Chimera: Accurate retrosynthesis prediction by ensembling models with diverse inductive biases

Planning and conducting chemical syntheses remains a major bottleneck in the discovery of functional small molecules, and prevents fully leveraging generative AI for molecular inverse design. While early work has shown that ML-based retrosynthesis models can predict reasonable routes, their low accuracy for less frequent, yet important reactions has been pointed out. As multi-step search algorithms are limited to reactions suggested by the underlying model, the applicability of those tools is inherently constrained by the accuracy of retrosynthesis prediction. Inspired by how chemists use different strategies to ideate reactions, we propose Chimera: a framework for building highly accurate reaction models that combine predictions from diverse sources with complementary inductive biases using a learning-based ensembling strategy. We instantiate the framework with two newly developed models, which already by themselves achieve state of the art in their categories. Through experiments across several orders of magnitude in data scale and time-splits, we show Chimera outperforms all major models by a large margin, owing both to the good individual performance of its constituents, but also to the scalability of our ensembling strategy. Moreover, we find that PhD-level organic chemists prefer predictions from Chimera over baselines in terms of quality. Finally, we transfer the largest-scale checkpoint to an internal dataset from a major pharmaceutical company, showing robust generalization under distribution shift. With the new dimension that our framework unlocks, we anticipate further acceleration in the development of even more accurate models.

Theoretically Guaranteed Distribution Adaptable Learning

In many open environment applications, data are collected in the form of a stream, which exhibits an evolving distribution over time. How to design algorithms to track these evolving data distributions with provable guarantees, particularly in terms of the generalization ability, remains a formidable challenge. To handle this crucial but rarely studied problem and take a further step toward robust artificial intelligence, we propose a novel framework called Distribution Adaptable Learning (DAL). It enables the model to effectively track the evolving data distributions. By Encoding Feature Marginal Distribution Information (EFMDI), we broke the limitations of optimal transport to characterize the environmental changes and enable model reuse across diverse data distributions. It can enhance the reusable and evolvable properties of DAL in accommodating evolving distributions. Furthermore, to obtain the model interpretability, we not only analyze the generalization error bound of the local step in the evolution process, but also investigate the generalization error bound associated with the entire classifier trajectory of the evolution based on the Fisher-Rao distance. For demonstration, we also present two special cases within the framework, together with their optimizations and convergence analyses. Experimental results over both synthetic and real-world data distribution evolving tasks validate the effectiveness and practical utility of the proposed framework.

EPContrast: Effective Point-level Contrastive Learning for Large-scale Point Cloud Understanding

The acquisition of inductive bias through point-level contrastive learning holds paramount significance in point cloud pre-training. However, the square growth in computational requirements with the scale of the point cloud poses a substantial impediment to the practical deployment and execution. To address this challenge, this paper proposes an Effective Point-level Contrastive Learning method for large-scale point cloud understanding dubbed \textbf{EPContrast}, which consists of AGContrast and ChannelContrast. In practice, AGContrast constructs positive and negative pairs based on asymmetric granularity embedding, while ChannelContrast imposes contrastive supervision between channel feature maps. EPContrast offers point-level contrastive loss while concurrently mitigating the computational resource burden. The efficacy of EPContrast is substantiated through comprehensive validation on S3DIS and ScanNetV2, encompassing tasks such as semantic segmentation, instance segmentation, and object detection. In addition, rich ablation experiments demonstrate remarkable bias induction capabilities under label-efficient and one-epoch training settings.

Learning-based Traversability Costmap for Autonomous Off-road Navigation

Traversability estimation in off-road terrains is an essential procedure for autonomous navigation. However, creating reliable labels for complex interactions between the robot and the surface is still a challenging problem in learning-based costmap generation. To address this, we propose a method that predicts traversability costmaps by leveraging both visual and geometric information of the environment. To quantify the surface properties like roughness and bumpiness, we introduce a novel way of risk-aware labelling with proprioceptive information for network training. We validate our method in costmap prediction and navigation tasks for complex off-road scenarios. Our results demonstrate that our costmap prediction method excels in terms of average accuracy and MSE. The navigation results indicate that using our learned costmaps leads to safer and smoother driving, outperforming previous methods in terms of the highest success rate, lowest normalized trajectory length, lowest time cost, and highest mean stability across two scenarios.

SE3Set: Harnessing equivariant hypergraph neural networks for molecular representation learning

In this paper, we develop SE3Set, an SE(3) equivariant hypergraph neural network architecture tailored for advanced molecular representation learning. Hypergraphs are not merely an extension of traditional graphs; they are pivotal for modeling high-order relationships, a capability that conventional equivariant graph-based methods lack due to their inherent limitations in representing intricate many-body interactions. To achieve this, we first construct hypergraphs via proposing a new fragmentation method that considers both chemical and three-dimensional spatial information of molecular system. We then design SE3Set, which incorporates equivariance into the hypergragh neural network. This ensures that the learned molecular representations are invariant to spatial transformations, thereby providing robustness essential for accurate prediction of molecular properties. SE3Set has shown performance on par with state-of-the-art (SOTA) models for small molecule datasets like QM9 and MD17. It excels on the MD22 dataset, achieving a notable improvement of approximately 20% in accuracy across all molecules, which highlights the prevalence of complex many-body interactions in larger molecules. This exceptional performance of SE3Set across diverse molecular structures underscores its transformative potential in computational chemistry, offering a route to more accurate and physically nuanced modeling.

