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Biological Network Visualization with Cytoscape
Keiichiro Ono

Cytoscape Core Developer Team

UC, San Diego Trey Ideker Lab / National Resource for Network Biology

!
5/12/2014 Workshop for Undergraduate Bioinformatics Club at UCSD
Sample Data Files:

http://cl.ly/VTJs
Made with Cytoscape
Keiichiro Ono
Cytoscape Core Developer

!
Area of Interest:

Data Integration & Visualization
Keiichiro Ono
Computer Science Biology
Keiichiro Ono
Computer Science
Keiichiro Ono
Data Visualization
Programming: Java, JavaScript, Python, R, etc
Software Engineering
Web Development


Practitioner > Researcher
Outline
• Part 1: Introduction to Cytoscape

• What is Cytoscape?

• Basic Features

• Part 2: Hands-On Tutorial

• Visualize gene expression
values and network

• Import data from public
databases (optional)
What is Cytoscape?
An Open Source Platform for Biological Network Data
Integration, Analysis and Visualization
Cytoscape
Cytoscape
- Open Source (LGPL)
- Free for both commercial and academic use
- Developed and maintained by universities,
companies, and research institutions
- De-facto standard software in biological network
research community
- Expandable by Apps

- This is why Cytoscape is a Platform, not a
simple desktop application
EP300
PPARG
SMARCD3
STMN1
SMARCA4
OPTN
ATP6V1C1
PSMD1
HTT
PRNP
HNRNPUL1
CCDC88A
CLU
HSP90AB1
SMARCD3
MAP4K4
MIF4GD
USP11
MARCH6TUBB
EDF1 CHD8
Protein-Protein Interactions
Directed Network
KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader
Large-Scale Network Analysis and Visualization
Human Interactome data from BioGRID visualized by Cytoscape
…But why we need such tool for biology?
C. Elegans Interactome from BioGRID Database
?
Biological Networks
- Tell us anything by themselves
- Just a big hairball…
Module 1
Module 2
In other words…
Module 1
Need a tool to extract
meaningful biological modules
Basic Use Case
Networks
Public Interaction Databases
List of
Genes
Other Data
Network Data Analysis
Analysis
Graph Analysis
NetworkX
igraph
Cytoscape
Python
Pandas
NumPy
SciPy
Excel
Visualization
Desktop
Gephi
Cytoscape
matplotlib
Web
Cytoscape.js
sigma.js
d3
NDV3
d3.chart
Google Charts
Data Storage
Graph
Neo4j
GraphX
Document
MongoDB
Relational
MySQL
IPython
3rd Party Apps
NetworkAnalyzer
Network Data Analysis
Analysis
Visualization
Desktop
Gephi
Cytoscape
matplotlib
Web
Cytoscape.js
sigma.js
d3
NDV3
d3.chart
Google Charts
Data Storage
Network Data Analysis
Analysis
Graph Analysis
NetworkX
igraph
Cytoscape
Python
Pandas
NumPy
SciPy
Excel
Visualization
IPython
3rd Party Apps
NetworkAnalyzer
3 Basic Steps of Data Visualization with Cytoscape
<?xml version="1.0" encoding="UTF-8"?>
<graphml xmlns="http://graphml.graphdrawing.org/xmlns"
xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
xsi:schemaLocation="http://graphml.graphdrawing.org/xmlns
http://graphml.graphdrawing.org/xmlns/1.0/graphml.xsd">
<!-- Created by igraph -->
<key id="degree" for="node" attr.name="degree" attr.type="double"/>
<key id="betweenness" for="node" attr.name="betweenness"
attr.type="double"/>
<graph id="G" edgedefault="directed">
<node id="n0">
<data key="degree">79</data>
<data key="betweenness">0</data>
</node>
<node id="n1">
<data key="degree">9</data>
<data key="betweenness">167</data>
</node>
<node id="n2">
<data key="degree">18</data>
<data key="betweenness">75</data>
</node>
<node id="n3">
<data key="degree">8</data>
<data key="betweenness">12</data>
</node>
<node id="n4">
<data key="degree">26</data>
<data key="betweenness">210</data>
</node>
<node id="n5">
<data key="degree">29</data>
<data key="betweenness">320</data>
</node>
Data Integration
Analysis
Visualization
Network Data
Annotated
Networks
Attributes
Analyzed Data
Apps
Cytoscape Apps
- Extension programs to
add new features to
Cytoscape (were called
Plugins)
- Large App developer/
user community
- This is why Cytoscape
is so successful in life
science community!
(As of 4/5/2014)
APPS.CYTOSCAPE.ORG
Quick Overview of Apps
A travel guide to Cytoscape plugins
!
Rintaro Saito, Michael E Smoot, Keiichiro Ono, Johannes Ruscheinski, Peng-
Liang Wang, Samad Lotia, Alexander R Pico, Gary D Bader, Trey Ideker (2012)
Nature Methods 9 (11) p. 1069-1076
Tips for Learning Tools
Choose a Right Tool
Choose a Right Tool
Analysis VisualizationData Preparation
Data Visualization Tools
http://selection.datavisualization.ch/
Data Visualization Tools
http://selection.datavisualization.ch/
Data Visualization Tools
http://selection.datavisualization.ch/
Tools
• In some cases, you can finish exact same tasks using different tools
• Example: Data preparation (cleansing)
• But if you choose right tools, you can do it 100x faster than
others.
• ex: Re-formatting complex data sets
• Excel vs Python Script
• Some recommendations:
• R/Bioconductor, Python/Pandas, Git/GitHub/Gist
Learning Tools = Saving Your Time
Hands-on:
Introduction to Data
Visualization with
Cytoscape
50-60 min.
Data Visualization
- Goal: Help others to
understand your data
- Emphasize what you
want to tell
- Use color, shape,
size of objects
effectively!
- Excellent resource for
data visualization
- Tamara Munzner’s Web Site: 

