ComClus: A Self-Grouping Framework for Multi-Network Clustering.

Joint clustering of multiple networks has been shown to be more accurate than performing clustering on individual networks separately. This is because multi-network clustering algorithms typically assume there is a common clustering structure shared by all networks, and different networks can provide compatible and complementary information for uncovering this underlying clustering structure. However, this assumption is too strict to hold in many emerging applications, where multiple networks usually have diverse data distributions. More popularly, the networks in consideration belong to different underlying groups. Only networks in the same underlying group share similar clustering structures. Better clustering performance can be achieved by considering such groups differently. As a result, an ideal method should be able to automatically detect network groups so that networks in the same group share a common clustering structure. To address this problem, we propose a new method, ComClus, to simultaneously group and cluster multiple networks. ComClus is novel in combining the clustering approach of non-negative matrix factorization (NMF) and the feature subspace learning approach of metric learning. Specifically, it treats node clusters as features of networks and learns proper subspaces from such features to differentiate different network groups. During the learning process, the two procedures of network grouping and clustering are coupled and mutually enhanced. Moreover, ComClus can effectively leverage prior knowledge on how to group networks such that network grouping can be conducted in a semi-supervised manner. This will enable users to guide the grouping process using domain knowledge so that network clustering accuracy can be further boosted. Extensive experimental evaluations on a variety of synthetic and real datasets demonstrate the effectiveness and scalability of the proposed method.

Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model.

BACKGROUND: Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although successful, a common limitation of the existing methods is that they assume all diseases share the same molecular network and a single generic molecular network is used to predict candidate genes for all diseases. However, different diseases tend to manifest in different tissues, and the molecular networks in different tissues are usually different. An ideal method should be able to incorporate tissue-specific molecular networks for different diseases. RESULTS: In this paper, we develop a robust and flexible method to integrate tissue-specific molecular networks for disease gene prioritization. Our method allows each disease to have its own tissue-specific network(s). We formulate the problem of candidate gene prioritization as an optimization problem based on network propagation. When there are multiple tissue-specific networks available for a disease, our method can automatically infer the relative importance of each tissue-specific network. Thus it is robust to the noisy and incomplete network data. To solve the optimization problem, we develop fast algorithms which have linear time complexities in the number of nodes in the molecular networks. We also provide rigorous theoretical foundations for our algorithms in terms of their optimality and convergence properties. Extensive experimental results show that our method can significantly improve the accuracy of candidate gene prioritization compared with the state-of-the-art methods. CONCLUSIONS: In our experiments, we compare our methods with 7 popular network-based disease gene prioritization algorithms on diseases from Online Mendelian Inheritance in Man (OMIM) database. The experimental results demonstrate that our methods recover true associations more accurately than other methods in terms of AUC values, and the performance differences are significant (with paired t-test p-values less than 0.05). This validates the importance to integrate tissue-specific molecular networks for studying disease gene prioritization and show the superiority of our network models and ranking algorithms toward this purpose. The source code and datasets are available at http://nijingchao.github.io/CRstar/ .

Self-Grouping Multi-Network Clustering.

Joint clustering of multiple networks has been shown to be more accurate than performing clustering on individual networks separately. Many multi-view and multi-domain network clustering methods have been developed for joint multi-network clustering. These methods typically assume there is a common clustering structure shared by all networks, and different networks can provide complementary information on this underlying clustering structure. However, this assumption is too strict to hold in many emerging real-life applications, where multiple networks have diverse data distributions. More popularly, the networks in consideration belong to different underlying groups. Only networks in the same underlying group share similar clustering structures. Better clustering performance can be achieved by considering such groups differently. As a result, an ideal method should be able to automatically detect network groups so that networks in the same group share a common clustering structure. To address this problem, we propose a novel method, ComClus, to simultaneously group and cluster multiple networks. ComClus treats node clusters as features of networks and uses them to differentiate different network groups. Network grouping and clustering are coupled and mutually enhanced during the learning process. Extensive experimental evaluation on a variety of synthetic and real datasets demonstrates the effectiveness of our method.