Guoqing Liu

Qingyan Guo, Rui Wang, Junliang Guo et al. · microsoft-research

Large Language Models (LLMs) excel in various tasks, but they rely on carefully crafted prompts that often demand substantial human effort. To automate this process, in this paper, we propose a novel framework for discrete prompt optimization, called EvoPrompt, which borrows the idea of evolutionary algorithms (EAs) as they exhibit good performance and fast convergence. To enable EAs to work on discrete prompts, which are natural language expressions that need to be coherent and human-readable, we connect LLMs with EAs. This approach allows us to simultaneously leverage the powerful language processing capabilities of LLMs and the efficient optimization performance of EAs. Specifically, abstaining from any gradients or parameters, EvoPrompt starts from a population of prompts and iteratively generates new prompts with LLMs based on the evolutionary operators, improving the population based on the development set. We optimize prompts for both closed- and open-source LLMs including GPT-3.5 and Alpaca, on 31 datasets covering language understanding, generation tasks, as well as BIG-Bench Hard (BBH) tasks. EvoPrompt significantly outperforms human-engineered prompts and existing methods for automatic prompt generation (e.g., up to 25% on BBH). Furthermore, EvoPrompt demonstrates that connecting LLMs with EAs creates synergies, which could inspire further research on the combination of LLMs and conventional algorithms.

Guoqing Liu, Di Xue, Shufang Xie et al.

Retrosynthesis, which aims to find a route to synthesize a target molecule from commercially available starting materials, is a critical task in drug discovery and materials design. Recently, the combination of ML-based single-step reaction predictors with multi-step planners has led to promising results. However, the single-step predictors are mostly trained offline to optimize the single-step accuracy, without considering complete routes. Here, we leverage reinforcement learning (RL) to improve the single-step predictor, by using a tree-shaped MDP to optimize complete routes. Specifically, we propose a novel online training algorithm, called Planning with Dual Value Networks (PDVN), which alternates between the planning phase and updating phase. In PDVN, we construct two separate value networks to predict the synthesizability and cost of molecules, respectively. To maintain the single-step accuracy, we design a two-branch network structure for the single-step predictor. On the widely-used USPTO dataset, our PDVN algorithm improves the search success rate of existing multi-step planners (e.g., increasing the success rate from 85.79% to 98.95% for Retro*, and reducing the number of model calls by half while solving 99.47% molecules for RetroGraph). Additionally, PDVN helps find shorter synthesis routes (e.g., reducing the average route length from 5.76 to 4.83 for Retro*, and from 5.63 to 4.78 for RetroGraph). Our code is available at \url{https://github.com/DiXue98/PDVN}.

Guoqing Liu, Mengzhang Cai, Li Zhao et al.

Deep reinforcement learning (DRL) has attracted much attention in automated game testing. Early attempts rely on game internal information for game space exploration, thus requiring deep integration with games, which is inconvenient for practical applications. In this work, we propose using only screenshots/pixels as input for automated game testing and build a general game testing agent, Inspector, that can be easily applied to different games without deep integration with games. In addition to covering all game space for testing, our agent tries to take human-like behaviors to interact with key objects in a game, since some bugs usually happen in player-object interactions. Inspector is based on purely pixel inputs and comprises three key modules: game space explorer, key object detector, and human-like object investigator. Game space explorer aims to explore the whole game space by using a curiosity-based reward function with pixel inputs. Key object detector aims to detect key objects in a game, based on a small number of labeled screenshots. Human-like object investigator aims to mimic human behaviors for investigating key objects via imitation learning. We conduct experiments on two popular video games: Shooter Game and Action RPG Game. Experiment results demonstrate the effectiveness of Inspector in exploring game space, detecting key objects, and investigating objects. Moreover, Inspector successfully discovers two potential bugs in those two games. The demo video of Inspector is available at https://github.com/Inspector-GameTesting/Inspector-GameTesting.

Junyuan Deng, Xieyuanli Chen, Songpengcheng Xia et al.

