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Introduction to Biological Network Visualizatio...

Introduction to Biological Network Visualization with Cytoscape: A Hands-On Tutorial

Presentation slides for hands-on tutorial session on 2/25/2013 at U. of Tokyo.

Cytoscape Consortium

February 25, 2013
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  1. Cytoscape Hands-On: Introduction to Biological Network Analysis and Visualization with

    Cytoscape Feb. 25, 2013 University of Tokyo HGC Keiichiro Ono Cytoscape Core Developer Team University of California, San Diego Trey Ideker Lab
  2. Welcome! - Keiichiro Ono - Cytoscape Core Developer since 2005

    - Area of Interest: Data Integration & Visualization - University of California, San Diego Trey Ideker Lab - This presentation file is available on my Speaker Deck account - speakerdeck.com/keiono
  3. Please Ask Questions! - Anytime you can atop me and

    ask questions - In English or Japanese
  4. Today’s Agenda - Basic Concepts - Browsing Network Data -

    Networks and Attributes - Visualization Techniques - Basic Analysis - Expression Data Analysis - Advanced Topics
  5. Prerequisites - Cytoscape 2.8.3 and EnhancedSearch Plugin should be installed

    on your machine. - Cytoscape 3.0.0 release is available, but at this point, it is for power users due to missing plugins. - Differences between 3.x and 2.x will be discussed
  6. Other Recommended Apps - Shortest Path v1.1 - PSICQUIC Client

    v 0.31 - KGMLReader v 0.15 - ClusterMaker v1.10 - MCODE v1.32
  7. Machine Requirement - Faster, larger is better! - Cytoscape is

    a Java application, and it uses lots of memory - 4+ GB of memory is recommended for large network analysis / visualization
  8. Data Types in Cytoscape - There are two types of

    data in Cytoscape - Network - Attribute (Data Table)
  9. Network - Mathematical Graph - G = (V, E) -

    Nodes - Any objects - Edges - Relationships between objects
  10. Basic Scope - Cytoscape is a tool for extracting meaningful

    information, or modules, out of large biological networks
  11. Cytoscape is for... - Data integration - Join networks and

    attributes - Network data analysis - Visualization
  12. 1.Load Networks (Get network data)‏ 2.Load Attributes (Get data about

    networks)‏ 3.Analyze and Visualize Networks Cytoscape Workflow
  13. 1.Load Networks (Get network data)‏ 2.Load Attributes (Get data about

    networks)‏ 3.Analyze and Visualize Networks 4.Prepare for Publication Cytoscape Workflow
  14. 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: Cytoscape Workflow
  15. 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). Cytoscape Workflow
  16. BRCA1 NCBI Gene ID 672 On Chromosome 17 GO Terms:

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

    DNA Repair Cell Cycle DNA Binding Ensemble ID ENSG00000012048
  18. Edge Attributes - Interaction Detection Methods - Y2H, NMR, affinity

    chromatography, etc. - Interaction Type - Physical, genetic, predicted - Publication ID
  19. Summary - There are two types of data - Networks

    - Attributes - Analysis and visualization will be performed for the integrated data (networks+attributes)
  20. Define Your Goal - You need to define your goal

    first - e.g. visualize relationships between group of genes and known targets of FDA approved drugs - What kind of tools are required for your goal?
  21. Know What Cytoscape Can Do - There is no silver

    bullet! - Understand Cytoscape Core Features - Research available Apps - Data pre-processing/post-processing may be required - Excel, R / Bioconductor, Scripts, Web Tools
  22. Goal of This Lesson - Understand Basic UI - Loading

    a sample Session file - Learn how to browse the network and attributes - Know useful basic shortcuts/commands
  23. Session File - Snapshot of your workspace - Networks -

    Attributes - Visual Styles - System Properties
  24. Saving & Opening - In Cytoscape, Save means saving your

    workspace states into a Session File - Open means loading a Session file - You can open only one session at a time - Merge Session feature will be implemented in the future version of Cytoscape 3.x
  25. Open a Session - Click folder icon - Or, File

