Gene module level analysis: identification to networks and dynamics

Abstract

Nature exhibits modular design in biological systems. Gene module level analysis is based on this module concept, aiming to understand biological network design and systems behavior in disease and development by emphasizing on modules of genes rather than individual genes. Module level analysis has been extensively applied in genome wide level analysis, exploring the organization of biological systems from identifying modules to reconstructing module networks and analyzing module dynamics. Such module level perspective provides a high level representation of the regulatory scenario and design of biological systems, promising to revolutionize our view of systems biology, genetic engineering as well as disease mechanisms and molecular medicine.

Figure 1. Schematic representation of gene-module level analysis, from module identification to module network and dynamics

The first level of analysis is module identification. The modules may be identified using different methods, including network-based, expression-based and pathway-based approaches. Based on these approaches, different types of modules may be obtained (as indicated in the box with dash line), including condense subnetworks, clusters of co-expressed genes and altered pathways. After identifying the modules, higher level of analysis including module network reconstruction and module dynamic analysis, may be performed on the modules. Module networks aim to represent the relationships between modules in network form; such networks have been constructed based on correlation between the expressions of the genes in the modules or physical interactions between the genes in the modules. Module dynamics aim to analyze and predict the temporal behavior of modules; dynamic models, such as state-space models, may be used for this purpose.

Figure 2. A representative network with 7 vertices (v1, v2, … v7) and 9 edges (e1, e2, … e9)

A path is a sequence of vertices and edges that start from one vertex and end at another vertex and passes through each vertex only once. An example of a path between vertices v4 and v1 is a sequence of v4, e3, e2, v1. However, this is not the only possible path between v4 and v1. Among the different possible paths between two vertices, vertex-independent paths do not share any vertices except the first and the last vertices, whereas edge-independent paths do not share any edges. For example, another path between v4 and v1 is a sequence of v4, e4, v1. Excluding the starting and ending vertices, this path does not share any edges or vertices with the previous path (v4, e3, e2, v1), therefore these two paths are both vertex and edge-independent. Note, all paths between v4 and v5 are both edge and vertex-dependent, because all paths have to pass through v1 and e1. Two different modules can be identified in this figure, with the first module consisting of v1, v2, v3, v4 and the second module consisting of v5, v6, v7. The first module contains 5 edges and the second module contains 3 edges, whereas there is only one edge between the modules. The figure was generated by using Cytoscape[100].