informatics
6th July, 2015
Ansuman Chattopadhyay, PhD
Head, Molecular Biology Information Services
Health Sciences Library System
University of Pittsburgh
ansuman@pitt.edu
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
Gene list to pathways
Gene List
Biological Interaction Network
B-factor, properdin
APEX nuclease (multifunctional DNA repair enzyme) 1
ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)
proliferating cell nuclear antigen
heterogeneous nuclear ribonucleoprotein A1
fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
three prime repair exonuclease 2
ligase I, DNA, ATP-dependent
flap structure-specific endonuclease 1
cyclin A2
cyclin-dependent kinase inhibitor 1A (P21)
checkpoint kinase 1 homolog (S. pombe)
replication protein A1, 70kDa
Werner syndrome
exonuclease 1
uracil-DNA glycosylase 2
Biological Table
Name
Time 0 Time 15 mins Time 1 hr Time 5 hr
IL6
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%
http://www.hsls.pitt.edu/molbio
Topics

Databases

Biological Pathway Maps

Protein-Protein Interaction

High-throughput gene
expression (Microarray)
Database
http://www.hsls.pitt.edu/molbio
Topics

Software

Create a gene list: Geo2R, NextBio

Pathway Analysis : NIH DAVID, Ingenuity
Metacore,
http://www.hsls.pitt.edu/molbio
IPA,
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
- Retrieve interacting partners of a protein of
your interest
-What proteins interact with human EGFR?
Resources
BioGrid:
http://thebiogrid.org/
STRING: http://string-db.org/
Link to the video tutorial:
http://media.hsls.pitt.edu/media/molbiovideos/ppi.swf
BioGrid
http://www.hsls.pitt.edu/molbio
BioGrid Search Result Page
http://www.hsls.pitt.edu/molbio
STRING - Known and Predicted ProteinProtein 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
Treated
A549 cell
+
Ethanol (25mmol/L) 48 hr
A549 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
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
Levels of abstraction
Gene Ontology (GO)
Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565
Copyright restrictions may apply.
Evolution history of GO-based functional analysis software
Development of gene ontology based tools
Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565
Copyright restrictions may apply.
http://www.hsls.pitt.edu/molbio
Gene list to Biology
Biological List
B-factor, properdin
APEX nuclease (multifunctional DNA repair enzyme) 1
ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)
proliferating cell nuclear antigen
heterogeneous nuclear ribonucleoprotein A1
fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
three prime repair exonuclease 2
ligase I, DNA, ATP-dependent
flap structure-specific endonuclease 1
cyclin A2
cyclin-dependent kinase inhibitor 1A (P21)
checkpoint kinase 1 homolog (S. pombe)
replication protein A1, 70kDa
Werner syndrome
exonuclease 1
uracil-DNA glycosylase 2
Functions
Pathways
Biological Table
Name
Time 0 Time 15 mins Time 1 hr Time 5 hr
IL6
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%
Interaction Networks
http://www.hsls.pitt.edu/molbio
Discovery Step: Pathway Analysis
Ingenuity
IPA
DAVID
Gene List
Metacore
http://www.hsls.pitt.edu/molbio
Pathway Analysis Software
NLP Driven
PathwayArchitect
PathwayStudio
Human Curated
Ingenuity IPA
GeneGO’s Metacore
Biobase Explain
“ Axin binds beta-catenin, GSK-3beta and APC.”
Extracted Facts:
Axin - beta-catenin interaction: Binding
Axin - GSK-3beta interaction: Binding
Axin - 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)
C-Myc
p53
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 Chattopadhyay
ansuman@pitt.edu
http://www.hsls.pitt.edu/molbio