Yanjun Lyu

Jing Zhang, Norman Scheel, Minheng Chen et al.

Understanding how structural connections are associated with tau propagation in Alzheimer's disease (AD) remains a central open question, yet existing computational models either rely heavily on biophysical assumptions or lack neurobiologically interpretable pathway maps. We present SC-TauPath, a structural connectivity (SC) attribution framework that maps tau propagation pathways from in vivo neuroimaging data. SC-TauPath combines a Network Diffusion Model (NDM)-augmented multilayer perceptron with gradient $\times$ input attribution to score each SC edge's contribution to tau prediction, then translates these attribution scores into multi-scale pathway maps (backbone edges, high-traffic routes, and hub ROIs), which validates established Braak staging anatomy. Applied to 234 ADNI participants with paired DTI SC and 18F-Flortaucipir PET, SC-TauPath achieves strong cross-validated tau prediction and yields attribution-based pathway maps consistent with established Braak staging anatomy, demonstrating that SC encode spatially specific information about regional tau distribution in AD.

Tianyang Zhong, Zhengliang Liu, Yi Pan et al.

This comprehensive study evaluates the performance of OpenAI's o1-preview large language model across a diverse array of complex reasoning tasks, spanning multiple domains, including computer science, mathematics, natural sciences, medicine, linguistics, and social sciences. Through rigorous testing, o1-preview demonstrated remarkable capabilities, often achieving human-level or superior performance in areas ranging from coding challenges to scientific reasoning and from language processing to creative problem-solving. Key findings include: -83.3% success rate in solving complex competitive programming problems, surpassing many human experts. -Superior ability in generating coherent and accurate radiology reports, outperforming other evaluated models. -100% accuracy in high school-level mathematical reasoning tasks, providing detailed step-by-step solutions. -Advanced natural language inference capabilities across general and specialized domains like medicine. -Impressive performance in chip design tasks, outperforming specialized models in areas such as EDA script generation and bug analysis. -Remarkable proficiency in anthropology and geology, demonstrating deep understanding and reasoning in these specialized fields. -Strong capabilities in quantitative investing. O1 has comprehensive financial knowledge and statistical modeling skills. -Effective performance in social media analysis, including sentiment analysis and emotion recognition. The model excelled particularly in tasks requiring intricate reasoning and knowledge integration across various fields. While some limitations were observed, including occasional errors on simpler problems and challenges with certain highly specialized concepts, the overall results indicate significant progress towards artificial general intelligence.

Xiaowei Yu, Lu Zhang, Haixing Dai et al.

Designing more efficient, reliable, and explainable neural network architectures is critical to studies that are based on artificial intelligence (AI) techniques. Previous studies, by post-hoc analysis, have found that the best-performing ANNs surprisingly resemble biological neural networks (BNN), which indicates that ANNs and BNNs may share some common principles to achieve optimal performance in either machine learning or cognitive/behavior tasks. Inspired by this phenomenon, we proactively instill organizational principles of BNNs to guide the redesign of ANNs. We leverage the Core-Periphery (CP) organization, which is widely found in human brain networks, to guide the information communication mechanism in the self-attention of vision transformer (ViT) and name this novel framework as CP-ViT. In CP-ViT, the attention operation between nodes is defined by a sparse graph with a Core-Periphery structure (CP graph), where the core nodes are redesigned and reorganized to play an integrative role and serve as a center for other periphery nodes to exchange information. We evaluated the proposed CP-ViT on multiple public datasets, including medical image datasets (INbreast) and natural image datasets. Interestingly, by incorporating the BNN-derived principle (CP structure) into the redesign of ViT, our CP-ViT outperforms other state-of-the-art ANNs. In general, our work advances the state of the art in three aspects: 1) This work provides novel insights for brain-inspired AI: we can utilize the principles found in BNNs to guide and improve our ANN architecture design; 2) We show that there exist sweet spots of CP graphs that lead to CP-ViTs with significantly improved performance; and 3) The core nodes in CP-ViT correspond to task-related meaningful and important image patches, which can significantly enhance the interpretability of the trained deep model.

