Ke Song

Ke Song, Quan Xia, Guoqiang Liang et al.

Non-exemplar class-incremental learning refers to classifying new and old classes without storing samples of old classes. Since only new class samples are available for optimization, it often occurs catastrophic forgetting of old knowledge. To alleviate this problem, many new methods are proposed such as model distillation, class augmentation. In this paper, we propose an effective non-exemplar method called RAMF consisting of Random Auxiliary classes augmentation and Mixed Feature. On the one hand, we design a novel random auxiliary classes augmentation method, where one augmentation is randomly selected from three augmentations and applied on the input to generate augmented samples and extra class labels. By extending data and label space, it allows the model to learn more diverse representations, which can prevent the model from being biased towards learning task-specific features. When learning new tasks, it will reduce the change of feature space and improve model generalization. On the other hand, we employ mixed feature to replace the new features since only using new feature to optimize the model will affect the representation that was previously embedded in the feature space. Instead, by mixing new and old features, old knowledge can be retained without increasing the computational complexity. Extensive experiments on three benchmarks demonstrate the superiority of our approach, which outperforms the state-of-the-art non-exemplar methods and is comparable to high-performance replay-based methods.

Song Li, Song Ke, Chenxing Yang et al.

Gonadotrophin-releasing hormone receptor (GnRH1R) is a promising therapeutic target for the treatment of uterine diseases. To date, several GnRH1R antagonists are available in clinical investigation without satisfying multiple property constraints. To fill this gap, we aim to develop a deep learning-based framework to facilitate the effective and efficient discovery of a new orally active small-molecule drug targeting GnRH1R with desirable properties. In the present work, a ligand-and-structure combined model, namely LS-MolGen, was firstly proposed for molecular generation by fully utilizing the information on the known active compounds and the structure of the target protein, which was demonstrated by its superior performance than ligand- or structure-based methods separately. Then, a in silico screening including activity prediction, ADMET evaluation, molecular docking and FEP calculation was conducted, where ~30,000 generated novel molecules were narrowed down to 8 for experimental synthesis and validation. In vitro and in vivo experiments showed that three of them exhibited potent inhibition activities (compound 5 IC50 = 0.856 nM, compound 6 IC50 = 0.901 nM, compound 7 IC50 = 2.54 nM) against GnRH1R, and compound 5 performed well in fundamental PK properties, such as half-life, oral bioavailability, and PPB, etc. We believed that the proposed ligand-and-structure combined molecular generative model and the whole computer-aided workflow can potentially be extended to similar tasks for de novo drug design or lead optimization.