Identifying drug-pathway association pairs based on L_2,1-integrative penalized matrix decomposition

Background: Traditional drug identification methods follow the "one drug-one target" thought. But those methods ignore the natural characters of human diseases. To overcome this limitation, many identification methods of drug-pathway association pairs have been developed, such as the integrative penalized matrix decomposition (iPaD) method. The iPaD method imposes the L₁-norm penalty on the regularization term. However, lasso-type penalties have an obvious disadvantage, that is, the sparsity produced by them is too dispersive. Results: Therefore, to improve the performance of the iPaD method, we propose a novel method named L_2,1-iPaD to identify paired drug-pathway associations. In the L_2,1-iPaD model, we use the L_2,1-norm penalty to replace the L₁-norm penalty since the L_2,1-norm penalty can produce row sparsity. Conclusions: By applying the L_2,1-iPaD method to the CCLE and NCI-60 datasets, we demonstrate that the performance of L_2,1-iPaD method is superior to existing methods. And the proposed method can achieve better enrichment in terms of discovering validated drug-pathway association pairs than the iPaD method by performing permutation test. The results on the two real datasets prove that our method is effective.