Nanqing Dong

Dongxin Ye, Fang Hu, Han Hu et al.

Nucleotide sequences constitute the fundamental genetic basis of biological systems, rendering viral genomic analysis critical for biomedical advancement. Despite progress in biological foundation models, specifically nucleotide foundation models (NFMs), the field lacks a unified standard for viral genomics to facilitate community development and enforce biosecurity constraints. To address this, we introduce ViroBench, the first comprehensive and large-scale benchmark specifically designed for NFMs in viral settings. ViroBench evaluates models across two critical dimensions: biological understanding and latent biosecurity risk, covering 18 diverse scenarios within 4 task types. Extensive evaluation of 66 NFMs across diverse architectures yields three critical conclusions. Firstly, NFMs exhibit a performance degradation in biological understanding under phylogenetic and temporal shifts, indicating weak extrapolation capabilities. Secondly, generation tasks reveal a decoupling between statistical likelihood and biological functional validity, posing latent biosecurity risks. Thirdly, controlled ablation studies reveal that taxonomic diversity in pretraining data outweighs parameter scale. Specifically, a lightweight baseline trained on diverse data achieves a 67.5% performance gain over its original model. Overall, ViroBench provides interpretable, diagnostic evaluations and a reproducible measurement framework for future research on viral nucleotide foundation models. The datasets and code are publicly available at https://github.com/QIANJINYDX/ViroBench.

Zhongying Deng, Cheng Tang, Ziyan Huang et al. · pku

Foundation models have demonstrated remarkable success across diverse domains and tasks, primarily due to the thrive of large-scale, diverse, and high-quality datasets. However, in the field of medical imaging, the curation and assembling of such medical datasets are highly challenging due to the reliance on clinical expertise and strict ethical and privacy constraints, resulting in a scarcity of large-scale unified medical datasets and hindering the development of powerful medical foundation models. In this work, we present the largest survey to date of medical image datasets, covering over 1,000 open-access datasets with a systematic catalog of their modalities, tasks, anatomies, annotations, limitations, and potential for integration. Our analysis exposes a landscape that is modest in scale, fragmented across narrowly scoped tasks, and unevenly distributed across organs and modalities, which in turn limits the utility of existing medical image datasets for developing versatile and robust medical foundation models. To turn fragmentation into scale, we propose a metadata-driven fusion paradigm (MDFP) that integrates public datasets with shared modalities or tasks, thereby transforming multiple small data silos into larger, more coherent resources. Building on MDFP, we release an interactive discovery portal that enables end-to-end, automated medical image dataset integration, and compile all surveyed datasets into a unified, structured table that clearly summarizes their key characteristics and provides reference links, offering the community an accessible and comprehensive repository. By charting the current terrain and offering a principled path to dataset consolidation, our survey provides a practical roadmap for scaling medical imaging corpora, supporting faster data discovery, more principled dataset creation, and more capable medical foundation models.

Nanqing Dong, Zhipeng Wang, Jiahao Sun et al.

In the era of deep learning, federated learning (FL) presents a promising approach that allows multi-institutional data owners, or clients, to collaboratively train machine learning models without compromising data privacy. However, most existing FL approaches rely on a centralized server for global model aggregation, leading to a single point of failure. This makes the system vulnerable to malicious attacks when dealing with dishonest clients. In this work, we address this problem by proposing a secure and reliable FL system based on blockchain and distributed ledger technology. Our system incorporates a peer-to-peer voting mechanism and a reward-and-slash mechanism, which are powered by on-chain smart contracts, to detect and deter malicious behaviors. Both theoretical and empirical analyses are presented to demonstrate the effectiveness of the proposed approach, showing that our framework is robust against malicious client-side behaviors.

Nanqing Dong, Linus Ericsson, Yongxin Yang et al.

Self-supervised pre-training, based on the pretext task of instance discrimination, has fueled the recent advance in label-efficient object detection. However, existing studies focus on pre-training only a feature extractor network to learn transferable representations for downstream detection tasks. This leads to the necessity of training multiple detection-specific modules from scratch in the fine-tuning phase. We argue that the region proposal network (RPN), a common detection-specific module, can additionally be pre-trained towards reducing the localization error of multi-stage detectors. In this work, we propose a simple pretext task that provides an effective pre-training for the RPN, towards efficiently improving downstream object detection performance. We evaluate the efficacy of our approach on benchmark object detection tasks and additional downstream tasks, including instance segmentation and few-shot detection. In comparison with multi-stage detectors without RPN pre-training, our approach is able to consistently improve downstream task performance, with largest gains found in label-scarce settings.

Zhonghang Yuan, Zhefan Wang, Fang Hu et al.

Reinforcement learning with verifiable rewards (RLVR) has demonstrated promising potential to enhance the reasoning capabilities of large language models (LLMs) in domains such as mathematics and coding. However, its applications on knowledge-intensive domains have not been effectively explored due to the scarcity of high-quality verifiable data. Furthermore, current RLVR focuses solely on the correctness of final answers, leading to the limitations of flawed reasoning and sparse reward signals. In this work, we propose Knowledge-to-Verification (K2V), a framework that extends RLVR to knowledge-intensive domains through automated verifiable data synthesis, while enabling verification of the LLM's reasoning process. Extensive experiments demonstrate that K2V enhances the reasoning of LLM in knowledge-intensive domains without significantly compromising the model's general capabilities. This study also suggests that integrating automated data synthesis with reasoning verification is a promising direction to enhance model capabilities in these broader domains. Code is available at https://github.com/SeedScientist/K2V.

Yang Tan, Yuanxi Yu, Can Wu et al.

