Jian Peng

Shitong Luo, Jiahan Li, Jiaqi Guan et al. · mit

Equivariance has been a long-standing concern in various fields ranging from computer vision to physical modeling. Most previous methods struggle with generality, simplicity, and expressiveness -- some are designed ad hoc for specific data types, some are too complex to be accessible, and some sacrifice flexible transformations. In this work, we propose a novel and simple framework to achieve equivariance for point cloud analysis based on the message passing (graph neural network) scheme. We find the equivariant property could be obtained by introducing an orientation for each point to decouple the relative position for each point from the global pose of the entire point cloud. Therefore, we extend current message passing networks with a module that learns orientations for each point. Before aggregating information from the neighbors of a point, the networks transforms the neighbors' coordinates based on the point's learned orientations. We provide formal proofs to show the equivariance of the proposed framework. Empirically, we demonstrate that our proposed method is competitive on both point cloud analysis and physical modeling tasks. Code is available at https://github.com/luost26/Equivariant-OrientedMP .

Xingang Peng, Shitong Luo, Jiaqi Guan et al. · mit

Deep generative models have achieved tremendous success in designing novel drug molecules in recent years. A new thread of works have shown the great potential in advancing the specificity and success rate of in silico drug design by considering the structure of protein pockets. This setting posts fundamental computational challenges in sampling new chemical compounds that could satisfy multiple geometrical constraints imposed by pockets. Previous sampling algorithms either sample in the graph space or only consider the 3D coordinates of atoms while ignoring other detailed chemical structures such as bond types and functional groups. To address the challenge, we develop Pocket2Mol, an E(3)-equivariant generative network composed of two modules: 1) a new graph neural network capturing both spatial and bonding relationships between atoms of the binding pockets and 2) a new efficient algorithm which samples new drug candidates conditioned on the pocket representations from a tractable distribution without relying on MCMC. Experimental results demonstrate that molecules sampled from Pocket2Mol achieve significantly better binding affinity and other drug properties such as druglikeness and synthetic accessibility.

Jiaqi Guan, Wesley Wei Qian, Xingang Peng et al.

Rich data and powerful machine learning models allow us to design drugs for a specific protein target \textit{in silico}. Recently, the inclusion of 3D structures during targeted drug design shows superior performance to other target-free models as the atomic interaction in the 3D space is explicitly modeled. However, current 3D target-aware models either rely on the voxelized atom densities or the autoregressive sampling process, which are not equivariant to rotation or easily violate geometric constraints resulting in unrealistic structures. In this work, we develop a 3D equivariant diffusion model to solve the above challenges. To achieve target-aware molecule design, our method learns a joint generative process of both continuous atom coordinates and categorical atom types with a SE(3)-equivariant network. Moreover, we show that our model can serve as an unsupervised feature extractor to estimate the binding affinity under proper parameterization, which provides an effective way for drug screening. To evaluate our model, we propose a comprehensive framework to evaluate the quality of sampled molecules from different dimensions. Empirical studies show our model could generate molecules with more realistic 3D structures and better affinities towards the protein targets, and improve binding affinity ranking and prediction without retraining.

Yuanyi Zhong, Haoran Tang, Junkun Chen et al.

Self-supervised contrastive learning is a powerful tool to learn visual representation without labels. Prior work has primarily focused on evaluating the recognition accuracy of various pre-training algorithms, but has overlooked other behavioral aspects. In addition to accuracy, distributional robustness plays a critical role in the reliability of machine learning models. We design and conduct a series of robustness tests to quantify the behavioral differences between contrastive learning and supervised learning to downstream or pre-training data distribution changes. These tests leverage data corruptions at multiple levels, ranging from pixel-level gamma distortion to patch-level shuffling and to dataset-level distribution shift. Our tests unveil intriguing robustness behaviors of contrastive and supervised learning. On the one hand, under downstream corruptions, we generally observe that contrastive learning is surprisingly more robust than supervised learning. On the other hand, under pre-training corruptions, we find contrastive learning vulnerable to patch shuffling and pixel intensity change, yet less sensitive to dataset-level distribution change. We attempt to explain these results through the role of data augmentation and feature space properties. Our insight has implications in improving the downstream robustness of supervised learning.

Zhizhou Ren, Anji Liu, Yitao Liang et al.

