Han Li

Han Li, Dan Zhao, Jianyang Zeng

Designing accurate deep learning models for molecular property prediction plays an increasingly essential role in drug and material discovery. Recently, due to the scarcity of labeled molecules, self-supervised learning methods for learning generalizable and transferable representations of molecular graphs have attracted lots of attention. In this paper, we argue that there exist two major issues hindering current self-supervised learning methods from obtaining desired performance on molecular property prediction, that is, the ill-defined pre-training tasks and the limited model capacity. To this end, we introduce Knowledge-guided Pre-training of Graph Transformer (KPGT), a novel self-supervised learning framework for molecular graph representation learning, to alleviate the aforementioned issues and improve the performance on the downstream molecular property prediction tasks. More specifically, we first introduce a high-capacity model, named Line Graph Transformer (LiGhT), which emphasizes the importance of chemical bonds and is mainly designed to model the structural information of molecular graphs. Then, a knowledge-guided pre-training strategy is proposed to exploit the additional knowledge of molecules to guide the model to capture the abundant structural and semantic information from large-scale unlabeled molecular graphs. Extensive computational tests demonstrated that KPGT can offer superior performance over current state-of-the-art methods on several molecular property prediction tasks.

Yaosen Min, Ye Wei, Peizhuo Wang et al.

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because they only take advantage of static crystal structures while the actual binding affinities are generally determined by the thermodynamic ensembles between proteins and ligands. One effective way to approximate such a thermodynamic ensemble is to use molecular dynamics (MD) simulation. Here, an MD dataset containing 3,218 different protein-ligand complexes is curated, and Dynaformer, a graph-based deep learning model is further developed to predict the binding affinities by learning the geometric characteristics of the protein-ligand interactions from the MD trajectories. In silico experiments demonstrated that the model exhibits state-of-the-art scoring and ranking power on the CASF-2016 benchmark dataset, outperforming the methods hitherto reported. Moreover, in a virtual screening on heat shock protein 90 (HSP90) using Dynaformer, 20 candidates are identified and their binding affinities are further experimentally validated. Dynaformer displayed promising results in virtual drug screening, revealing 12 hit compounds (two are in the submicromolar range), including several novel scaffolds. Overall, these results demonstrated that the approach offer a promising avenue for accelerating the early drug discovery process.

Han Li, Hu Han, S. Kevin Zhou

Natural images exhibit label diversity (clean vs. noisy) in noisy-labeled image classification and prevalence diversity (abundant vs. sparse) in long-tailed image classification. Similarly, medical images in universal lesion detection (ULD) exhibit substantial variations in image quality, encompassing attributes such as clarity and label correctness. How to effectively leverage training images with diverse qualities becomes a problem in learning deep models. Conventional training mechanisms, such as self-paced curriculum learning (SCL) and online hard example mining (OHEM), relieve this problem by reweighting images with high loss values. Despite their success, these methods still confront two challenges: (i) the loss-based measure of sample hardness is imprecise, preventing optimum handling of different cases, and (ii) there exists under-utilization in SCL or over-utilization OHEM with the identified hard samples. To address these issues, this paper revisits the minibatch sampling (MBS), a technique widely used in deep network training but largely unexplored concerning the handling of diverse-quality training samples. We discover that the samples within a minibatch influence each other during training; thus, we propose a novel Mixed-order Minibatch Sampling (MoMBS) method to optimize the use of training samples with diverse qualities. MoMBS introduces a measure that takes both loss and uncertainty into account to surpass a sole reliance on loss and allows for a more refined categorization of high-loss samples by distinguishing them as either poorly labeled and under represented or well represented and overfitted. We prioritize under represented samples as the main gradient contributors in a minibatch and keep them from the negative influences of poorly labeled or overfitted samples with a mixed-order minibatch sampling design.

Junqi Jin, Chengru Song, Han Li et al.

Real-time advertising allows advertisers to bid for each impression for a visiting user. To optimize specific goals such as maximizing revenue and return on investment (ROI) led by ad placements, advertisers not only need to estimate the relevance between the ads and user's interests, but most importantly require a strategic response with respect to other advertisers bidding in the market. In this paper, we formulate bidding optimization with multi-agent reinforcement learning. To deal with a large number of advertisers, we propose a clustering method and assign each cluster with a strategic bidding agent. A practical Distributed Coordinated Multi-Agent Bidding (DCMAB) has been proposed and implemented to balance the tradeoff between the competition and cooperation among advertisers. The empirical study on our industry-scaled real-world data has demonstrated the effectiveness of our methods. Our results show cluster-based bidding would largely outperform single-agent and bandit approaches, and the coordinated bidding achieves better overall objectives than purely self-interested bidding agents.