Zero-shot mutation prediction is vital for low-resource protein engineering, yet existing protein language models (PLMs) often yield statistically confident results that ignore fundamental biophysical constraints. Currently, selecting candidates for wet-lab validation relies on manual expert auditing of PLM outputs, a process that is inefficient, subjective, and highly dependent on domain expertise. To address this, we propose Rank-and-Reason (VenusRAR), a two-stage agentic framework to automate this workflow and maximize expected wet-lab fitness. In the Rank-Stage, a Computational Expert and Virtual Biologist aggregate a context-aware multi-modal ensemble, establishing a new Spearman correlation record of 0.551 (vs. 0.518) on ProteinGym. In the Reason-Stage, an agentic Expert Panel employs chain-of-thought reasoning to audit candidates against geometric and structural constraints, improving the Top-5 Hit Rate by up to 367% on ProteinGym-DMS99. The wet-lab validation on Cas12i3 nuclease further confirms the framework's efficacy, achieving a 46.7% positive rate and identifying two novel mutants with 4.23-fold and 5.05-fold activity improvements. Code and datasets are released on GitHub (https://github.com/ai4protein/VenusRAR/).

Nanqing Dong, Michael Kampffmeyer, Irina Voiculescu

Using decentralized data for federated training is one promising emerging research direction for alleviating data scarcity in the medical domain. However, in contrast to large-scale fully labeled data commonly seen in general object recognition tasks, the local medical datasets are more likely to only have images annotated for a subset of classes of interest due to high annotation costs. In this paper, we consider a practical yet under-explored problem, where underrepresented classes only have few labeled instances available and only exist in a few clients of the federated system. We show that standard federated learning approaches fail to learn robust multi-label classifiers with extreme class imbalance and address it by proposing a novel federated learning framework, FedFew. FedFew consists of three stages, where the first stage leverages federated self-supervised learning to learn class-agnostic representations. In the second stage, the decentralized partially labeled data are exploited to learn an energy-based multi-label classifier for the common classes. Finally, the underrepresented classes are detected based on the energy and a prototype-based nearest-neighbor model is proposed for few-shot matching. We evaluate FedFew on multi-label thoracic disease classification tasks and demonstrate that it outperforms the federated baselines by a large margin.

Nanqing Dong, Jiayi Wang, Irina Voiculescu

Due to the high human cost of annotation, it is non-trivial to curate a large-scale medical dataset that is fully labeled for all classes of interest. Instead, it would be convenient to collect multiple small partially labeled datasets from different matching sources, where the medical images may have only been annotated for a subset of classes of interest. This paper offers an empirical understanding of an under-explored problem, namely partially supervised multi-label classification (PSMLC), where a multi-label classifier is trained with only partially labeled medical images. In contrast to the fully supervised counterpart, the partial supervision caused by medical data scarcity has non-trivial negative impacts on the model performance. A potential remedy could be augmenting the partial labels. Though vicinal risk minimization (VRM) has been a promising solution to improve the generalization ability of the model, its application to PSMLC remains an open question. To bridge the methodological gap, we provide the first VRM-based solution to PSMLC. The empirical results also provide insights into future research directions on partially supervised learning under data scarcity.

Nanqing Dong, Jiahao Sun, Zhipeng Wang et al.

Federated learning (FL) is a promising way to allow multiple data owners (clients) to collaboratively train machine learning models without compromising data privacy. Yet, existing FL solutions usually rely on a centralized aggregator for model weight aggregation, while assuming clients are honest. Even if data privacy can still be preserved, the problem of single-point failure and data poisoning attack from malicious clients remains unresolved. To tackle this challenge, we propose to use distributed ledger technology (DLT) to achieve FLock, a secure and reliable decentralized Federated Learning system built on blockchain. To guarantee model quality, we design a novel peer-to-peer (P2P) review and reward/slash mechanism to detect and deter malicious clients, powered by on-chain smart contracts. The reward/slash mechanism, in addition, serves as incentives for participants to honestly upload and review model parameters in the FLock system. FLock thus improves the performance and the robustness of FL systems in a fully P2P manner.

Chaoqi Liang, Lifeng Qiao, Peng Ye et al.

With the success of large-scale pre-training in language tasks, there is an increasing trend of applying it to the domain of life sciences. In particular, pre-training methods based on DNA sequences have received increasing attention because of their potential to capture general information about genes. However, existing pre-training methods for DNA sequences largely rely on direct adoptions of BERT pre-training from NLP, lacking a comprehensive understanding and a specifically tailored approach. To address this research gap, we provide the first empirical study with three insightful observations. Based on the empirical study, we notice that overlapping tokenizer can benefit the fine-tuning of downstream tasks but leads to inadequate pre-training with fast convergence. To unleash the pre-training potential, we introduce a novel approach called RandomMask, which gradually increases the task difficulty of BERT-like pre-training by continuously expanding its mask boundary, forcing the model to learn more knowledge. RandomMask is simple but effective, achieving state-of-the-art performance across 6 downstream tasks. RandomMask achieves a staggering 68.16\% in Matthew's correlation coefficient for Epigenetic Mark Prediction, a groundbreaking increase of 19.85\% over the baseline and a remarkable 3.69\% improvement over the previous state-of-the-art result.

Wanghan Xu, Yuhao Zhou, Yifan Zhou et al.

Despite advances in scientific AI, a coherent framework for Scientific General Intelligence (SGI)-the ability to autonomously conceive, investigate, and reason across scientific domains-remains lacking. We present an operational SGI definition grounded in the Practical Inquiry Model (PIM: Deliberation, Conception, Action, Perception) and operationalize it via four scientist-aligned tasks: deep research, idea generation, dry/wet experiments, and experimental reasoning. SGI-Bench comprises over 1,000 expert-curated, cross-disciplinary samples inspired by Science's 125 Big Questions, enabling systematic evaluation of state-of-the-art LLMs. Results reveal gaps: low exact match (10--20%) in deep research despite step-level alignment; ideas lacking feasibility and detail; high code executability but low execution result accuracy in dry experiments; low sequence fidelity in wet protocols; and persistent multimodal comparative-reasoning challenges. We further introduce Test-Time Reinforcement Learning (TTRL), which optimizes retrieval-augmented novelty rewards at inference, enhancing hypothesis novelty without reference answer. Together, our PIM-grounded definition, workflow-centric benchmark, and empirical insights establish a foundation for AI systems that genuinely participate in scientific discovery.