Xiaowei Yu, Lu Zhang, Lin Zhao et al.

How to identify and characterize functional brain networks (BN) is fundamental to gain system-level insights into the mechanisms of brain organizational architecture. Current functional magnetic resonance (fMRI) analysis highly relies on prior knowledge of specific patterns in either spatial (e.g., resting-state network) or temporal (e.g., task stimulus) domain. In addition, most approaches aim to find group-wise common functional networks, individual-specific functional networks have been rarely studied. In this work, we propose a novel Twin-Transformers framework to simultaneously infer common and individual functional networks in both spatial and temporal space, in a self-supervised manner. The first transformer takes space-divided information as input and generates spatial features, while the second transformer takes time-related information as input and outputs temporal features. The spatial and temporal features are further separated into common and individual ones via interactions (weights sharing) and constraints between the two transformers. We applied our TwinTransformers to Human Connectome Project (HCP) motor task-fMRI dataset and identified multiple common brain networks, including both task-related and resting-state networks (e.g., default mode network). Interestingly, we also successfully recovered a set of individual-specific networks that are not related to task stimulus and only exist at the individual level.

Zhengliang Liu, Hanqi Jiang, Tianyang Zhong et al.

In this paper, we present a large-scale evaluation probing GPT-4V's capabilities and limitations for biomedical image analysis. GPT-4V represents a breakthrough in artificial general intelligence (AGI) for computer vision, with applications in the biomedical domain. We assess GPT-4V's performance across 16 medical imaging categories, including radiology, oncology, ophthalmology, pathology, and more. Tasks include modality recognition, anatomy localization, disease diagnosis, report generation, and lesion detection. The extensive experiments provide insights into GPT-4V's strengths and weaknesses. Results show GPT-4V's proficiency in modality and anatomy recognition but difficulty with disease diagnosis and localization. GPT-4V excels at diagnostic report generation, indicating strong image captioning skills. While promising for biomedical imaging AI, GPT-4V requires further enhancement and validation before clinical deployment. We emphasize responsible development and testing for trustworthy integration of biomedical AGI. This rigorous evaluation of GPT-4V on diverse medical images advances understanding of multimodal large language models (LLMs) and guides future work toward impactful healthcare applications.

Haixing Dai, Lu Zhang, Lin Zhao et al.

With the popularity of deep neural networks (DNNs), model interpretability is becoming a critical concern. Many approaches have been developed to tackle the problem through post-hoc analysis, such as explaining how predictions are made or understanding the meaning of neurons in middle layers. Nevertheless, these methods can only discover the patterns or rules that naturally exist in models. In this work, rather than relying on post-hoc schemes, we proactively instill knowledge to alter the representation of human-understandable concepts in hidden layers. Specifically, we use a hierarchical tree of semantic concepts to store the knowledge, which is leveraged to regularize the representations of image data instances while training deep models. The axes of the latent space are aligned with the semantic concepts, where the hierarchical relations between concepts are also preserved. Experiments on real-world image datasets show that our method improves model interpretability, showing better disentanglement of semantic concepts, without negatively affecting model classification performance.

Yanjun Lyu, Zihao Wu, Lu Zhang et al.

Pre-trained large language models(LLMs) have attracted increasing attention in biomedical domains due to their success in natural language processing. However, the complex traits and heterogeneity of multi-sources genomics data pose significant challenges when adapting these models to the bioinformatics and biomedical field. To address these challenges, we present GP-GPT, the first specialized large language model for genetic-phenotype knowledge representation and genomics relation analysis. Our model is fine-tuned in two stages on a comprehensive corpus composed of over 3,000,000 terms in genomics, proteomics, and medical genetics, derived from multiple large-scale validated datasets and scientific publications. GP-GPT demonstrates proficiency in accurately retrieving medical genetics information and performing common genomics analysis tasks, such as genomics information retrieval and relationship determination. Comparative experiments across domain-specific tasks reveal that GP-GPT outperforms state-of-the-art LLMs, including Llama2, Llama3 and GPT-4. These results highlight GP-GPT's potential to enhance genetic disease relation research and facilitate accurate and efficient analysis in the fields of genomics and medical genetics. Our investigation demonstrated the subtle changes of bio-factor entities' representations in the GP-GPT, which suggested the opportunities for the application of LLMs to advancing gene-phenotype research.