Simultaneously odometry and mapping using LiDAR data is an important task for mobile systems to achieve full autonomy in large-scale environments. However, most existing LiDAR-based methods prioritize tracking quality over reconstruction quality. Although the recently developed neural radiance fields (NeRF) have shown promising advances in implicit reconstruction for indoor environments, the problem of simultaneous odometry and mapping for large-scale scenarios using incremental LiDAR data remains unexplored. To bridge this gap, in this paper, we propose a novel NeRF-based LiDAR odometry and mapping approach, NeRF-LOAM, consisting of three modules neural odometry, neural mapping, and mesh reconstruction. All these modules utilize our proposed neural signed distance function, which separates LiDAR points into ground and non-ground points to reduce Z-axis drift, optimizes odometry and voxel embeddings concurrently, and in the end generates dense smooth mesh maps of the environment. Moreover, this joint optimization allows our NeRF-LOAM to be pre-trained free and exhibit strong generalization abilities when applied to different environments. Extensive evaluations on three publicly available datasets demonstrate that our approach achieves state-of-the-art odometry and mapping performance, as well as a strong generalization in large-scale environments utilizing LiDAR data. Furthermore, we perform multiple ablation studies to validate the effectiveness of our network design. The implementation of our approach will be made available at https://github.com/JunyuanDeng/NeRF-LOAM.

Shangkun Sun, Jiaming Liu, Thomas H. Li et al.

Occlusions between consecutive frames have long posed a significant challenge in optical flow estimation. The inherent ambiguity introduced by occlusions directly violates the brightness constancy constraint and considerably hinders pixel-to-pixel matching. To address this issue, multi-frame optical flow methods leverage adjacent frames to mitigate the local ambiguity. Nevertheless, prior multi-frame methods predominantly adopt recursive flow estimation, resulting in a considerable computational overlap. In contrast, we propose a streamlined in-batch framework that eliminates the need for extensive redundant recursive computations while concurrently developing effective spatio-temporal modeling approaches under in-batch estimation constraints. Specifically, we present a Streamlined In-batch Multi-frame (SIM) pipeline tailored to video input, attaining a similar level of time efficiency to two-frame networks. Furthermore, we introduce an efficient Integrative Spatio-temporal Coherence (ISC) modeling method for effective spatio-temporal modeling during the encoding phase, which introduces no additional parameter overhead. Additionally, we devise a Global Temporal Regressor (GTR) that effectively explores temporal relations during decoding. Benefiting from the efficient SIM pipeline and effective modules, StreamFlow not only excels in terms of performance on the challenging KITTI and Sintel datasets, with particular improvement in occluded areas but also attains a remarkable $63.82\%$ enhancement in speed compared with previous multi-frame methods. The code will be available soon at https://github.com/littlespray/StreamFlow.

Krzysztof Maziarz, Austin Tripp, Guoqing Liu et al.

Automated Synthesis Planning has recently re-emerged as a research area at the intersection of chemistry and machine learning. Despite the appearance of steady progress, we argue that imperfect benchmarks and inconsistent comparisons mask systematic shortcomings of existing techniques, and unnecessarily hamper progress. To remedy this, we present a synthesis planning library with an extensive benchmarking framework, called syntheseus, which promotes best practice by default, enabling consistent meaningful evaluation of single-step models and multi-step planning algorithms. We demonstrate the capabilities of syntheseus by re-evaluating several previous retrosynthesis algorithms, and find that the ranking of state-of-the-art models changes in controlled evaluation experiments. We end with guidance for future works in this area, and call the community to engage in the discussion on how to improve benchmarks for synthesis planning.

Xiaowen Fu, Bingxin Wang, Xinzhou Guo et al.

Recently, multimodal electroencephalogram (EEG) learning has shown great promise in disease detection. At the same time, ensuring privacy in clinical studies has become increasingly crucial due to legal and ethical concerns. One widely adopted scheme for privacy protection is differential privacy (DP) because of its clear interpretation and ease of implementation. Although numerous methods have been proposed under DP, it has not been extensively studied for multimodal EEG data due to the complexities of models and signal data considered there. In this paper, we propose a novel Differentially Private Multimodal Laplacian Dropout (DP-MLD) scheme for multimodal EEG learning. Our approach proposes a novel multimodal representative learning model that processes EEG data by language models as text and other modal data by vision transformers as images, incorporating well-designed cross-attention mechanisms to effectively extract and integrate cross-modal features. To achieve DP, we design a novel adaptive feature-level Laplacian dropout scheme, where randomness allocation and performance are dynamically optimized within given privacy budgets. In the experiment on an open-source multimodal dataset of Freezing of Gait (FoG) in Parkinson's Disease (PD), our proposed method demonstrates an approximate 4\% improvement in classification accuracy, and achieves state-of-the-art performance in multimodal EEG learning under DP.

Yongcheng Zeng, Guoqing Liu, Weiyu Ma et al.

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.

Dongjie Huo, Haoyun Liu, Guoqing Liu et al.