Zhi Jin, Sheng Xu, Xiang Zhang et al.

De novo peptide sequencing from mass spectrometry (MS) data is a critical task in proteomics research. Traditional de novo algorithms have encountered a bottleneck in accuracy due to the inherent complexity of proteomics data. While deep learning-based methods have shown progress, they reduce the problem to a translation task, potentially overlooking critical nuances between spectra and peptides. In our research, we present ContraNovo, a pioneering algorithm that leverages contrastive learning to extract the relationship between spectra and peptides and incorporates the mass information into peptide decoding, aiming to address these intricacies more efficiently. Through rigorous evaluations on two benchmark datasets, ContraNovo consistently outshines contemporary state-of-the-art solutions, underscoring its promising potential in enhancing de novo peptide sequencing. The source code is available at https://github.com/BEAM-Labs/ContraNovo.

Lei Bai, Zhongrui Cai, Yuhang Cao et al.

In recent years, a plethora of open-source foundation models have emerged, achieving remarkable progress in some widely attended fields, with performance being quite close to that of closed-source models. However, in high-value but more challenging scientific professional fields, either the fields still rely on expert models, or the progress of general foundation models lags significantly compared to those in popular areas, far from sufficient for transforming scientific research and leaving substantial gap between open-source models and closed-source models in these scientific domains. To mitigate this gap and explore a step further toward Artificial General Intelligence (AGI), we introduce Intern-S1, a specialized generalist equipped with general understanding and reasoning capabilities with expertise to analyze multiple science modal data. Intern-S1 is a multimodal Mixture-of-Experts (MoE) model with 28 billion activated parameters and 241 billion total parameters, continually pre-trained on 5T tokens, including over 2.5T tokens from scientific domains. In the post-training stage, Intern-S1 undergoes offline and then online reinforcement learning (RL) in InternBootCamp, where we propose Mixture-of-Rewards (MoR) to synergize the RL training on more than 1000 tasks simultaneously. Through integrated innovations in algorithms, data, and training systems, Intern-S1 achieved top-tier performance in online RL training. On comprehensive evaluation benchmarks, Intern-S1 demonstrates competitive performance on general reasoning tasks among open-source models and significantly outperforms open-source models in scientific domains, surpassing closed-source state-of-the-art models in professional tasks, such as molecular synthesis planning, reaction condition prediction, predicting thermodynamic stabilities for crystals. Our models are available at https://huggingface.co/internlm/Intern-S1.

Haoyang Su, Renqi Chen, Shixiang Tang et al.

The rapid advancement of scientific progress requires innovative tools that can accelerate knowledge discovery. Although recent AI methods, particularly large language models (LLMs), have shown promise in tasks such as hypothesis generation and experimental design, they fall short of replicating the collaborative nature of real-world scientific practices, where diverse experts work together in teams to tackle complex problems. To address the limitations, we propose an LLM-based multi-agent system, i.e., Virtual Scientists (VirSci), designed to mimic the teamwork inherent in scientific research. VirSci organizes a team of agents to collaboratively generate, evaluate, and refine research ideas. Through comprehensive experiments, we demonstrate that this multi-agent approach outperforms the state-of-the-art method in producing novel scientific ideas. We further investigate the collaboration mechanisms that contribute to its tendency to produce ideas with higher novelty, offering valuable insights to guide future research and illuminating pathways toward building a robust system for autonomous scientific discovery. The code is available at https://github.com/open-sciencelab/Virtual-Scientists.

Yang Tan, Lingrong Zhang, Mingchen Li et al.

Protein scientific discovery is bottlenecked by the manual orchestration of information and algorithms, while general agents are insufficient in complex domain projects. VenusFactory2 provides an autonomous framework that shifts from static tool usage to dynamic workflow synthesis via a self-evolving multi-agent infrastructure to address protein-related demands. It outperforms a set of well-known agents on the VenusAgentEval benchmark, and autonomously organizes the discovery and optimization of proteins from a single natural language prompt.

Jie Ying, Zihong Chen, Zhefan Wang et al.

Seed science is essential for modern agriculture, directly influencing crop yields and global food security. However, challenges such as interdisciplinary complexity and high costs with limited returns hinder progress, leading to a shortage of experts and insufficient technological support. While large language models (LLMs) have shown promise across various fields, their application in seed science remains limited due to the scarcity of digital resources, complex gene-trait relationships, and the lack of standardized benchmarks. To address this gap, we introduce SeedBench -- the first multi-task benchmark specifically designed for seed science. Developed in collaboration with domain experts, SeedBench focuses on seed breeding and simulates key aspects of modern breeding processes. We conduct a comprehensive evaluation of 26 leading LLMs, encompassing proprietary, open-source, and domain-specific fine-tuned models. Our findings not only highlight the substantial gaps between the power of LLMs and the real-world seed science problems, but also make a foundational step for research on LLMs for seed design.

Xinzhe Zheng, Hao Du, Fanding Xu et al.

Deep learning-based computational methods have achieved promising results in predicting protein-protein interactions (PPIs). However, existing benchmarks predominantly focus on isolated pairwise evaluations, overlooking a model's capability to reconstruct biologically meaningful PPI networks, which is crucial for biology research. To address this gap, we introduce PRING, the first comprehensive benchmark that evaluates protein-protein interaction prediction from a graph-level perspective. PRING curates a high-quality, multi-species PPI network dataset comprising 21,484 proteins and 186,818 interactions, with well-designed strategies to address both data redundancy and leakage. Building on this golden-standard dataset, we establish two complementary evaluation paradigms: (1) topology-oriented tasks, which assess intra and cross-species PPI network construction, and (2) function-oriented tasks, including protein complex pathway prediction, GO module analysis, and essential protein justification. These evaluations not only reflect the model's capability to understand the network topology but also facilitate protein function annotation, biological module detection, and even disease mechanism analysis. Extensive experiments on four representative model categories, consisting of sequence similarity-based, naive sequence-based, protein language model-based, and structure-based approaches, demonstrate that current PPI models have potential limitations in recovering both structural and functional properties of PPI networks, highlighting the gap in supporting real-world biological applications. We believe PRING provides a reliable platform to guide the development of more effective PPI prediction models for the community. The dataset and source code of PRING are available at https://github.com/SophieSarceau/PRING.

