Presentation slides for Cytoscape Workshop at Salk 12/4/2012.

1. Cytoscape
An Open Source Platform for Biological
Network Analysis and Visualization
Keiichiro Ono
Cytoscape Core Developer Team
University of California, San Diego
Trey Ideker Lab
1

2. Thanks for Attending!
- Who am I?
- Keiichiro Ono
- Cytoscape Core Developer since 2005
- Area of Interest: Data Integration & Visualization
- University of California, San Diego Trey Ideker Lab
2

3. Outline
- What is Cytoscape?
- How to Use Basic Features of
Cytoscape
- Cytoscape 3 and Beyond
3

4. What is Cytoscape?

5. Cytoscape
- Open source platform for
biological network data
integration, analysis, and
visualization
5

6. 6

7. - Free! (LGPL)
- Developed and maintained by
universities, companies, and
research institutions
- De-facto standard software in
biological network research
community
- Expandable by Apps

8. JUN
FANCB GATA3 KRT14 HSPA8
FBXL3
DDB1
TSPAN17
CDC25A CDC45 CDKN1A PAX6
APLP2
EIF4G1 TOP3A
PEG3
CHEK2
TUBB2A POU2F1
HIC1
FLI1 CTCFL PML MAP3K4
NUP153
DCAF11 EZH2
RNF31
ERCC2
EGFR SMARCE1
AKAP10
NUSAP1
FANCA
MED21
RAD9A
CDKN1B HMMR
WRN
MRE11A
ETS1
AP2B1
ESR1
UBE2I
XRCC5 RBL1
TSPAN9 NMI RNF144B
SHFM1 ERCC1
RNF8
SUGT1
WT1 UBC
ELK1 RBMXL2
UBB
JUND CNR1
MELK
PPP1R3A
SUMO2
ERCC4
BRCA1
LMO7
MDM2
NBR1
PMS1
IGF1R
TOPBP1 TUBA4A UBA52
PPT1
CSTF1 SMARCA4
RNF168
JUNB TERF2
PPM1D DHFR
CDK16
FBXO25 SMARCC1
SMARCD2 NCOA3
FAM175B BRCA1
STK11 MED13
WHSC2 CREB1
SMAD3 E2F4
RBBP7
CHD8
ERBB2 BRE HDAC2
WWP1 TP53 LMO4
FANCC
KIAA1182
RAD17 EP300
BRAP CDK2
FANCE NUFIP1
DCUN1D1 HIST1H4A
PMS2 RNF53
BARD1
POLL RBBP8 BRCC1
FANCL FGFR2 CLSPN
RFC1 BRCA1
NBR2 MYC
FANCF
SMAD1
TFDP2
GTF2H4
DCLRE1C MAP3K3
RAD54B DDB2 BRIP1
RBBP4
BAP1
RAD51 DPPA3
AR
FBXO9 NFYA
RNF11 ZCCHC8
C5orf4
PSMC3IP

9. 9

10. 10

11. Introduction to Biological
Network Analysis Using
Cytoscape
11

12. Network?
12

13. Human Interactome data from BioGRID visualized by Cytoscape

14. Twitter Visualization

15. Network of Networks M6
M2
M17
M1
M8
M9 M4
M10
M14
M3 M5
M7 M11
M16
M19 M18
M13
M20
M15
15 M12

16. Human-Curated Pathways
16

17. Network = Nodes + Edges
17

18. Nodes and Edges in Biology
Node
- Protein - Protein
- Protein - DNA
Node
Edge - Genetic (Epistasis)
- Synthetic lethality
- Biochemical
Reactions
- Compound - Enzyme - Compound
18
Cartoon representation of a complex between DNA and the protein p53

19. Undirected Network
- Protein - Protein Interaction
19

20. Directed Network
KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader
20

21. KEGG Global Map Visualized by Cytoscape
21

22. Cytoscape Workflow
1.Load Networks (Get network data)‫‏‬
2.Load Attributes (Get data about networks)‫‏‬
3.Analyze and Visualize Networks
4.Prepare for Publication
- A specific example of this workflow:
− Cline, et al. “Integration of biological networks and gene
expression data using Cytoscape”, Nature Protocols, 2,
2366-2382 (2007).
22

23. Network Data
Attributes
Apps
Annotated
Networks
Analyzed Data

24. <?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>
Import Networks
<data key="betweenness">320</data>
</node>
24

25. Network Data Formats
- SIF
- GML
- Excel
- XGMML
- Delimited Text
- GraphML
Table
- BioPAX
- CSV
- PSI-MI
- Tab
- SBML
- KGML (KEGG)
25

26. I Don’t Have a Network!
- Don’t worry - There are tons of public
interaction data sets
- Cytoscape can import those public
data sets directly via Internet.
26

27. Which Database?
- Protein - Protein
- STRING, IntAct
- Genetic
- BioGRID
- Protein - Compound
- ChEMBL
- Human-Curated
Pathways
- KEGG, Reactome,
PathwayCommons
27

28. PSICQUIC
- Standardized
mechanism to
access public
interaction data
sets
- In short, you can
search multiple
databases at
once
28

29. Import Attributes
29

30. What are Attributes?
- Any data that describes or provides
details about nodes, edges, and
networks.
30

31. GO Terms:
DNA Repair NCBI Gene ID 672
Cell Cycle
DNA Binding
BRCA1
Ensemble ID
On Chromosome 17 ENSG00000012048
31

32. Why we need attributes?
- Analysis
- It is hard to get biologically meaningful analysis
result only from network topology (= structure)
- Meaningful Visualization
- Expression values - Node Color
- Gene Function - Node Shape
- etc.
32