Current embodied intelligent systems still face a substantial gap between high-level reasoning and low-level physical execution in open-world environments. Although Vision-Language-Action (VLA) models provide strong perception and intuitive responses, their open-loop nature limits long-horizon performance. Agents incorporating System 2 cognitive mechanisms improve planning, but usually operate in closed sandboxes with predefined toolkits and limited real-system control. OpenClaw provides a localized runtime with full system privileges, but lacks the embodied control architecture required for long-duration, multi-robot execution. We therefore propose ABot-Claw, an embodied extension of OpenClaw that integrates: 1) a unified embodiment interface with capability-driven scheduling for heterogeneous robot coordination; 2) a visual-centric cross-embodiment multimodal memory for persistent context retention and grounded retrieval; and 3) a critic-based closed-loop feedback mechanism with a generalist reward model for online progress evaluation, local correction, and replanning. With a decoupled architecture spanning the OpenClaw layer, shared service layer, and robot embodiment layer, ABot-Claw enables real-world interaction, closes the loop from natural language intent to physical action, and supports progressively self-evolving robotic agents in open, dynamic environments.

Guoqing Liu, Junren Li, Zihan Zhao et al.

Solving computer-aided synthesis planning is essential for enabling fully automated, robot-assisted synthesis workflows and improving the efficiency of drug discovery. A key challenge, however, is bridging the gap between computational route design and practical laboratory execution, particularly the accurate prediction of viable experimental procedures for each synthesis step. In this work, we present QFANG, a scientific reasoning language model capable of generating precise, structured experimental procedures directly from reaction equations, with explicit chain-of-thought reasoning. To develop QFANG, we curated a high-quality dataset comprising 905,990 chemical reactions paired with structured action sequences, extracted and processed from patent literature using large language models. We introduce a Chemistry-Guided Reasoning (CGR) framework that produces chain-of-thought data grounded in chemical knowledge at scale. The model subsequently undergoes supervised fine-tuning to elicit complex chemistry reasoning. Finally, we apply Reinforcement Learning from Verifiable Rewards (RLVR) to further enhance procedural accuracy. Experimental results demonstrate that QFANG outperforms advanced general-purpose reasoning models and nearest-neighbor retrieval baselines, measured by traditional NLP similarity metrics and a chemically aware evaluator using an LLM-as-a-judge. Moreover, QFANG generalizes to certain out-of-domain reaction classes and adapts to variations in laboratory conditions and user-specific constraints. We believe that QFANG's ability to generate high-quality synthesis procedures represents an important step toward bridging the gap between computational synthesis planning and fully automated laboratory synthesis.

Xiuyuan Hu, Guoqing Liu, Yang Zhao et al. · tsinghua

De novo drug design is a pivotal issue in pharmacology and a new area of focus in AI for science research. A central challenge in this field is to generate molecules with specific properties while also producing a wide range of diverse candidates. Although advanced technologies such as transformer models and reinforcement learning have been applied in drug design, their potential has not been fully realized. Therefore, we propose MolRL-MGPT, a reinforcement learning algorithm with multiple GPT agents for drug molecular generation. To promote molecular diversity, we encourage the agents to collaborate in searching for desirable molecules in diverse directions. Our algorithm has shown promising results on the GuacaMol benchmark and exhibits efficacy in designing inhibitors against SARS-CoV-2 protein targets. The codes are available at: https://github.com/HXYfighter/MolRL-MGPT.

Xuerui Su, Shufang Xie, Guoqing Liu et al. · microsoft-research

Recently, Large Language Models (LLMs) have rapidly evolved, approaching Artificial General Intelligence (AGI) while benefiting from large-scale reinforcement learning to enhance Human Alignment (HA) and Reasoning. Recent reward-based optimization algorithms, such as Proximal Policy Optimization (PPO) and Group Relative Policy Optimization (GRPO) have achieved significant performance on reasoning tasks, whereas preference-based optimization algorithms such as Direct Preference Optimization (DPO) significantly improve the performance of LLMs on human alignment. However, despite the strong performance of reward-based optimization methods in alignment tasks , they remain vulnerable to reward hacking. Furthermore, preference-based algorithms (such as Online DPO) haven't yet matched the performance of reward-based optimization algorithms (like PPO) on reasoning tasks, making their exploration in this specific area still a worthwhile pursuit. Motivated by these challenges, we propose the Trust Region Preference Approximation (TRPA) algorithm, which integrates rule-based optimization with preference-based optimization for reasoning tasks. As a preference-based algorithm, TRPA naturally eliminates the reward hacking issue. TRPA constructs preference levels using predefined rules, forms corresponding preference pairs, and leverages a novel optimization algorithm for RL training with a theoretical monotonic improvement guarantee. Experimental results demonstrate that TRPA not only achieves competitive performance on reasoning tasks but also exhibits robust stability. The code of this paper are released and updating on https://github.com/XueruiSu/Trust-Region-Preference-Approximation.git.