Weizhen Liu, Jiayu Tan, Guangyu Lan et al.

Accurate phenotypic analysis in aquaculture breeding necessitates the quantification of subtle morphological phenotypes. Existing datasets suffer from limitations such as small scale, limited species coverage, and inadequate annotation of keypoints for measuring refined and complex morphological phenotypes of fish body parts. To address this gap, we introduce FishPhenoKey, a comprehensive dataset comprising 23,331 high-resolution images spanning six fish species. Notably, FishPhenoKey includes 22 phenotype-oriented annotations, enabling the capture of intricate morphological phenotypes. Motivated by the nuanced evaluation of these subtle morphologies, we also propose a new evaluation metric, Percentage of Measured Phenotype (PMP). It is designed to assess the accuracy of individual keypoint positions and is highly sensitive to the phenotypes measured using the corresponding keypoints. To enhance keypoint detection accuracy, we further propose a novel loss, Anatomically-Calibrated Regularization (ACR), that can be integrated into keypoint detection models, leveraging biological insights to refine keypoint localization. Our contributions set a new benchmark in fish phenotype analysis, addressing the challenges of precise morphological quantification and opening new avenues for research in sustainable aquaculture and genetic studies. Our dataset and code are available at https://github.com/WeizhenLiuBioinform/Fish-Phenotype-Detect.

Xiang Zhang, Jiaqi Wei, Zijie Qiu et al.

Autoregressive (AR) models, common in sequence generation, are limited in many biological tasks such as de novo peptide sequencing and protein modeling by their unidirectional nature, failing to capture crucial global bidirectional token dependencies. Non-Autoregressive (NAR) models offer holistic, bidirectional representations but face challenges with generative coherence and scalability. To transcend this, we propose a hybrid framework enhancing AR generation by dynamically integrating rich contextual information from non-autoregressive mechanisms. Our approach couples a shared input encoder with two decoders: a non-autoregressive one learning latent bidirectional biological features, and an AR decoder synthesizing the biological sequence by leveraging these bidirectional features. A novel cross-decoder attention module enables the AR decoder to iteratively query and integrate these bidirectional features, enriching its predictions. This synergy is cultivated via a tailored training strategy with importance annealing for balanced objectives and cross-decoder gradient blocking for stable, focused learning. Evaluations on a demanding nine-species benchmark of de novo peptide sequencing show that our model substantially surpasses AR and NAR baselines. It uniquely harmonizes AR stability with NAR contextual awareness, delivering robust, superior performance on diverse downstream data. This research advances biological sequence modeling techniques and contributes a novel architectural paradigm for augmenting AR models with enhanced bidirectional understanding for complex sequence generation. Code is available at https://github.com/BEAM-Labs/denovo.

Zhefan Wang, Huanjun Kong, Jie Ying et al.

Large language models (LLMs) commonly struggle with specialized or emerging topics which are rarely seen in the training corpus. Graph-based retrieval-augmented generation (GraphRAG) addresses this by structuring domain knowledge as a graph for dynamic retrieval. However, existing pipelines involve complex engineering workflows, making it difficult to isolate the impact of individual components. It is also challenging to evaluate the retrieval effectiveness due to the overlap between the pretraining and evaluation datasets. In this work, we introduce ROGRAG, a Robustly Optimized GraphRAG framework. Specifically, we propose a multi-stage retrieval mechanism that integrates dual-level with logic form retrieval methods to improve retrieval robustness without increasing computational cost. To further refine the system, we incorporate various result verification methods and adopt an incremental database construction approach. Through extensive ablation experiments, we rigorously assess the effectiveness of each component. Our implementation includes comparative experiments on SeedBench, where Qwen2.5-7B-Instruct initially underperformed. ROGRAG significantly improves the score from 60.0% to 75.0% and outperforms mainstream methods. Experiments on domain-specific datasets reveal that dual-level retrieval enhances fuzzy matching, while logic form retrieval improves structured reasoning, highlighting the importance of multi-stage retrieval.ROGRAG is released as an open-source resource and supports installation with pip.

Haonan He, Yuchen Ren, Yining Tang et al.

Large language models (LLMs) have shown remarkable capabilities in general domains, but their application to multi-omics biology remains underexplored. To address this gap, we introduce Biology-Instructions, the first large-scale instruction-tuning dataset for multi-omics biological sequences, including DNA, RNA, proteins, and multi-molecules. This dataset bridges LLMs and complex biological sequence-related tasks, enhancing their versatility and reasoning while maintaining conversational fluency. We also highlight significant limitations of current state-of-the-art LLMs on multi-omics tasks without specialized training. To overcome this, we propose ChatMultiOmics, a strong baseline with a novel three-stage training pipeline, demonstrating superior biological understanding through Biology-Instructions. Both resources are publicly available, paving the way for better integration of LLMs in multi-omics analysis. The Biology-Instructions is publicly available at: https://github.com/hhnqqq/Biology-Instructions.

Jiaqi Wei, Yuejin Yang, Xiang Zhang et al. · tsinghua

Artificial intelligence (AI) is reshaping scientific discovery, evolving from specialized computational tools into autonomous research partners. We position Agentic Science as a pivotal stage within the broader AI for Science paradigm, where AI systems progress from partial assistance to full scientific agency. Enabled by large language models (LLMs), multimodal systems, and integrated research platforms, agentic AI shows capabilities in hypothesis generation, experimental design, execution, analysis, and iterative refinement -- behaviors once regarded as uniquely human. This survey provides a domain-oriented review of autonomous scientific discovery across life sciences, chemistry, materials science, and physics. We unify three previously fragmented perspectives -- process-oriented, autonomy-oriented, and mechanism-oriented -- through a comprehensive framework that connects foundational capabilities, core processes, and domain-specific realizations. Building on this framework, we (i) trace the evolution of AI for Science, (ii) identify five core capabilities underpinning scientific agency, (iii) model discovery as a dynamic four-stage workflow, (iv) review applications across the above domains, and (v) synthesize key challenges and future opportunities. This work establishes a domain-oriented synthesis of autonomous scientific discovery and positions Agentic Science as a structured paradigm for advancing AI-driven research.

