Received Xth XXXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX First published on the web Xth XXXXXXXXXX 20XX

Networks are ubiquitous in biology, and computational approaches have been largely investigated for their inference. In partic-ular, supervised machine learning methods can be used to complete a partially known network by integrating various measure-ments. Two main supervised frameworks have been proposed: the local approach, which trains a separate model for each network node, and the global approach, which trains a single model over pairs of nodes. Here, we systematically investigate, theoretically and empirically, the exploitation of tree-based ensemble methods in the context of these two approaches for biological network inference. We first formalize the problem of network inference as classification of pairs, unifying in the process homogeneous and bipartite graphs and discussing two main sampling schemes. We then present the global and the local approaches, extending the later for the prediction of interactions between two unseen network nodes, and discuss their specializations to tree-based ensemble methods, highlighting their interpretability and drawing links with clustering techniques. Extensive computational experiments are carried out with these methods on various biological networks that clearly highlight that these methods are competitive with existing methods.