1. August 2012 This work is licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. 1 KAM Navigator

2. KAM Navigator Overview KAM Navigator is a Cytoscape plugin which enables the exploration of large BEL Knowledge Assembly Models (KAMs) and creation of sub-networks 2

3. Contents Installation and Requirements Configuration Adding nodes to a network – By node function – From a list of identifiers – By finding neighbors of existing nodes Investigating KAM Node and Edge Properties 3

4. Installation and Requirements See wiki for more details: – https://github.com/OpenBEL/Cytoscape-Plugins/wiki https://github.com/OpenBEL/Cytoscape-Plugins/wiki Current version 0.9 Requirements – BEL Framework 2.0.0 or later – BEL Framework Server must be running – Cytoscape 2.8 – At least one KAM available in the KAM store Installation – Can use the plugin manager 4

5. Installation In Cytoscape, select Plugins -> Manage Plugins – The plugin manager window will be displayed Click the Settings tab at the top of the Window 5

6. Installation Click the Add button to add a new Plugins download site Add a name and URL, then click OK – https://raw.github.com/OpenBEL/Cytoscape- Plugins/master/plugins.xml https://raw.github.com/OpenBEL/Cytoscape- Plugins/master/plugins.xml 6

7. Installation Select the BEL Portal bookmark you just created and the available plugins will be shown Navigate through the Theme folder and select the desired version of KAM Navigator – Click Install – Click Close 7

8. Contents Installation and Requirements Configuration Adding nodes to a network – By node function – From a list of identifiers – By finding neighbors of existing nodes Investigating KAM Node and Edge Properties 8

9. Configuration The default WSDL URL (for locally installed BEL Framework) is: – http://localhost:8080/openbel-ws/belframework.wsdl http://localhost:8080/openbel-ws/belframework.wsdl – Make sure to start your server! OpenBEL demo server WSDL (use provided KAMs) – http://demo.openbel.org/openbel-ws/belframework.wsdl http://demo.openbel.org/openbel-ws/belframework.wsdl You may want to increase the timeout for working with larger KAMs 9

10. Contents Installation and Requirements Configuration Adding nodes to a network – By node function – From a list of identifiers – By finding neighbors of existing nodes Investigating KAM Node and Edge Properties 10

11. Adding Nodes to a Network – Getting Started First, open a new empty network – File -> New -> Network -> Empty Network Change Visual Style to "KAM Visualization" (optional) – From VizMapper tab in the Control Panel – The KAM Navigator comes with two specific Visual Styles 11

12. Adding Nodes to a Network - By Node Function Go to Plugins -> KAM Navigator -> Add KAM Nodes 12

13. Adding Nodes to a Network - By Node Function Select a KAM – Here "Large Corpus" is selected – If you have already added nodes to your network from one KAM, you will be limited to that KAM Select a Function Type – Here "PHOSPHATASE_ACTIVITY" is selected Click Search – All nodes in the selected KAM with the selected function will be returned 13

14. Adding Nodes to a Network - By Node Function To limit your results, type a text string in the Filter window – Here the PHOSPHATASE_ACTIVITY results have been filtered with the text string "RGD" – This returns all of the phosphatase activity nodes in the KAM that have labels using the RGD namespace for Rat Gene Symbols 14

15. Adding Nodes to a Network - By Node Function Select one or more KAM nodes – Here phos(p(RGD:Pten)) is selected Select from Expand Edge Options – None – adds only the selected node(s) – All Edges - adds all associated edges – Downstream Edges – adds all edges directed out – Upstream Edges – adds all edges directed in – Interconnect Nodes – adds any edges connecting the selected nodes Click Add 15

16. Adding Nodes to a Network - By Node Function Your nodes and edges will be added to the network Tip – Apply a layout to arrange your network – Here, the Apply force- directed layout button was used Note that the node you added by your search is selected (yellow) and its neighbors (other colors) are not © 2012, Open BEL Community16

17. Adding Nodes to a Network – From List You will need a text file containing a list of values from any namespace supported by your BEL Framework installation – E.g., Entrez Gene IDs, Affymetrix probe set IDs, human gene symbols Go to Plugins -> KAM Navigator -> Add KAM Nodes From List © 2012, Open BEL Community17

18. Adding Nodes to a Network – From List Select a KAM Select a Function Type Select the Namespace that contains the identifiers from your list Click Browse to load the file with your list Select Expand Edges option Click Search, then Add – All nodes found will be added © 2012, Open BEL Community18

19. Adding Nodes to a Network – From List In this example, a file with a list of Affymetrix Mouse Genome 430 2.0 probe set identifiers was selected – Selected RNA_ABUNDANCE as function type – 37 identifiers in the file map to 24 unique RNA abundance nodes in the selected KAM © 2012, Open BEL Community19

20. Adding Nodes to a Network – From List This network resulted from adding the selected RNA abundance nodes (yellow) and expanding to upstream edges © 2012, Open BEL Community20

21. Adding Nodes to a Network - By Finding Neighbors of Existing Nodes Once you have selected a KAM and added node(s) to your network you can select and add neighboring nodes and edges – First select one or more nodes – Move the cursor over any node and right-click – From KAM Node, select option for expanding the network – Options are similar to those for the Add KAM Nodes menus – Knowledge Neighborhood provides the most user control © 2012, Open BEL Community21

22. Adding Nodes to a Network - By Finding Neighbors of Existing Nodes Knowledge Neighborhood allow selection of – Direction of expansion – Source term function and/or label – Relationship – Target term function and/or label Select desired edges and click Add © 2012, Open BEL Community22

23. Contents Installation and Requirements Configuration Adding nodes to a network – By node function – From a list of identifiers – By finding neighbors of existing nodes Investigating KAM Node and Edge Properties 23

24. Investigating KAM Node and Edge Properties Go to View -> Show Results Panel Select a KAM Node – The terms for the selected node will appear in the KAM Node Info tab – Here, r(HGNC:DDIT3) represents the equivalent terms r(HGNC:DDIT3) and r(EG:1649) © 2012, Open BEL Community24

25. Investigating KAM Node and Edge Properties Select a KAM Edge – The statements for the selected edge will appear in the KAM Edge Info Tab Select a supporting BEL statement to see citation and other Annotation information © 2012, Open BEL Community25