http://www.cs.ubc.ca/~tmm/
Data Visualization
Today’s Goal
Story:
!
I want to show gene expression changes over time
as a network diagram
YPL201C YPL211W YML007WYPL131W YOR327CYDR171W YCL067C
YGL208WYER074WYBL050W YLR134WYPL149W
YDR050C YMR311CYGL134W YBR112CYKL101W YNL199C
YPL222W
YLR264W
YNL098C
YLL028W
YOR039W YNL135C YPR041WYDR174W YIL074C YKL028W
YIL162W
YNL189W
YOR212W
YPR080W
YPR145W
YLL019C
YLR284CYPL031C YFR037CYML074C YPL240CYPR048W YBR274W YBR050C YML032C
YJR022WYBR248C YDR382W YER081WYIR009W YDR244W YOL016C
YER103W YGR058WYLR256WYAL003W YOR355WYIL061C YER111C YMR309C
YPL248CYBR019CYLR362W YGL035CYPR167C YML123C
YBL026WYNL091W YOR178C YIL113WYLR321C YML064C YMR117C YDL194WYNR007C
YOL058WYBR045CYER065CYNL167C YGL097WYHR071W YDL078C YDL081CYDR354W
YER145C YGR136WYDR311W YPR119WYER112W YLR214W
YER143W YBR043CYKL204W
YGR019WYEL041W YER133W
YBR118WYAL038W YDR167WYMR058WYER079W YMR291W
YKL012W YDL113CYDR299W YDL075W YDL236WYLR377C YNL145W
YNL236W
YOL156W
YGL013C
YHR171W
YMR021C YFL038C
YER090WYPR062W YAR007C YNL307CYML024WYDR335W YLR075W
YNL050CYGR046W YAL040CYLR191W YMR138WYIL045W YHR005C
YKL211CYLR452C YPL075WYML051W YOL123WYHR198C YMR300C
YJR060W YMR043WYPR124WYLR081W YLR319CYKL074C YKL001C
YDR100W
YDR395W
YDR009W
YDR309C
YPR102C
YAL030W
YHR084W
YLR345W
YBR170C
YJL089WYFL026W YBR018C YGL115W YDL215CYGR009C YOL120C
YFL017C YDR429C
YIL052C YGL073W
YGR108WYPR035W
YJL190CYOL086CYBL005WYKR026C
YBR155W
YOR264W YKL109W
YOR167C
YDR070CYEL015W
YIL133C
YGL166WYHR030CYGL008C
YMR146C YBR160W
YBR020W YBR190WYDR323CYLR197W YFR014CYKL161C
YML054C YKR099WYLR340WYGL106W YBR093CYCL040W
YLR044C
YCR086WYDL130W
YJL203W
YEL009CYBR135W
YOR361C YGR085C
YNL216W
YBR109C
YER124C
YJL157C YDR461WYNL154CYLR117C YKR097W YIL069CYMR186W YJR109CYIL015W
YER040W YGR074WYER052C YIL160CYOR290C YLR249W
YGL153WYOR215CYGR254W YLR432WYCR084CYOR089C YOR303W
YGL161C YLR293CYDL030WYNL036W YHR135CYER179W YDR277CYDR184C YML114C YFL039CYER054C YER110CYLR109W YLR116WYNL214W YBL069W
YHR141CYER116CYJL219W YDL023C YGL202WYER062C YMR183CYFR034CYGL122C
YIL105C YDL088CYPR010C YJR048W YIL070C YEL039CYDR412WYMR108W
