Post on 16-Apr-2017
Keiichiro Ono UC, San Diego Trey Ideker Lab
Bioinformatics Summit 2014 4/11/2014
Cytoscape An Open Source Platform for Biological Network Analysis and Visualization
-
Thanks for Attending!
- Keiichiro Ono - Cytoscape Core Developer since 2005
- Core module design & implementation
- Area of Interest: Data Integration & Visualization
- University of California, San Diego Trey Ideker Lab
Made with Cytoscape
Agenda
- What is Cytoscape?
- Data Integration, Analysis, and Visualization with Cytoscape
- Cytoscape Ecosystem - Cytoscape Future Plan
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
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
GraphXDocument
MongoDB
Relational
MySQL
IPython
3rd Party Apps
NetworkAnalyzer
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
GraphXDocument
MongoDB
Relational
MySQL
IPython
3rd Party Apps
NetworkAnalyzer
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
GraphXDocument
MongoDB
Relational
MySQL
IPython
3rd Party Apps
NetworkAnalyzer
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
GraphXDocument
MongoDB
Relational
MySQL
IPython
3rd Party Apps
NetworkAnalyzer
Network?
Network = Nodes + Edges
Nodes and Edges in Biology
- Protein - Protein- Protein - DNA- Genetic (Epistasis)
- Synthetic lethality
- Biochemical Reactions
- Compound - Enzyme - Compound
Cartoon representation of a complex between DNA and the protein p53
Node
NodeEdge
Undirected Network
EP300
PPARG
SMARCD3
STMN1
SMARCA4
OPTN
ATP6V1C1
PSMD1
HTT
PRNP
HNRNPUL1
CCDC88A
CLU
HSP90AB1
SMARCD3
MAP4K4
MIF4GDUSP11
MARCH6TUBB
EDF1 CHD8
Protein-Protein Interactions
Directed Network
KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader
Human-Curated Pathways
KEGG Pathway Visualized by Cytoscape
KEGG Global Map Visualized by Cytoscape
The Challenge in Network 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
is NOT a...
- Cytoscape is a powerful tool, but cannot do everything - Simulator - Fully-featured Pathway diagram editor - Statistical network analysis tool suite
- Still, you can implement these as Apps though
Our Focus
Large-Scale Network Analysis and Visualization
Human Interactome data from BioGRID visualized by Cytoscape
Agenda
- What is Cytoscape? - Data Integration, Analysis, and
Visualization with Cytoscape - Cytoscape Ecosystem - Cytoscape Future Plan
Introduction to Biological Network
Analysis with Cytoscape
1. Data Integration (Load Networks and Tables)
2. Data Analysis
3. Visualization
Basic Workflow
4. Prepare for Publication
Network Data
Annotated Networks
Attributes
Analyzed Data
Cline, et al. “Integration of biological networks and gene expression data using Cytoscape”, Nature Protocols, 2, 2366-2382 (2007).
Protocol Paper
<?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>
Import Networks
Network Data Formats
- SIF - GML - XGMML - GraphML - BioPAX - PSI-MI - SBML - KGML (KEGG)
- Excel - Text Table
- CSV - Tab
Network Data Source
- From your own experiment - Public database
- Search known interactions by list of genes
Public Interaction Databases
Which Database?- Protein - Protein
- STRING- IntAct
- Genetic- BioGRID
- Protein - Compound- ChEMBL
Which Database?- Human-Curated Pathways
- KEGG - Reactome - WikiPathways - PathwayCommons
Import Tables
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
Network Data
Annotated Networks
Attributes
Analyzed Data
Analysis
Network Analysis
- Filtering - Calculate network statistics by
Network Analyzer - Degree distribution,centrality, etc.
