L21-iPaD: An efficient method for drug-pathway association pairs inference

Pathway-based drug discovery overcomes the disadvantages of the “one drug-one target” method, which aims to find the effective drugs to act on single targets. The current method “iPaD” identities the drug-pathway association pairs by taking the lasso-type penalty on the drug-pathway association matrix. In order to enhance the robustness of the methods and be more effective to find the novel drug-pathway association pairs, we introduce a new method named “L2,1-iPaD”. Compared with the iPaD method, we impose the L2,1-norm constraint on the drug-pathway association coefficient matrix. By applying our method to a real widely datasets (CCLE dataset), we demonstrate that our method is superior to the iPaD method. And our method can obtain the smaller P-values than the iPaD method by performing permutation test to assess the significance of the identified drug-pathway association pairs. More importantly, compared with the iPaD method, our method can identify larger numbers of validated drug-pathway association pairs. The experimental results on the real dataset demonstrate the effectiveness of our method.