BiologicalNetworks Quick Start Guide
Quick Start Guide demonstrates how to:
- Run BiologicalNetworks, see Section 1.1, to 1.3
- Explore opened pathway, see Section 1.4
- Search the database, see Section 1.5, 1.6
- Explore curated pathways, see Section 1.7
- Build and edit pathways, see Sections from 1.8 to 1.12
- Manage groups, see Section 1.13
- Work with Microarray data, see Section 1.15
1.1 Java Web Start
Make sure that Java Web Start is installed on your computer. If BiologicalNetworks does not start, you may need to install last version of JAVA with Java Web Start inside.
The errors can occur if your computer does not meet hardware requirements available from Section 1.2.
1.2 Hardware Requirements
BiologicalNetworksis a Java Web Start and desktop application for visualization and analysis of biological pathways.
Recommended configuration:
Windows
1GHz Intel Pentium CPU
Microsoft Windows 95, 98, 2000 and XP
256MB RAM
50MB Free Disk Space
Linux
Linux 2.2.* Kernel on i686 processors
256MB RAM
50MB Free Disk Space
Macintosh
800MHz PowerPC G3 or G4
Mac OS X 10.1 and above
256MB RAM
50MB Free Disk Space
1.3 Launching BiologicalNetworks
To launch BiologicalNetworks begin by clicking WEB START version of the BiologicalNetworks (download size: ~20 MB; download time: depending on your internet connection ~2 minutes first download and ~20 seconds all subsequent runs). This starts BiologicalNetworks on your own computer, after downloading the program and annotation from our website. (On subsequent runs, the program or annotation will not be downloaded again unless we have new versions or new annotation for you to use.) If BiologicalNetworks does not start, you may need to install last version of JAVA with Java Web Start inside.
To exit BiologicalNetworks, save your data, then choose File>Exit menu.
BiologicalNetworks first appears on the screen with the Default Pathway Pane See Figure 1.3.1 and Project Panel.
Fig.1.3.1 Default Pathway
Project Panel shows the database and your project contents See Figure Project Panel 1.3.2
Fig.1.3.2 Project Panel
1.4 Exploring Opened Project/ Pathway
Node Properties.
To explore opened Project/Pathway:
Click on the node. On the right pane Node properties Pane shows details of the chosen bioentity. See Figure 1.4.1
Fig.1.4.1 Node Properties Panel
There are default, editable, expandable and reference fields on the Node Properties Pane.
Default fields: non editable fields for example GeneOntology annotation which are loaded with the data;
Editable fields: fields that could be edited or additional annotation could be added and saved either to local file or to database;
Expandable fields: fields that themselves have internal structure. See Figure 1.4.2
Fig.1.4.2 Example of expanded field: Localization.
On the top of Node Properties Panel there is the Expand all properties button which shows all information available for this bioentity. Figure 1.4.3
Fig.1.4.3 Expanded Node Properties.
Reference fields: fields that refer to Internet resource that have information about this bioentity. See Figure 1.4.4
Fig. 1.4.4 Example of reference field.
Interaction/Process/Reaction properties
Double click on the Process/Reaction node. The Process/Reaction properties Panel will appear. See Figure 1.4.5
Fig. 1.4.5 Interaction/Process Properties.
Interaction/Process/Reaction properties Panel is represented as tabbed panel with two tabs:
Process properties. See Figure1.4.5
Process Kinetics. See Figure 1.4.6
Fig. 1.4.6 Reaction/Process kinetics.
1.5 Quick Search
The Quick Search box is located at the top of the Project Pane. See Figure 1.5.1
Fig. 1.5.1 Quick search field.
Type your favorite gene name or keywords to search for all available information about it presented in our database.
Your search results will be listed in the List Pane. See Figure 1.5.2
Fig.1.5.2 List Pane: quick search results.
You can drag and drop rows from the List Pane to your active pathway, or save the search results as an individual group in the Groups/Clusters folder.
1.6 Querying database to explore gene relationships
You can Build a Pathway from selected group of bioentities. See Figure 1.6.1
Fig.1.6.1 List Pane context menu.