- Advanced analysis by Apps
Filtering (Selection)- Simple, but powerful feature to extract sub
networks from large data sets - Select nodes and edges with specific
conditions - Pick nodes with degree > 5 - Select edges extracted from publication
X - Find nodes on KEGG Pathway X
Other Selection Command: First Neighbor of Nodes
CTR+6
Create New Sub-Network From Selection
CTR+N
Summary: Selection- Create filter from your biological question:
- Select all nodes annotated with GO term “DNA repair” and have two or more know interaction
- Select all genes directly interact with brca1, brca2, etc.
- Extract subnetwork by CTR+N
Network Data
Annotated Networks
Attributes
Analyzed 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
Map Attributes to Visual Properties
Visual Style
- Collection of mappings from Attributes to Visual Properties
Visual Style- Example Mappings:
- Expression profiles to node color - Object type (protein, compounds,
complex, etc.) to node shape - Interaction type (Protein-Protein,
Protein-DNA, etc.) to edge line style
Layouts
Previous Example
GCN4
HIS7ILV2
RPL16A
CBF1
YOR264WYGR058W
YGR136W YBR190W
YCR086W
YNL050CACS2
FPR1SNP1HMO1 PRP21
TAH18
SIP4HOM3
PGK1RPS17A
RPL18B
HSP42ARG1
FCY1
SRP1
MCK1
YDR412W
PHO13 PHO4
PHO84
RPS24B
PDC1
RPL18A
RPS24A
PFK27
YPT1RAP1
ENO1
SEC17
GCR1
PHO5
GDS1
TPI1
CLB2
ADH1
CDC19
ENO2
ICL1
MSN5
SNC2 SEC9
DDI1CBF5
SNC1
SSO2
YGR203W
GCR2
HXT11
RFA2PDR3
SYF3
CAR1
PDR1
AST1
YNL047C CLB1
TIF5
HSL1
CKS1
NIP1
YML114C PMA1
TIF35
PRT1
RPS8B
GPD2PRE10
GNA1
TIF34
YDR070C
RLM1HSP150
CDC6
YDL023C
YIL113W
SSN6
BFR2
KNS1TUP1
YKL161C
SSL2
VPS21
RPL25
HIS3
TFA1
HIS4 PEP7
TFB1
NCE103
SIN4
GPA1
MSL5
ATC1
SST2
CNS1
PRP40
TOR1
BUD6
YGR046W
HSC82
MSL1
BAS1
YGL161C
SKO1
PEP12
YDR100W
YNL164C
YNL091W
SUC2
RPL42B
HSP82
MUD2
AHP1
CIN4
RPL34B
RPL11B
SXM1
RPL16B
RPL11A
RPL31A
RPL10
CUP1BSSA4
GFD1
GCN3
HRP1
RNA15
NAB2 CHK1
APG7
YLR345W
SFH1 ADE4
RAD52
MET16TRP4
HXT9
RFA1
HSP26
GIP1
PCL10
PHO85
PCL5
GSY2
PIG2
HSF1
GAC1
CUP1A
YOR315W
GLC7
APG12
REG2
AUT1
GIP2
APG5
GLC8
PIS1CTT1
CYC7CLN3
SLT2
CDC42
MFA2MCM1
MFA1
STE12SWI4
FBP1LYS9
DMC1
MLS1
DCP1
PCK1
GAL3
SWI5
GAL1
MIG1
GAL80
FAR1
GAL11
GAL10
HAP4
GAL4
GAL7
STE4
GAL2GCY1
RPA135
MAM33
CYB2
YDR032C
SPC24
ASN1
HEX3 LSM8
YEL015W
PRP9
TEM1
YMR044W
ECI1
YNR053C
TAF25
MTH1
YHR198C
MPT1
GLN1
GDH2
YER116C
UGA1
SNF3YLR432W
GLN3
PDC5
YIL105C
RPS28B
RPS28A
LSM4
LSM2
HAP1
STE11
SPA2
STE50
STE5
CYC1
HAP3
YER124C
HAP2
GIC2CDC28STE2
BAR1
ALPHA2
YBR190W
YCR086W
YNL050CACS2 SNP1 PRP21
TAH18
SIP4
PGK1RPS17A
RPL18B
HSP42ARG1
FCY1
SRP1
MCK1
YDR412W
PHO13 PHO4
PHO84
RPS24B
PDC1
RPL18A
RPS24A
PFK27
YPT1RAP1
ENO1
SEC17
GCR1
PHO5
GDS1
TPI1
CLB2
ADH1
CDC19
ENO2
ICL1
MSN5
SNC2 SEC9CBF5
SNC1
SSO2
YGR203W
GCR2
YNL047C CLB1HSL1
YML114C PMA1
RLM1HSP150
CDC6
