Algorithmic and Artificial Intelligence Methods for Protein Bioinformatics

Chapter 20

Protein Functional Module Analysis With Protein–Protein Interaction (PPI) Networks

LEI SHI, XIUJUAN LEI, and AIDONG ZHANG

The inherent, dynamic, and structural behaviors of complex biological networks in a topological perspective have been widely studied. These studies have attempted to discover hidden functional knowledge on a system level since biological networks provide insights into the underlying mechanisms of biological processes and molecular functions. A functional modules can be identified from biological networks as a subnetwork whose components are highly associated with each other through links. Conventional graph-theoretic algorithms had a limitation on accuracy of functional modules detection because of complex connectivity and overlapping modules. Whereas partition-based or hierarchical clustering methods produce pairwise disjoint clusters, density-based clustering methods that search densely connected subnetworks are able to generate overlapping clusters. However, they are not applicable to identifying functional modules from a biological network that is generally sparse. A more recently proposed functional influence-based approach effectively handles the complex but sparse biological networks, generating large overlapping modules. A better understanding of higher-order organizations in biological networks reveals functional behaviors of molecular components, and can be utilized in practical biomedical applications, such as drug development and disease ...