Regulatory DNA sequence Design with Reinforcement Learning

Cis-regulatory elements (CREs), such as promoters and enhancers, are relatively short DNA sequences that directly regulate gene expression. The fitness of CREs, measured by their ability to modulate gene expression, highly depends on the nucleotide sequences, especially specific motifs known as transcription factor binding sites (TFBSs). Designing high-fitness CREs is crucial for therapeutic and bioengineering applications. Current CRE design methods are limited by two major drawbacks: (1) they typically rely on iterative optimization strategies that modify existing sequences and are prone to local optima, and (2) they lack the guidance of biological prior knowledge in sequence optimization. In this paper, we address these limitations by proposing a generative approach that leverages reinforcement learning (RL) to fine-tune a pre-trained autoregressive (AR) model. Our method incorporates data-driven biological priors by deriving computational inference-based rewards that simulate the addition of activator TFBSs and removal of repressor TFBSs, which are then integrated into the RL process. We evaluate our method on promoter design tasks in two yeast media conditions and enhancer design tasks for three human cell types, demonstrating its ability to generate high-fitness CREs while maintaining sequence diversity. The code is available at https://github.com/yangzhao1230/TACO.

DualDiff+: Dual-Branch Diffusion for High-Fidelity Video Generation with Reward Guidance

Accurate and high-fidelity driving scene reconstruction demands the effective utilization of comprehensive scene information as conditional inputs. Existing methods predominantly rely on 3D bounding boxes and BEV road maps for foreground and background control, which fail to capture the full complexity of driving scenes and adequately integrate multimodal information. In this work, we present DualDiff, a dual-branch conditional diffusion model designed to enhance driving scene generation across multiple views and video sequences. Specifically, we introduce Occupancy Ray-shape Sampling (ORS) as a conditional input, offering rich foreground and background semantics alongside 3D spatial geometry to precisely control the generation of both elements. To improve the synthesis of fine-grained foreground objects, particularly complex and distant ones, we propose a Foreground-Aware Mask (FGM) denoising loss function. Additionally, we develop the Semantic Fusion Attention (SFA) mechanism to dynamically prioritize relevant information and suppress noise, enabling more effective multimodal fusion. Finally, to ensure high-quality image-to-video generation, we introduce the Reward-Guided Diffusion (RGD) framework, which maintains global consistency and semantic coherence in generated videos. Extensive experiments demonstrate that DualDiff achieves state-of-the-art (SOTA) performance across multiple datasets. On the NuScenes dataset, DualDiff reduces the FID score by 4.09% compared to the best baseline. In downstream tasks, such as BEV segmentation, our method improves vehicle mIoU by 4.50% and road mIoU by 1.70%, while in BEV 3D object detection, the foreground mAP increases by 1.46%. Code will be made available at https://github.com/yangzhaojason/DualDiff.

IC-Mapper: Instance-Centric Spatio-Temporal Modeling for Online Vectorized Map Construction

Online vector map construction based on visual data can bypass the processes of data collection, post-processing, and manual annotation required by traditional map construction, which significantly enhances map-building efficiency. However, existing work treats the online mapping task as a local range perception task, overlooking the spatial scalability required for map construction. We propose IC-Mapper, an instance-centric online mapping framework, which comprises two primary components: 1) Instance-centric temporal association module: For the detection queries of adjacent frames, we measure them in both feature and geometric dimensions to obtain the matching correspondence between instances across frames. 2) Instance-centric spatial fusion module: We perform point sampling on the historical global map from a spatial dimension and integrate it with the detection results of instances corresponding to the current frame to achieve real-time expansion and update of the map. Based on the nuScenes dataset, we evaluate our approach on detection, tracking, and global mapping metrics. Experimental results demonstrate the superiority of IC-Mapper against other state-of-the-art methods. Code will be released on https://github.com/Brickzhuantou/IC-Mapper.

Diffusion Models for Tabular Data: Challenges, Current Progress, and Future Directions

In recent years, generative models have achieved remarkable performance across diverse applications, including image generation, text synthesis, audio creation, video generation, and data augmentation. Diffusion models have emerged as superior alternatives to Generative Adversarial Networks (GANs) and Variational Autoencoders (VAEs) by addressing their limitations, such as training instability, mode collapse, and poor representation of multimodal distributions. This success has spurred widespread research interest. In the domain of tabular data, diffusion models have begun to showcase similar advantages over GANs and VAEs, achieving significant performance breakthroughs and demonstrating their potential for addressing unique challenges in tabular data modeling. However, while domains like images and time series have numerous surveys summarizing advancements in diffusion models, there remains a notable gap in the literature for tabular data. Despite the increasing interest in diffusion models for tabular data, there has been little effort to systematically review and summarize these developments. This lack of a dedicated survey limits a clear understanding of the challenges, progress, and future directions in this critical area. This survey addresses this gap by providing a comprehensive review of diffusion models for tabular data. Covering works from June 2015, when diffusion models emerged, to December 2024, we analyze nearly all relevant studies, with updates maintained in a \href{https://github.com/Diffusion-Model-Leiden/awesome-diffusion-models-for-tabular-data}{GitHub repository}. Assuming readers possess foundational knowledge of statistics and diffusion models, we employ mathematical formulations to deliver a rigorous and detailed review, aiming to promote developments in this emerging and exciting area.

