This document provides an outline for a presentation on biological networks, including introducing biological networks, describing their basic components and types, methods for predicting and building networks, sources of interaction data, tools for network visualization and analysis, and a demonstration of building, visualizing and analyzing biological networks using Cytoscape. The presentation covers topics like nodes and edges in networks, features used to analyze networks, methods for predicting networks from sequences and omics data, integrated databases for interaction data, and popular tools for searching, visualizing and performing network analysis.

1. 1
Vijayaraj Nagarajan PhD
Computational Biologist, BCBB/OCICB/NIAID/NIH
Biological Networks :
building, visualization and analysis
OFFICE OF CYBER INFRASTRUCTURE AND COMPUTATIONAL BIOLOGY
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

2. Outline
• Introduc)on
to
Biological
Networks
• Basic
components
of
a
network
• Types
of
biological
networks
• Predic)ng/Building
Biological
Networks
• Methods
-­‐ Logic
and
concept
• Available
Interac)on
data
• Integrated
protein-­‐protein
interac)on
databases
• Searching
for
interac)on
data
• Network
Visualiza)on
and
Analysis
tools
• Popular
visualiza)on
tools
• Network
analysis
• Demonstra)on
• Building,
visualiza)on
and
analysis
of
the
biological
networks
(Cytoscape)

3. • Nodes
o DNA/RNA/Protein/Metabolite/Ontology
• Edges
Directed
o Dis)nc)on
between
source
and
target
-­‐ Ac)va)on
(direct/indirect)
-­‐ Repression
(direct/indirect)
Undirected
o No
dis)nc)on
between
source
and
target
-­‐ Co-­‐expression
(indirect)
-­‐ Binding
(direct)
-­‐ Similarity/strength
Biological
Networks
–
Basic
Components

4. Biological
Networks
-­‐
Basic
Features
• Degree
• Number
of
connec)ons
that
a
node
has
• Distance
• Number
of
connec)ons
between
two
nodes,
in
a
shortest
path
• Path
• A
sequence
of
connec)ons
• Is
there
a
path
(reachability)
• Mean
Shortest
Path
distance
(closeness)
• In
how
many
shortest
paths
(betweenness)

5. • Size
of
a
network
(Number
of
nodes)
• Density
of
a
network
(Propor)on
of
the
connec)ons)
• Mo)fs/Cliques/Clusters/Sub-­‐networks
Loops
Chains
Parallels
Multi-input Single input
Biological
Networks
-­‐
Basic
Features

6. Types
of
Biological
Networks
• DNA-­‐Protein
-­‐ Transcrip)onal
regulatory
networks
-­‐ Methyla)on
networks
• RNA-­‐RNA
-­‐ miRNA
regulatory
networks
• RNA-­‐Protein
-­‐ Splicing
regulatory
networks
• Protein-­‐Protein
-­‐ Co-­‐expression
networks
-­‐ Co-­‐localiza)on
networks
-­‐ Co-­‐evolu)on
networks
-­‐ Structure
networks
-­‐ Pathway
networks
-­‐ Protease
regulatory
networks
-­‐ Signal
transduc)on
networks
-­‐ Gene
Ontology
networks

7. Single
gene
o Regulators/Co-­‐regulators
o Upstream/Downstream
elements
in
the
network
o Global
connec)vity/interconnec)vity
o Func)onal
features
o Differen)ally
expressed
subnetworks
o One
gene
–
one
disease
:
bunch
of
genes
–
pathways
o Nextgen
sequencing
data
o Meta-­‐analysis
List
of
genes
Why
Build/Analyze
Biological
Networks
?

8. Outline
• Introduc)on
to
Biological
Networks
• Basic
components
of
a
network
• Types
of
biological
networks
• Predic)ng/Building
Biological
Networks
• Methods
-­‐ Logic
and
concept
• Available
Interac)on
data
• Integrated
protein-­‐protein
interac)on
databases
• Searching
for
interac)on
data
• Network
Visualiza)on
and
Analysis
tools
• Popular
visualiza)on
tools
• Network
analysis
• Demonstra)on
• Building,
visualiza)on
and
analysis
of
the
biological
networks
(Cytoscape)

9. How
to
Build
Biological
Networks
?
• Search/Retrieve
from
knowledge
bases
• Predict
from
genome
sequences
• Predict
from
omics
data
• Predict
from
literature
• Integrate
and
analyze
• Meta-­‐networks
from
genome
scale
data
analysis

10. Protein Engineering, Vol. 14, No. 9, 609-614, September 2001
PredicEon
from
genome
sequences
• Gene
neighbor
(gene
cluster,
gene
order)
• Gene
fusion
(RoseVa
stone)
• Phylogene)c
profiling
• Co-­‐evolu)on
• Mirror
tree

11. PredicEon
from
omics
data
• Co-­‐expression
(Correla)on,
Mutual
Informa)on)
• Integrated
(Classifica)on)
• Literature
mining
(Natural
Language
Processing)

12. Outline
• Introduc)on
to
Biological
Networks
• Basic
components
of
a
network
• Types
of
Biological
networks
• Predic)ng/Building
Biological
Networks
• Methods
-­‐ Logic
and
concept
• Available
network
data
• Integrated
interac)on
databases
• Searching
for
interac)on
data
• Network
Visualiza)on
and
Analysis
tools
• Popular
visualiza)on
tools
• Network
analysis
• Demonstra)on
• Building,
visualiza)on
and
analysis
of
the
predicted
network
(Cytoscape)