Learning new task-specific skills from a few trials is a fundamental challenge for artificial intelligence. Meta reinforcement learning (meta-RL) tackles this problem by learning transferable policies that support few-shot adaptation to unseen tasks. Despite recent advances in meta-RL, most existing methods require the access to the environmental reward function of new tasks to infer the task objective, which is not realistic in many practical applications. To bridge this gap, we study the problem of few-shot adaptation in the context of human-in-the-loop reinforcement learning. We develop a meta-RL algorithm that enables fast policy adaptation with preference-based feedback. The agent can adapt to new tasks by querying human's preference between behavior trajectories instead of using per-step numeric rewards. By extending techniques from information theory, our approach can design query sequences to maximize the information gain from human interactions while tolerating the inherent error of non-expert human oracle. In experiments, we extensively evaluate our method, Adaptation with Noisy OracLE (ANOLE), on a variety of meta-RL benchmark tasks and demonstrate substantial improvement over baseline algorithms in terms of both feedback efficiency and error tolerance.

Tanmay Gangwani, Yuan Zhou, Jian Peng

Learning to perform tasks by leveraging a dataset of expert observations, also known as imitation learning from observations (ILO), is an important paradigm for learning skills without access to the expert reward function or the expert actions. We consider ILO in the setting where the expert and the learner agents operate in different environments, with the source of the discrepancy being the transition dynamics model. Recent methods for scalable ILO utilize adversarial learning to match the state-transition distributions of the expert and the learner, an approach that becomes challenging when the dynamics are dissimilar. In this work, we propose an algorithm that trains an intermediary policy in the learner environment and uses it as a surrogate expert for the learner. The intermediary policy is learned such that the state transitions generated by it are close to the state transitions in the expert dataset. To derive a practical and scalable algorithm, we employ concepts from prior work on estimating the support of a probability distribution. Experiments using MuJoCo locomotion tasks highlight that our method compares favorably to the baselines for ILO with transition dynamics mismatch.

Daniel D Kim, Rajat S Chandra, Jian Peng et al.

Deep learning models have demonstrated great potential in medical 3D imaging, but their development is limited by the expensive, large volume of annotated data required. Active learning (AL) addresses this by training a model on a subset of the most informative data samples without compromising performance. We compared different AL strategies and propose a framework that minimizes the amount of data needed for state-of-the-art performance. 638 multi-institutional brain tumor MRI images were used to train a 3D U-net model and compare AL strategies. We investigated uncertainty sampling, annotation redundancy restriction, and initial dataset selection techniques. Uncertainty estimation techniques including Bayesian estimation with dropout, bootstrapping, and margins sampling were compared to random query. Strategies to avoid annotation redundancy by removing similar images within the to-be-annotated subset were considered as well. We determined the minimum amount of data necessary to achieve similar performance to the model trained on the full dataset (α = 0.1). A variance-based selection strategy using radiomics to identify the initial training dataset is also proposed. Bayesian approximation with dropout at training and testing showed similar results to that of the full data model with less than 20% of the training data (p=0.293) compared to random query achieving similar performance at 56.5% of the training data (p=0.814). Annotation redundancy restriction techniques achieved state-of-the-art performance at approximately 40%-50% of the training data. Radiomics dataset initialization had higher Dice with initial dataset sizes of 20 and 80 images, but improvements were not significant. In conclusion, we investigated various AL strategies with dropout uncertainty estimation achieving state-of-the-art performance with the least annotated data.

Julong Young, Junhui Chen, Feihu Huang et al.

Transformers have demonstrated impressive strength in long-term series forecasting. Existing prediction research mostly focused on mapping past short sub-series (lookback window) to future series (forecast window). The longer training dataset time series will be discarded, once training is completed. Models can merely rely on lookback window information for inference, which impedes models from analyzing time series from a global perspective. And these windows used by Transformers are quite narrow because they must model each time-step therein. Under this point-wise processing style, broadening windows will rapidly exhaust their model capacity. This, for fine-grained time series, leads to a bottleneck in information input and prediction output, which is mortal to long-term series forecasting. To overcome the barrier, we propose a brand-new methodology to utilize Transformer for time series forecasting. Specifically, we split time series into patches by day and reform point-wise to patch-wise processing, which considerably enhances the information input and output of Transformers. To further help models leverage the whole training set's global information during inference, we distill the information, store it in time representations, and replace series with time representations as the main modeling entities. Our designed time-modeling Transformer -- Dateformer yields state-of-the-art accuracy on 7 real-world datasets with a 33.6\% relative improvement and extends the maximum forecast range to half-year.

Jiahan Li, Shitong Luo, Congyue Deng et al.

