Structure-based molecule optimization (SBMO) aims to optimize molecules with both continuous coordinates and discrete types against protein targets. A promising direction is to exert gradient guidance on generative models given its remarkable success in images, but it is challenging to guide discrete data and risks inconsistencies between modalities. To this end, we leverage a continuous and differentiable space derived through Bayesian inference, presenting Molecule Joint Optimization (MolJO), the first gradient-based SBMO framework that facilitates joint guidance signals across different modalities while preserving SE(3)-equivariance. We introduce a novel backward correction strategy that optimizes within a sliding window of the past histories, allowing for a seamless trade-off between explore-and-exploit during optimization. Our proposed MolJO achieves state-of-the-art performance on CrossDocked2020 benchmark (Success Rate 51.3% , Vina Dock -9.05 and SA 0.78), more than 4x improvement in Success Rate compared to the gradient-based counterpart, and 2x "Me-Better" Ratio as much as 3D baselines. Furthermore, we extend MolJO to a wide range of optimization settings, including multi-objective optimization and challenging tasks in drug design such as R-group optimization and scaffold hopping, further underscoring its versatility and potential.

Given the inherent non-stationarity prevalent in real-world applications, continual Reinforcement Learning (RL) aims to equip the agent with the capability to address a series of sequentially presented decision-making tasks. Within this problem setting, a pivotal challenge revolves around \textit{catastrophic forgetting} issue, wherein the agent is prone to effortlessly erode the decisional knowledge associated with past encountered tasks when learning the new one. In recent progresses, the \textit{generative replay} methods have showcased substantial potential by employing generative models to replay data distribution of past tasks. Compared to storing the data from past tasks directly, this category of methods circumvents the growing storage overhead and possible data privacy concerns. However, constrained by the expressive capacity of generative models, existing \textit{generative replay} methods face challenges in faithfully reconstructing the data distribution of past tasks, particularly in scenarios with a myriad of tasks or high-dimensional data. Inspired by the success of diffusion models in various generative tasks, this paper introduces a novel continual RL algorithm DISTR (Diffusion-based Trajectory Replay) that employs a diffusion model to memorize the high-return trajectory distribution of each encountered task and wakeups these distributions during the policy learning on new tasks. Besides, considering the impracticality of replaying all past data each time, a prioritization mechanism is proposed to prioritize the trajectory replay of pivotal tasks in our method. Empirical experiments on the popular continual RL benchmark \texttt{Continual World} demonstrate that our proposed method obtains a favorable balance between \textit{stability} and \textit{plasticity}, surpassing various existing continual RL baselines in average success rate.

World models play a crucial role in decision-making within embodied environments, enabling cost-free explorations that would otherwise be expensive in the real world. To facilitate effective decision-making, world models must be equipped with strong generalizability to support faithful imagination in out-of-distribution (OOD) regions and provide reliable uncertainty estimation to assess the credibility of the simulated experiences, both of which present significant challenges for prior scalable approaches. This paper introduces WHALE, a framework for learning generalizable world models, consisting of two key techniques: behavior-conditioning and retracing-rollout. Behavior-conditioning addresses the policy distribution shift, one of the primary sources of the world model generalization error, while retracing-rollout enables efficient uncertainty estimation without the necessity of model ensembles. These techniques are universal and can be combined with any neural network architecture for world model learning. Incorporating these two techniques, we present Whale-ST, a scalable spatial-temporal transformer-based world model with enhanced generalizability. We demonstrate the superiority of Whale-ST in simulation tasks by evaluating both value estimation accuracy and video generation fidelity. Additionally, we examine the effectiveness of our uncertainty estimation technique, which enhances model-based policy optimization in fully offline scenarios. Furthermore, we propose Whale-X, a 414M parameter world model trained on 970K trajectories from Open X-Embodiment datasets. We show that Whale-X exhibits promising scalability and strong generalizability in real-world manipulation scenarios using minimal demonstrations.

As a prominent category of imitation learning methods, adversarial imitation learning (AIL) has garnered significant practical success powered by neural network approximation. However, existing theoretical studies on AIL are primarily limited to simplified scenarios such as tabular and linear function approximation and involve complex algorithmic designs that hinder practical implementation, highlighting a gap between theory and practice. In this paper, we explore the theoretical underpinnings of online AIL with general function approximation. We introduce a new method called optimization-based AIL (OPT-AIL), which centers on performing online optimization for reward functions and optimism-regularized Bellman error minimization for Q-value functions. Theoretically, we prove that OPT-AIL achieves polynomial expert sample complexity and interaction complexity for learning near-expert policies. To our best knowledge, OPT-AIL is the first provably efficient AIL method with general function approximation. Practically, OPT-AIL only requires the approximate optimization of two objectives, thereby facilitating practical implementation. Empirical studies demonstrate that OPT-AIL outperforms previous state-of-the-art deep AIL methods in several challenging tasks.

Combining offline and online reinforcement learning (RL) techniques is indeed crucial for achieving efficient and safe learning where data acquisition is expensive. Existing methods replay offline data directly in the online phase, resulting in a significant challenge of data distribution shift and subsequently causing inefficiency in online fine-tuning. To address this issue, we introduce an innovative approach, \textbf{E}nergy-guided \textbf{DI}ffusion \textbf{S}ampling (EDIS), which utilizes a diffusion model to extract prior knowledge from the offline dataset and employs energy functions to distill this knowledge for enhanced data generation in the online phase. The theoretical analysis demonstrates that EDIS exhibits reduced suboptimality compared to solely utilizing online data or directly reusing offline data. EDIS is a plug-in approach and can be combined with existing methods in offline-to-online RL setting. By implementing EDIS to off-the-shelf methods Cal-QL and IQL, we observe a notable 20% average improvement in empirical performance on MuJoCo, AntMaze, and Adroit environments. Code is available at \url{https://github.com/liuxhym/EDIS}.

