Finding Functional Modules

Abstract

Biological systems can be modeled as complex network systems with many interactions between the components. These interactions give rise to the function and behavior of that system. For example, the protein–protein interaction (PPI) network is the physical basis of multiple cellular functions. One goal of emerging systems biology is to analyze very large complex biological networks such as protein–protein interaction networks, metabolic networks, and regulatory networks to identify functional modules and assign functions to certain components of the system. Network modules do not occur by chance, so identification of modules is likely to capture the biologically meaningful interactions in large-scale PPI data. Unfortunately, existing computer-based clustering methods developed to find those modules are either not so accurate or are too slow. We devised a new methodology called SCAN (Structural Clustering Algorithm for Networks) that can efficiently find clusters or functional modules in complex biological networks as well as hubs and outliers. More specifically, we demonstrated that we can find functional modules in complex networks and classify nodes into various roles based on their structures. In this chapter, we show the effectiveness of our methodology using the budding yeast (Saccharomyces cerevisiae) PPI network. To validate our clustering results, we compared our clusters with the known functions of each protein. Our predicted functional modules achieved very high purity comparing with state-of-the-art approaches. Additionally the theoretical and empirical analysis demonstrated a linear running time of the algorithm, which is the fastest approach for networks. We compare our algorithm with well-known modularity-based clustering algorithm CNM. We successfully detect functional groups that are annotated with putative Gene Ontology (GO) terms. Top-10 clusters with minimum p-value theoretically prove that newly proposed algorithm partitions network more accurately then CNM. Furthermore, manual interpretations of functional groups found by SCAN show superior performance over CNM.