Ming Hu, Chenglong Ma, Wei Li et al. · pku

Scientific Large Language Models (Sci-LLMs) are transforming how knowledge is represented, integrated, and applied in scientific research, yet their progress is shaped by the complex nature of scientific data. This survey presents a comprehensive, data-centric synthesis that reframes the development of Sci-LLMs as a co-evolution between models and their underlying data substrate. We formulate a unified taxonomy of scientific data and a hierarchical model of scientific knowledge, emphasizing the multimodal, cross-scale, and domain-specific challenges that differentiate scientific corpora from general natural language processing datasets. We systematically review recent Sci-LLMs, from general-purpose foundations to specialized models across diverse scientific disciplines, alongside an extensive analysis of over 270 pre-/post-training datasets, showing why Sci-LLMs pose distinct demands -- heterogeneous, multi-scale, uncertainty-laden corpora that require representations preserving domain invariance and enabling cross-modal reasoning. On evaluation, we examine over 190 benchmark datasets and trace a shift from static exams toward process- and discovery-oriented assessments with advanced evaluation protocols. These data-centric analyses highlight persistent issues in scientific data development and discuss emerging solutions involving semi-automated annotation pipelines and expert validation. Finally, we outline a paradigm shift toward closed-loop systems where autonomous agents based on Sci-LLMs actively experiment, validate, and contribute to a living, evolving knowledge base. Collectively, this work provides a roadmap for building trustworthy, continually evolving artificial intelligence (AI) systems that function as a true partner in accelerating scientific discovery.

Zijie Qiu, Jiaqi Wei, Xiang Zhang et al.

De novo peptide sequencing is a critical task in proteomics. However, the performance of current deep learning-based methods is limited by the inherent complexity of mass spectrometry data and the heterogeneous distribution of noise signals, leading to data-specific biases. We present RankNovo, the first deep reranking framework that enhances de novo peptide sequencing by leveraging the complementary strengths of multiple sequencing models. RankNovo employs a list-wise reranking approach, modeling candidate peptides as multiple sequence alignments and utilizing axial attention to extract informative features across candidates. Additionally, we introduce two new metrics, PMD (Peptide Mass Deviation) and RMD (residual Mass Deviation), which offer delicate supervision by quantifying mass differences between peptides at both the sequence and residue levels. Extensive experiments demonstrate that RankNovo not only surpasses its base models used to generate training candidates for reranking pre-training, but also sets a new state-of-the-art benchmark. Moreover, RankNovo exhibits strong zero-shot generalization to unseen models whose generations were not exposed during training, highlighting its robustness and potential as a universal reranking framework for peptide sequencing. Our work presents a novel reranking strategy that fundamentally challenges existing single-model paradigms and advances the frontier of accurate de novo sequencing. Our source code is provided on GitHub.

Lifeng Qiao, Peng Ye, Yuchen Ren et al.

Foundation models have made significant strides in understanding the genomic language of DNA sequences. However, previous models typically adopt the tokenization methods designed for natural language, which are unsuitable for DNA sequences due to their unique characteristics. In addition, the optimal approach to tokenize DNA remains largely under-explored, and may not be intuitively understood by humans even if discovered. To address these challenges, we introduce MxDNA, a novel framework where the model autonomously learns an effective DNA tokenization strategy through gradient decent. MxDNA employs a sparse Mixture of Convolution Experts coupled with a deformable convolution to model the tokenization process, with the discontinuous, overlapping, and ambiguous nature of meaningful genomic segments explicitly considered. On Nucleotide Transformer Benchmarks and Genomic Benchmarks, MxDNA demonstrates superior performance to existing methods with less pretraining data and time, highlighting its effectiveness. Finally, we show that MxDNA learns unique tokenization strategy distinct to those of previous methods and captures genomic functionalities at a token level during self-supervised pretraining. Our MxDNA aims to provide a new perspective on DNA tokenization, potentially offering broad applications in various domains and yielding profound insights.

Xiang Zhang, Jiaqi Wei, Zijie Qiu et al.

Peptide sequencing-the process of identifying amino acid sequences from mass spectrometry data-is a fundamental task in proteomics. Non-Autoregressive Transformers (NATs) have proven highly effective for this task, outperforming traditional methods. Unlike autoregressive models, which generate tokens sequentially, NATs predict all positions simultaneously, leveraging bidirectional context through unmasked self-attention. However, existing NAT approaches often rely on Connectionist Temporal Classification (CTC) loss, which presents significant optimization challenges due to CTC's complexity and increases the risk of training failures. To address these issues, we propose an improved non-autoregressive peptide sequencing model that incorporates a structured protein sequence curriculum learning strategy. This approach adjusts protein's learning difficulty based on the model's estimated protein generational capabilities through a sampling process, progressively learning peptide generation from simple to complex sequences. Additionally, we introduce a self-refining inference-time module that iteratively enhances predictions using learned NAT token embeddings, improving sequence accuracy at a fine-grained level. Our curriculum learning strategy reduces NAT training failures frequency by more than 90% based on sampled training over various data distributions. Evaluations on nine benchmark species demonstrate that our approach outperforms all previous methods across multiple metrics and species.

Renqi Chen, Wenwei Han, Haohao Zhang et al.

Genomic selection (GS), as a critical crop breeding strategy, plays a key role in enhancing food production and addressing the global hunger crisis. The predominant approaches in GS currently revolve around employing statistical methods for prediction. However, statistical methods often come with two main limitations: strong statistical priors and linear assumptions. A recent trend is to capture the non-linear relationships between markers by deep learning. However, as crop datasets are commonly long sequences with limited samples, the robustness of deep learning models, especially Transformers, remains a challenge. In this work, to unleash the unexplored potential of attention mechanism for the task of interest, we propose a simple yet effective Transformer-based framework that enables end-to-end training of the whole sequence. Via experiments on rice3k and wheat3k datasets, we show that, with simple tricks such as k-mer tokenization and random masking, Transformer can achieve overall superior performance against seminal methods on GS tasks of interest.

