1. Copyright OpenHelix. No use or reproduction without express written consent1

2. BiologicalNetworks Materials prepared by: Cynthia Foote, Ph.D. www.openhelix.com Updated: Q1 2009 Copyright © 2009 The Regents of the University of California. All Rights Reserved. Used by permission. Version 1.0_0109

3. Copyright OpenHelix. No use or reproduction without express written consent3 BiologicalNetworks Agenda Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php

4. Copyright OpenHelix. No use or reproduction without express written consent4 BiologicalNetworks Introduction Vizualize and analyze complex protein interaction networks Built on PathSys Database Many integrated analysis tools, including for microarray data! Complex Protein Interaction Network

5. Copyright OpenHelix. No use or reproduction without express written consent5 PathSys Introduction BiologicalNetworks: built on PathSys, a scalable warehousing database system http://biologicalnetworks.net/PathSys/index.php Representative Species Data Sources

6. Copyright OpenHelix. No use or reproduction without express written consent6 PathSys Data Model Three types of nodes: primary, connector and graph Powerful data model allowing concepts such as biological objects, molecular states, and interaction types Allows PSI-MI, BioPAX and SBML data formats for input Primary Node (physical): Macromolecules (DNA, proteins), Small molecules (ions, ATP), and Physical events (radiation, heat) Connector Node: Shows the relationship properties between Nodes (binding, chemical reaction, and expression interactions) Graph Node: represents all complex objects (protein complexes, cellular processes) that might contain graphs

7. Copyright OpenHelix. No use or reproduction without express written consent7 BiologicalNetworks Homepage Introduction Main Tool Bar Click here to download BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php List of Publications and Posters Documentation

8. Copyright OpenHelix. No use or reproduction without express written consent8 BiologicalNetworks Homepage, Tabs BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Home Software, PathSys, Projects – background information Influenza DB, Internal – currently no public access Screenshots, Tutorials, FAQ – documentation Bug Report – contact link to send comments

9. Copyright OpenHelix. No use or reproduction without express written consent9 Credits BiologicalNetworks and PathSys database developed by: San Diego SuperComputer Center Keck Graduate Institute Funded by grants from the National Science Foundation, National Institutes of Health and the National Biomedical Computational Resource Amarnath Gupta Michael Baitaluk Xufei Qian Mayya Sedova Animesh Ray Alpan Raval Shubhada Godbole

10. Copyright OpenHelix. No use or reproduction without express written consent10 Publications and Citations http://nar.oxfordjournals.org/cgi/screenpdf/34/suppl_2/W466 http://www.biomedcentral.com/content/pdf/1471-2105-7-55.pdf

11. Copyright OpenHelix. No use or reproduction without express written consent11 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

12. Copyright OpenHelix. No use or reproduction without express written consent12 Accessing Graphical User Interface Download as a Java Start web-based application: Must install latest version of Java with Java Webstart (http://www.java.com/en/)http://www.java.com/en/ Hardware Requirements: Manual Start Problems? Click here to start

13. Copyright OpenHelix. No use or reproduction without express written consent13 Graphical User Interface Introduction Node Properties Main tool bar Tabs for Project Pane Search Results Description Window Pathway Navigation Search Input Project Properties

14. Copyright OpenHelix. No use or reproduction without express written consent14 Main Menu and Tool Bar File: Open, Load, or Save a Project Select: From file, By Name, or From database Layout: Select Data Layout Algorithm to arrange network Visualization: access options for visualizing biological data

15. Copyright OpenHelix. No use or reproduction without express written consent15 Main Menu and Tool Bar, cont. Analysis: Find cycles…Finds independent cycles in the network Statistics…… Window with pathway statistics Network Blast…. Finds conserved pathways among different networks

16. Copyright OpenHelix. No use or reproduction without express written consent16 Main Menu and Tool Bar, cont. Microarray: Main menu for Microarray analysis Tools: access Directed Acyclic Graph Engine and Querying Language GUI Window: Arrange pathway windows to cascade, tile vertically or horizontally

17. Copyright OpenHelix. No use or reproduction without express written consent17 Main Menu and Tool Bar, Icons - Load Graph - Save Graph - Pick - Transform - Zoom Out or In - Zoom In on a Region - Display All - GO Analysis - Build Pathways - Magnify - 3D

18. Copyright OpenHelix. No use or reproduction without express written consent18 Project Pane Define Properties here Choose Organism Project Folders Tabs Click here

19. Copyright OpenHelix. No use or reproduction without express written consent19 Search Input and Results List Pane Input Search parameters here Results displayed as a list with name, type and description

20. Copyright OpenHelix. No use or reproduction without express written consent20 Pathway Navigation Pane Click here Full Node Description Pathway Navigation Pane Node Attributes

21. Copyright OpenHelix. No use or reproduction without express written consent21 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

22. Copyright OpenHelix. No use or reproduction without express written consent22 Curated Pathways Tab View pathways curated by KEGG Pathway Database Click here

23. Copyright OpenHelix. No use or reproduction without express written consent23 KEGG Pathways Click here to view list of organisms Click here to view list of Human pathways Click here to view