YOR204W YMR255W YLR175W YHR115CYNL164C YJL013C YDL063C YNL117W
YIL143CYOR315W YDR146CYLR310CYGR014WYBR217W
YJL036W
YNL116W
YOR120W
YDR032C
YPR113W
YLR153C
YGR048W
YGR203W
YNL113WYOR202W
YNR050C
YCL030C
YJL159W
YHR053CYPR110C?YLR258W YBL079W
YNL069C YNL311CYDR142C YGL044CYMR044W
What is Great
Visualization…?
Design is complicated,
because humans are complicated.
Design is a process to avoid bad designs.
Mike Bostock (New York Times Visualization Team. Creator of D3.js)
It is hard to generalize the design process, but we
can avoid pitfalls by following some basic rules.
Avoid Chartjunk
Edward Tufte
http://en.wikipedia.org/wiki/File:Chartjunk-example.svg
Every pixel should
carry information.
Edward Tufte
Avoid Data Overload
• Mapping too many attributes makes your visualization
awful!
• It is hard to see the overall trend of your data sets if too
many channels are used in a image
“Great Artists Steal…”
MUD
HAP4
GC
HA
GAL1
GAL7
GAL80
GAL3
GAL11
GAL4
GAL2
SIP4
FBP1
GAL10
SWI5
SUC2
MIG1
ADH1
PGK1
CDC19
GCR1
CBF1
ENO1
ENO2
MCK1
NCE103
SSL2
TFB1
YNL091W
TRP4
ARG1
GCN4
SKO1
HIS3
ADE4 ILV2
RPS17A
BAS1
HIS7
RPS24B
MSL1
HIS4
PDC5
PHO84
PHO4
YIL105C
MET16
RPL11B
RPS8B
RPL11A
RPL31A
PHO13
PDC1
SXM1
RPL34B
RPL16B
ATC1
CAR1
FCY1
ICL1SRP1
TPI1
RPL18B
RPL25
PHO5
RPS24A
RPL18A
DMC1
RAP1
RPL16A
HSP42
MUD
HAP4
GC
HA
GAL1
GAL7
GAL80
GAL3
GAL11
GAL4
GAL2
SIP4
FBP1
GAL10
SWI5
SUC2
MIG1
ADH1
PGK1
CDC19
GCR1
CBF1
ENO1
ENO2
MCK1
NCE103
SSL2
TFB1
YNL091W
TRP4
ARG1
GCN4
SKO1
HIS3
ADE4 ILV2
RPS17A
BAS1
HIS7
RPS24B
MSL1
HIS4
PDC5
PHO84
PHO4
YIL105C
MET16
RPL11B
RPS8B
RPL11A
RPL31A
PHO13
PDC1
SXM1
RPL34B
RPL16B
ATC1
CAR1
FCY1
ICL1SRP1
TPI1
RPL18B
RPL25
PHO5
RPS24A
RPL18A
DMC1
RAP1
RPL16A
HSP42
Map gene expression
values to color
Avoid using more colors in other
components (edge/label)
If necessary, map other data
into non-overlapping visual properties
(edge score to width)
Part 1: Session File and Basic Navigation
Cytoscape 3.1 Desktop
Toolbar
Network Panel
Bird’s Eve View
Table Browser
Network Views
Table Browser
Local Column
Table Tabs
List Data

