Generative Flows on Synthetic Pathway for Drug Design

Generative models in drug discovery have recently gained attention as efficient alternatives to brute-force virtual screening. However, most existing models do not account for synthesizability, limiting their practical use in real-world scenarios. In this paper, we propose RxnFlow, which sequentially assembles molecules using predefined molecular building blocks and chemical reaction templates to constrain the synthetic chemical pathway. We then train on this sequential generating process with the objective of generative flow networks (GFlowNets) to generate both highly rewarded and diverse molecules. To mitigate the large action space of synthetic pathways in GFlowNets, we implement a novel action space subsampling method. This enables RxnFlow to learn generative flows over extensive action spaces comprising combinations of 1.2 million building blocks and 71 reaction templates without significant computational overhead. Additionally, RxnFlow can employ modified or expanded action spaces for generation without retraining, allowing for the introduction of additional objectives or the incorporation of newly discovered building blocks. We experimentally demonstrate that RxnFlow outperforms existing reaction-based and fragment-based models in pocket-specific optimization across various target pockets. Furthermore, RxnFlow achieves state-of-the-art performance on CrossDocked2020 for pocket-conditional generation, with an average Vina score of -8.85kcal/mol and 34.8% synthesizability.

Improved Off-policy Reinforcement Learning in Biological Sequence Design

Designing biological sequences with desired properties is a significant challenge due to the combinatorially vast search space and the high cost of evaluating each candidate sequence. To address these challenges, reinforcement learning (RL) methods, such as GFlowNets, utilize proxy models for rapid reward evaluation and annotated data for policy training. Although these approaches have shown promise in generating diverse and novel sequences, the limited training data relative to the vast search space often leads to the misspecification of proxy for out-of-distribution inputs. We introduce $\delta$-Conservative Search, a novel off-policy search method for training GFlowNets designed to improve robustness against proxy misspecification. The key idea is to incorporate conservativeness, controlled by parameter $\delta$, to constrain the search to reliable regions. Specifically, we inject noise into high-score offline sequences by randomly masking tokens with a Bernoulli distribution of parameter $\delta$ and then denoise masked tokens using the GFlowNet policy. Additionally, $\delta$ is adaptively adjusted based on the uncertainty of the proxy model for each data point. This enables the reflection of proxy uncertainty to determine the level of conservativeness. Experimental results demonstrate that our method consistently outperforms existing machine learning methods in discovering high-score sequences across diverse tasks-including DNA, RNA, protein, and peptide design-especially in large-scale scenarios.

Adaptive teachers for amortized samplers

Amortized inference is the task of training a parametric model, such as a neural network, to approximate a distribution with a given unnormalized density where exact sampling is intractable. When sampling is implemented as a sequential decision-making process, reinforcement learning (RL) methods, such as generative flow networks, can be used to train the sampling policy. Off-policy RL training facilitates the discovery of diverse, high-reward candidates, but existing methods still face challenges in efficient exploration. We propose to use an adaptive training distribution (the Teacher) to guide the training of the primary amortized sampler (the Student) by prioritizing high-loss regions. The Teacher, an auxiliary behavior model, is trained to sample high-error regions of the Student and can generalize across unexplored modes, thereby enhancing mode coverage by providing an efficient training curriculum. We validate the effectiveness of this approach in a synthetic environment designed to present an exploration challenge, two diffusion-based sampling tasks, and four biochemical discovery tasks demonstrating its ability to improve sample efficiency and mode coverage.

Learning Strategy Representation for Imitation Learning in Multi-Agent Games

The offline datasets for imitation learning (IL) in multi-agent games typically contain player trajectories exhibiting diverse strategies, which necessitate measures to prevent learning algorithms from acquiring undesirable behaviors. Learning representations for these trajectories is an effective approach to depicting the strategies employed by each demonstrator. However, existing learning strategies often require player identification or rely on strong assumptions, which are not appropriate for multi-agent games. Therefore, in this paper, we introduce the Strategy Representation for Imitation Learning (STRIL) framework, which (1) effectively learns strategy representations in multi-agent games, (2) estimates proposed indicators based on these representations, and (3) filters out sub-optimal data using the indicators. STRIL is a plug-in method that can be integrated into existing IL algorithms. We demonstrate the effectiveness of STRIL across competitive multi-agent scenarios, including Two-player Pong, Limit Texas Hold'em, and Connect Four. Our approach successfully acquires strategy representations and indicators, thereby identifying dominant trajectories and significantly enhancing existing IL performance across these environments.

PARCO: Learning Parallel Autoregressive Policies for Efficient Multi-Agent Combinatorial Optimization

Multi-agent combinatorial optimization problems such as routing and scheduling have great practical relevance but present challenges due to their NP-hard combinatorial nature, hard constraints on the number of possible agents, and hard-to-optimize objective functions. This paper introduces PARCO (Parallel AutoRegressive Combinatorial Optimization), a novel approach that learns fast surrogate solvers for multi-agent combinatorial problems with reinforcement learning by employing parallel autoregressive decoding. We propose a model with a Multiple Pointer Mechanism to efficiently decode multiple decisions simultaneously by different agents, enhanced by a Priority-based Conflict Handling scheme. Moreover, we design specialized Communication Layers that enable effective agent collaboration, thus enriching decision-making. We evaluate PARCO in representative multi-agent combinatorial problems in routing and scheduling and demonstrate that our learned solvers offer competitive results against both classical and neural baselines in terms of both solution quality and speed. We make our code openly available at https://github.com/ai4co/parco.