24. Copyright OpenHelix. No use or reproduction without express written consent24 Open New Project Click and Drag Pathway into new window Select Click and drag Select

25. Copyright OpenHelix. No use or reproduction without express written consent25 View Pathway

26. Copyright OpenHelix. No use or reproduction without express written consent26 Pathway Navigation Full Description Node Properties Information Box

27. Copyright OpenHelix. No use or reproduction without express written consent27 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

28. Copyright OpenHelix. No use or reproduction without express written consent28 Pathway Introduction Load pathway from database or SBML files (.bnm) Manually create new pathway/model Open New Project Window Click open “Palette”

29. Copyright OpenHelix. No use or reproduction without express written consent29 Palette Pane Contains nodes and control types and their graphical representation Shape and color of the node describes the property value Contains representations for different interaction types (Connector Nodes) Buttons to specify Interaction Type Buttons to define Pathway parts Buttons to create Primary Nodes

30. Copyright OpenHelix. No use or reproduction without express written consent30 Create a Node Click here Add ID and Name, other properties Vim Click Add a new node, then add properties to the node.

31. Copyright OpenHelix. No use or reproduction without express written consent31 Create Connector Node Select Click Drag

32. Copyright OpenHelix. No use or reproduction without express written consent32 Process Properties Define Attributes of Process Add Reference Details Copy And Paste Abstract Reactant and Product details Select tab to add Kinetics Add Experimental Evidence

33. Copyright OpenHelix. No use or reproduction without express written consent33 Process Kinetics Only Mass action rate law supported in this version of software Menu of Kinetic Methods Input Rate Constants

34. Copyright OpenHelix. No use or reproduction without express written consent34 Save File Select.bnm format to save file Click here to Save Pathway Simple Interaction Network File name: “vimentin.bnm”

35. Copyright OpenHelix. No use or reproduction without express written consent35 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

36. Copyright OpenHelix. No use or reproduction without express written consent36 Microarray Menu Example data files can be downloaded at: http://BiologicalNetworks.net/MicroarrayData.zip http://BiologicalNetworks.net/MicroarrayData.zip

37. Copyright OpenHelix. No use or reproduction without express written consent37 Stanford File Wizard Select File to Load Select Upper Leftmost Expression Value Select Load Data

38. Copyright OpenHelix. No use or reproduction without express written consent38 Expression Experiment Viewer Panel Expression Experiment Viewer

39. Copyright OpenHelix. No use or reproduction without express written consent39 Expression Experiment Viewer Panel, details Designed to display a graphical representation of gene expression data Expression Image Table Expression Graphs Image Data Time

40. Copyright OpenHelix. No use or reproduction without express written consent40 Expression Experiment Viewer Panel, icons Tool bar allows quick access to functions and algorithms -Open data -Save data -Zoom in or out -Set size -Color nodes-Extract networks-Search-Sort-Expression filter -Data transformation -GO analysis -Build pathways

41. Copyright OpenHelix. No use or reproduction without express written consent41 Gene Expression Graph Each row is a gene View expression levels across all time points

42. Copyright OpenHelix. No use or reproduction without express written consent42 Build Pathway Select multiple genes by holding Shift key Select Build Pathway icon in tool bar To expand Window, click up arrow Click here

43. Copyright OpenHelix. No use or reproduction without express written consent43 Pathway Wizard Click here

44. Copyright OpenHelix. No use or reproduction without express written consent44 Expression Pathway Results Interaction pathway from selected expression data

45. Copyright OpenHelix. No use or reproduction without express written consent45 Color Nodes by Expression Values Click on Color Nodes icon and choose time point Node colors will change to match expression level Click On Color Nodes Icon Choose Time Point Node Color Matches Expression

46. Copyright OpenHelix. No use or reproduction without express written consent46 Gene Ontology Analysis Select GO analysis Click here to add files Click here to start Added GO files shown here

47. Copyright OpenHelix. No use or reproduction without express written consent47 GO Analysis Results IndexFileTerm Pop. Hits Pop. Size

48. Copyright OpenHelix. No use or reproduction without express written consent48 GO Analysis Menu

49. Copyright OpenHelix. No use or reproduction without express written consent49 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

50. Copyright OpenHelix. No use or reproduction without express written consent50 BiologicalNetworks Node Properties Main tool bar Search input Project Pane Tabs for Project Pane Search Results Pane Description Window Pathway Navigation Pane

51. Copyright OpenHelix. No use or reproduction without express written consent51 Build Pathways Palette Pane Pathway window Node Properties Process Properties

52. Copyright OpenHelix. No use or reproduction without express written consent52 Visualize Microarray Data Expression Image Build Pathway

53. Copyright OpenHelix. No use or reproduction without express written consent53 BiologicalNetworks Summary More PathSys Info. Poster Presentations Tutorial Section

54. Copyright OpenHelix. No use or reproduction without express written consent54 BiologicalNetworks Agenda BiologicalNetworks: http://biologicalnetworks.net/index.phphttp://biologicalnetworks.net/index.php Introduction and Credits Graphical User Interface Exploring Curated Pathways Create New Pathways/Models Load and Visualize Microarray Data Summary Exercises

55. Copyright OpenHelix. No use or reproduction without express written consent55