(Values in [ ])
Shared Column
Session File
- Snapshot of your workspace
- Networks
- Tables
- Visual Styles
- System Properties
Open a Session
- Click folder icon
- Or, File → Open
Exercise 1: Loading a session
Navigation
- Pan: Middle-Click + Drag or 

Command + Left-Click + Drag on Mac
- Zoom
- IN: Mouse Wheel UP
- OUT: Mouse Wheel DOWN
- Selection: Left-Click and Drag
- Fit to Window
- Selected region
- Entire network
First Neighbor of Nodes
CTR+6
Create New Sub-Network From Selection
CTR+N
- CTR (Command on Mac) + G
Part 2: Data Import
Network Data Formats
- SIF
- GML
- XGMML
- GraphML
- BioPAX
- PSI-MI
- SBML
- KGML (KEGG)
- Excel
- Text Table
- CSV
- Tab
NCBI Gene ID 672
On Chromosome 17
GO Terms
DNA Repair
Cell Cycle
DNA Binding
Ensemble ID
ENSG00000012048
BRCA1
Data Tables for Cytoscape
- Example:
- Numeric

- Gene expression profiles
- Network statistics calculated in other
applications, such as R
- Confidence scores for edges
- Text (or categorical)

- GO annotation for genes
- List of genes related to disease X
- Targets for FDA approved drugs
- Genes on KEGG Pathway Y
- Clusters / group / community calculated
in external programs
- …
Your Data Sets
- Anything saved as a table can be
loaded into Cytoscape
- Excel
- Tab Delimited Document
- CSV
- As long as proper mapping key is
available, Cytoscape can map them to
your networks.
Mapping Key in
the Network
Mapping Key in
the Table
Exercise 2: Loading network and tables
Part 3: Visualization
Layouts
Automatic Layout
- Choose proper algorithm
- Tree-like data - Hierarchical Layout
- Scale-Free Network - Force-directed
- Circular process - Circular Layout
- Tweak parameters if necessary
Manual Layout
- Tweak result from
automatic layout
- Scale
- Align
- Rotate
Exercise 3: Apply layouts
Visual Style
- Collection of mappings from
Attributes to Visual
Properties
Visual Styles
- Defaults + Mappings
- Expression values to node color
- Gene function to node shape
- Interaction detection method to edge line
type
- Confidence score to edge width
Core Idea: Data Controls The View
Data Controls The View
• Photoshop / Illustrator
• You control the pixels and objects on the display
• Data Visualization Tools (including Cytoscape)
• Data points are mapped to visual properties
• Color
• Size
Data Controls The View
Expression Values
To Node Colors
Discrete Mapping Editor
Continuous Mapping Editor
Exercise 4: Create New Visual Style
Part 4: Web Services (Optional)
Cytoscape Ecosystem
Dawn of Web-Based Visualization
Cytoscape Family
- cytoscape.js:
Library for web
applications
JS
Cytoscape 3.1.0
JS
JS
Cytoscape.js Network Visualization Library Running on Web Browsers
What is cytoscape.js?
A Javascript Library for network visualization,
not a web application!
Need to write some code to use it on the web browsers…
Complete desktop
application for network
analysis and visualization
!
Written in Java
!
Expandable by Apps
!
For Users
A Javascript Library for
network visualization,
not a web application!
!
Written in JavaScript
!
Expandable by Extensions
!
For Developers
JS
Analysis
Data Integration
Cytoscape Desktop
Cytoscape.js
Visualization
Minimal Analysis
Cytoscape
Web
Desktop
Layout
Visual Style
Visual Style
Layout
Visualization
Integration to Cytoscape
New in Cytoscape 3.1.0:
Export Networks and Visual Styles to Cytoscape.js Format
JS
Future
Cytoscape Cyberinfrastructure
Internet
Service 1 Service 2
NDEx (DB)
Web Browser
Cytoscape Desktop
-
- Two Google Groups
- cytoscape-
discuss@googlegroups.com
- cytoscape-
helpdesk@googlegroups.com
- ANY question is OK!
Getting Help
Further Readings
Further Readings
• My presentation slides
• http://www.slideshare.net/keiono
• (This deck of slides will be uploaded tonight)
Further Readings 1
- Introduction to Network Biology
- Deciphering Protein–Protein Interactions. Part I. Experimental
Techniques and Databases



Shoemaker BA, Panchenko AR (2007) Deciphering Protein–Protein
Interactions. Part I. Experimental Techniques and Databases. PLoS
Comput Biol 3(3): e42.doi:10.1371/journal.pcbi.0030042
- Deciphering Protein–Protein Interactions. Part II. Computational
Methods to Predict Protein and Domain Interaction Partners



Shoemaker BA, Panchenko AR (2007) Deciphering Protein–Protein
Interactions. Part II. Computational Methods to Predict Protein and
Domain Interaction Partners. PLoS Comput Biol 3(4): e43. doi:10.1371/
journal.pcbi.0030043
Further Readings 2
- Overview of Cytoscape Apps (Plugins)
- A travel guide to Cytoscape plugins



Rintaro Saito, Michael E Smoot, Keiichiro Ono, Johannes Ruscheinski,
Peng-Liang Wang, Samad Lotia, Alexander R Pico, Gary D Bader, Trey
Ideker (2012) Nature Methods 9 (11) p. 1069-1076
- Sample Protocol (based on 2.x)
− Integration of biological networks and gene expression data using
Cytoscape



Cline, et al. Nature Protocols, 2, 2366-2382 (2007).
Further Readings 3
- Cytoscape Tutorial Booklet:



Analysis and Visualization of Biological Networks with Cytoscape
- http://www.rbvi.ucsf.edu/Outreach/Workshops/ISMBTutorial.pdf
!
2014 Keiichiro Ono
kono@ucsd.edu

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