Weilun Yu, Shixiang Tang, Yonggui Huang et al.

Scientific progress increasingly relies on effective collaboration among researchers, a dynamic that large language models (LLMs) have only begun to emulate. While recent LLM-based scientist agents show promise in autonomous scientific discovery, they often lack the interactive reasoning and evaluation mechanisms essential to real-world research. We propose IDVSCI (Internal Discussion and Vote SCIentists), a multi-agent framework built on LLMs that incorporates two key innovations: a Dynamic Knowledge Exchange mechanism enabling iterative feedback among agents, and a Dual-Diversity Review paradigm that simulates heterogeneous expert evaluation. These components jointly promote deeper reasoning and the generation of more creative and impactful scientific ideas. To evaluate the effectiveness and generalizability of our approach, we conduct experiments on two datasets: a widely used benchmark in computer science and a new dataset we introduce in the health sciences domain. Results show that IDVSCI consistently achieves the best performance across both datasets, outperforming existing systems such as AI Scientist and VIRSCI. These findings highlight the value of modeling interaction and peer review dynamics in LLM-based autonomous research.

Yuchen Ren, Wenwei Han, Qianyuan Zhang et al.

As key elements within the central dogma, DNA, RNA, and proteins play crucial roles in maintaining life by guaranteeing accurate genetic expression and implementation. Although research on these molecules has profoundly impacted fields like medicine, agriculture, and industry, the diversity of machine learning approaches-from traditional statistical methods to deep learning models and large language models-poses challenges for researchers in choosing the most suitable models for specific tasks, especially for cross-omics and multi-omics tasks due to the lack of comprehensive benchmarks. To address this, we introduce the first comprehensive multi-omics benchmark COMET (Benchmark for Biological COmprehensive Multi-omics Evaluation Tasks and Language Models), designed to evaluate models across single-omics, cross-omics, and multi-omics tasks. First, we curate and develop a diverse collection of downstream tasks and datasets covering key structural and functional aspects in DNA, RNA, and proteins, including tasks that span multiple omics levels. Then, we evaluate existing foundational language models for DNA, RNA, and proteins, as well as the newly proposed multi-omics method, offering valuable insights into their performance in integrating and analyzing data from different biological modalities. This benchmark aims to define critical issues in multi-omics research and guide future directions, ultimately promoting advancements in understanding biological processes through integrated and different omics data analysis.

Renqi Chen, Haoyang Su, Shixiang Tang et al.

The Science of Science (SoS) explores the mechanisms underlying scientific discovery, and offers valuable insights for enhancing scientific efficiency and fostering innovation. Traditional approaches often rely on simplistic assumptions and basic statistical tools, such as linear regression and rule-based simulations, which struggle to capture the complexity and scale of modern research ecosystems. The advent of artificial intelligence (AI) presents a transformative opportunity for the next generation of SoS, enabling the automation of large-scale pattern discovery and uncovering insights previously unattainable. This paper offers a forward-looking perspective on the integration of Science of Science with AI for automated research pattern discovery and highlights key open challenges that could greatly benefit from AI. We outline the advantages of AI over traditional methods, discuss potential limitations, and propose pathways to overcome them. Additionally, we present a preliminary multi-agent system as an illustrative example to simulate research societies, showcasing AI's ability to replicate real-world research patterns and accelerate progress in Science of Science research.

Dingning Liu, Jinzhe Li, Haoyang Su et al.

Weed control is a critical challenge in modern agriculture, as weeds compete with crops for essential nutrient resources, significantly reducing crop yield and quality. Traditional weed control methods, including chemical and mechanical approaches, have real-life limitations such as associated environmental impact and efficiency. An emerging yet effective approach is laser weeding, which uses a laser beam as the stem cutter. Although there have been studies that use deep learning in weed recognition, its application in intelligent laser weeding still requires a comprehensive understanding. Thus, this study represents the first empirical investigation of weed recognition for laser weeding. To increase the efficiency of laser beam cut and avoid damaging the crops of interest, the laser beam shall be directly aimed at the weed root. Yet, weed stem detection remains an under-explored problem. We integrate the detection of crop and weed with the localization of weed stem into one end-to-end system. To train and validate the proposed system in a real-life scenario, we curate and construct a high-quality weed stem detection dataset with human annotations. The dataset consists of 7,161 high-resolution pictures collected in the field with annotations of 11,151 instances of weed. Experimental results show that the proposed system improves weeding accuracy by 6.7% and reduces energy cost by 32.3% compared to existing weed recognition systems.

Weizhen Liu, Ao Li, Ze Wu et al.

Hierarchical leaf vein segmentation is a crucial but under-explored task in agricultural sciences, where analysis of the hierarchical structure of plant leaf venation can contribute to plant breeding. While current segmentation techniques rely on data-driven models, there is no publicly available dataset specifically designed for hierarchical leaf vein segmentation. To address this gap, we introduce the HierArchical Leaf Vein Segmentation (HALVS) dataset, the first public hierarchical leaf vein segmentation dataset. HALVS comprises 5,057 real-scanned high-resolution leaf images collected from three plant species: soybean, sweet cherry, and London planetree. It also includes human-annotated ground truth for three orders of leaf veins, with a total labeling effort of 83.8 person-days. Based on HALVS, we further develop a label-efficient learning paradigm that leverages partial label information, i.e. missing annotations for tertiary veins. Empirical studies are performed on HALVS, revealing new observations, challenges, and research directions on leaf vein segmentation.

Zhipeng Wang, Nanqing Dong, Jiahao Sun et al.

