Planning a kinodynamically feasible path for a tractor-trailer vehicle is challenging for both search-based and learning-based methods due to the vehicle's unique kinematics and complex obstacles. These factors increase the likelihood of infeasible paths and exacerbate long-horizon issues. We introduce ME-PATS: a framework that mutually enhances the search-based planner and the learning-based agent for tractortrailer systems. The search-based planner provides successful trajectories to help the learning-based agent update its policy, while the agent improves the planner's efficiency through direct path simulation. Additionally, we propose two approaches to apply our framework to more challenging tasks: designing obstacle-aware networks to enhance the learning-based agents capabilities, and combining the planner's paths with the trained agent's simulated paths through multi-segment integration. Full details and results are available on our project website at https://github.com/FrankSinatral/TTsystems.

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.

Predicting the effects of protein mutations is crucial for analyzing protein functions and understanding genetic diseases. However, existing models struggle to effectively extract mutation-related local structure motifs from protein databases, which hinders their predictive accuracy and robustness. To tackle this problem, we design a novel retrieval-augmented framework for incorporating similar structure information in known protein structures. We create a vector database consisting of local structure motif embeddings from a pre-trained protein structure encoder, which allows for efficient retrieval of similar local structure motifs during mutation effect prediction. Our findings demonstrate that leveraging this method results in the SOTA performance across multiple protein mutation prediction datasets, and offers a scalable solution for studying mutation effects.

We study deep reinforcement learning (RL) algorithms with delayed rewards. In many real-world tasks, instant rewards are often not readily accessible or even defined immediately after the agent performs actions. In this work, we first formally define the environment with delayed rewards and discuss the challenges raised due to the non-Markovian nature of such environments. Then, we introduce a general off-policy RL framework with a new Q-function formulation that can handle the delayed rewards with theoretical convergence guarantees. For practical tasks with high dimensional state spaces, we further introduce the HC-decomposition rule of the Q-function in our framework which naturally leads to an approximation scheme that helps boost the training efficiency and stability. We finally conduct extensive experiments to demonstrate the superior performance of our algorithms over the existing work and their variants.

Designing protein sequences with a particular biological function is a long-lasting challenge for protein engineering. Recent advances in machine-learning-guided approaches focus on building a surrogate sequence-function model to reduce the burden of expensive in-lab experiments. In this paper, we study the exploration mechanism of model-guided sequence design. We leverage a natural property of protein fitness landscape that a concise set of mutations upon the wild-type sequence are usually sufficient to enhance the desired function. By utilizing this property, we propose Proximal Exploration (PEX) algorithm that prioritizes the evolutionary search for high-fitness mutants with low mutation counts. In addition, we develop a specialized model architecture, called Mutation Factorization Network (MuFacNet), to predict low-order mutational effects, which further improves the sample efficiency of model-guided evolution. In experiments, we extensively evaluate our method on a suite of in-silico protein sequence design tasks and demonstrate substantial improvement over baseline algorithms.

Coordination graph is a promising approach to model agent collaboration in multi-agent reinforcement learning. It conducts a graph-based value factorization and induces explicit coordination among agents to complete complicated tasks. However, one critical challenge in this paradigm is the complexity of greedy action selection with respect to the factorized values. It refers to the decentralized constraint optimization problem (DCOP), which and whose constant-ratio approximation are NP-hard problems. To bypass this systematic hardness, this paper proposes a novel method, named Self-Organized Polynomial-time Coordination Graphs (SOP-CG), which uses structured graph classes to guarantee the accuracy and the computational efficiency of collaborated action selection. SOP-CG employs dynamic graph topology to ensure sufficient value function expressiveness. The graph selection is unified into an end-to-end learning paradigm. In experiments, we show that our approach learns succinct and well-adapted graph topologies, induces effective coordination, and improves performance across a variety of cooperative multi-agent tasks.

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.

