Tutorial session 1 Network generation Exploring PPI networks using Cytoscape EMBO Practical Course Session 8 Nadezhda Doncheva and Piet Molenaar

Overview  Focus: Network generation  Importing pre-formatted networks  Generating new networks  Visualizing networks  Saving and exporting network data  Concepts  Layouts  Data  Drosophila protein network 11/24/20152

Let’s start: GUI basics (Demo) 11/24/20153

Loading networks  Import pre-formatted networks  SIF  GML, XGMML  BioPAX  PSI-MI 1 & 2.5  SBML Level 2  Import your own data from a table  Excel file  Delimited text (tab, comma, etc…) 11/24/20154

Loading networks (Demo) 11/24/20155

Layouts  Many algorithms available through plugins  Simple: grid, not very informative  Hierarchical: layout data as a tree or hierarchy (works best when there are no loops)  Circular (Radial): arrange nodes around a circle, could use node attributes to govern position, e.g. degree sorted  Force-Directed: simulate edges as springs (nodes repel and edges pull), good for up to 500 nodes  Multi-layer layouts: partition graph, layout each partition and then layout partitions  … 11/24/20156

Layouts (Demo) 11/24/20157

Tips & Tricks: Layouts  Use layouts to convey the relationships between the nodes  Layout algorithms may need to be ”tuned” to fit your network (Layouts  Settings... menu)  Consider laying out portions of your network  Adjust the layout manually  Load network into a drawing program (e.g. Illustrator) and adjust labels 11/24/20158

Use case: Drosophila Protein network  Although from fly, serves as model for human  Groundbreaking work now done in model systems  What did they do  Bait-Protein interactions  Statistical analysis; highly confident set 11/24/20159

Use case: Assignment Open the DrosophilaBasicSession.cys file 2. Test several layouts; which one is informative? Free-Format Table Files Layout Algorithms 11/24/201510

Assignment 1.1 results 1. Creating the network 2. Testing layouts: take the edge weight in consideration; best bet: edge weighted spring embedded 11/24/201511

Generating networks  Import network from web services supported by Cytoscape  Pathway commons (only well-studied organisms)  PSICQUIC Universal Client (collection of many public databases)  MiMI (Michigan Molecular Interactions database)  BisoGenet (SysBiomics database)  Generate a network using a Cytoscape plugin  AgilentLiteratureSearch (based on text mining) 11/24/201512

Generating networks (Demo) 11/24/201513

Use case; Assignment Try to locate the protein complexes found in the article in the network 2. Lookup existing interactions for one of the MCM genes in the PathwayCommons webservice #3: Retrieving Pathways and Networks from Pathway Commons 11/24/201514

Assignment 1.2 results 1. Look for the denser regions 11/24/201515

Assignment 1.2 results 1. Look for the denser regions 2. PathwayCommons: Reactome interactions: 2 Complexes 11/24/201516

Tips & Tricks: Network view  When you open a large network, you will not get a view by default  To improve interactive performance, Cytoscape has the concept of ”Levels of Detail”  Some visual attributes will only be apparent when you zoom in  The level of detail for various attributes can be changed in the preferences  To see what things will look like at full detail: go to View  Show Graphics Details 11/24/201517

Exporting & saving data  Sessions save pretty much everything: Networks, Properties, Visual styles, Screen sizes  Export networks in different formats: SIF, GML, XGMML, BioPAX, PSI-MI 1 & 2.5  Publication quality graphics in several formats: PDF, EPS, SVG, PNG, JPEG, and BMP  Export Session to HTML for Web (SessionForWeb plugin) 11/24/201518

Exporting & saving data (Demo) 11/24/201519

Tips & Tricks: Memory  Cytoscape uses lots of it  Doesn’t like to let go of it  An occasional restart when working with large networks is a good thing  Destroy views when you don’t need them  Java does not provide a good way to get the memory right at start time  Cytoscape 2.7 and later releases do a much better job at ”guessing” good default memory sizes than previous versions  Increase Cytoscape’s default memory size: y_for_Cytoscape 11/24/201520

Tips & Tricks: General  By default, Cytoscape writes it’s logs to the Error Dialog: Help  Error Dialog  Change the ”logger.console” preference in Edit  Preferences  Properties... to write it to the console .cytoscape directory  Your defaults and any plugins downloaded from the plugin manager will go here  Sometimes, if things get really messed up, deleting (or renaming) this directory can give you a ”clean slate”  Plugin manager  ”Outdated” doesn’t necessarily mean ”won’t work”  Plugin authors don’t always update their plugins immediately after new releases  Open source; sometimes bugs occur! 11/24/201521

Use case: Assignment Export the network view as figure 2. Find out in which format you’d best save your network 3. Save your session for later use Network File Formats 11/24/201522

Assignment 1.3 results 1. Exporting figures 1. Mind the settings 2. Achieve high resolution by toying with zoom and dpi 2. Best export format 1. usually *.xgmml: maintains most (or even better; whole session) 2. For use in other tools; attribute files can be easily converted to tab separated 3. Also the data attributes panel can be used to exported as table 3. Saving sessions is always a good plan! 1. Avoids cluttering of attributes 11/24/201523

Cytoscape extended functionality 11/24/  Cytoscape extends its functionality with plugins  Developed by third parties  Listed at  Usually available through the Plugin Manager  Can be downloaded from the plugins’s websites  Cover many diverse areas of application

Cytoscape Plugin Manager (Demo) 11/24/201525

Use case: Assignment Explore available plugins for PPi relevance and the Plugin Manager 11/24/201526

Assignment 1.4 results  Use the app store via cytoscape.org  Interaction databases  Genemania, Bisogenet, Mimi, Cpath  Structural information  StructureViz,  Note: not all apps/plugins available through the plugin manager; exploring PubMed using Cytoscape citation will reveal more… 11/24/201527

To be continued…  Build, visualize and analyze your own network with Cytoscape  Network generation  Network annotation and visualization  Loading and manipulating attributes  Identifier mapping  Mapping data onto the network  Use visuals to convey data  Network analysis 11/24/201528