YIL113W
SSL2
VPS21
RPL25
HIS3
HIS4 PEP7
TFB1
NCE103
SIN4
GPA1
MSL5
ATC1
SST2
CNS1
PRP40
TOR1
BUD6
HSC82
MSL1
BAS1
YGL161C
SKO1
PEP12
YDR100W
YNL164C
YNL091W
SUC2
RPL42B
HSP82
MUD2
AHP1
CIN4
PIS1CTT1
CYC7CLN3
SLT2
CDC42
MFA2MCM1
MFA1
STE12SWI4
FBP1LYS9
DMC1
MLS1
DCP1
PCK1
GAL3
SWI5
GAL1
MIG1
GAL80
FAR1
GAL11
GAL10
HAP4
GAL4
GAL7
STE4
GAL2GCY1
HEX3 LSM8
YEL015W
PRP9
TEM1
YMR044W YNR053C
TAF25
MTH1MPT1
GDH2
YER116C
SNF3YLR432W
GLN3
PDC5
YIL105C
RPS28B
RPS28A
LSM4
LSM2
HAP1
STE11
SPA2
STE50
STE5
CYC1
HAP3
YER124C
HAP2
GIC2CDC28STE2
BAR1
ALPHA2
Real World Exampleshttp://cytoscape-publications.tumblr.com
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!
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
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
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
Agenda
- What is Cytoscape? - Data Integration, Analysis, and
Visualization with Cytoscape - Cytoscape Ecosystem
- Cytoscape Future Plan
Cytoscape EcosystemJS
Cytoscape Family- Version 2.x - Legacy version
- Last release for 2.x is 2.8.3.
- Version 3.x - Current production version
- Latest version: 3.1.0
- Important Note: Apps for 2.x is not compatible with 3.x (We have similar problem like Python…)
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
Export to HTML5 Session
Feature for users: you can view networks on web browsers with Cytoscape.js
Under development… We need early adapters for testing!
JS
Future Plan
Future Plan
- Integration to external tools - Access from
Python, R, Perl, etc. - More integration to
Cytoscape.js - Cytoscape
Cyberinfrastructure (Cytoscape CI)
Cytoscape CI: Background- The size of data biologists have
to analyze is still growing - Desktop machines are
powerful, but not enough for large scale data analysis - Clusters / Clouds
- Using multiple computing resources as external service is normal for biological data analysis…
- ScalabilityService 1
Service 2
Cytoscape Cyberinfrastructure
Internet
Service 1 Service 2
NDEx (DB)
Web Browser
Cytoscape Desktop
App Development
Developer Documents
- http://opentutorials.cgl.ucsf.edu/index.php/Portal:Cytoscape3
Collaboration
Collaboration- Once you are ready to use Cytoscape for real-world
problems, National Resources for Network Biology (NRNB) is always open for collaboration!
- NRNB Provides support for both of - Scientific Research - Application / Tool Development - nrnb.org
-
- Two Google Groups
- cytoscape-discuss@googlegroups.com
- cytoscape-helpdesk@googlegroups.com
- ANY question is OK!
Getting Help
General Introduction !!!!!
Advanced Topics - Effective Visualization
Techniques - External Tools
!!
Part 2Part 1
Q1. How many of you have never
used Cytoscape?
Q2. How many of you regularly use
R/Python/MATLAB?