13. Available
InteracEon
Network
Data
• MINT
• Molecular
Interac)on
Database
• BIND
• Biomolecular
Interac)on
Network
Database
• DIP
• Database
of
Interac)ng
Proteins
• IntAct
• InterAc)on
Database
at
EBI

14. Integrated
Data
Sources
• Pathway
Commons
• BioGRID
• MiMI
(Michigan
Molecular
Interac)ons)
• STRING
(Search
Tool
for
Retrieval
of
Interac)ng
Genes/Proteins)
• Genes2Network
• VisANT
(Integra)ve
Visual
Analysis
Tool)
• BIOBASE
• IPA
(Ingenuity
Pathway
Analysis)
• MetaCore
Open Source
Proprietary

15. IP3Rs
• Inositol
triphosphate
receptor
• ip3r1
• ip3r2
• ip3r3
-­‐ Calcium
ion
channels
-­‐ ER
• s)m1
(stromal
interac)on
molecule
1)
-­‐ PM
-­‐ Calcium
sensor
protein
• orai1
(calcium
release
ac)vated
calcium
modulator)
-­‐ PM
-­‐ Accessory
protein
downstream
of
s)m1

16. Searching
for
InteracEon
Data
STRING
IPA

25. IPA

32. Outline
• Introduc)on
to
Biological
Networks
• Basic
components
of
a
network
• Types
of
Biological
networks
• Predic)ng/Building
Biological
Networks
• Methods
-­‐ Logic
and
concept
• Available
network
data
• Integrated
interac)on
databases
• Searching
for
interac)on
data
• Network
Visualiza)on
and
Analysis
tools
• Popular
visualiza)on
tools
• Network
analysis
• Demonstra)on
• Building,
visualiza)on
and
analysis
of
the
predicted
network
(Cytoscape)

33. • Cytoscape
• VisANT
(Integra)ve
Visual
Analysis
Tool)
• Osprey
• BioLayout
Popular
VisualizaEon
Tools

34. Analysis
Tools
• Phunkee
(Pairing
subgraphs
Using
Network
Environment
Equivalence
–
finds
similar
subnets)
• mfinder
(mo)f
detec)on)
• MAVisto
(Mo)f
Analysis
and
Visualiza)on
tool
–
explora)on
of
mo)fs)
• GraphMatch
(Search
for
similar
sub-­‐nets)
• NeAT
(Network
Analysis
Tools
–
mo)f
finding,
node
sta)s)cs)
• Cfinder
(Finds
clusters
–
dense
group
of
nodes)
• NetworkBLAST
(Compares
mul)ple
networks
to
infer
complexes
&
paths)

35. Outline
• Introduc)on
to
Biological
Networks
• Basic
components
of
a
network
• Types
of
Biological
networks
• Predic)ng/Building
Biological
Networks
• Methods
-­‐ Logic
and
concept
• Available
network
data
• Integrated
interac)on
databases
• Searching
for
interac)on
data
• Network
Visualiza)on
and
Analysis
tools
• Popular
visualiza)on
tools
• Network
analysis
• Demonstra)on
• Building,
visualiza)on
and
analysis
of
the
predicted
network
(Cytoscape)

36. PPI
PredicEon
Using
Microarray
Data
• Co-­‐expression
concept
• Correla)on
Coefficient
-­‐ SIMoNE
(Sta)s)cal
Inference
for
Modular
Networks)
-­‐
R
• Mutual
Informa)on
-­‐ Reference
Networks
-­‐ ARACNE
(Algorithm
for
Reconstruc)on
of
Accurate
Cellular
Networks)
–
R,
geWorkbench
-­‐ CLR
(Context
Likelihood
of
Relatedness)
–
R
-­‐ MRNET
(Maximum
Relevance/Minimum
Redundancy)
–
R
-­‐ MONET
(Modularized
NETwork
Learning)
-­‐
Cytoscape
• Bayesian
Network

37. PPI
PredicEon
Using
Microarray
Data
• Melanoma
metastasis
• 83
samples
• Affymetrix
• GEO
• ARACNE
• geWorkbench
• IP3R1,
IP3R2,
IP3R3,
STIM1,
ORAI1

49. GML File

50. Predicted
PPI
Network
• Could
form
a
complex
• Could
be
func)onally
associated
• Could
be
involved
in
a
same
metabolic
pathway
• Could
be
involved
in
a
specific
signal
transduc)on
path
• False
posi)ve

51. VisualizaEon
and
Analysis
Using
Cytoscape
• Cytoscape
• Opensource
• Works
in
Windows,
Linux,
Mac
• One
of
the
first
developed
tools
• Great
number
of
PLUGINS
• Excellent
help
from
community

52. Literature
Based
PPI
PredicEon
Using
Cytoscape

56. Retrieving
PPI
Using
Cytoscape

60. Data
VisualizaEon,
IntegraEon,
Analysis
• Import
ARACNE
predicted
network
• Import
VisANT
retrieved
network
• Merge
all
networks
• Mo)f
finding

70. 70

71. 71

72. ScienceApps@niaid.nih.gov
nagarajanv@mail.nih.gov
Thank
You