Module Identification for Biological Networks

Advances in high-throughput techniques have enabled researchers to produce large-scale data on molecular interactions. Systematic analysis of these large-scale interactome datasets based on their graph representations has the potential to yield a better understanding of the functional organization of the corresponding biological systems. One way to chart out the underlying cellular functional organization is to identify functional modules in these biological networks. However, there are several challenges of module identification for biological networks. First, different from social and computer networks, molecules work together with different interaction patterns; groups of molecules working together may have different sizes. Second, the degrees of nodes in biological networks obey the power-law distribution, which indicates that there exist many nodes with very low degrees and few nodes with high degrees. Third, molecular interaction data contain a large number of false positives and false negatives. In this dissertation, we propose computational algorithms to overcome those challenges. To identify functional modules based on interaction patterns, we develop efficient algorithms based on the concept of block modeling. We propose a subgradient Frank-Wolfe algorithm with path generation method to identify functional modules and recognize the functional organization of biological networks. Additionally, inspired by random walk on networks, we propose a novel two-hop random walk strategy to detect fine-size functional modules based on interaction patterns. To overcome the degree heterogeneity problem, we propose an algorithm to identify functional modules with the topological structure that is well separated from the rest of the network as well as densely connected. In order to minimize the impact of the existence of noisy interactions in biological networks, we propose methods to detect conserved functional modules for multiple biological networks by integrating the topological and orthology information across different biological networks. For every algorithm we developed, we compare each of them with the state-of-the-art algorithms on several biological networks. The comparison results on the known gold standard biological function annotations show that our methods can enhance the accuracy of predicting protein complexes and protein functions