SyNDock: N Rigid Protein Docking via Learnable Group Synchronization

The regulation of various cellular processes heavily relies on the protein complexes within a living cell, necessitating a comprehensive understanding of their three-dimensional structures to elucidate the underlying mechanisms. While neural docking techniques have exhibited promising outcomes in binary protein docking, the application of advanced neural architectures to multimeric protein docking remains uncertain. This study introduces SyNDock, an automated framework that swiftly assembles precise multimeric complexes within seconds, showcasing performance that can potentially surpass or be on par with recent advanced approaches. SyNDock possesses several appealing advantages not present in previous approaches. Firstly, SyNDock formulates multimeric protein docking as a problem of learning global transformations to holistically depict the placement of chain units of a complex, enabling a learning-centric solution. Secondly, SyNDock proposes a trainable two-step SE(3) algorithm, involving initial pairwise transformation and confidence estimation, followed by global transformation synchronization. This enables effective learning for assembling the complex in a globally consistent manner. Lastly, extensive experiments conducted on our proposed benchmark dataset demonstrate that SyNDock outperforms existing docking software in crucial performance metrics, including accuracy and runtime. For instance, it achieves a 4.5% improvement in performance and a remarkable millionfold acceleration in speed.

Reweighted Mixup for Subpopulation Shift

Subpopulation shift exists widely in many real-world applications, which refers to the training and test distributions that contain the same subpopulation groups but with different subpopulation proportions. Ignoring subpopulation shifts may lead to significant performance degradation and fairness concerns. Importance reweighting is a classical and effective way to handle the subpopulation shift. However, recent studies have recognized that most of these approaches fail to improve the performance especially when applied to over-parameterized neural networks which are capable of fitting any training samples. In this work, we propose a simple yet practical framework, called reweighted mixup (RMIX), to mitigate the overfitting issue in over-parameterized models by conducting importance weighting on the ''mixed'' samples. Benefiting from leveraging reweighting in mixup, RMIX allows the model to explore the vicinal space of minority samples more, thereby obtaining more robust model against subpopulation shift. When the subpopulation memberships are unknown, the training-trajectories-based uncertainty estimation is equipped in the proposed RMIX to flexibly characterize the subpopulation distribution. We also provide insightful theoretical analysis to verify that RMIX achieves better generalization bounds over prior works. Further, we conduct extensive empirical studies across a wide range of tasks to validate the effectiveness of the proposed method.

Fairness-guided Few-shot Prompting for Large Language Models

Large language models have demonstrated surprising ability to perform in-context learning, i.e., these models can be directly applied to solve numerous downstream tasks by conditioning on a prompt constructed by a few input-output examples. However, prior research has shown that in-context learning can suffer from high instability due to variations in training examples, example order, and prompt formats. Therefore, the construction of an appropriate prompt is essential for improving the performance of in-context learning. In this paper, we revisit this problem from the view of predictive bias. Specifically, we introduce a metric to evaluate the predictive bias of a fixed prompt against labels or a given attributes. Then we empirically show that prompts with higher bias always lead to unsatisfactory predictive quality. Based on this observation, we propose a novel search strategy based on the greedy search to identify the near-optimal prompt for improving the performance of in-context learning. We perform comprehensive experiments with state-of-the-art mainstream models such as GPT-3 on various downstream tasks. Our results indicate that our method can enhance the model's in-context learning performance in an effective and interpretable manner.

Deploying Offline Reinforcement Learning with Human Feedback

Reinforcement learning (RL) has shown promise for decision-making tasks in real-world applications. One practical framework involves training parameterized policy models from an offline dataset and subsequently deploying them in an online environment. However, this approach can be risky since the offline training may not be perfect, leading to poor performance of the RL models that may take dangerous actions. To address this issue, we propose an alternative framework that involves a human supervising the RL models and providing additional feedback in the online deployment phase. We formalize this online deployment problem and develop two approaches. The first approach uses model selection and the upper confidence bound algorithm to adaptively select a model to deploy from a candidate set of trained offline RL models. The second approach involves fine-tuning the model in the online deployment phase when a supervision signal arrives. We demonstrate the effectiveness of these approaches for robot locomotion control and traffic light control tasks through empirical validation.