Guoqing Liu, Yu Guo, Caiying Wu et al.

Skin lesion segmentation is of great significance for skin lesion analysis and subsequent treatment. It is still a challenging task due to the irregular and fuzzy lesion borders, and diversity of skin lesions. In this paper, we propose Triple-UNet to automatically segment skin lesions. It is an organic combination of three UNet architectures with suitable modules. In order to concatenate the first and second sub-networks more effectively, we design a region of interest enhancement module (ROIE). The ROIE enhances the target object region of the image by using the predicted score map of the first UNet. The features learned by the first UNet and the enhanced image help the second UNet obtain a better score map. Finally, the results are fine-tuned by the third UNet. We evaluate our algorithm on a publicly available dataset of skin lesion segmentation. Experiments show that Triple-UNet outperforms the state-of-the-art on skin lesion segmentation.

Xiuyuan Hu, Guoqing Liu, Can Chen et al. · tsinghua

Structure-based drug discovery, encompassing the tasks of protein-ligand docking and pocket-aware 3D drug design, represents a core challenge in drug discovery. However, no existing work can deal with both tasks to effectively leverage the duality between them, and current methods for each task are hindered by challenges in modeling 3D information and the limitations of available data. To address these issues, we propose 3DMolFormer, a unified dual-channel transformer-based framework applicable to both docking and 3D drug design tasks, which exploits their duality by utilizing docking functionalities within the drug design process. Specifically, we represent 3D pocket-ligand complexes using parallel sequences of discrete tokens and continuous numbers, and we design a corresponding dual-channel transformer model to handle this format, thereby overcoming the challenges of 3D information modeling. Additionally, we alleviate data limitations through large-scale pre-training on a mixed dataset, followed by supervised and reinforcement learning fine-tuning techniques respectively tailored for the two tasks. Experimental results demonstrate that 3DMolFormer outperforms previous approaches in both protein-ligand docking and pocket-aware 3D drug design, highlighting its promising application in structure-based drug discovery. The code is available at: https://github.com/HXYfighter/3DMolFormer .

Yaxin Feng, Yuan Lan, Luchan Zhang et al.

Urban segmentation and lane detection are two important tasks for traffic scene perception. Accuracy and fast inference speed of visual perception are crucial for autonomous driving safety. Fine and complex geometric objects are the most challenging but important recognition targets in traffic scene, such as pedestrians, traffic signs and lanes. In this paper, a simple and efficient topology-aware energy loss function-based network training strategy named EIEGSeg is proposed. EIEGSeg is designed for multi-class segmentation on real-time traffic scene perception. To be specific, the convolutional neural network (CNN) extracts image features and produces multiple outputs, and the elastic interaction energy loss function (EIEL) drives the predictions moving toward the ground truth until they are completely overlapped. Our strategy performs well especially on fine-scale structure, \textit{i.e.} small or irregularly shaped objects can be identified more accurately, and discontinuity issues on slender objects can be improved. We quantitatively and qualitatively analyze our method on three traffic datasets, including urban scene segmentation data Cityscapes and lane detection data TuSimple and CULane. Our results demonstrate that EIEGSeg consistently improves the performance, especially on real-time, lightweight networks that are better suited for autonomous driving.

Zedong Chu, Shichao Xie, Xiaolong Wu et al.

Embodied navigation has long been fragmented by task-specific architectures. We introduce ABot-N0, a unified Vision-Language-Action (VLA) foundation model that achieves a ``Grand Unification'' across 5 core tasks: Point-Goal, Object-Goal, Instruction-Following, POI-Goal, and Person-Following. ABot-N0 utilizes a hierarchical ``Brain-Action'' architecture, pairing an LLM-based Cognitive Brain for semantic reasoning with a Flow Matching-based Action Expert for precise, continuous trajectory generation. To support large-scale learning, we developed the ABot-N0 Data Engine, curating 16.9M expert trajectories and 5.0M reasoning samples across 7,802 high-fidelity 3D scenes (10.7 $\text{km}^2$). ABot-N0 achieves new SOTA performance across 7 benchmarks, significantly outperforming specialized models. Furthermore, our Agentic Navigation System integrates a planner with hierarchical topological memory, enabling robust, long-horizon missions in dynamic real-world environments.

