Fan Wang

Jie Gao, Jing Hu, Wanqing Sun et al.

Predicting clinical outcomes to anti-cancer drugs on a personalized basis is challenging in cancer treatment due to the heterogeneity of tumors. Traditional computational efforts have been made to model the effect of drug response on individual samples depicted by their molecular profile, yet overfitting occurs because of the high dimension for omics data, hindering models from clinical application. Recent research shows that deep learning is a promising approach to build drug response models by learning alignment patterns between drugs and samples. However, existing studies employed the simple feature fusion strategy and only considered the drug features as a whole representation while ignoring the substructure information that may play a vital role when aligning drugs and genes. Hereby in this paper, we propose TCR (Transformer based network for Cancer drug Response) to predict anti-cancer drug response. By utilizing an attention mechanism, TCR is able to learn the interactions between drug atom/sub-structure and molecular signatures efficiently in our study. Furthermore, a dual loss function and cross sampling strategy were designed to improve the prediction power of TCR. We show that TCR outperformed all other methods under various data splitting strategies on all evaluation matrices (some with significant improvement). Extensive experiments demonstrate that TCR shows significantly improved generalization ability on independent in-vitro experiments and in-vivo real patient data. Our study highlights the prediction power of TCR and its potential value for cancer drug repurpose and precision oncology treatment.

Zhiyuan Chen, Xiaomin Fang, Zixu Hua et al.

Efficient exploration of the chemical space to search the candidate drugs that satisfy various constraints is a fundamental task of drug discovery. Advanced deep generative methods attempt to optimize the molecules in the compact latent space instead of the discrete original space, but the mapping between the original and latent spaces is always kept unchanged during the entire optimization process. The unchanged mapping makes those methods challenging to fast adapt to various optimization scenes and leads to the great demand for assessed molecules (samples) to provide optimization direction, which is a considerable expense for drug discovery. To this end, we design a sample-efficient molecular generative method, HelixMO, which explores the scene-sensitive latent space to promote sample efficiency. The scene-sensitive latent space focuses more on modeling the promising molecules by dynamically adjusting the space mapping by leveraging the correlations between the general and scene-specific characteristics during the optimization process. Extensive experiments demonstrate that HelixMO can achieve competitive performance with only a few assessed samples on four molecular optimization scenes. Ablation studies verify the positive impact of the scene-specific latent space, which is capable of identifying the critical characteristics of the promising molecules. We also deployed HelixMO on the website PaddleHelix (https://paddlehelix.baidu.com/app/drug/drugdesign/forecast) to provide drug design service.

Zijing Liu, Xianbin Ye, Xiaomin Fang et al.

Machine learning shows great potential in virtual screening for drug discovery. Current efforts on accelerating docking-based virtual screening do not consider using existing data of other previously developed targets. To make use of the knowledge of the other targets and take advantage of the existing data, in this work, we apply multi-task learning to the problem of docking-based virtual screening. With two large docking datasets, the results of extensive experiments show that multi-task learning can achieve better performances on docking score prediction. By learning knowledge across multiple targets, the model trained by multi-task learning shows a better ability to adapt to a new target. Additional empirical study shows that other problems in drug discovery, such as the experimental drug-target affinity prediction, may also benefit from multi-task learning. Our results demonstrate that multi-task learning is a promising machine learning approach for docking-based virtual screening and accelerating the process of drug discovery.

Shuangli Li, Jingbo Zhou, Tong Xu et al.

Drug discovery often relies on the successful prediction of protein-ligand binding affinity. Recent advances have shown great promise in applying graph neural networks (GNNs) for better affinity prediction by learning the representations of protein-ligand complexes. However, existing solutions usually treat protein-ligand complexes as topological graph data, thus the biomolecular structural information is not fully utilized. The essential long-range interactions among atoms are also neglected in GNN models. To this end, we propose a structure-aware interactive graph neural network (SIGN) which consists of two components: polar-inspired graph attention layers (PGAL) and pairwise interactive pooling (PiPool). Specifically, PGAL iteratively performs the node-edge aggregation process to update embeddings of nodes and edges while preserving the distance and angle information among atoms. Then, PiPool is adopted to gather interactive edges with a subsequent reconstruction loss to reflect the global interactions. Exhaustive experimental study on two benchmarks verifies the superiority of SIGN.

Jingbo Zhou, Shuangli Li, Liang Huang et al.

Accurately predicting the binding affinity between drugs and proteins is an essential step for computational drug discovery. Since graph neural networks (GNNs) have demonstrated remarkable success in various graph-related tasks, GNNs have been considered as a promising tool to improve the binding affinity prediction in recent years. However, most of the existing GNN architectures can only encode the topological graph structure of drugs and proteins without considering the relative spatial information among their atoms. Whereas, different from other graph datasets such as social networks and commonsense knowledge graphs, the relative spatial position and chemical bonds among atoms have significant impacts on the binding affinity. To this end, in this paper, we propose a diStance-aware Molecule graph Attention Network (S-MAN) tailored to drug-target binding affinity prediction. As a dedicated solution, we first propose a position encoding mechanism to integrate the topological structure and spatial position information into the constructed pocket-ligand graph. Moreover, we propose a novel edge-node hierarchical attentive aggregation structure which has edge-level aggregation and node-level aggregation. The hierarchical attentive aggregation can capture spatial dependencies among atoms, as well as fuse the position-enhanced information with the capability of discriminating multiple spatial relations among atoms. Finally, we conduct extensive experiments on two standard datasets to demonstrate the effectiveness of S-MAN.

Fan Wang, Bo Zhou, Ke Chen et al.

Combining deep neural networks with reinforcement learning has shown great potential in the next-generation intelligent control. However, there are challenges in terms of safety and cost in practical applications. In this paper, we propose the Intervention Aided Reinforcement Learning (IARL) framework, which utilizes human intervened robot-environment interaction to improve the policy. We used the Unmanned Aerial Vehicle (UAV) as the test platform. We built neural networks as our policy to map sensor readings to control signals on the UAV. Our experiment scenarios cover both simulation and reality. We show that our approach substantially reduces the human intervention and improves the performance in autonomous navigation, at the same time it ensures safety and keeps training cost acceptable.