Transcript From Functional Genomics to Physiological Model: the Gene

Pathways analysis
Iowa State Workshop
11 June 2009
All tools and materials from this workshop are
available online at the AgBase database
Educational Resources link.
 For continuing support and assistance please
contact:
[email protected]

This workshop is supported by USDA CSREES grant number MISV-329140.
Pathways analysis enables
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Analysis of data in the context of molecular mechanisms to move
beyond statistical analysis of expression to novel biological insights
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Applying biological filters to focus in on the changes most relevant
to experimental model
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Comparison of affected pathways and phenotypes across platform,
time, dose etc
(www.ingenuity.com)
What regulatory relationships
exist between the genes, proteins
in my dataset?
Networks
Which biological and disease
processes are most relevant to my
genes of interest?
Functional
analysis
Which well-characterized cell
signaling and metabolic pathways
are most relevant to my
experimental data?
Metabolic
And
Signaling
pathways
http://www.ingenuity.com
Cytoscape
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Cytoscape is a freely-available (open-source,
java-based) bioinformatics software platform
for
visualizing biological networks (e.g. molecular
interaction networks) and
analyzing networks with gene expression
profiles and other data
Core Features

Customize network data display using visual
styles
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Powerful graph layout tools
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Easily organize multiple networks
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Easily navigate large networks
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Filter the network
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Plugin API
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Cytoscape includes a flexible plugin
architecture that enables developers to add extra
functionality beyond that provided in the core
Some plugins
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jActiveModules: identify significant “active” subnetworks
Expression Correlation Network: cluster expression data
Agilent Literature Search: build networks by extracting interactions from
scientific literature.
MCODE: finds clusters of highly interconnected regions in networks
cPath: query, retrieve and visualize interactions from the MSKCC Cancer
Pathway database
BiNGO: determine which Gene Ontology (GO) categories are statistically
over-represented in a set of genes
Motif Finder: runs a Gibbs sampling motif detector on sequences for
nodes in a Cytoscape network.
Exhaustive list at http://chianti.ucsd.edu/cyto_web/plugins/index.php
Gene Ontology enrichment analysis
BiNGO plugin
Gene Ontology structure
Analysis tools (commercial)
Networks
Ingenuity Pathway
Analysis
http://www.ingenuity.com
Pathways
Functions and diseases
Gene Ontology (GO) groups
Pathway studio
http://www.ariadnegenomics.com/
GSEA
Pathways
IPA analysis included as IPA.txt
Data curation
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Ingenuity : Manually curated database by Ph.D
level scientists (mining 32 different peer reviewed
journals).
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Pathway studio : Automated curation by Medscan
Reader using Natural language processing (NLP)
technology. Mining Pubmed abstracts and peer
reviewed journals
(users can do their own text mining)
Comparison Criteria
Features
 Proportion of proteins involved in modeling
 Data generation
 Display
 Test Dataset: 3,600 bovine spermatozoa
proteins
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(Comparison by Divya Swetha Peddinti)
Feature
Ingenuity Pathway analysis
(IPA)
Pathway studio
Input
GI number
Microarray ID
Affymetrix ID
GenBank
Swiss Prot Accession
Unigene ID
Name orAlias
HUGO ID
Entrez gene
GenBank
Microarray ID
Swiss Prot Accession
Unigene ID
Name or Alias
HUGO ID
Databases
Contains biological interactions
data for human, mouse, rat
Orthologous mapping available
for dog, Cow, Chimp,
Chicken, Rhesus macaque
monkey, Arabidopsis thaliana,
Saccharomyces cerevisiae,
Drosophila melanogaster,
Caenorhabditis elegans,
Danio rerio
Contains biological data for
human, mouse, rat, bacteria,
chicken, Zebra fish, frog, cow,
bee, dog, Arabidopsis,
Drosophila, Yeast, and
transplantation research etc..
Ingenuity Pathway
analysis (IPA)
Pathway studio
Statistical test
The significance value(
p value) assigned to
the function / pathways
using Fischer’s exact
test
The statistical
significance of the
overlap between the
protein list and a GO
group or pathway
using the Fischer’s
exact test.
Updates
Quarterly
Quarterly
Networks
Builds networks with a
maximum of 35 genes/
proteins
-
Proteins involved in modeling
120
100
80
0.15
42.5
60
99.85
40
20
57.5
Proteins not involved
in modeling
Proteins involved in
modeling
0
Pathwaystudio
Ingenuity
Data generation
50
44
40
33
Ingenuity
pathway anlaysis
30
20
Pathway studio
10
0
Pathways
37
7
26
Pathway display
EGF signaling pathway
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Equally efficient at drawing networks of
relationships.
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IPA : simplifies the pathway display and
creates more manageable user friendly
network for users to analyze.
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Pathway Studio: Shows the relations in a table
format.
Ariadne supported database statistics
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Mamamlian ResNet
1.5 Million molecular interactions and functional
relationships from the entire PubMed
(17,000,000 abstracts) and 61 full text journals
for
110,435 proteins
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13,533 small molecules
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2814 cellular processes
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2,410 diseases
Pathways:
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227 Receptor signaling pathways
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21 new cellular process regulation pathways
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Atlas of Signaling - all cellular signaling on one
map
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Plant ResNet
Relations to Arabidopsis proteins, (and rice
genes that are mapped to Arabidopsis), Protein
annotation for eight other plant species;
Over 90,000 functional relationships and
molecular interactions from 117,000 plantspecific abstracts and 8 plant-specific full-text
journals for
71,501 proteins
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3,831 small molecules
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915 cellular processes
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97 plant diseases
Pathways:
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17 Plant Signaling Pathways
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315 AraCyc pathways
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Journals: Annals of Botany
Crop Science
Journal of Experimental Botany
New Phytologist
Plant Cell
Plant, Cell and Environment
Plant Journal
Plant Physiology