Tianxiang Ye, Qi Wu, Junyuan Deng et al.

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.

Yingce Xia, Peiran Jin, Shufang Xie et al. · microsoft-research

Foundation models have revolutionized natural language processing and artificial intelligence, significantly enhancing how machines comprehend and generate human languages. Inspired by the success of these foundation models, researchers have developed foundation models for individual scientific domains, including small molecules, materials, proteins, DNA, RNA and even cells. However, these models are typically trained in isolation, lacking the ability to integrate across different scientific domains. Recognizing that entities within these domains can all be represented as sequences, which together form the "language of nature", we introduce Nature Language Model (NatureLM), a sequence-based science foundation model designed for scientific discovery. Pre-trained with data from multiple scientific domains, NatureLM offers a unified, versatile model that enables various applications including: (i) generating and optimizing small molecules, proteins, RNA, and materials using text instructions; (ii) cross-domain generation/design, such as protein-to-molecule and protein-to-RNA generation; and (iii) top performance across different domains, matching or surpassing state-of-the-art specialist models. NatureLM offers a promising generalist approach for various scientific tasks, including drug discovery (hit generation/optimization, ADMET optimization, synthesis), novel material design, and the development of therapeutic proteins or nucleotides. We have developed NatureLM models in different sizes (1 billion, 8 billion, and 46.7 billion parameters) and observed a clear improvement in performance as the model size increases.

Mingqian Ma, Guoqing Liu, Chuan Cao et al. · microsoft-research

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to process ultra-long DNA sequences while preserving single-nucleotide resolution, as individual nucleotides play a critical role in DNA function. Second, success in this domain requires excelling at both generative and understanding tasks: generative tasks hold potential for therapeutic and industrial applications, while understanding tasks provide crucial insights into biological mechanisms and diseases. To address these challenges, we propose HybriDNA, a decoder-only DNA language model that incorporates a hybrid Transformer-Mamba2 architecture, seamlessly integrating the strengths of attention mechanisms with selective state-space models. This hybrid design enables HybriDNA to efficiently process DNA sequences up to 131kb in length with single-nucleotide resolution. HybriDNA achieves state-of-the-art performance across 33 DNA understanding datasets curated from the BEND, GUE, and LRB benchmarks, and demonstrates exceptional capability in generating synthetic cis-regulatory elements (CREs) with desired properties. Furthermore, we show that HybriDNA adheres to expected scaling laws, with performance improving consistently as the model scales from 300M to 3B and 7B parameters. These findings underscore HybriDNA's versatility and its potential to advance DNA research and applications, paving the way for innovations in understanding and engineering the "language of life".

Yongcheng Zeng, Xinyu Cui, Xuanfa Jin et al.

Self-Refinement refers to a model's ability to revise its own responses to produce improved outputs. This capability can also serve as a fundamental mechanism for Self-Improvement, for example, by reconstructing datasets with refined results to enhance intrinsic model performance. However, our comprehensive experiments reveal that large language models (LLMs) show no clear evidence of inherent Self-Refinement and may even experience response quality degradation after Self-Refinement. To address this issue, we propose EVOLVE, a simple and effective framework for eliciting and tracking the evolution of Self-Refinement through iterative training. We first explore optimization methods during training to activate the model's Self-Refinement capability. Then, at inference, we investigate various generation strategies to further enhance and utilize Self-Refinement while supplying the necessary data for training. Through synergistic optimization of training and inference stages, we continually evolve the model's Self-Refinement ability, enabling it to better refine its own responses. Moreover, we demonstrate the potential of leveraging Self-Refinement to achieve broader Self-Improvement of intrinsic model abilities. Experiments show that the evolved Self-Refinement ability enables the Llama-3.1-8B base model to surpass GPT-4o, achieving 62.3% length-controlled and 63.3% raw win rates on AlpacaEval 2, and 50.3% on Arena-Hard. It also generalizes effectively to out-of-domain reasoning tasks, improving performance on mathematical reasoning benchmarks such as GSM8K and MATH.