Towards Stable Test-Time Adaptation in Dynamic Wild World

Test-time adaptation (TTA) has shown to be effective at tackling distribution shifts between training and testing data by adapting a given model on test samples. However, the online model updating of TTA may be unstable and this is often a key obstacle preventing existing TTA methods from being deployed in the real world. Specifically, TTA may fail to improve or even harm the model performance when test data have: 1) mixed distribution shifts, 2) small batch sizes, and 3) online imbalanced label distribution shifts, which are quite common in practice. In this paper, we investigate the unstable reasons and find that the batch norm layer is a crucial factor hindering TTA stability. Conversely, TTA can perform more stably with batch-agnostic norm layers, \ie, group or layer norm. However, we observe that TTA with group and layer norms does not always succeed and still suffers many failure cases. By digging into the failure cases, we find that certain noisy test samples with large gradients may disturb the model adaption and result in collapsed trivial solutions, \ie, assigning the same class label for all samples. To address the above collapse issue, we propose a sharpness-aware and reliable entropy minimization method, called SAR, for further stabilizing TTA from two aspects: 1) remove partial noisy samples with large gradients, 2) encourage model weights to go to a flat minimum so that the model is robust to the remaining noisy samples. Promising results demonstrate that SAR performs more stably over prior methods and is computationally efficient under the above wild test scenarios.

Handling Missing Data via Max-Entropy Regularized Graph Autoencoder

Graph neural networks (GNNs) are popular weapons for modeling relational data. Existing GNNs are not specified for attribute-incomplete graphs, making missing attribute imputation a burning issue. Until recently, many works notice that GNNs are coupled with spectral concentration, which means the spectrum obtained by GNNs concentrates on a local part in spectral domain, e.g., low-frequency due to oversmoothing issue. As a consequence, GNNs may be seriously flawed for reconstructing graph attributes as graph spectral concentration tends to cause a low imputation precision. In this work, we present a regularized graph autoencoder for graph attribute imputation, named MEGAE, which aims at mitigating spectral concentration problem by maximizing the graph spectral entropy. Notably, we first present the method for estimating graph spectral entropy without the eigen-decomposition of Laplacian matrix and provide the theoretical upper error bound. A maximum entropy regularization then acts in the latent space, which directly increases the graph spectral entropy. Extensive experiments show that MEGAE outperforms all the other state-of-the-art imputation methods on a variety of benchmark datasets.

Predicting Protein-Ligand Binding Affinity with Equivariant Line Graph Network

Binding affinity prediction of three-dimensional (3D) protein ligand complexes is critical for drug repositioning and virtual drug screening. Existing approaches transform a 3D protein-ligand complex to a two-dimensional (2D) graph, and then use graph neural networks (GNNs) to predict its binding affinity. However, the node and edge features of the 2D graph are extracted based on invariant local coordinate systems of the 3D complex. As a result, the method can not fully learn the global information of the complex, such as, the physical symmetry and the topological information of bonds. To address these issues, we propose a novel Equivariant Line Graph Network (ELGN) for affinity prediction of 3D protein ligand complexes. The proposed ELGN firstly adds a super node to the 3D complex, and then builds a line graph based on the 3D complex. After that, ELGN uses a new E(3)-equivariant network layer to pass the messages between nodes and edges based on the global coordinate system of the 3D complex. Experimental results on two real datasets demonstrate the effectiveness of ELGN over several state-of-the-art baselines.

Robust Offline Reinforcement Learning with Gradient Penalty and Constraint Relaxation

A promising paradigm for offline reinforcement learning (RL) is to constrain the learned policy to stay close to the dataset behaviors, known as policy constraint offline RL. However, existing works heavily rely on the purity of the data, exhibiting performance degradation or even catastrophic failure when learning from contaminated datasets containing impure trajectories of diverse levels. e.g., expert level, medium level, etc., while offline contaminated data logs exist commonly in the real world. To mitigate this, we first introduce gradient penalty over the learned value function to tackle the exploding Q-functions. We then relax the closeness constraints towards non-optimal actions with critic weighted constraint relaxation. Experimental results show that the proposed techniques effectively tame the non-optimal trajectories for policy constraint offline RL methods, evaluated on a set of contaminated D4RL Mujoco and Adroit datasets.

Pareto-aware Neural Architecture Generation for Diverse Computational Budgets

Designing feasible and effective architectures under diverse computational budgets, incurred by different applications/devices, is essential for deploying deep models in real-world applications. To achieve this goal, existing methods often perform an independent architecture search process for each target budget, which is very inefficient yet unnecessary. More critically, these independent search processes cannot share their learned knowledge (i.e., the distribution of good architectures) with each other and thus often result in limited search results. To address these issues, we propose a Pareto-aware Neural Architecture Generator (PNAG) which only needs to be trained once and dynamically produces the Pareto optimal architecture for any given budget via inference. To train our PNAG, we learn the whole Pareto frontier by jointly finding multiple Pareto optimal architectures under diverse budgets. Such a joint search algorithm not only greatly reduces the overall search cost but also improves the search results. Extensive experiments on three hardware platforms (i.e., mobile device, CPU, and GPU) show the superiority of our method over existing methods.