    → Open - Use sampleData/galFiltered.cys
  26. Browsing Networks - 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
  27. Useful Commands - First neighbor of nodes - Create new

    sub-network from selection - Tile network views - Show Graphics Details - Linkouts
  28. Linkout - Send ID as a query to external resources

    - Open a browser window and displays the result
  29. Lesson 1: Summary - Session File is a snapshot of

    your workspace - Creating subnetworks from selection is easy - Attribute browser is a spreadsheet-like viewer for your attributes
  30. Data Integration - Loading networks and mapping attributes onto them

    - Cytoscape provides: - Data import from files - Direct access to remote data sources
  31. Import & Export - Import - Load any type of

    data - Network, Attributes, Visual Styles, etc. - Export - as network files, tables, or images
  32. Network Data Formats - SIF - GML - XGMML -

    GraphML - BioPAX - PSI-MI - SBML - KGML (KEGG) - Excel - Delimited Text Table - CSV - Tab 47
  33. Network Import - Usually, imported from pre-formatted data file -

    Or, use Table Import feature to select columns to be used as edges
  34. Loading & Mapping Attributes - In most cases you need

    to import them from tables - e.g. Expression matrix saved as Excel workbook
  35. Load Table as a Network - Simple list of binary

    interactions can be loaded as networks - Source - Interaction Type - Target - Or, Source - Target
  36. ID Mapping - General (and old) problem in bioinformatics... -

    Tips - Use widely used, standard ID sets in your data files - Entrez Gene ID - Ensemble Gene ID - Use external application or Cytoscape App for mapping
  37. Lesson 2: Summary - Cytoscape supports many standard network data

    formats - Any table data can be imported to Cytoscape by Table Import function - Preparing your table data with widely-used ID is important for easy mapping
  38. Goal of This Section - Calculate network statistics by Network

    Analyzer - Filtering based on statistics - Basic search by EnhancedSearch Plugin - Try some more realistic example (requires faster machine!)
  39. Network Analyzer - Provides basic statistics of networks - Degree

    - Centrality - Shortest Pass Length Distribution - etc.
  40. Filtering by Network Statistics - NetworkAnalyzer provides all results as

    regular attributes - Can be used for filtering
  41. Optional: Shortest Path - Shortest Path Plugin v1.1 is required

    - Primitive, but still useful for pathway analysis
  42. Filtering Example - 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
  43. EnhancedSearch Query Syntax Cytoscape ESP: simple search of complex biological

    networks Maital Ashkenazi, Gary D. Bader, Allan Kuchinsky, Menachem Moshelion, David J. States Bioinformatics. 2008 June 15; 24(12): 1465–1466. Published online 2008 April 28. doi: 10.1093/bioinformatics/btn208 PMCID: PMC2427162
  44. Combination of Basic Commands - Search & Select First Neighbors

    - Use EnhancedSearch to locate set of nodes/edges you are interested in - Press CTR-6 to find first neighbors
  45. Scenario - You have a list of oncogenes - In

    addition, you have a list of known druggable targets - You want to visualize relationship between oncogenes and druggable targets
  46. Loading Human Interactome - BioGRID Release 3.2.97 - Human -

    Pre-filtered to remove cross-species interactions - Session file is available for download
  47. Import List Attributes - You need to specify delimiters to

    import list attributes correctly! - Select comma for this example
  48. Filtering by Browser - DO NOT CREATE VIEW YET! -

    It is not necessary for filtering - Select → Nodes → Select All Nodes OR CTR-A - Sort by Drug Target (Click Column Name) - Select all rows with non-empty Drug Target cells - Right click and select from table
  49. Attribute Batch Editor - Now sort by Group and select

    from table again - Now the selected nodes are druggable AND cancer genes. - Set values by Attribute Batch Editor. - Select Druggable genes again - Select rows with empty Group cells. These are druggable, non-cancer genes. - Group:* selects all
  50. Real World Problems - Data files are not always clean!