NatureLM: Deciphering the Language of Nature for Scientific Discovery

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, and RNA. 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 (briefly, 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) achieving state-of-the-art performance in tasks like SMILES-to-IUPAC translation and retrosynthesis on USPTO-50k. 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.

Fact-Preserved Personalized News Headline Generation

Personalized news headline generation, aiming at generating user-specific headlines based on readers' preferences, burgeons a recent flourishing research direction. Existing studies generally inject a user interest embedding into an encoderdecoder headline generator to make the output personalized, while the factual consistency of headlines is inadequate to be verified. In this paper, we propose a framework Fact-Preserved Personalized News Headline Generation (short for FPG), to prompt a tradeoff between personalization and consistency. In FPG, the similarity between the candidate news to be exposed and the historical clicked news is used to give different levels of attention to key facts in the candidate news, and the similarity scores help to learn a fact-aware global user embedding. Besides, an additional training procedure based on contrastive learning is devised to further enhance the factual consistency of generated headlines. Extensive experiments conducted on a real-world benchmark PENS validate the superiority of FPG, especially on the tradeoff between personalization and factual consistency.

Interpretable Enzyme Function Prediction via Residue-Level Detection

Predicting multiple functions labeled with Enzyme Commission (EC) numbers from the enzyme sequence is of great significance but remains a challenge due to its sparse multi-label classification nature, i.e., each enzyme is typically associated with only a few labels out of more than 6000 possible EC numbers. However, existing machine learning algorithms generally learn a fixed global representation for each enzyme to classify all functions, thereby they lack interpretability and the fine-grained information of some function-specific local residue fragments may be overwhelmed. Here we present an attention-based framework, namely ProtDETR (Protein Detection Transformer), by casting enzyme function prediction as a detection problem. It uses a set of learnable functional queries to adaptatively extract different local representations from the sequence of residue-level features for predicting different EC numbers. ProtDETR not only significantly outperforms existing deep learning-based enzyme function prediction methods, but also provides a new interpretable perspective on automatically detecting different local regions for identifying different functions through cross-attentions between queries and residue-level features. Code is available at https://github.com/yangzhao1230/ProtDETR.

World Models Increase Autonomy in Reinforcement Learning

Reinforcement learning (RL) is an appealing paradigm for training intelligent agents, enabling policy acquisition from the agent's own autonomously acquired experience. However, the training process of RL is far from automatic, requiring extensive human effort to reset the agent and environments. To tackle the challenging reset-free setting, we first demonstrate the superiority of model-based (MB) RL methods in such setting, showing that a straightforward adaptation of MBRL can outperform all the prior state-of-the-art methods while requiring less supervision. We then identify limitations inherent to this direct extension and propose a solution called model-based reset-free (MoReFree) agent, which further enhances the performance. MoReFree adapts two key mechanisms, exploration and policy learning, to handle reset-free tasks by prioritizing task-relevant states. It exhibits superior data-efficiency across various reset-free tasks without access to environmental reward or demonstrations while significantly outperforming privileged baselines that require supervision. Our findings suggest model-based methods hold significant promise for reducing human effort in RL. Website: https://sites.google.com/view/morefree

Pruning via Merging: Compressing LLMs via Manifold Alignment Based Layer Merging

While large language models (LLMs) excel in many domains, their complexity and scale challenge deployment in resource-limited environments. Current compression techniques, such as parameter pruning, often fail to effectively utilize the knowledge from pruned parameters. To address these challenges, we propose Manifold-Based Knowledge Alignment and Layer Merging Compression (MKA), a novel approach that uses manifold learning and the Normalized Pairwise Information Bottleneck (NPIB) measure to merge similar layers, reducing model size while preserving essential performance. We evaluate MKA on multiple benchmark datasets and various LLMs. Our findings show that MKA not only preserves model performance but also achieves substantial compression ratios, outperforming traditional pruning methods. Moreover, when coupled with quantization, MKA delivers even greater compression. Specifically, on the MMLU dataset using the Llama3-8B model, MKA achieves a compression ratio of 43.75% with a minimal performance decrease of only 2.82\%. The proposed MKA method offers a resource-efficient and performance-preserving model compression technique for LLMs.

Improving Zero-shot LLM Re-Ranker with Risk Minimization

In the Retrieval-Augmented Generation (RAG) system, advanced Large Language Models (LLMs) have emerged as effective Query Likelihood Models (QLMs) in an unsupervised way, which re-rank documents based on the probability of generating the query given the content of a document. However, directly prompting LLMs to approximate QLMs inherently is biased, where the estimated distribution might diverge from the actual document-specific distribution. In this study, we introduce a novel framework, $\mathrm{UR^3}$, which leverages Bayesian decision theory to both quantify and mitigate this estimation bias. Specifically, $\mathrm{UR^3}$ reformulates the problem as maximizing the probability of document generation, thereby harmonizing the optimization of query and document generation probabilities under a unified risk minimization objective. Our empirical results indicate that $\mathrm{UR^3}$ significantly enhances re-ranking, particularly in improving the Top-1 accuracy. It benefits the QA tasks by achieving higher accuracy with fewer input documents.