Federated learning (FL) is a machine learning paradigm, which enables multiple and decentralized clients to collaboratively train a model under the orchestration of a central aggregator. FL can be a scalable machine learning solution in big data scenarios. Traditional FL relies on the trust assumption of the central aggregator, which forms cohorts of clients honestly. However, a malicious aggregator, in reality, could abandon and replace the client's training models, or insert fake clients, to manipulate the final training results. In this work, we introduce zkFL, which leverages zero-knowledge proofs to tackle the issue of a malicious aggregator during the training model aggregation process. To guarantee the correct aggregation results, the aggregator provides a proof per round, demonstrating to the clients that the aggregator executes the intended behavior faithfully. To further reduce the verification cost of clients, we use blockchain to handle the proof in a zero-knowledge way, where miners (i.e., the participants validating and maintaining the blockchain data) can verify the proof without knowing the clients' local and aggregated models. The theoretical analysis and empirical results show that zkFL achieves better security and privacy than traditional FL, without modifying the underlying FL network structure or heavily compromising the training speed.

Zhaoming Qin, Nanqing Dong, Di Liu et al.

As a data-driven approach, multi-agent reinforcement learning (MARL) has made remarkable advances in solving cooperative residential load scheduling problems. However, centralized training, the most common paradigm for MARL, limits large-scale deployment in communication-constrained cloud-edge environments. As a remedy, distributed training shows unparalleled advantages in real-world applications but still faces challenge with system scalability, e.g., the high cost of communication overhead during coordinating individual agents, and needs to comply with data governance in terms of privacy. In this work, we propose a novel MARL solution to address these two practical issues. Our proposed approach is based on actor-critic methods, where the global critic is a learned function of individual critics computed solely based on local observations of households. This scheme preserves household privacy completely and significantly reduces communication cost. Simulation experiments demonstrate that the proposed framework achieves comparable performance to the state-of-the-art actor-critic framework without data governance and communication constraints.

Nanqing Dong, Irina Voiculescu

A label-efficient paradigm in computer vision is based on self-supervised contrastive pre-training on unlabeled data followed by fine-tuning with a small number of labels. Making practical use of a federated computing environment in the clinical domain and learning on medical images poses specific challenges. In this work, we propose FedMoCo, a robust federated contrastive learning (FCL) framework, which makes efficient use of decentralized unlabeled medical data. FedMoCo has two novel modules: metadata transfer, an inter-node statistical data augmentation module, and self-adaptive aggregation, an aggregation module based on representational similarity analysis. To the best of our knowledge, this is the first FCL work on medical images. Our experiments show that FedMoCo can consistently outperform FedAvg, a seminal federated learning framework, in extracting meaningful representations for downstream tasks. We further show that FedMoCo can substantially reduce the amount of labeled data required in a downstream task, such as COVID-19 detection, to achieve a reasonable performance.

Nanqing Dong, Matteo Maggioni, Yongxin Yang et al.

This paper is concerned with contrastive learning (CL) for low-level image restoration and enhancement tasks. We propose a new label-efficient learning paradigm based on residuals, residual contrastive learning (RCL), and derive an unsupervised visual representation learning framework, suitable for low-level vision tasks with noisy inputs. While supervised image reconstruction aims to minimize residual terms directly, RCL alternatively builds a connection between residuals and CL by defining a novel instance discrimination pretext task, using residuals as the discriminative feature. Our formulation mitigates the severe task misalignment between instance discrimination pretext tasks and downstream image reconstruction tasks, present in existing CL frameworks. Experimentally, we find that RCL can learn robust and transferable representations that improve the performance of various downstream tasks, such as denoising and super resolution, in comparison with recent self-supervised methods designed specifically for noisy inputs. Additionally, our unsupervised pre-training can significantly reduce annotation costs whilst maintaining performance competitive with fully-supervised image reconstruction.

Nanqing Dong, Michael Kampffmeyer, Irina Voiculescu et al.

Entanglement is a physical phenomenon, which has fueled recent successes of quantum algorithms. Although quantum neural networks (QNNs) have shown promising results in solving simple machine learning tasks recently, for the time being, the effect of entanglement in QNNs and the behavior of QNNs in binary pattern classification are still underexplored. In this work, we provide some theoretical insight into the properties of QNNs by presenting and analyzing a new form of invariance embedded in QNNs for both quantum binary classification and quantum representation learning, which we term negational symmetry. Given a quantum binary signal and its negational counterpart where a bitwise NOT operation is applied to each quantum bit of the binary signal, a QNN outputs the same logits. That is to say, QNNs cannot differentiate a quantum binary signal and its negational counterpart in a binary classification task. We further empirically evaluate the negational symmetry of QNNs in binary pattern classification tasks using Google's quantum computing framework. The theoretical and experimental results suggest that negational symmetry is a fundamental property of QNNs, which is not shared by classical models. Our findings also imply that negational symmetry is a double-edged sword in practical quantum applications.

Nanqing Dong, Michael Kampffmeyer, Xiaodan Liang et al.

The data-driven nature of deep learning (DL) models for semantic segmentation requires a large number of pixel-level annotations. However, large-scale and fully labeled medical datasets are often unavailable for practical tasks. Recently, partially supervised methods have been proposed to utilize images with incomplete labels in the medical domain. To bridge the methodological gaps in partially supervised learning (PSL) under data scarcity, we propose Vicinal Labels Under Uncertainty (VLUU), a simple yet efficient framework utilizing the human structure similarity for partially supervised medical image segmentation. Motivated by multi-task learning and vicinal risk minimization, VLUU transforms the partially supervised problem into a fully supervised problem by generating vicinal labels. We systematically evaluate VLUU under the challenges of small-scale data, dataset shift, and class imbalance on two commonly used segmentation datasets for the tasks of chest organ segmentation and optic disc-and-cup segmentation. The experimental results show that VLUU can consistently outperform previous partially supervised models in these settings. Our research suggests a new research direction in label-efficient deep learning with partial supervision.

Zeya Wang, Baoyu Jing, Yang Ni et al.