By folding into particular 3D structures, proteins play a key role in living beings. To learn meaningful representation from a protein structure for downstream tasks, not only the global backbone topology but the local fine-grained orientational relations between amino acids should also be considered. In this work, we propose the Orientation-Aware Graph Neural Networks (OAGNNs) to better sense the geometric characteristics in protein structure (e.g. inner-residue torsion angles, inter-residue orientations). Extending a single weight from a scalar to a 3D vector, we construct a rich set of geometric-meaningful operations to process both the classical and SO(3) representations of a given structure. To plug our designed perceptron unit into existing Graph Neural Networks, we further introduce an equivariant message passing paradigm, showing superior versatility in maintaining SO(3)-equivariance at the global scale. Experiments have shown that our OAGNNs have a remarkable ability to sense geometric orientational features compared to classical networks. OAGNNs have also achieved state-of-the-art performance on various computational biology applications related to protein 3D structures. The code is available at https://github.com/Ced3-han/OAGNN/tree/main.

Yuanyi Zhong, Jianfeng Wang, Jian Peng et al.

In this paper, we propose an effective knowledge transfer framework to boost the weakly supervised object detection accuracy with the help of an external fully-annotated source dataset, whose categories may not overlap with the target domain. This setting is of great practical value due to the existence of many off-the-shelf detection datasets. To more effectively utilize the source dataset, we propose to iteratively transfer the knowledge from the source domain by a one-class universal detector and learn the target-domain detector. The box-level pseudo ground truths mined by the target-domain detector in each iteration effectively improve the one-class universal detector. Therefore, the knowledge in the source dataset is more thoroughly exploited and leveraged. Extensive experiments are conducted with Pascal VOC 2007 as the target weakly-annotated dataset and COCO/ImageNet as the source fully-annotated dataset. With the proposed solution, we achieved an mAP of $59.7\%$ detection performance on the VOC test set and an mAP of $60.2\%$ after retraining a fully supervised Faster RCNN with the mined pseudo ground truths. This is significantly better than any previously known results in related literature and sets a new state-of-the-art of weakly supervised object detection under the knowledge transfer setting. Code: \url{https://github.com/mikuhatsune/wsod_transfer}.

Jiaqi Guan, Jiahan Li, Xiangxin Zhou et al.

Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation. Inspired by the biochemical observation that ligands binding to the same target protein tend to adopt similar poses, we propose \textsc{GroupBind}, a novel molecular docking framework that simultaneously considers multiple ligands docking to a protein. This is achieved by introducing an interaction layer for the group of ligands and a triangle attention module for embedding protein-ligand and group-ligand pairs. By integrating our approach with diffusion-based docking model, we set a new S performance on the PDBBind blind docking benchmark, demonstrating the effectiveness of our proposed molecular docking paradigm.

Jiahan Li, Chaoran Cheng, Zuofan Wu et al.

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first multi-modal deep generative model grounded in the flow-matching framework for the design of full-atom peptides that target specific protein receptors. Drawing inspiration from the crucial roles of residue backbone orientations and side-chain dynamics in protein-peptide interactions, we characterize the peptide structure using rigid backbone frames within the $\mathrm{SE}(3)$ manifold and side-chain angles on high-dimensional tori. Furthermore, we represent discrete residue types in the peptide sequence as categorical distributions on the probability simplex. By learning the joint distributions of each modality using derived flows and vector fields on corresponding manifolds, our method excels in the fine-grained design of full-atom peptides. Harnessing the multi-modal paradigm, our approach adeptly tackles various tasks such as fix-backbone sequence design and side-chain packing through partial sampling. Through meticulously crafted experiments, we demonstrate that PepFlow exhibits superior performance in comprehensive benchmarks, highlighting its significant potential in computational peptide design and analysis.

Zhizhou Ren, Ruihan Guo, Yuan Zhou et al.

Many practical applications of reinforcement learning require agents to learn from sparse and delayed rewards. It challenges the ability of agents to attribute their actions to future outcomes. In this paper, we consider the problem formulation of episodic reinforcement learning with trajectory feedback. It refers to an extreme delay of reward signals, in which the agent can only obtain one reward signal at the end of each trajectory. A popular paradigm for this problem setting is learning with a designed auxiliary dense reward function, namely proxy reward, instead of sparse environmental signals. Based on this framework, this paper proposes a novel reward redistribution algorithm, randomized return decomposition (RRD), to learn a proxy reward function for episodic reinforcement learning. We establish a surrogate problem by Monte-Carlo sampling that scales up least-squares-based reward redistribution to long-horizon problems. We analyze our surrogate loss function by connection with existing methods in the literature, which illustrates the algorithmic properties of our approach. In experiments, we extensively evaluate our proposed method on a variety of benchmark tasks with episodic rewards and demonstrate substantial improvement over baseline algorithms.