Token-level Direct Preference Optimization

Fine-tuning pre-trained Large Language Models (LLMs) is essential to align them with human values and intentions. This process often utilizes methods like pairwise comparisons and KL divergence against a reference LLM, focusing on the evaluation of full answers generated by the models. However, the generation of these responses occurs in a token level, following a sequential, auto-regressive fashion. In this paper, we introduce Token-level Direct Preference Optimization (TDPO), a novel approach to align LLMs with human preferences by optimizing policy at the token level. Unlike previous methods, which face challenges in divergence efficiency, TDPO incorporates forward KL divergence constraints for each token, improving alignment and diversity. Utilizing the Bradley-Terry model for a token-based reward system, TDPO enhances the regulation of KL divergence, while preserving simplicity without the need for explicit reward modeling. Experimental results across various text tasks demonstrate TDPO's superior performance in balancing alignment with generation diversity. Notably, fine-tuning with TDPO strikes a better balance than DPO in the controlled sentiment generation and single-turn dialogue datasets, and significantly improves the quality of generated responses compared to both DPO and PPO-based RLHF methods. Our code is open-sourced at https://github.com/Vance0124/Token-level-Direct-Preference-Optimization.

TON-VIO: Online Time Offset Modeling Networks for Robust Temporal Alignment in High Dynamic Motion VIO

Temporal misalignment (time offset) between sensors is common in low cost visual-inertial odometry (VIO) systems. Such temporal misalignment introduces inconsistent constraints for state estimation, leading to a significant positioning drift especially in high dynamic motion scenarios. In this article, we focus on online temporal calibration to reduce the positioning drift caused by the time offset for high dynamic motion VIO. For the time offset observation model, most existing methods rely on accurate state estimation or stable visual tracking. For the prediction model, current methods oversimplify the time offset as a constant value with white Gaussian noise. However, these ideal conditions are seldom satisfied in real high dynamic scenarios, resulting in the poor performance. In this paper, we introduce online time offset modeling networks (TON) to enhance real-time temporal calibration. TON improves the accuracy of time offset observation and prediction modeling. Specifically, for observation modeling, we propose feature velocity observation networks to enhance velocity computation for features in unstable visual tracking conditions. For prediction modeling, we present time offset prediction networks to learn its evolution pattern. To highlight the effectiveness of our method, we integrate the proposed TON into both optimization-based and filter-based VIO systems. Simulation and real-world experiments are conducted to demonstrate the enhanced performance of our approach. Additionally, to contribute to the VIO community, we will open-source the code of our method on: https://github.com/Franky-X/FVON-TPN.

Thermal-NeRF: Neural Radiance Fields from an Infrared Camera

In recent years, Neural Radiance Fields (NeRFs) have demonstrated significant potential in encoding highly-detailed 3D geometry and environmental appearance, positioning themselves as a promising alternative to traditional explicit representation for 3D scene reconstruction. However, the predominant reliance on RGB imaging presupposes ideal lighting conditions: a premise frequently unmet in robotic applications plagued by poor lighting or visual obstructions. This limitation overlooks the capabilities of infrared (IR) cameras, which excel in low-light detection and present a robust alternative under such adverse scenarios. To tackle these issues, we introduce Thermal-NeRF, the first method that estimates a volumetric scene representation in the form of a NeRF solely from IR imaging. By leveraging a thermal mapping and structural thermal constraint derived from the thermal characteristics of IR imaging, our method showcasing unparalleled proficiency in recovering NeRFs in visually degraded scenes where RGB-based methods fall short. We conduct extensive experiments to demonstrate that Thermal-NeRF can achieve superior quality compared to existing methods. Furthermore, we contribute a dataset for IR-based NeRF applications, paving the way for future research in IR NeRF reconstruction.

Reinforcement Learning from Bagged Reward: A Transformer-based Approach for Instance-Level Reward Redistribution

In reinforcement Learning (RL), an instant reward signal is generated for each action of the agent, such that the agent learns to maximize the cumulative reward to obtain the optimal policy. However, in many real-world applications, the instant reward signals are not obtainable by the agent. Instead, the learner only obtains rewards at the ends of bags, where a bag is defined as a partial sequence of a complete trajectory. In this situation, the learner has to face the significant difficulty of exploring the unknown instant rewards in the bags, which could not be addressed by existing approaches, including those trajectory-based approaches that consider only complete trajectories and ignore the inner reward distributions. To formally study this situation, we introduce a novel RL setting termed Reinforcement Learning from Bagged Rewards (RLBR), where only the bagged rewards of sequences can be obtained. We provide the theoretical study to establish the connection between RLBR and standard RL in Markov Decision Processes (MDPs). To effectively explore the reward distributions within the bagged rewards, we propose a Transformer-based reward model, the Reward Bag Transformer (RBT), which uses the self-attention mechanism for interpreting the contextual nuances and temporal dependencies within each bag. Extensive experimental analyses demonstrate the superiority of our method, particularly in its ability to mimic the original MDP's reward distribution, highlighting its proficiency in contextual understanding and adaptability to environmental dynamics.

Empirical Evidence for the Fragment level Understanding on Drug Molecular Structure of LLMs

AI for drug discovery has been a research hotspot in recent years, and SMILES-based language models has been increasingly applied in drug molecular design. However, no work has explored whether and how language models understand the chemical spatial structure from 1D sequences. In this work, we pre-train a transformer model on chemical language and fine-tune it toward drug design objectives, and investigate the correspondence between high-frequency SMILES substrings and molecular fragments. The results indicate that language models can understand chemical structures from the perspective of molecular fragments, and the structural knowledge learned through fine-tuning is reflected in the high-frequency SMILES substrings generated by the model.