    - ID Mapping - Data cleansing - Scripting - Excel - Solution - Semantic Web?
  51. Lesson 4: Summary - Combination of browser and EnhancedSearch is

    very powerful - Create new attributes from your selection - Can be used for your visualization
  52. Don’t be Too Cool! - Cool visualizations are sometime useless

    for other scientists - e.g. 3D is network view is cool, but in most cases, it is useless - Balance coolness and meaningfulness
  53. I am NOT a Designer! - But still, you can

    improve your visualization by following some simple rules - Info-Graphics != Data Visualization - Art : Science - Infographics 6:4 - Scientific Visualization 2:8
  54. Jock Mackinlay. 1986. Automating the design of graphical presentations of

    relational information.ACM Trans. Graph. 5, 2 (April 1986), 110-141.
  55. Resources - Jock Mackinlay. 1986. Automating the design of graphical

    presentations of relational information.ACM Trans. Graph. 5, 2 (April 1986), 110-141.
  56. Tip 1: Don’t use too many colors - Simply awful

    - Hard to understand - Doesn’t tell anything!
  57. Automatic Layout - Choose proper algorithm - Tree-like data -

    Hierarchical Layout - Scale-Free Network - Force-directed - Circular process - Circular Layout - Tweak parameters if necessary
  58. Coloring - Relatively lower accuracy channel - but still very

    important in network visualization - Emphasize: - Changes, Differences, Importance
  59. Avoid Data Overload - Mapping too many attributes makes your

    image awful! - It is hard to see the overall trend if too many channels are used in a image
  60. Tiling Time-Series Data - Use same network, with same layout

    - Copy multiple instances of the network - Tile them and apply different Visual Styles
  61. Apps - Extending Cytoscape features - 140+ for version 2.x

    series - Lots of categories - (Almost) all of them are free, so just play with it to learn what’s possible
  62. 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
  63. Installing Apps - Easy - Just install from App manager.

    - For browsing, just visit App Store - http://apps.cytoscape.org/
  64. Advanced Topics - Cytoscape 3 - Differences - App Development

    - Collaboration with NRNB - Google Summer of Code
  65. A KPNA3 HRAS BUB1 EN FAM175A CDK8 ARIH1 CHGA ELAC2

    FBXW4 FGF11 EP400 UBA1 GTF2F1 HERC2 MLH1 GTF2E1 TRIM28 HSD17B1 TAF2G PLK1 AURKA BIRC5 NEK2 YRDC PLK3 RNF2 JUN DNAJA3 CDK1 CREBBP CCNA2 ORC2L ID4 CDC25C TRRAP NEK10 XRCC3 ACACA ORC3L C11orf30 GMNN C17orf70 CASP3 PGR CHGB 9606.ENSP00000358154 RNASEL RCHY1 UIMC1 CDK13 RARB FAM175B ERBB2 PMS2 STK11 SMAD3 TP53 FANCE FANCC CHD8 RAD17 WHSC2 MED13 HIST1H4A RNF53 CREB1 PSAP MAP2K1 RPA1 WWP1 ANTXR1 PALB2 BRCC3 PEG3 FBXL7 JUND AP2B1 FLI1 TOPBP1 ECHDC1 MSH2 FANCB TSPAN9 DCUN1D1 FBXO25 MED17 CDC25A PARP2 RNF31 ELK4 TOX3 ECT2 CDK4 PPP1CA SMARCB1 SMARCC2 FBXO11 HYRC GSTP1 SMC1A MED24 PIAS4 BATF MAD2L1 PIAS1 SUMO2 CNR1 MDM2 PMS1 RNF8 SUGT1 UBA52 ELK1 MELK UBB RBM LMO7 WT1 NBR1 PPP1R3A ERCC4 RBL1 ERCC1 XRCC5 MRE11A RNF144B ETS1 WRN NMI SHFM1 EZH2 ERCC2 TUBB2A MAP3K4 HIC1 PML DCAF11 CDKN1A APLP2 CDC45 TSPAN17 NUP153 EGFR FBXL3 CTCFL SMARCE1 GATA3 CHEK2 TOP3A EIF4G1 DDB1 PAX6 KRT14 PPT1 CDK16 SMARCD2 SMARCC DHFR TUBA4A IGF1R RNF168 BRCA1 PPM1D JUNB MED21 FANCA HMMR CDKN1B NUSAP1 RAD9A
  66. MED13 SMARCC1 EP300 MAP3K3 GFI1B NUFIP1 GTF2F1 ENSG00000234012 G5A EP400