Adversarial training is a useful approach to promote the learning of transferable representations across the source and target domains, which has been widely applied for domain adaptation (DA) tasks based on deep neural networks. Until very recently, existing adversarial domain adaptation (ADA) methods ignore the useful information from the label space, which is an important factor accountable for the complicated data distributions associated with different semantic classes. Especially, the inter-class semantic relationships have been rarely considered and discussed in the current work of transfer learning. In this paper, we propose a novel relationship-aware adversarial domain adaptation (RADA) algorithm, which first utilizes a single multi-class domain discriminator to enforce the learning of inter-class dependency structure during domain-adversarial training and then aligns this structure with the inter-class dependencies that are characterized from training the label predictor on source domain. Specifically, we impose a regularization term to penalize the structure discrepancy between the inter-class dependencies respectively estimated from domain discriminator and label predictor. Through this alignment, our proposed method makes the adversarial domain adaptation aware of the class relationships. Empirical studies show that the incorporation of class relationships significantly improves the performance on benchmark datasets.

Wei Dai, Yi Zhou, Nanqing Dong et al.

Many distributed machine learning (ML) systems adopt the non-synchronous execution in order to alleviate the network communication bottleneck, resulting in stale parameters that do not reflect the latest updates. Despite much development in large-scale ML, the effects of staleness on learning are inconclusive as it is challenging to directly monitor or control staleness in complex distributed environments. In this work, we study the convergence behaviors of a wide array of ML models and algorithms under delayed updates. Our extensive experiments reveal the rich diversity of the effects of staleness on the convergence of ML algorithms and offer insights into seemingly contradictory reports in the literature. The empirical findings also inspire a new convergence analysis of stochastic gradient descent in non-convex optimization under staleness, matching the best-known convergence rate of O(1/\sqrt{T}).

Nanqing Dong, Michael Kampffmeyer, Xiaodan Liang et al.

Convolutional neural networks have led to significant breakthroughs in the domain of medical image analysis. However, the task of breast cancer segmentation in whole-slide images (WSIs) is still underexplored. WSIs are large histopathological images with extremely high resolution. Constrained by the hardware and field of view, using high-magnification patches can slow down the inference process and using low-magnification patches can cause the loss of information. In this paper, we aim to achieve two seemingly conflicting goals for breast cancer segmentation: accurate and fast prediction. We propose a simple yet efficient framework Reinforced Auto-Zoom Net (RAZN) to tackle this task. Motivated by the zoom-in operation of a pathologist using a digital microscope, RAZN learns a policy network to decide whether zooming is required in a given region of interest. Because the zoom-in action is selective, RAZN is robust to unbalanced and noisy ground truth labels and can efficiently reduce overfitting. We evaluate our method on a public breast cancer dataset. RAZN outperforms both single-scale and multi-scale baseline approaches, achieving better accuracy at low inference cost.

Nanqing Dong, Michael Kampffmeyer, Xiaodan Liang et al.

The cardiothoracic ratio (CTR), a clinical metric of heart size in chest X-rays (CXRs), is a key indicator of cardiomegaly. Manual measurement of CTR is time-consuming and can be affected by human subjectivity, making it desirable to design computer-aided systems that assist clinicians in the diagnosis process. Automatic CTR estimation through chest organ segmentation, however, requires large amounts of pixel-level annotated data, which is often unavailable. To alleviate this problem, we propose an unsupervised domain adaptation framework based on adversarial networks. The framework learns domain invariant feature representations from openly available data sources to produce accurate chest organ segmentation for unlabeled datasets. Specifically, we propose a model that enforces our intuition that prediction masks should be domain independent. Hence, we introduce a discriminator that distinguishes segmentation predictions from ground truth masks. We evaluate our system's prediction based on the assessment of radiologists and demonstrate the clinical practicability for the diagnosis of cardiomegaly. We finally illustrate on the JSRT dataset that the semi-supervised performance of our model is also very promising.

Michael Kampffmeyer, Nanqing Dong, Xiaodan Liang et al.

Salient segmentation aims to segment out attention-grabbing regions, a critical yet challenging task and the foundation of many high-level computer vision applications. It requires semantic-aware grouping of pixels into salient regions and benefits from the utilization of global multi-scale contexts to achieve good local reasoning. Previous works often address it as two-class segmentation problems utilizing complicated multi-step procedures including refinement networks and complex graphical models. We argue that semantic salient segmentation can instead be effectively resolved by reformulating it as a simple yet intuitive pixel-pair based connectivity prediction task. Following the intuition that salient objects can be naturally grouped via semantic-aware connectivity between neighboring pixels, we propose a pure Connectivity Net (ConnNet). ConnNet predicts connectivity probabilities of each pixel with its neighboring pixels by leveraging multi-level cascade contexts embedded in the image and long-range pixel relations. We investigate our approach on two tasks, namely salient object segmentation and salient instance-level segmentation, and illustrate that consistent improvements can be obtained by modeling these tasks as connectivity instead of binary segmentation tasks for a variety of network architectures. We achieve state-of-the-art performance, outperforming or being comparable to existing approaches while reducing inference time due to our less complex approach.

Wei Dai, Joseph Doyle, Xiaodan Liang et al.

Chest X-ray (CXR) is one of the most commonly prescribed medical imaging procedures, often with over 2-10x more scans than other imaging modalities such as MRI, CT scan, and PET scans. These voluminous CXR scans place significant workloads on radiologists and medical practitioners. Organ segmentation is a crucial step to obtain effective computer-aided detection on CXR. In this work, we propose Structure Correcting Adversarial Network (SCAN) to segment lung fields and the heart in CXR images. SCAN incorporates a critic network to impose on the convolutional segmentation network the structural regularities emerging from human physiology. During training, the critic network learns to discriminate between the ground truth organ annotations from the masks synthesized by the segmentation network. Through this adversarial process the critic network learns the higher order structures and guides the segmentation model to achieve realistic segmentation outcomes. Extensive experiments show that our method produces highly accurate and natural segmentation. Using only very limited training data available, our model reaches human-level performance without relying on any existing trained model or dataset. Our method also generalizes well to CXR images from a different patient population and disease profiles, surpassing the current state-of-the-art.