Gongbo Zhang, Yanting Li, Renqian Luo et al. · microsoft-research

Function in natural systems arises from one-dimensional sequences forming three-dimensional structures with specific properties. However, current generative models suffer from critical limitations: training objectives seldom target function directly, discrete sequences and continuous coordinates are optimized in isolation, and conformational ensembles are under-modeled. We present UniGenX, a unified generative foundation model that addresses these gaps by co-generating sequences and coordinates under direct functional and property objectives across proteins, molecules, and materials. UniGenX represents heterogeneous inputs as a mixed stream of symbolic and numeric tokens, where a decoder-only autoregressive transformer provides global context and a conditional diffusion head generates numeric fields steered by task-specific tokens. Besides the new high SOTAs on structure prediction tasks, the model demonstrates state-of-the-art or competitive performance for the function-aware generation across domains: in materials, it achieves "conflicted" multi-property conditional generation, yielding 436 crystal candidates meeting triple constraints, including 11 with novel compositions; in chemistry, it sets new benchmarks on five property targets and conformer ensemble generation on GEOM; and in biology, it improves success in modeling protein induced fit (RMSD < 2 Å) by over 23-fold and enhances EC-conditioned enzyme design. Ablation studies and cross-domain transfer substantiate the benefits of joint discrete-continuous training, establishing UniGenX as a significant advance from prediction to controllable, function-aware generation.

Xiuyuan Hu, Guoqing Liu, Can Chen et al. · tsinghua

Structure-based drug design (SBDD) is a critical task in drug discovery, requiring the generation of molecular information across two distinct modalities: discrete molecular graphs and continuous 3D coordinates. However, existing SBDD methods often overlook two key challenges: (1) the multi-modal nature of this task and (2) the causal relationship between these modalities, limiting their plausibility and performance. To address both challenges, we propose TransDiffSBDD, an integrated framework combining autoregressive transformers and diffusion models for SBDD. Specifically, the autoregressive transformer models discrete molecular information, while the diffusion model samples continuous distributions, effectively resolving the first challenge. To address the second challenge, we design a hybrid-modal sequence for protein-ligand complexes that explicitly respects the causality between modalities. Experiments on the CrossDocked2020 benchmark demonstrate that TransDiffSBDD outperforms existing baselines.

Zhiyi Pan, Guoqing Liu, Wei Gao et al.

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.

Krzysztof Maziarz, Guoqing Liu, Hubert Misztela et al.

Chemical synthesis remains a critical bottleneck in the discovery and manufacture of functional small molecules. AI-based synthesis planning models could be a potential remedy to find effective syntheses, and have made progress in recent years. However, they still struggle with less frequent, yet critical reactions for synthetic strategy, as well as hallucinated, incorrect predictions. This hampers multi-step search algorithms that rely on models, and leads to misalignment with chemists' expectations. Here we propose RetroChimera: a frontier retrosynthesis model, built upon two newly developed components with complementary inductive biases, which we fuse together using a new framework for integrating predictions from multiple sources via a learning-based ensembling strategy. Through experiments across several orders of magnitude in data scale and splitting strategy, we show RetroChimera outperforms all major models by a large margin, demonstrating robustness outside the training data, as well as for the first time the ability to learn from even a very small number of examples per reaction class. Moreover, industrial organic chemists prefer predictions from RetroChimera over the reactions it was trained on in terms of quality, revealing high levels of alignment. Finally, we demonstrate zero-shot transfer to an internal dataset from a major pharmaceutical company, showing robust generalization under distribution shift. With the new dimension that our ensembling framework unlocks, we anticipate further acceleration in the development of even more accurate models.

Songlin Fan, Wei Gao, Zhineng Chen et al.

The evolution of point cloud processing algorithms necessitates an accurate assessment for their quality. Previous works consistently regard point cloud quality assessment (PCQA) as a MOS regression problem and devise a deterministic mapping, ignoring the stochasticity in generating MOS from subjective tests. This work presents the first probabilistic architecture for no-reference PCQA, motivated by the labeling process of existing datasets. The proposed method can model the quality judging stochasticity of subjects through a tailored conditional variational autoencoder (CVAE) and produces multiple intermediate quality ratings. These intermediate ratings simulate the judgments from different subjects and are then integrated into an accurate quality prediction, mimicking the generation process of a ground truth MOS. Specifically, our method incorporates a Prior Module, a Posterior Module, and a Quality Rating Generator, where the former two modules are introduced to model the judging stochasticity in subjective tests, while the latter is developed to generate diverse quality ratings. Extensive experiments indicate that our approach outperforms previous cutting-edge methods by a large margin and exhibits gratifying cross-dataset robustness. Codes are available at https://git.openi.org.cn/OpenPointCloud/nrpcqa.

Xiuyuan Hu, Guoqing Liu, Yang Zhao et al. · tsinghua

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.