    CBLL1 RAD51 CHGB ID4 WHSC2 FBXW4 BAP1 BRE CDK8 NCK1 8KDE69BZMi87N7sAF1369Ab14So-2 Q8NHQ3 Brca2 uBEqgVbNZFpKdFvwcyL6sloSw0g9606 GSTP1 Ncoa2 FANCL LDpqfKYgCfLDptQIUCIlr9Yfwb49606 UBB Dd2vI8mq8orSfrL52KvLX4sD/Ho-2 BRCA1 SMAD4 PPP1CA 2099 3725 2005 9972 10111 1487 9606.ENSP00000358154 3838 9412 9093 140690 4609 PAXIP1 JUN RNF2 CSTF2 GPR3 ENSG00000137337 MZT1 BMI1 VCP G5A MGF BARS RPB2 RBBP4 RIM PP-1A EWS-ATF1 JUND OSRC RCC JTK3 RBBP3 X2HRIP110 DKFZp686B04100 IPOA1 BRAP LMO4 CLSPN DHX9 RBBP7 E2F4 hRad50 HDAC2 MAP3K3 hSNF2a DBP AURKB HIST1H4L FA-H MLH1 BLM JAK2 LCFS2 HD1 LAT H2A/X WNT2B UBE2I UBE3A UbcM4 HSPA8 MRPL39 TRIP2 SP1 DKFZp686L20222 PEG3 DKFZp686N23123 DDIT1 SMARCA4 MDC1 DEF1 TRRAP hSNF2b BRCC1 NUP120 TERF2 PP1425 FIP p85-ALPHA CCNA MGC131997 XRCC3 SKP2 RSTS 6657 BRCA2 010204 000008035 6 6 FP00000007136 00000012830 SAP Cdk1 Ccnd1 Ercc1 Racgap1 Topbp1 Aspm RPA2 Immp2l FANCD1 Aurkb peptide-linker Birc5 HNRNPL efqpO06SDGYmzwbMpJ+t06UDlsY MPP-2 JXK67Oy2Ny+i96e1jAFkVJTCF50 DD2eG+gmXMcK4KCVbtT54i9U1xc9606 USF1 2lutkxFaFwUJS+5PatDg/qCXa/8 JsH9sHdvJhJOYXW58i3HjQWBu0E FANCD2 WDR16 +2eXiWJK61JwsRevyDVe+z6LKIg UBE2D1 NUP188 RPL31 MAP4K4 ABL1 MED17 TERF1 Q8IZU3 NUP2 C13orf15 dl6L440zevhf86Ba5SdPQ3cStkQ9606 ZNF350 HMG20B Bap1 PDS5B MED21 bAL7aWxtvUXKdB1zZ+HHMKM9FT89606 FLI1 ELK4 KIF1B MLP2 RPA1 MTA2 SMC3L1 CCR4 FYN MTA2 NEK1 XRCC9 ETS1 OQtyYL8HGbvuX0heZ5qCycS8zI8 kEU79P2/HWd7/1I2NJOLvFiSlBQ nDnqwbN+UgKzMvfaP0EIekAhiZQ Cyclin 02nZZfkeIi3mdZR6KqEjgW4gIO0 MAPK14 CCNE1 ERBB2 SMAD3 PGR XRCC3 HMMR PSMD14 ERCC1 PSMB3 NCOA2 MPP3 FLNA CAMKK1 E2F6 BRD7 FBXO8 FBXO10 FGFR2 MLH1 GADD45A RAD51AP1 PTEN SMAD1 HIC1 UBC RAD52 AURKB CBX1 MEN1 MAD1L1 JAK2 MDC1 SLC4A7 C11orf58 RASEF ACVR1B MAP2K4 TSSK3 OPTC PLEC LPHN3 PALLD BCCIP MLH3 XPA PHF21A SP1 ATRX NFKB1 CHEK1 MSH3 PMS2 RAD54B TP53 CHEK2 DEPDC1B FANCB PLK1 NBN BACH1 CDH1 RB1 ESR1 RAD50 FANCM MCPH1 DPH1 PARP1 HRAS MAP3K1 LIG3 ERCC4 STAT5A BLM 2962 207 SIAH3 RNASEL 7503 CCND1 BUB1B DMC1 Mad2l1 Fancc Rad51l1 Dmc1 SUMO1 Mgmt Ppp2r5b Bub1 Pten Bard1 Brca2 Cdca7 Trp53 Prdx2 Tcp1 Chek1 Fanca Rb1 1 qo2 Nfkb1 Slco4a1 Hmmr LSP1 NEK10 UBE2D3 ATM FANCI CCNA2 TP53BP1 AR FANCD2 H2AFX RPA2 PMS1 FHIT RAD51L3 PIK3CA LIG4 ELAC2 9448 XPC XRCC4 CDKN1A MSH6 SMAD4 RAD51C FANCA CDKN2A TIPARP BRCC3 SMAD2 AURKA INSC XRCC1 RAD51 TWSG1 PALB2 MRE11A BUB1 STK11 HYRC CDK1 C17orf70 UBA52 CYP17A1 641 C11orf30 MSH2 C19orf40 