Choosing Build Pathway opens PathwayWizard Panel. See Figure 1.6.2
Check starting entities for your pathway, See Figure 1.6.3
Choose an algorithm for pathway building, See Figure 1.6.3
Fig.1.6.2 Build Pathway Wizard Window.
Pathway Wizard
PathwayWizard allows you to create pathways, using molecular interaction data from the database. It starts by suggesting several ways to determine starting entities, and then opens the Build Pathway dialog box. See Figure 1.6.3
Fig.1.6.3 Build Pathway Wizard Window.
The Pathway Wizard button is located on the toolbar of the Main window
Check the Filter option and set up the filter, if needed, See Figure 1.6.4.see (3)
Refer to the Tutorials to learn more about the BuildPathway Wizard
Fig.1.6.4 Build Pathway Filters Wizard.
Apply advanced attributes search to specify any logical combination of searched bioentities and bioprocesses properties. See Figure 1.6.5
Fig.1.6.5 Search by Attribute and Node type window.
Press the Start button to start data mining, and then click OK when done (4). The new pathway diagram appears in the Pathway Pane.
1.7 Exploring Curated Project/ Pathway
To explore a repository of our Curated Pathways:
Click Curated Pathways tap in the left panel of application window to bring up Curated Pathways tab pane on the left Project Frame. See Figure 1.7.1
Fig.1.7.1 Curated Pathways Pane.
The Curated Pathways tab pane has database tree panel.
Click the KEGG node to show available organisms in KEGG database.
After retrieving the data, 213 organism nodes are appeared. (Number of nodes may vary from this value.) See Figure 1.7.1
Double click one of the organism nodes to show the accompanying pathways. See Figure 1.7.2
Fig.1.7.2 Curated Pathways: Organisms, Pathways, Reactions, Metabolites.
Double click one of the pathways shows list of reaction nodes. See Figure 1.7.2
To load the pathways into the Pathway Panel simply drag a node and drop to the Pathway Panel window. See Figure 1.7.3
The loaded pathways containing reactions, compounds and their interactions are drawn in model workspace window.
To get nice positioning force-directed layout is used.
Fig.1.7.3 Drag and drop curated pathways into the Main Pathway Window.
1.8 Creating New Projects/ Pathways
To create a new Projects/Pathways :
Call the File > New>Project menu, or click on the Create New Pathway button. See Figure 1.8.1
Fig.1.8.1 Build New Pathway.
The Palette Pane opens, and an empty pathway appears in the Pathway Pane and in the Project Pane.
1.9 Loading existing Projects/ Pathways
To load existing Projects/ Pathways :
Call the File >Load> Project menu, or click on the Open Project button.
The Palette Pane opens, and pathway appears in the Pathway Pane and in the Project Pane.
1.10 Saving Projects/ Pathways
To save a Project/ Pathway , choose File > Save> Project;
To save pathway as a picture, choose Edit ; > Save Picture As;
To save pathway as HTML, choose Edit ; > Save Pathway as HTML.
1.11 Adding Entities and Relations to Pathways
To add entities to a pathway, drag and drop them from Palette Pane, or use the Quick Search option, see Section 1.5.
To add a relation, select the relation from the Palette Pane, and click on two entities that should be connected, one after another, or select
two entities and press the Connect Selected Entities button on the Toolbar. Refer to Figure 1.11.1
Fig.1.11.1 Edit pathway, add new bioentities and interactions/processes.
1.12 Viewing Pathways
Open the Public Pathways, or Curated Pathways folder in the Curated Pathways Pane;
The pathway diagram appears in the Pathway Pane;
Use the Zoom by Rectangle, or Magnifier option to zoom in on parts of the pathway;
Use Force-Directed or Hierarchical Layout option to layout the pathway by cell localization. Refer to the Tutorials to learn more about pathway editing.
1.13 Working with Functional Groups
You can create groups from your imported gene or protein lists, or from other objects, and highlight objects belonging to various groups on your pathway diagrams. You can work with grouped objects in the Project Properties Pane, as if they were a single object. Objects in a group cannot be selected individually, unless you open the group.