Ning Yang, Pengyu Wang, Guoqing Liu et al.

Safe Reinforcement Learning (RL) often faces significant issues such as constraint violations and instability, necessitating the use of constrained policy optimization, which seeks optimal policies while ensuring adherence to specific constraints like safety. Typically, constrained optimization problems are addressed by the Lagrangian method, a post-violation remedial approach that may result in oscillations and overshoots. Motivated by this, we propose a novel method named Proactive Constrained Policy Optimization (PCPO) that incorporates a preemptive penalty mechanism. This mechanism integrates barrier items into the objective function as the policy nears the boundary, imposing a cost. Meanwhile, we introduce a constraint-aware intrinsic reward to guide boundary-aware exploration, which is activated only when the policy approaches the constraint boundary. We establish theoretical upper and lower bounds for the duality gap and the performance of the PCPO update, shedding light on the method's convergence characteristics. Additionally, to enhance the optimization performance, we adopt a policy iteration approach. An interesting finding is that PCPO demonstrates significant stability in experiments. Experimental results indicate that the PCPO framework provides a robust solution for policy optimization under constraints, with important implications for future research and practical applications.

Ning Yang, Hai Lin, Yibo Liu et al.

Ensuring that large language models (LLMs) generate outputs aligned with human preferences is important for safe and effective AI interactions. While Direct Preference Optimization (DPO) employs an implicit reward function to optimize the policy model, however, it and its related variants overlook the differential importance of individual tokens and are sensitive to judgment noise in preference datasets during generation. Although recent methods attempt to assess the important weight of tokens via probability prediction or simplistic weighting schemes, these evaluation methods are prone to biases and still cannot fully address these issues. To solve this problem, we propose the Token-Importance Guided Direct Preference Optimization (TI-DPO), which introduces two key innovations: the gradient-based token-importance weights that dynamically prioritize critical tokens, and a triple loss that explicitly guides model outputs to approach human-preferred responses and stay away from non-preferred responses. Experimental results show that TI-DPO achieves higher accuracy and stronger generative diversity, providing more stable and computationally efficient solutions compared with DPO and other RLHF methods.

Chao Xu, Xijia Tang, Guoqing Liu et al.

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.

Yuting Tang, Xin-Qiang Cai, Yao-Xiang Ding et al.

In Reinforcement Learning (RL), it is commonly assumed that an immediate reward signal is generated for each action taken by the agent, helping the agent maximize cumulative rewards to obtain the optimal policy. However, in many real-world scenarios, designing immediate reward signals is difficult; instead, agents receive a single reward that is contingent upon a partial sequence or a complete trajectory. In this work, we define this challenging problem as RL from Bagged Reward (RLBR), where sequences of data are treated as bags with non-Markovian bagged rewards, leading to the formulation of Bagged Reward Markov Decision Processes (BRMDPs). Theoretically, we demonstrate that RLBR can be addressed by solving a standard MDP with properly redistributed bagged rewards allocated to each instance within a bag. Empirically, we find that reward redistribution becomes more challenging as the bag length increases, due to reduced informational granularity. Existing reward redistribution methods are insufficient to address these challenges. Therefore, we propose a novel reward redistribution method equipped with a bidirectional attention mechanism, enabling the accurate interpretation of contextual nuances and temporal dependencies within each bag. We experimentally demonstrate that our proposed method consistently outperforms existing approaches.

Mingfei Sun, Vitaly Kurin, Guoqing Liu et al.

Proximal Policy Optimization (PPO) methods learn a policy by iteratively performing multiple mini-batch optimization epochs of a surrogate objective with one set of sampled data. Ratio clipping PPO is a popular variant that clips the probability ratios between the target policy and the policy used to collect samples. Ratio clipping yields a pessimistic estimate of the original surrogate objective, and has been shown to be crucial for strong performance. We show in this paper that such ratio clipping may not be a good option as it can fail to effectively bound the ratios. Instead, one can directly optimize the original surrogate objective for multiple epochs; the key is to find a proper condition to early stop the optimization epoch in each iteration. Our theoretical analysis sheds light on how to determine when to stop the optimization epoch, and call the resulting algorithm Early Stopping Policy Optimization (ESPO). We compare ESPO with PPO across many continuous control tasks and show that ESPO significantly outperforms PPO. Furthermore, we show that ESPO can be easily scaled up to distributed training with many workers, delivering strong performance as well.

Guoqing Liu, Chuheng Zhang, Li Zhao et al.