TOX3 FBXL7 WRN KLHDC8B 7321 ECHDC1 XRCC2 6597 10499 C5orf4 UIMC1 FAM175A 51720 59348 595 GATA3 FANCC XRCC6 FANCF XRCC5 Uba52 Men1 Pes1 Brca1 Nme2 Cdc45l Fam175a Twsg1 KPNA6 Fancm Sumo2 GCGR Terf2 DHX9 DNAH8 NEK2 Ezh1 Trp53bp1 ASPM Lmo4 853808 3717 PRDX2 SRD5A2 PPP2R5B CDCA7 COX11 3716 KIF4A NCOA3 HSD17B4 PSMD3 ZMYND11 RNF146 ZNF217 RBBP8 TOP2A TGFBR2 CSNK2B WDR16 ARL11 MND1 ZAR1L SERPINH1 ARIH1 CNTLN EZH1 851212 855055 CDKL4 RNF20 ASB9 DHX32 RAD23B USP11 PSMD6 GGNBP1 UBE2H UBE2L6 PRSS1 SKP2 SERAC1 DAPK1 BRAF RAD51L1 6599 9969 BRCA2 ECD BRCA1 6772 000024255 SCAFP00000026442 GALK1 9615.ENSCAFP00000023980 5.ENSCAFP00000028394 0028192 9615.ENSCAFP00000025953 9615.ENSCAFP00000035179 9615.ENSCAFP00000024343 BRCA1 9615.ENSCAFP00000030064 9615.ENSCAFP00000029451 POLR2A 9615.ENSCAFP00000030922 9615.ENSCAFP00000028763 Cks2 Obox3 Pik3ca 9615.ENSCAFP00000007566 Shfm1 9615.ENSCAFP00000006799 Tiparp Lphn3 9615.ENSCAFP00000027562 AFP00000023734 9615.ENSCAFP00000025994 9615.ENSCAFP00000028888 ADRA2B CCNA1 CREB1 CCNB1 TUBG MSH6 ATM MGC163290 3312 VCP 367 BRCC3 CDK4 BACH1 CSNK2A1 NCOA2 NMI 9555 PPP1CB POU2F1 HsT16930 ORC2 PDS5B CTCFL CCDC DNAJA3 Anti Zuai-1 FLNA VIM HMG20B PLK1 NCKalpha SMARCA2 EMSY HIST2H2AC SMARCC2 KAT2A SMAD3 PPP1CA RBL1 RBL2 UBA1 SMARCB1 AR H2AFY ACACA ABL1 SUB1 POLR2A MED23 GTF2H4 PRKDC NPM1 TOP2A MSH3 SMARCD2 CDK5 MED24 FANCD2 FHL2 ARNT CSTF2 CDKN2D TRP53 NF-kappaB FLJ12847 852199 ATR p150 853957 KPNA2 CDK8 851470 CCND1 SUMO1 853811 APLP2 HIST2H3A SRC MRPL36 6603 GTF2F1 MGC141879 Piasg SPT5 SPT4 DKFZp762J2115 oJw0JiiF0ME7x7eSGqUXn1ujDsg 79728 1020 OPD1 7415 898 UCpeqyqxh zU q6W0BO8vHuuZh PRM TzbYjLhQfYYis5ZHoOIz1MogPM CCNA2 CHEK2 ATDC DHX9 MYC AKT1 BRIP1 ZCCHC8 6601 2968 SSK1 PALB2 MGC45350 TOK1 S3 TP53 STAT5A DSS1 BARD1 CDK2 Ifi204 UQCC RFC1 NUP170 DHH1 FANCE ETS1 POM34 1019 USP1 RAD23A ROCK2 B3GALTL ZFHX3 TBX2 eKcZNhe4o3Sj9t+CWeVB2UBxvgk9606 9862 BRCC2 8202 9439 2Nu9AAWbBoSXW1y9FPjEO6691mU9606 CDK1 5981 983 BRCA1 KIAA0204 SGA-113M HHR23A RPA1 CDK16 Brca2 GTF2E1 ESR1 ASH RNF11 891 NUP153 SHFM1 NUP133 ASM4 KAT2B FANCG 1874 4800 CDC45 dJ199H16.1MGC149819 RAD21 6595 2175 HjbdLaovED6ZlK/153JO9Hsm86o FN+kJjmaxWZr/lWSN4mXugd0TPc 5GNzWn6eJ41h8viIYZEnxs7GUYI vDCqLkifRBymdYzE8Q8boNEF1ZY Vhaq0CUSlWCGivG2ObT5Xa7IB+E BUB1B p65 MCPH1 BCCIP FLNA CHK1 USP11 CCNE1
  67. What’s New in 3? - New Visualization features - Edge

