WSMD: weakly-supervised motif discovery in transcription factor ChIP-seq data.

Although discriminative motif discovery (DMD) methods are promising for eliciting motifs from high-throughput experimental data, due to consideration of computational expense, most of existing DMD methods have to choose approximate schemes that greatly restrict the search space, leading to significant loss of predictive accuracy. In this paper, we propose Weakly-Supervised Motif Discovery (WSMD) to discover motifs from ChIP-seq datasets. In contrast to the learning strategies adopted by previous DMD methods, WSMD allows a "global" optimization scheme of the motif parameters in continuous space, thereby reducing the information loss of model representation and improving the quality of resultant motifs. Meanwhile, by exploiting the connection between DMD framework and existing weakly supervised learning (WSL) technologies, we also present highly scalable learning strategies for the proposed method. The experimental results on both real ChIP-seq datasets and synthetic datasets show that WSMD substantially outperforms former DMD methods (including DREME, HOMER, XXmotif, motifRG and DECOD) in terms of predictive accuracy, while also achieving a competitive computational speed.