33. Node Attributes
- Gene Expression Data
- Human-readable gene names
- Gene Ontology Terms
33

34. Edge Attributes
- Interaction Detection Methods
- Y2H, NMR, affinity chromatography, etc.
- Interaction Type
- Physical, genetic, predicted
- Publication ID
34

35. Network Attributes
- Experiment details
- Pathway Metadata
- Description
- Publication ID
35

36. Public Data Source
- Access directly from
Cytoscape, or
- Import as Table (Text/Excel)
36

37. Mapping Key in the Network
Mapping Key in
the Table
37

38. Analysis
38

39. Network Analysis
- Analysis is a huge topic in
Cytoscape, so I’ll show you only
the very basic features only.
- Filtering
- Calculate network statistics by
Network Analyzer
- Degree distribution,centrality, etc.
- Advanced analysis by Apps
39

40. Filtering
- Find nodes and edges with specific
conditions
- Pick nodes with degree > 5
- Select edges extracted from
publication X
- Find nodes annotated by GO term ID Y
40

41. 41

42. 42

43. 43

44. Visualization
44

45. ?
45

46. Layouts
46

47. Biological Data Visualization
- Help others to understand your data
- Emphasize what you want to tell by the image
テキスト
- Use color, shape, size of objects effectively!
- Tamara Munzner Web Site:
http://www.cs.ubc.ca/~tmm/
47

48. Visual Style
- Collection of mappings
from Attributes to
Visual Properties
48

49. Default View Editor
Discrete Mapping Editor
Continuous Mapping Editor
49

50. 50

51. 51

52. 52

53. 53

54. 54

55. Prepare for Publication
- Network images can be exported as PDF/
PS/PNG/JPG.
- Use PDF for your publications
55

56. Real World Examples
http://cytoscape-publications.tumblr.com
56

57. Expanding Cytoscape with Apps
57

58. Cytoscape Apps
- Were called Plugins
- Add new features to Cytoscape
- Large app developer/user community
- This is the reason why Cytoscape
is so popular!
58

59. http://apps.cytoscape.org
59

60. AllegroMCODE APCluster APID2NET BioQualiPlugin BLAST2SimilarityGraph BNMatch CABIN
CalculateNodeDegree CentiScaPe ChemViz clusterExplorerPlugin clusterMaker ClusterONE
ClusterViz COMA CommFinder CyClus3D CyOog cytoHubba Cytomcl DualLayout
dynamicXpr EnhancedSearch EnrichmentMap ExprEssence GraMoFoNe GraphletCounter
HiderSlider jActiveModules mcl-new MCODE MINE NeMo NetAtlas NetCirChro netMatch
NetworkAnalyzer NetworkEvolution OmicsAnalyzer OmicsViz OrthoNets PanGIA
PerturbationAnalyzer PinnacleZ RandomNetworks RDFScsape Reactome FIs
RemainingDegreeDistribution ReOrientPlugin ShortestPath Plugin SimTrek structureViz
TransClust VennDiagramGenerator VistaClaraPlugin WordCloud BiNoM bioCycPlugin
BiogridPlugin BiomartClient BioNetBuilder BisoGenet ConsensusPathDBplugin
140+ Apps
CoryneRegNetLoader CyThesaurus-ID-Mapping CytoSQL DroID Genoscape GPML-Plugin
GraphMLReader IntActWSClient iRefScape KGMLReader MetScape MiMIplugin NCBIClient
NCBIEntrezGeneUserInterface Pathintegrator PhosphositePlus Web Service Client Module
PICRClient PSICQUICUniversalClient ReConn SessionForWeb SFLDLoader StringWSClient
Superpathways-Plugin 3DScape AgilentLiteratureSearch Cytoprophet DisGeNET
DomainGraph ExpressionCorrelation GeneMANIA MetaNetter MONET BiNGO BubbleRouter
ClueGO CommonAttributes DisplayNetworkFromFlatFile FluxViz FunNetViz HyperEdgeEditor
PiNGO CyGoose CytoscapeRPC GroovyScriptingEngine JavaScriptEngine MiSink
PythonScriptingEngine RubyScriptingEngine ScriptEngineManager addParentNeighbors
AdvancedNetworkMerge batchTool BiLayout commandTool coreCommands CyAnimator
edgeLengthPlugin edgeLister EpiTrace FERN FM3 GoogleChartFunctions GroupTool
MetaNodePlugin2 MultilevelLayoutPlugin NamedSelection NatureProtocolsWorkflow
NeighborHighlight NetLink nodeCharts PhyloTree VennDiagrams

61. A Must Read
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
61

62. Advanced Topics
62

63. Custom Graphics
63

64. Nested Networks
64

65. Upcoming Projects
65

66. - Cytoscape 3
3
- Integration to Web
66

67. HUGE Update
C
2 3
67

68. 68

69. What’s New in 3?
- New Visualization features
- Edge Bend, Background Images
- Server-side applications
- Headless Mode (Command-line)
- More advanced visualization by new
rendering engines
- For developers: Cleaner API
69

70. Release Schedule
- User Beta - available now
- 3.0 Final Release
- At Cytoscape Retreat 2012 @UCSF
- December 13, 14
- For more information, please visit:
http://www.cytoscape.org/cy3.html
70

71. cytoscape.js
- JavaScript version of Cytoscape for network
visualization on the web browsers
- Subset of Cytoscape functions
- Will be integrated more to Cytoscape 3!
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72. 72

73. 73

74. Getting Help
- Two Google Groups
- cytoscape-discuss@googlegroups.com
- cytoscape-helpdesk@googlegroups.com
- ANY question is OK!
74

75. P41 RR031228 (NRNB)
NIH GM070743-01
P01 HG005062
75

76. www.cytoscape.org