Microbe-disease associations prediction by graph regularized non-negative matrix factorization with L 2 , 1 $$...

Microbes are involved in a wide range of biological processes and are closely associated with disease. Inferring potential disease-associated microbes as the biomarkers or drug targets may help prevent, diagnose and treat complex human diseases. However, biological experiments are time-consuming and expensive. In this study, we introduced a new method called iPALM-GLMF, which modelled microbe-disease association prediction as a problem of non-negative matrix factorization with graph dual regularization terms and $L_{2,1}$ norm regularization terms. The graph dual regularization terms were used to capture potential features in the microbe and disease space, and the $L_{2,1}$ norm regularization terms were used to ensure the sparsity of the feature matrices obtained from the non-negative matrix factorization and to improve the interpretability. To solve the model, iPALM-GLMF used a non-negative double singular value decomposition to initialize the matrix factorization and adopted an inertial Proximal Alternating Linear Minimization iterative process to obtain the final matrix factorization results. As a result, iPALM-GLMF performed better than other existing methods in leave-one-out cross-validation and fivefold cross-validation. In addition, case studies of different diseases demonstrated that iPALM-GLMF could effectively predict potential microbial-disease associations. iPALM-GLMF is publicly available at https://github.com/LiangzheZhang/iPALM-GLMF.