Yu Li

Zhihang Hu, Qinze Yu, Yucheng Guo et al.

Drug combination therapy is a well-established strategy for disease treatment with better effectiveness and less safety degradation. However, identifying novel drug combinations through wet-lab experiments is resource intensive due to the vast combinatorial search space. Recently, computational approaches, specifically deep learning models have emerged as an efficient way to discover synergistic combinations. While previous methods reported fair performance, their models usually do not take advantage of multi-modal data and they are unable to handle new drugs or cell lines. In this study, we collected data from various datasets covering various drug-related aspects. Then, we take advantage of large-scale pre-training models to generate informative representations and features for drugs, proteins, and diseases. Based on that, a message-passing graph is built on top to propagate information together with graph structure learning flexibility. This is first introduced in the biological networks and enables us to generate pseudo-relations in the graph. Our framework achieves state-of-the-art results in comparison with other deep learning-based methods on synergistic prediction benchmark datasets. We are also capable of inferencing new drug combination data in a test on an independent set released by AstraZeneca, where 10% of improvement over previous methods is observed. In addition, we're robust against unseen drugs and surpass almost 15% AU ROC compared to the second-best model. We believe our framework contributes to both the future wet-lab discovery of novel drugs and the building of promising guidance for precise combination medicine.

Chu-Min Li, Fan Xiao, Mao Luo et al.

Original and learnt clauses in Conflict-Driven Clause Learning (CDCL) SAT solvers often contain redundant literals. This may have a negative impact on performance because redundant literals may deteriorate both the effectiveness of Boolean constraint propagation and the quality of subsequent learnt clauses. To overcome this drawback, we propose a clause vivification approach that eliminates redundant literals by applying unit propagation. The proposed clause vivification is activated before the SAT solver triggers some selected restarts, and only affects a subset of original and learnt clauses, which are considered to be more relevant according to metrics like the literal block distance (LBD). Moreover, we conducted an empirical investigation with instances coming from the hard combinatorial and application categories of recent SAT competitions. The results show that a remarkable number of additional instances are solved when the proposed approach is incorporated into five of the best performing CDCL SAT solvers (Glucose, TC_Glucose, COMiniSatPS, MapleCOMSPS and MapleCOMSPS_LRB). More importantly, the empirical investigation includes an in-depth analysis of the effectiveness of clause vivification. It is worth mentioning that one of the SAT solvers described here was ranked first in the main track of SAT Competition 2017 thanks to the incorporation of the proposed clause vivification. That solver was further improved in this paper and won the bronze medal in the main track of SAT Competition 2018.