Recently, various auxiliary tasks have been proposed to accelerate representation learning and improve sample efficiency in deep reinforcement learning (RL). However, existing auxiliary tasks do not take the characteristics of RL problems into consideration and are unsupervised. By leveraging returns, the most important feedback signals in RL, we propose a novel auxiliary task that forces the learnt representations to discriminate state-action pairs with different returns. Our auxiliary loss is theoretically justified to learn representations that capture the structure of a new form of state-action abstraction, under which state-action pairs with similar return distributions are aggregated together. In low data regime, our algorithm outperforms strong baselines on complex tasks in Atari games and DeepMind Control suite, and achieves even better performance when combined with existing auxiliary tasks.

Junjie Li, Sotetsu Koyamada, Qiwei Ye et al.

Artificial Intelligence (AI) has achieved great success in many domains, and game AI is widely regarded as its beachhead since the dawn of AI. In recent years, studies on game AI have gradually evolved from relatively simple environments (e.g., perfect-information games such as Go, chess, shogi or two-player imperfect-information games such as heads-up Texas hold'em) to more complex ones (e.g., multi-player imperfect-information games such as multi-player Texas hold'em and StartCraft II). Mahjong is a popular multi-player imperfect-information game worldwide but very challenging for AI research due to its complex playing/scoring rules and rich hidden information. We design an AI for Mahjong, named Suphx, based on deep reinforcement learning with some newly introduced techniques including global reward prediction, oracle guiding, and run-time policy adaptation. Suphx has demonstrated stronger performance than most top human players in terms of stable rank and is rated above 99.99% of all the officially ranked human players in the Tenhou platform. This is the first time that a computer program outperforms most top human players in Mahjong.

Ikuro Sato, Kohta Ishikawa, Guoqing Liu et al.

This study addresses an issue of co-adaptation between a feature extractor and a classifier in a neural network. A naive joint optimization of a feature extractor and a classifier often brings situations in which an excessively complex feature distribution adapted to a very specific classifier degrades the test performance. We introduce a method called Feature-extractor Optimization through Classifier Anonymization (FOCA), which is designed to avoid an explicit co-adaptation between a feature extractor and a particular classifier by using many randomly-generated, weak classifiers during optimization. We put forth a mathematical proposition that states the FOCA features form a point-like distribution within the same class in a class-separable fashion under special conditions. Real-data experiments under more general conditions provide supportive evidences.

Xiaogang Cheng, Guoqing Liu, Anders Hedman et al.

Vision-based methods for visibility estimation can play a critical role in reducing traffic accidents caused by fog and haze. To overcome the disadvantages of current visibility estimation methods, we present a novel data-driven approach based on Gaussian image entropy and piecewise stationary time series analysis (SPEV). This is the first time that Gaussian image entropy is used for estimating atmospheric visibility. To lessen the impact of landscape and sunshine illuminance on visibility estimation, we used region of interest (ROI) analysis and took into account relative ratios of image entropy, to improve estimation accuracy. We assume fog and haze cause blurred images and that fog and haze can be considered as a piecewise stationary signal. We used piecewise stationary time series analysis to construct the piecewise causal relationship between image entropy and visibility. To obtain a real-world visibility measure during fog and haze, a subjective assessment was established through a study with 36 subjects who performed visibility observations. Finally, a total of two million videos were used for training the SPEV model and validate its effectiveness. The videos were collected from the constantly foggy and hazy Tongqi expressway in Jiangsu, China. The contrast model of visibility estimation was used for algorithm performance comparison, and the validation results of the SPEV model were encouraging as 99.14% of the relative errors were less than 10%.

Jianxin Wu, Bin-Bin Gao, Guoqing Liu

In computer vision, an entity such as an image or video is often represented as a set of instance vectors, which can be SIFT, motion, or deep learning feature vectors extracted from different parts of that entity. Thus, it is essential to design efficient and effective methods to compare two sets of instance vectors. Existing methods such as FV, VLAD or Super Vectors have achieved excellent results. However, this paper shows that these methods are designed based on a generative perspective, and a discriminative method can be more effective in categorizing images or videos. The proposed D3 (discriminative distribution distance) method effectively compares two sets as two distributions, and proposes a directional total variation distance (DTVD) to measure how separated are they. Furthermore, a robust classifier-based method is proposed to estimate DTVD robustly. The D3 method is evaluated in action and image recognition tasks and has achieved excellent accuracy and speed. D3 also has a synergy with FV. The combination of D3 and FV has advantages over D3, FV, and VLAD.