Episodic memory-based methods can rapidly latch onto past successful strategies by a non-parametric memory and improve sample efficiency of traditional reinforcement learning. However, little effort is put into the continuous domain, where a state is never visited twice, and previous episodic methods fail to efficiently aggregate experience across trajectories. To address this problem, we propose Generalizable Episodic Memory (GEM), which effectively organizes the state-action values of episodic memory in a generalizable manner and supports implicit planning on memorized trajectories. GEM utilizes a double estimator to reduce the overestimation bias induced by value propagation in the planning process. Empirical evaluation shows that our method significantly outperforms existing trajectory-based methods on various MuJoCo continuous control tasks. To further show the general applicability, we evaluate our method on Atari games with discrete action space, which also shows a significant improvement over baseline algorithms.

Double Q-learning is a classical method for reducing overestimation bias, which is caused by taking maximum estimated values in the Bellman operation. Its variants in the deep Q-learning paradigm have shown great promise in producing reliable value prediction and improving learning performance. However, as shown by prior work, double Q-learning is not fully unbiased and suffers from underestimation bias. In this paper, we show that such underestimation bias may lead to multiple non-optimal fixed points under an approximate Bellman operator. To address the concerns of converging to non-optimal stationary solutions, we propose a simple but effective approach as a partial fix for the underestimation bias in double Q-learning. This approach leverages an approximate dynamic programming to bound the target value. We extensively evaluate our proposed method in the Atari benchmark tasks and demonstrate its significant improvement over baseline algorithms.

Value factorization is a popular and promising approach to scaling up multi-agent reinforcement learning in cooperative settings, which balances the learning scalability and the representational capacity of value functions. However, the theoretical understanding of such methods is limited. In this paper, we formalize a multi-agent fitted Q-iteration framework for analyzing factorized multi-agent Q-learning. Based on this framework, we investigate linear value factorization and reveal that multi-agent Q-learning with this simple decomposition implicitly realizes a powerful counterfactual credit assignment, but may not converge in some settings. Through further analysis, we find that on-policy training or richer joint value function classes can improve its local or global convergence properties, respectively. Finally, to support our theoretical implications in practical realization, we conduct an empirical analysis of state-of-the-art deep multi-agent Q-learning algorithms on didactic examples and a broad set of StarCraft II unit micromanagement tasks.

Object-based approaches for learning action-conditioned dynamics has demonstrated promise for generalization and interpretability. However, existing approaches suffer from structural limitations and optimization difficulties for common environments with multiple dynamic objects. In this paper, we present a novel self-supervised learning framework, called Multi-level Abstraction Object-oriented Predictor (MAOP), which employs a three-level learning architecture that enables efficient object-based dynamics learning from raw visual observations. We also design a spatial-temporal relational reasoning mechanism for MAOP to support instance-level dynamics learning and handle partial observability. Our results show that MAOP significantly outperforms previous methods in terms of sample efficiency and generalization over novel environments for learning environment models. We also demonstrate that learned dynamics models enable efficient planning in unseen environments, comparable to true environment models. In addition, MAOP learns semantically and visually interpretable disentangled representations.

Goal-oriented reinforcement learning has recently been a practical framework for robotic manipulation tasks, in which an agent is required to reach a certain goal defined by a function on the state space. However, the sparsity of such reward definition makes traditional reinforcement learning algorithms very inefficient. Hindsight Experience Replay (HER), a recent advance, has greatly improved sample efficiency and practical applicability for such problems. It exploits previous replays by constructing imaginary goals in a simple heuristic way, acting like an implicit curriculum to alleviate the challenge of sparse reward signal. In this paper, we introduce Hindsight Goal Generation (HGG), a novel algorithmic framework that generates valuable hindsight goals which are easy for an agent to achieve in the short term and are also potential for guiding the agent to reach the actual goal in the long term. We have extensively evaluated our goal generation algorithm on a number of robotic manipulation tasks and demonstrated substantially improvement over the original HER in terms of sample efficiency.