Support for Modules in Cytoscape

Introduction

In many cases, biologists are interested in relationship between functional modules first. Then, they look into the details inside the modules, i.e., actual interactions. Cytoscape can partially handle this problem using Group API and some related plugins, but it's not a standard feature. Also, there is no simple file format to represent hierarchy/substructures. In this project, we are going to implement a mechanism to handle output of module finding algorithms as a hierarchy of subnetworks and make Cytoscape core module-aware.

Usecases

Module Finding Plugins

Currently, there are several plugins finding functional modules from large networks. In some cases, they produce subnetworks, but there is no universal UI or function to keep the structure in the session or other files.

Pathway Overview

Cytoscape has function to import KEGG/Reactome data as attributes. It is useful if Cytoscape has a function to generate substructure automatically based on such annotation.

Implementation

File Formats

Most of popular XML graph file formats support hierarchical structure.

DOT

This is a standard file format in graphviz. It has XML-like structure in the text file, and can represent substructure.

Pajek

This program has 3 types of files to represent substructure:

• Partitions – they tell for each vertex to which class vertex belong. Default extension: .clu.
• Clusters – subset of vertices (e.g. one class from partition). Default extension: .cls.
• Hierarchies – hierarchically ordered vertices. Default extension: .hie.

Therefore, user needs to load 4 files (network, partition, cluster, hierarchy) to reconstruct the saved substructures.

igraph

This package does not have its own file format to represents subgraph. Instead, supporting GraphML and dot.

Cytoscape New File Format for Subgraphs

Standard XML file formats such as GraphML or XGMML can represent substructures. However, they are not easy to edit by hand for many biologists. We need to implement a simple table/text style file format which is editable on spreadsheet programs.

Sample

• Network Overview

• Modules (A ~ D)

Option 1: Two Files

This approach needs two files, standard SIF file and subnetwork definition file (SDF?). This is similar to pajek, but less number of files are required to rebuild the substructures and hierarchies.

SIF

We need to introduce two types of special value for interaction edge attributes:

• child_of - Defines inclusion.
• interact_with

The sample graph above can be represented in the following:

node7   DirectedEdge    node3
node6   DirectedEdge    node2
node5   DirectedEdge    node4
node4   DirectedEdge    node2
node4   DirectedEdge    node3
node1   DirectedEdge    node2
node1   DirectedEdge    node0
node0   DirectedEdge    node6
node0   DirectedEdge    node2
moduleA child_of        moduleB
moduleD         interact_with   moduleB
moduleD         interact_with   moduleC

If parser finds these two keywords in interaction edge attribute, treat it as a module relationship definition.

SDF

This file defines members of each subnetwork.

subnet1 a b c
subnet2 a d
subnet3 c e f

Based on the information above, Cytoscape can rebuild the module relation map:

Option 2: One File (extended SFI?)

(Not finished yet)

Option 3: Simply Support DOT

As far as I know, DOT is the most complete solution for non-XML file format for representing modules. If we support this format, we can use it to represent

User Interface