To create a functional group:
Select entities you would like to group together manually, or using tools from the Select menu;
Click the Create Group button on the Project Pane toolbar, or right click and choose Create Group from the popup menu;
The new group folder appears in the Project Pane. Right click on the new group, and choose Properties from the popup menu;
Specify the group name, properties, and highlight color in the Group/Clusters Properties dialog box;
To highlight items belonging to a group on an active pathway, right click on the group folder, and select the Highlight menu.
1.14 Complex Entities
You can also add or delete components from the following complex entities: Functional Class , Complex , and Pathway . To open any of these entities in the List Pane, right click on the entity, and choose the Open in Separate Window menu.
1.15 Working with Microarray Data
Before using Microarray data environment of BiologicalNetworks make sure you have Microarray qs/files to open.
Example data qs/files could be downloaded here:
Expression data are easily imported from Microarray submenu of BiologicalNetwroks main window. See Figure 1.15.1
Fig.1.15.1 Load Microarray Data.
Choosing one of the available file types will open one Import Expression Data Wizard:
See Figure 1.15.2
Fig.1.15.2 Load Stanford(tab delimited) data type file Wizard.
For other Microarray data type qs/files see Tutorials.
Loaded Microarray data appears on the Expression Experiment Viewer Panel on the bottom of BiologicalNetworks Main window.
See Figure 1.15.3
Fig.1.15.3 Microarray data file loaded.
Apply different clustering algorithms available from Microarray>Cluster Analysis> Clustering Algorithms>KMC
Clustering analysis results appear in the Project Properties Panel.
Functionalities available from Microarray submenu and Microarray Experiment Manager Menu bar, allows the user to:
- sort the experiment by a particular sample.
- Create new> pathways as well as new groups from an expression experiment.
- Select a number of genes and create a group or a pathway from them.
- Expression data can be visually displayed on an existing pathway diagram by showing different shades of green/red depending on the fold change of expression.
1.16 Color network by expression values.
To overlay Expression Experiment results onto an existing pathway diagram:
- Open an expression experiment;
- Open a pathway of interest;
- Press the Coloring by Expression Values Toolbar button to color the active pathway by expression values;
- From drop down menu choose the sample time point you would like to visualize on the active Pathway Pane
Fig.1.16.1 Color network by expression values.
1.17 Build Pathways for selected expression values
To create a new pathway from an expression experiment:
- Open the Expression Experiment and select the genes by clicking on them while holding the SHIFT key;
- Press the Build Pathway from Selected Genes button on the Microarray Toolbar;
- The Build Pathway dialog box appears;
- In the Build Pathway dialog box, choose the method for creating a pathway; See Chapter 6.3.4 of Tutorials to learn more on how to create a pathway from the list of genes.
- For example, it can be the Find All Nodes Connected to Selected Nodes or Expand Pathway algorithm.
- Set up the Filter options.
- Press the Start button to start building a pathway.
- The New Pathway appears in the Project Properties Pane and in the Graph View.
Fig.1.17.1 Build Pathways for selected expression values.
1.18 Extract pathways from expression data.
This functionality is based on the expression correlation (for ex. Pearson) algorithms and is available from Microarray Panel Toolbar.
Correlation algorithms group genes according to similarities in patterns of expression variation over all the samples. A correlation network is a group of genes whose expression proqs/files are highly predictive of one another. Each pair of genes related by a correlation coefficient larger than a minimum threshold and smaller than a maximum threshold (assigned in the initialization dialog box) is connected by an edge (predicted interaction node).
Parameters:Sample Selection
The sample selection option indicates whether to cluster genes or samples.
Use Permutation Test
This check box is used to indicate that the minimum threshold R2 value should be selected based on a distribution constructed from element to element R2 values derived following permutation of the expression vectors.
Min Threshold
This is minimal correlation which you want to include in your network.
Max Threshold
This is maximal correlation which you want to include in your network.
Use Filter
This option allows the user to filter out elements with little dynamic change thus removing flat or uninteresting elements.
Distance Metric: Pearson squared
Fig.1.18.1 Extract pathways from expression data.
There are numerous clustering, filtering, normalization, search methods available in BiologicalNetworks. For details refer to Tutorials.