An Offline Meta Black-box Optimization Framework for Adaptive Design of Urban Traffic Light Management Systems

Complex urban road networks with high vehicle occupancy frequently face severe traffic congestion. Designing an effective strategy for managing multiple traffic lights plays a crucial role in managing congestion. However, most current traffic light management systems rely on human-crafted decisions, which may not adapt well to diverse traffic patterns. In this paper, we delve into two pivotal design components of the traffic light management system that can be dynamically adjusted to various traffic conditions: phase combination and phase time allocation. While numerous studies have sought an efficient strategy for managing traffic lights, most of these approaches consider a fixed traffic pattern and are limited to relatively small road networks. To overcome these limitations, we introduce a novel and practical framework to formulate the optimization of such design components using an offline meta black-box optimization. We then present a simple yet effective method to efficiently find a solution for the aforementioned problem. In our framework, we first collect an offline meta dataset consisting of pairs of design choices and corresponding congestion measures from various traffic patterns. After collecting the dataset, we employ the Attentive Neural Process (ANP) to predict the impact of the proposed design on congestion across various traffic patterns with well-calibrated uncertainty. Finally, Bayesian optimization, with ANP as a surrogate model, is utilized to find an optimal design for unseen traffic patterns through limited online simulations. Our experiment results show that our method outperforms state-of-the-art baselines on complex road networks in terms of the number of waiting vehicles. Surprisingly, the deployment of our method into a real-world traffic system was able to improve traffic throughput by 4.80\% compared to the original strategy.

Guided Trajectory Generation with Diffusion Models for Offline Model-based Optimization

Optimizing complex and high-dimensional black-box functions is ubiquitous in science and engineering fields. Unfortunately, the online evaluation of these functions is restricted due to time and safety constraints in most cases. In offline model-based optimization (MBO), we aim to find a design that maximizes the target function using only a pre-existing offline dataset. While prior methods consider forward or inverse approaches to address the problem, these approaches are limited by conservatism and the difficulty of learning highly multi-modal mappings. Recently, there has been an emerging paradigm of learning to improve solutions with synthetic trajectories constructed from the offline dataset. In this paper, we introduce a novel conditional generative modeling approach to produce trajectories toward high-scoring regions. First, we construct synthetic trajectories toward high-scoring regions using the dataset while injecting locality bias for consistent improvement directions. Then, we train a conditional diffusion model to generate trajectories conditioned on their scores. Lastly, we sample multiple trajectories from the trained model with guidance to explore high-scoring regions beyond the dataset and select high-fidelity designs among generated trajectories with the proxy function. Extensive experiment results demonstrate that our method outperforms competitive baselines on Design-Bench and its practical variants. The code is publicly available in \texttt{https://github.com/dbsxodud-11/GTG}.

RouteFinder: Towards Foundation Models for Vehicle Routing Problems

Vehicle Routing Problems (VRPs) are optimization problems with significant real-world implications in logistics, transportation, and supply chain management. Despite the recent progress made in learning to solve individual VRP variants, there is a lack of a unified approach that can effectively tackle a wide range of tasks, which is crucial for real-world impact. This paper introduces RouteFinder, a framework for developing foundation models for VRPs. Our key idea is that a foundation model for VRPs should be able to model variants by treating each variant as a subset of a larger VRP problem, equipped with different attributes. We introduce a parallelized environment that can handle any combination of attributes at the same time in a batched manner, and an efficient sampling procedure to train on a mix of problems at each optimization step that can greatly improve convergence robustness. We also introduce novel Global Feature Embeddings that project instance-wise attributes efficiently onto the latent space and help the model understand different VRP variants. Finally, we introduce Efficient Adapter Layers, a simple yet effective technique to finetune pre-trained RouteFinder models to solve novel variants with previously unseen attributes outside of the original feature space. We validate our approach through extensive experiments on 24 VRP variants, demonstrating competitive results over recent multi-task learning models. We make our code openly available at https://github.com/ai4co/routefinder.

Distributed Online Planning for Min-Max Problems in Networked Markov Games

Min-max problems are important in multi-agent sequential decision-making because they improve the performance of the worst-performing agent in the network. However, solving the multi-agent min-max problem is challenging. We propose a modular, distributed, online planning-based algorithm that is able to approximate the solution of the min-max objective in networked Markov games, assuming that the agents communicate within a network topology and the transition and reward functions are neighborhood-dependent. This set-up is encountered in the multi-robot setting. Our method consists of two phases at every planning step. In the first phase, each agent obtains sample returns based on its local reward function, by performing online planning. Using the samples from online planning, each agent constructs a concave approximation of its underlying local return as a function of only the action of its neighborhood at the next planning step. In the second phase, the agents deploy a distributed optimization framework that converges to the optimal immediate next action for each agent, based on the function approximations of the first phase. We demonstrate our algorithm's performance through formation control simulations.

GTA: Generative Trajectory Augmentation with Guidance for Offline Reinforcement Learning

Offline Reinforcement Learning (Offline RL) presents challenges of learning effective decision-making policies from static datasets without any online interactions. Data augmentation techniques, such as noise injection and data synthesizing, aim to improve Q-function approximation by smoothing the learned state-action region. However, these methods often fall short of directly improving the quality of offline datasets, leading to suboptimal results. In response, we introduce \textbf{GTA}, Generative Trajectory Augmentation, a novel generative data augmentation approach designed to enrich offline data by augmenting trajectories to be both high-rewarding and dynamically plausible. GTA applies a diffusion model within the data augmentation framework. GTA partially noises original trajectories and then denoises them with classifier-free guidance via conditioning on amplified return value. Our results show that GTA, as a general data augmentation strategy, enhances the performance of widely used offline RL algorithms in both dense and sparse reward settings. Furthermore, we conduct a quality analysis of data augmented by GTA and demonstrate that GTA improves the quality of the data. Our code is available at https://github.com/Jaewoopudding/GTA