Conditional diffusion models have exhibited superior performance in high-fidelity text-guided visual generation and editing. Nevertheless, prevailing text-guided visual diffusion models primarily focus on incorporating text-visual relationships exclusively into the reverse process, often disregarding their relevance in the forward process. This inconsistency between forward and reverse processes may limit the precise conveyance of textual semantics in visual synthesis results. To address this issue, we propose a novel and general contextualized diffusion model (ContextDiff) by incorporating the cross-modal context encompassing interactions and alignments between text condition and visual sample into forward and reverse processes. We propagate this context to all timesteps in the two processes to adapt their trajectories, thereby facilitating cross-modal conditional modeling. We generalize our contextualized diffusion to both DDPMs and DDIMs with theoretical derivations, and demonstrate the effectiveness of our model in evaluations with two challenging tasks: text-to-image generation, and text-to-video editing. In each task, our ContextDiff achieves new state-of-the-art performance, significantly enhancing the semantic alignment between text condition and generated samples, as evidenced by quantitative and qualitative evaluations. Our code is available at https://github.com/YangLing0818/ContextDiff

Model-based methods in reinforcement learning offer a promising approach to enhance data efficiency by facilitating policy exploration within a dynamics model. However, accurately predicting sequential steps in the dynamics model remains a challenge due to the bootstrapping prediction, which attributes the next state to the prediction of the current state. This leads to accumulated errors during model roll-out. In this paper, we propose the Any-step Dynamics Model (ADM) to mitigate the compounding error by reducing bootstrapping prediction to direct prediction. ADM allows for the use of variable-length plans as inputs for predicting future states without frequent bootstrapping. We design two algorithms, ADMPO-ON and ADMPO-OFF, which apply ADM in online and offline model-based frameworks, respectively. In the online setting, ADMPO-ON demonstrates improved sample efficiency compared to previous state-of-the-art methods. In the offline setting, ADMPO-OFF not only demonstrates superior performance compared to recent state-of-the-art offline approaches but also offers better quantification of model uncertainty using only a single ADM.

Diffusion models have demonstrated exceptional efficacy in various generative applications. While existing models focus on minimizing a weighted sum of denoising score matching losses for data distribution modeling, their training primarily emphasizes instance-level optimization, overlooking valuable structural information within each mini-batch, indicative of pair-wise relationships among samples. To address this limitation, we introduce Structure-guided Adversarial training of Diffusion Models (SADM). In this pioneering approach, we compel the model to learn manifold structures between samples in each training batch. To ensure the model captures authentic manifold structures in the data distribution, we advocate adversarial training of the diffusion generator against a novel structure discriminator in a minimax game, distinguishing real manifold structures from the generated ones. SADM substantially improves existing diffusion transformers (DiT) and outperforms existing methods in image generation and cross-domain fine-tuning tasks across 12 datasets, establishing a new state-of-the-art FID of 1.58 and 2.11 on ImageNet for class-conditional image generation at resolutions of 256x256 and 512x512, respectively.

Diffusion models have emerged as a powerful new family of deep generative models with record-breaking performance in many applications, including image synthesis, video generation, and molecule design. In this survey, we provide an overview of the rapidly expanding body of work on diffusion models, categorizing the research into three key areas: efficient sampling, improved likelihood estimation, and handling data with special structures. We also discuss the potential for combining diffusion models with other generative models for enhanced results. We further review the wide-ranging applications of diffusion models in fields spanning from computer vision, natural language generation, temporal data modeling, to interdisciplinary applications in other scientific disciplines. This survey aims to provide a contextualized, in-depth look at the state of diffusion models, identifying the key areas of focus and pointing to potential areas for further exploration. Github: https://github.com/YangLing0818/Diffusion-Models-Papers-Survey-Taxonomy.

Diffusion models are a new class of generative models, and have dramatically promoted image generation with unprecedented quality and diversity. Existing diffusion models mainly try to reconstruct input image from a corrupted one with a pixel-wise or feature-wise constraint along spatial axes. However, such point-based reconstruction may fail to make each predicted pixel/feature fully preserve its neighborhood context, impairing diffusion-based image synthesis. As a powerful source of automatic supervisory signal, context has been well studied for learning representations. Inspired by this, we for the first time propose ConPreDiff to improve diffusion-based image synthesis with context prediction. We explicitly reinforce each point to predict its neighborhood context (i.e., multi-stride features/tokens/pixels) with a context decoder at the end of diffusion denoising blocks in training stage, and remove the decoder for inference. In this way, each point can better reconstruct itself by preserving its semantic connections with neighborhood context. This new paradigm of ConPreDiff can generalize to arbitrary discrete and continuous diffusion backbones without introducing extra parameters in sampling procedure. Extensive experiments are conducted on unconditional image generation, text-to-image generation and image inpainting tasks. Our ConPreDiff consistently outperforms previous methods and achieves a new SOTA text-to-image generation results on MS-COCO, with a zero-shot FID score of 6.21.