Exercise 3: Pathway extension with drug target information - mkutmon/cytoscape-tutorials GitHub Wiki

Using the complement activation pathway, you will learn how pathways can be used as a resource for network biology. We will add drug-target information to see which drugs in the DrugBank database are known to target genes in the complement activation pathway. You can visualize the lung cancer dataset from exercise 2 on the pathway nodes for further interpretation.

Setup

  • Start Cytoscape or close the current session. Go to File → Close (if you want to save the currentsession, make sure you save the .cys file before)
  • Make sure the WikiPathways and CyTargetLinker apps are installed. Go to the app store (Apps > App Manager). Select the installed tab and check if WikiPathways and CyTargetLinker are installed.

Step 1: Open pathway

  • In the Network tab of the Control Panel at the top should be a text field with an icon at the left. Click on that icon and select WikiPathways. Search for "complement activation" (with quotes).
  • Select the human Complement Activation pathway (WP545) and import the pathway as a network.
  • A network with 39 nodes and 59 links is created.

Step 2: Extend network with drug-target interactions

  • Download the DrugBank linkset (v5.2.0). Remember in which folder you downloaded the file.
  • Go to "Apps → CyTargetLinker → Extend network"
  • Fill in the following settings (for the "Select Link Sets" browse to the folder in which you downloaded the DrugBank file).
  • Select to import only the DrugBank_v5.1.0.xgmml file.
  • The resulting network contains 65 nodes and 167 links. 26 drugs (purple) and 108 drug-target interactions were added.

Step 3: Improve visualization

  • By default, you only see the drug names. Go the Styles tab, and change the Label mapping column from "CTL.label" to "name". Then you will see the drug and gene names.
  • Let's add the lung cancer gene expression from exercise 2 and visualize the log2FC on the gene nodes.
  • Import expression data. First, we need to import the expression data for the new pathway network. Similar to the initial import, start by doing File → Import → Table from File. Select the lung-cancer-data-complete.xlsx file which contains also not significant genes. Make sure you select the correct Network collection which contains the extended network (Complement Activation - Homo sapiens_1). Change the Key Column for Network to Ensembl. Now select OK.
  • The new columns with the data will be added to the Node Table.
  • Create color gradient for expression data. To show the expression data, go the Style tab of the Control Panel and click on the middle square (Map.) of the three Fill Color controls. Set the Column to "log2FC" and set the Mapping Type to "Continuous Mapping". Double-click on the gradient to show the Continuous Mapping Editor. The default gradient is a Blue/Red color gradient, with blue representing underexpressed genes and red representing overexpressed genes.
  • To still see which nodes are drug nodes, create a mapping for the Shape attribute. Select the CTL.Type column and select a Discrete Mapping Type. Double click on the column next to drug and change the shape to a diamond shape.

Step 7: Examine the network.

  • Are the genes in the complement activation pathway up- or down-regulated?
  • Are there genes targeted by many drugs?
  • You can copy the DrugBank identifier of a drug and go to the DrugBank website to find more information about the drug.