We propose UPSA, a novel approach that accomplishes Unsupervised Paraphrasing by Simulated Annealing. We model paraphrase generation as an optimization problem and propose a sophisticated objective function, involving semantic similarity, expression diversity, and language fluency of paraphrases. UPSA searches the sentence space towards this objective by performing a sequence of local edits. We evaluate our approach on various datasets, namely, Quora, Wikianswers, MSCOCO, and Twitter. Extensive results show that UPSA achieves the state-of-the-art performance compared with previous unsupervised methods in terms of both automatic and human evaluations. Further, our approach outperforms most existing domain-adapted supervised models, showing the generalizability of UPSA. 1

Modeling the impact of amino acid mutations on protein-protein interaction plays a crucial role in protein engineering and drug design. In this study, we develop GeoPPI, a novel structure-based deep-learning framework to predict the change of binding affinity upon mutations. Based on the three-dimensional structure of a protein, GeoPPI first learns a geometric representation that encodes topology features of the protein structure via a self-supervised learning scheme. These representations are then used as features for training gradient-boosting trees to predict the changes of protein-protein binding affinity upon mutations. We find that GeoPPI is able to learn meaningful features that characterize interactions between atoms in protein structures. In addition, through extensive experiments, we show that GeoPPI achieves new state-of-the-art performance in predicting the binding affinity changes upon both single- and multi-point mutations on six benchmark datasets. Moreover, we show that GeoPPI can accurately estimate the difference of binding affinities between a few recently identified SARS-CoV-2 antibodies and the receptor-binding domain (RBD) of the S protein. These results demonstrate the potential of GeoPPI as a powerful and useful computational tool in protein design and engineering. Our code and datasets are available at: https://github.com/Liuxg16/GeoPPI.

Motivation Computational methods accelerate drug discovery and play an important role in biomedicine, such as molecular property prediction and compound–protein interaction (CPI) identification. A key challenge is to learn useful molecular representation. In the early years, molecular properties are mainly calculated by quantum mechanics or predicted by traditional machine learning methods, which requires expert knowledge and is often labor-intensive. Nowadays, graph neural networks have received significant attention because of the powerful ability to learn representation from graph data. Nevertheless, current graph-based methods have some limitations that need to be addressed, such as large-scale parameters and insufficient bond information extraction. Results In this study, we proposed a graph-based approach and employed a novel triplet message mechanism to learn molecular representation efficiently, named triplet message networks (TrimNet). We show that TrimNet can accurately complete multiple molecular representation learning tasks with significant parameter reduction, including the quantum properties, bioactivity, physiology and CPI prediction. In the experiments, TrimNet outperforms the previous state-of-the-art method by a significant margin on various datasets. Besides the few parameters and high prediction accuracy, TrimNet could focus on the atoms essential to the target properties, providing a clear interpretation of the prediction tasks. These advantages have established TrimNet as a powerful and useful computational tool in solving the challenging problem of molecular representation learning. Availability The quantum and drug datasets are available on the website of MoleculeNet: http://moleculenet.ai. The source code is available in GitHub: https://github.com/yvquanli/trimnet. Contact xjyao@lzu.edu.cn, songsen@tsinghua.edu.cn

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