Predicting Drug-Disease Associations via Multi-Task Learning Based on Collective Matrix Factorization.

Identifying drug-disease associations is integral to drug development. Computationally prioritizing candidate drug-disease associations has attracted growing attention due to its contribution to reducing the cost of laboratory screening. Drug-disease associations involve different association types, such as drug indications and drug side effects. However, the existing models for predicting drug-disease associations merely concentrate on independent tasks: recommending novel indications to benefit drug repositioning, predicting potential side effects to prevent drug-induced risk, or only determining the existence of drug-disease association. They ignore crucial prior knowledge of the correlations between different association types. Since the Comparative Toxicogenomics Database (CTD) annotates the drug-disease associations as therapeutic or marker/mechanism, we consider predicting the two types of association. To this end, we propose a collective matrix factorization-based multi-task learning method (CMFMTL) in this paper. CMFMTL handles the problem as multi-task learning where each task is to predict one type of association, and two tasks complement and improve each other by capturing the relatedness between them. First, drug-disease associations are represented as a bipartite network with two types of links representing therapeutic effects and non-therapeutic effects. Then, CMFMTL, respectively, approximates the association matrix regarding each link type by matrix tri-factorization, and shares the low-dimensional latent representations for drugs and diseases in the two related tasks for the goal of collective learning. Finally, CMFMTL puts the two tasks into a unified framework and an efficient algorithm is developed to solve our proposed optimization problem. In the computational experiments, CMFMTL outperforms several state-of-the-art methods both in the two tasks. Moreover, case studies show that CMFMTL helps to find out novel drug-disease associations that are not included in CTD, and simultaneously predicts their association types.