1 Version Information

R version: 4.0.2

Bioconductor version: 3.12

Cytoscape: 3.8.1

Cy3D (Cytoscape app): 1.1.3 (1.1.2 or later is required)

KEGGscape (Cytoscape app): 0.9.0

2 Introduction

Visualization of trans-omic networks helps biological interpretation by illustrating pathways where the signals are transmitted (Gehlenborg et al., 2010).

To characterize signals that go across multiple omic layers, Yugi and colleagues have proposed a method for network visualization (Yugi et al., 2014) by stacking multiple 2D pathways in a 3D space.

The 3D network visualization was realized by VANTED (Rohn et al., 2012). However, the visualization relies on time-consuming manual operation. Here we propose transomics2cytoscape, an R package that automatically creates 3D network visualization in combination with Cytoscape (Shannon, 2003), Cy3D App, and Cytoscape Automation (Otasek et al., 2019).

2.1 Installation

This package requires Cytoscape to be installed and you need to run Cytoscape before running the following R code.


3 Workflow

There is a function create3Dnetwork in transomics2cytoscape. In the create3Dnetwork, the following workflow is executed.



create3Dnetwork has 4 arguments.

The 1st one is a directory path where you put the network files to be layered in 3D space. The 2nd one is a file path of TSV for the Z-axis layout of the network files. The 3rd one is a file path of TSV used to create the edges between the network layers. The last one is a file path of XML used to style Cytoscape.

3.1 Input files

3.1.1 1. (Any number of) network files to be layered in 3D space

Files that Cytoscape can import. You need to put these files in the directory of the 1st argument of create3Dnetwork. You don’t need to put files for the KEGG pathway.

3.1.2 2. A TSV file for the Z-axis layout of the network files

A file that defines network layer index and the Z-height of the network in 3D space. The format is as follows.

layer1  rno04910    600
layer2  galFiltered.sif 400
layer3  rno00010    200
layer4  rno00010    1

The 1st column is the network layer index. This information is added to the node table column LAYER_INDEX. The 2nd column is the KEGG pathway ID or the network file name in the directory of the 1st argument of create3Dnetwork. You don’t need to prepare a network file for the KEGG pathway. You can import the KEGG pathway simply by writing the KEGG pathway ID. The last column is the Z-height of the network.

3.1.3 3. A TSV file of trans-omic network edges between the network layers

A file that defines trans-omic interactions (i.e., the edges that connect the different network layers). The format is as follows.

layer1  rno:84006   layer2  YMR300C transomicsType1
layer2  YMR300C layer3  rno:100364062   transomicsType2
layer3  rno:100364062   layer4  rno:100364062   transomicsType3

The 1st and 2nd columns are the information about source node of the trans-omic interaction. The 3rd and 4th columns are about the target node. The 1st and 3rd columns are the network layer index. The 2nd and 4th columns are the name or KEGG object ID that the node should have. The last column is the type of the trans-omic interaction. This information is added to the interaction column of the edge table.

3.1.4 4. A style file of Cytoscape

A Cytoscape style file. For more information about Cytoscape style file, see the Cytoscape user manual. Note that you can only use style properties that are supported by Cy3D.

3.2 Example

# suppressPackageStartupMessages(library(dplyr))
# suppressPackageStartupMessages(library(RCy3))
# suppressPackageStartupMessages(library(KEGGREST))
# Sys.setenv(LANGUAGE="en_US.UTF-8") 
networkDataDir <- tempfile(); dir.create(networkDataDir)
sif <- system.file("extdata","galFiltered.sif",package="RCy3")
file.copy(sif, networkDataDir)
networkLayers <- system.file("extdata", "networkLayers.tsv",
    package = "transomics2cytoscape")
transomicEdges <- system.file("extdata", "transomicEdges.tsv",
    package = "transomics2cytoscape")
stylexml <- system.file("extdata", "transomics.xml",
    package = "transomics2cytoscape")
create3Dnetwork(networkDataDir, networkLayers, transomicEdges, stylexml)

Then, you should have a 3D view with layered networks and transomic interactions between them. (Note that you need to perform operations such as zooming out or adjusting the camera angle.)