LMMO: A Large Margin Approach for Refining Regulatory Motifs

Although discriminative motif discovery (DMD) methods are promising for eliciting motifs from high-throughput experimental data, they usually have to sacrifice accuracy and may fail to fully leverage the potential of large datasets. Recently, it has been demonstrated that the motifs identified by DMDs can be significantly improved by maximizing the receiver-operating characteristic curve (AUC) metric, which has been widely used in the literature to rank the performance of elicited motifs. However, existing approaches for motif refinement choose to directly maximize the non-convex and discontinuous AUC itself, which is known to be difficult and may lead to suboptimal solutions. In this paper, we propose Large Margin Motif Optimizer (LMMO), a large-margin-type algorithm for refining regulatory motifs. By relaxing the AUC cost function with the surrogate convex hinge loss, we show that the resultant learning problem can be cast as an instance of difference-of-convex (DC) programs, and solve it iteratively using constrained concave-convex procedure (CCCP). To further save computational time, we combine LMMO with existing techniques for improving the scalability of large-margin-type algorithms, such as cutting plane method. Experimental evaluations on synthetic and real data illustrate the performance of the proposed approach. The code of LMMO is freely available at: https://github.com/ekffar/LMMO.