MD-Syn: Synergistic drug combination prediction based on the multidimensional feature fusion method and attention mechanisms

Drug combination therapies have shown promising therapeutic efficacy in complex diseases and have demonstrated the potential to reduce drug resistance. However, the huge number of possible drug combinations makes it difficult to screen them all in traditional experiments. In this study, we proposed MD-Syn, a computational framework, which is based on the multidimensional feature fusion method and multi-head attention mechanisms. Given drug pair-cell line triplets, MD-Syn considers one-dimensional and two-dimensional feature spaces simultaneously. It consists of a one-dimensional feature embedding module (1D-FEM), a two-dimensional feature embedding module (2D-FEM), and a deep neural network-based classifier for synergistic drug combination prediction. MD-Syn achieved the AUROC of 0.919 in 5-fold cross-validation, outperforming the state-of-the-art methods. Further, MD-Syn showed comparable results over two independent datasets. In addition, the multi-head attention mechanisms not only learn embeddings from different feature aspects but also focus on essential interactive feature elements, improving the interpretability of MD-Syn. In summary, MD-Syn is an interpretable framework to prioritize synergistic drug combination pairs with chemicals and cancer cell line gene expression profiles. To facilitate broader community access to this model, we have developed a web portal (https://labyeh104-2.life.nthu.edu.tw/) that enables customized predictions of drug combination synergy effects based on user-specified compounds.

Exposing the Functionalities of Neurons for Gated Recurrent Unit Based Sequence-to-Sequence Model

The goal of this paper is to report certain scientific discoveries about a Seq2Seq model. It is known that analyzing the behavior of RNN-based models at the neuron level is considered a more challenging task than analyzing a DNN or CNN models due to their recursive mechanism in nature. This paper aims to provide neuron-level analysis to explain why a vanilla GRU-based Seq2Seq model without attention can achieve token-positioning. We found four different types of neurons: storing, counting, triggering, and outputting and further uncover the mechanism for these neurons to work together in order to produce the right token in the right position.