edge2vec: Representation learning using edge semantics for biomedical knowledge discovery

Representation learning provides new and powerful graph analytical approaches and tools for the highly valued data science challenge of mining knowledge graphs. Since previous graph analytical methods have mostly focused on homogeneous graphs, an important current challenge is extending this methodology for richly heterogeneous graphs and knowledge domains. The biomedical sciences are such a domain, reflecting the complexity of biology, with entities such as genes, proteins, drugs, diseases, and phenotypes, and relationships such as gene co-expression, biochemical regulation, and biomolecular inhibition or activation. Therefore, the semantics of edges and nodes are critical for representation learning and knowledge discovery in real world biomedical problems. In this paper, we propose the edge2vec model, which represents graphs considering edge semantics. An edge-type transition matrix is trained by an Expectation-Maximization approach, and a stochastic gradient descent model is employed to learn node embedding on a heterogeneous graph via the trained transition matrix. edge2vec is validated on three biomedical domain tasks: biomedical entity classification, compound-gene bioactivity prediction, and biomedical information retrieval. Results show that by considering edge-types into node embedding learning in heterogeneous graphs, \textbf{edge2vec}\ significantly outperforms state-of-the-art models on all three tasks. We propose this method for its added value relative to existing graph analytical methodology, and in the real world context of biomedical knowledge discovery applicability.Comment: 10 page

Communicability betweenness in complex networks

Betweenness measures provide quantitative tools to pick out fine details from the massive amount of interaction data that is available from large complex networks. They allow us to study the extent to which a node takes part when information is passed around the network. Nodes with high betweenness may be regarded as key players that have a highly active role. At one extreme, betweenness has been defined by considering information passing only through the shortest paths between pairs of nodes. At the other extreme, an alternative type of betweenness has been defined by considering all possible walks of any length. In this work, we propose a betweenness measure that lies between these two opposing viewpoints. We allow information to pass through all possible routes, but introduce a scaling so that longer walks carry less importance. This new definition shares a similar philosophy to that of communicability for pairs of nodes in a network, which was introduced by Estrada and Hatano [E. Estrada, N. Hatano, Phys. Rev. E 77 (2008) 036111]. Having defined this new communicability betweenness measure, we show that it can be characterized neatly in terms of the exponential of the adjacency matrix. We also show that this measure is closely related to a Fréchet derivative of the matrix exponential. This allows us to conclude that it also describes network sensitivity when the edges of a given node are subject to infinitesimally small perturbations. Using illustrative synthetic and real life networks, we show that the new betweenness measure behaves differently to existing versions, and in particular we show that it recovers meaningful biological information from a proteinprotein interaction network

Supervised Random Walks: Predicting and Recommending Links in Social Networks

Predicting the occurrence of links is a fundamental problem in networks. In the link prediction problem we are given a snapshot of a network and would like to infer which interactions among existing members are likely to occur in the near future or which existing interactions are we missing. Although this problem has been extensively studied, the challenge of how to effectively combine the information from the network structure with rich node and edge attribute data remains largely open. We develop an algorithm based on Supervised Random Walks that naturally combines the information from the network structure with node and edge level attributes. We achieve this by using these attributes to guide a random walk on the graph. We formulate a supervised learning task where the goal is to learn a function that assigns strengths to edges in the network such that a random walker is more likely to visit the nodes to which new links will be created in the future. We develop an efficient training algorithm to directly learn the edge strength estimation function. Our experiments on the Facebook social graph and large collaboration networks show that our approach outperforms state-of-the-art unsupervised approaches as well as approaches that are based on feature extraction

Random walks on mutual microRNA-target gene interaction network improve the prediction of disease-associated microRNAs

Background: MicroRNAs (miRNAs) have been shown to play an important role in pathological initiation, progression and maintenance. Because identification in the laboratory of disease-related miRNAs is not straightforward, numerous network-based methods have been developed to predict novel miRNAs in silico. Homogeneous networks (in which every node is a miRNA) based on the targets shared between miRNAs have been widely used to predict their role in disease phenotypes. Although such homogeneous networks can predict potential disease-associated miRNAs, they do not consider the roles of the target genes of the miRNAs. Here, we introduce a novel method based on a heterogeneous network that not only considers miRNAs but also the corresponding target genes in the network model. Results: Instead of constructing homogeneous miRNA networks, we built heterogeneous miRNA networks consisting of both miRNAs and their target genes, using databases of known miRNA-target gene interactions. In addition, as recent studies demonstrated reciprocal regulatory relations between miRNAs and their target genes, we considered these heterogeneous miRNA networks to be undirected, assuming mutual miRNA-target interactions. Next, we introduced a novel method (RWRMTN) operating on these mutual heterogeneous miRNA networks to rank candidate disease-related miRNAs using a random walk with restart (RWR) based algorithm. Using both known disease-associated miRNAs and their target genes as seed nodes, the method can identify additional miRNAs involved in the disease phenotype. Experiments indicated that RWRMTN outperformed two existing state-of-the-art methods: RWRMDA, a network-based method that also uses a RWR on homogeneous (rather than heterogeneous) miRNA networks, and RLSMDA, a machine learning-based method. Interestingly, we could relate this performance gain to the emergence of "disease modules" in the heterogeneous miRNA networks used as input for the algorithm. Moreover, we could demonstrate that RWRMTN is stable, performing well when using both experimentally validated and predicted miRNA-target gene interaction data for network construction. Finally, using RWRMTN, we identified 76 novel miRNAs associated with 23 disease phenotypes which were present in a recent database of known disease-miRNA associations. Conclusions: Summarizing, using random walks on mutual miRNA-target networks improves the prediction of novel disease-associated miRNAs because of the existence of "disease modules" in these networks

Learning Edge Representations via Low-Rank Asymmetric Projections

We propose a new method for embedding graphs while preserving directed edge information. Learning such continuous-space vector representations (or embeddings) of nodes in a graph is an important first step for using network information (from social networks, user-item graphs, knowledge bases, etc.) in many machine learning tasks. Unlike previous work, we (1) explicitly model an edge as a function of node embeddings, and we (2) propose a novel objective, the "graph likelihood", which contrasts information from sampled random walks with non-existent edges. Individually, both of these contributions improve the learned representations, especially when there are memory constraints on the total size of the embeddings. When combined, our contributions enable us to significantly improve the state-of-the-art by learning more concise representations that better preserve the graph structure. We evaluate our method on a variety of link-prediction task including social networks, collaboration networks, and protein interactions, showing that our proposed method learn representations with error reductions of up to 76% and 55%, on directed and undirected graphs. In addition, we show that the representations learned by our method are quite space efficient, producing embeddings which have higher structure-preserving accuracy but are 10 times smaller