    Bend, Background Images - Server-side applications - Headless Mode (in beta status) - More advanced visualization by new rendering engines - For developers: Cleaner API
  68. Data Model Differences - Cytoscape 2.8 - One network. All

    other networks are projections on that network. - Essentially a rooted tree - No way to duplicate nodes without sharing attributes - Cytoscape 3 - Allows multiple roots - Can have multiple trees - Each group of networks that shares a single root is called a collection
  69. Network 1 Network 2 SUID Shared Name Attr1 00001 Node

    1 00002 Node 2 00003 Node 3 00004 Node 4 Shared Node Table SUID Name Shared Name Attr1 Attr2 00001 Node 1 Node 1 00002 Node 2 Node 2 00004 Node 4 Node 4 Network 1 Local Node Table SUID Name Shared Name Attr1 Attr2 00001 Node 1 Node 1 00003 Node 3 Node 3 00004 Node 4 Node 4 Network 2 Local Node Table
  70. Upcoming Features - Official Release of Headless/Daemon Mode - Multiple

    Rendering Engine Support - Export session to cytoscape.js
  71. App Development - For new features, we recommend to implement

    for 3.x series - Two ways: - Simple App (Similar to 2.x development) - Bundle App (Essentially, an OSGi bundle)
  72. Google Summer of Code - Open-Source development opportunity for undergraduate

    / graduate students - Sponsored by Google - Students will be payed by Google - Please keep watching their web site - Application period for this year is mid April
  73. 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
  74. We Need Your Feedback - Cytoscape is an open platform

    developed by many research organizations - Improving user experience is an important TODO item! - Please send us your idea to improve UX
  75. 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
  76. 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 − Integration of biological networks and gene expression data using Cytoscape Cline, et al. Nature Protocols, 2, 2366-2382 (2007).
  77. Further Readings 3 - Cytoscape Tutorial Booklet: Analysis and Visualization

    of Biological Networks with Cytoscape - http://www.rbvi.ucsf.edu/Outreach/Workshops/ISMBTutorial.pdf