Yuanyi Zhong, Bodi Yuan, Hong Wu et al.

We present a novel semi-supervised semantic segmentation method which jointly achieves two desiderata of segmentation model regularities: the label-space consistency property between image augmentations and the feature-space contrastive property among different pixels. We leverage the pixel-level L2 loss and the pixel contrastive loss for the two purposes respectively. To address the computational efficiency issue and the false negative noise issue involved in the pixel contrastive loss, we further introduce and investigate several negative sampling techniques. Extensive experiments demonstrate the state-of-the-art performance of our method (PC2Seg) with the DeepLab-v3+ architecture, in several challenging semi-supervised settings derived from the VOC, Cityscapes, and COCO datasets.

Yuanyi Zhong, Jianfeng Wang, Lijuan Wang et al.

This paper presents a detection-aware pre-training (DAP) approach, which leverages only weakly-labeled classification-style datasets (e.g., ImageNet) for pre-training, but is specifically tailored to benefit object detection tasks. In contrast to the widely used image classification-based pre-training (e.g., on ImageNet), which does not include any location-related training tasks, we transform a classification dataset into a detection dataset through a weakly supervised object localization method based on Class Activation Maps to directly pre-train a detector, making the pre-trained model location-aware and capable of predicting bounding boxes. We show that DAP can outperform the traditional classification pre-training in terms of both sample efficiency and convergence speed in downstream detection tasks including VOC and COCO. In particular, DAP boosts the detection accuracy by a large margin when the number of examples in the downstream task is small.

Yuanyi Zhong, Jianfeng Wang, Jian Peng et al.

In this paper, we propose a general approach to optimize anchor boxes for object detection. Nowadays, anchor boxes are widely adopted in state-of-the-art detection frameworks. However, these frameworks usually pre-define anchor box shapes in heuristic ways and fix the sizes during training. To improve the accuracy and reduce the effort of designing anchor boxes, we propose to dynamically learn the anchor shapes, which allows the anchors to automatically adapt to the data distribution and the network learning capability. The learning approach can be easily implemented with stochastic gradient descent and can be plugged into any anchor box-based detection framework. The extra training cost is almost negligible and it has no impact on the inference time or memory cost. Exhaustive experiments demonstrate that the proposed anchor optimization method consistently achieves significant improvement ($\ge 1\%$ mAP absolute gain) over the baseline methods on several benchmark datasets including Pascal VOC 07+12, MS COCO and Brainwash. Meanwhile, the robustness is also verified towards different anchor initialization methods and the number of anchor shapes, which greatly simplifies the problem of anchor box design.

Haifeng Li, Jian Peng, Chao Tao et al.

Recently, deep convolutional neural network (DCNN) achieved increasingly remarkable success and rapidly developed in the field of natural image recognition. Compared with the natural image, the scale of remote sensing image is larger and the scene and the object it represents are more macroscopic. This study inquires whether remote sensing scene and natural scene recognitions differ and raises the following questions: What are the key factors in remote sensing scene recognition? Is the DCNN recognition mechanism centered on object recognition still applicable to the scenarios of remote sensing scene understanding? We performed several experiments to explore the influence of the DCNN structure and the scale of remote sensing scene understanding from the perspective of scene complexity. Our experiment shows that understanding a complex scene depends on an in-depth network and multiple-scale perception. Using a visualization method, we qualitatively and quantitatively analyze the recognition mechanism in a complex remote sensing scene and demonstrate the importance of multi-objective joint semantic support.

Qingming Tang, Chao Yang, Jian Peng et al.

This paper considers the problem of estimating multiple related Gaussian graphical models from a $p$-dimensional dataset consisting of different classes. Our work is based upon the formulation of this problem as group graphical lasso. This paper proposes a novel hybrid covariance thresholding algorithm that can effectively identify zero entries in the precision matrices and split a large joint graphical lasso problem into small subproblems. Our hybrid covariance thresholding method is superior to existing uniform thresholding methods in that our method can split the precision matrix of each individual class using different partition schemes and thus split group graphical lasso into much smaller subproblems, each of which can be solved very fast. In addition, this paper establishes necessary and sufficient conditions for our hybrid covariance thresholding algorithm. The superior performance of our thresholding method is thoroughly analyzed and illustrated by a few experiments on simulated data and real gene expression data.