Zihao Wu, Steven Xu, Bowen Chen et al.

With the emergence of large language models (LLMs) and AI agent frameworks, the human-AI co-work paradigm known as Vibe Coding is changing how people code, making it more accessible and productive. In scientific research, where workflows are more complex and the burden of specialized labor limits independent researchers and those in low-resource areas, the potential impact is even greater, particularly in biomedicine, which involves heterogeneous data modalities and multi-step analytical pipelines. In this paper, we introduce Vibe Medicine, a co-work paradigm in which clinicians and researchers direct skill-augmented AI agents through natural language to execute complex, multi-step biomedical workflows, while retaining the role of research director who specifies objectives, reviews intermediate results, and makes domain-informed decisions. The enabling infrastructure consists of three layers: capable LLMs, agent frameworks such as OpenClaw and Hermes Agent, and the OpenClaw medical skills collection, which includes more than 1,000 curated skills from multiple open-source repositories. We analyze the architecture and skill categories of this collection across ten biomedical domains, and present case studies covering rare disease diagnosis, drug repurposing, and clinical trial design that demonstrate end-to-end workflows in practice. We also identify the principal risks, such as hallucination, data privacy, and over-reliance, and outline directions toward more reliable, trustworthy, and clinically integrated agent-assisted research that advances research and technological equity and reduces health care resource disparities.

Yiwei Li, Huaqin Zhao, Hanqi Jiang et al.

The rapid advances in Large Language Models (LLMs) have the potential to transform manufacturing industry, offering new opportunities to optimize processes, improve efficiency, and drive innovation. This paper provides a comprehensive exploration of the integration of LLMs into the manufacturing domain, focusing on their potential to automate and enhance various aspects of manufacturing, from product design and development to quality control, supply chain optimization, and talent management. Through extensive evaluations across multiple manufacturing tasks, we demonstrate the remarkable capabilities of state-of-the-art LLMs, such as GPT-4V, in understanding and executing complex instructions, extracting valuable insights from vast amounts of data, and facilitating knowledge sharing. We also delve into the transformative potential of LLMs in reshaping manufacturing education, automating coding processes, enhancing robot control systems, and enabling the creation of immersive, data-rich virtual environments through the industrial metaverse. By highlighting the practical applications and emerging use cases of LLMs in manufacturing, this paper aims to provide a valuable resource for professionals, researchers, and decision-makers seeking to harness the power of these technologies to address real-world challenges, drive operational excellence, and unlock sustainable growth in an increasingly competitive landscape.

Wei Ruan, Yanjun Lyu, Jing Zhang et al.

With the rapid advancements in large language model (LLM) technology and the emergence of bioinformatics-specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and limitations inherent in BioLMs, including data privacy and security concerns, interpretability issues, biases in training data and model outputs, and domain adaptation complexities. Finally, we highlight emerging trends and future directions, offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.

Jing Zhang, Xiaowei Yu, Yanjun Lyu et al.

Understanding brain disorders is crucial for accurate clinical diagnosis and treatment. Recent advances in Multimodal Large Language Models (MLLMs) offer a promising approach to interpreting medical images with the support of text descriptions. However, previous research has primarily focused on 2D medical images, leaving richer spatial information of 3D images under-explored, and single-modality-based methods are limited by overlooking the critical clinical information contained in other modalities. To address this issue, this paper proposes Brain-Adapter, a novel approach that incorporates an extra bottleneck layer to learn new knowledge and instill it into the original pre-trained knowledge. The major idea is to incorporate a lightweight bottleneck layer to train fewer parameters while capturing essential information and utilize a Contrastive Language-Image Pre-training (CLIP) strategy to align multimodal data within a unified representation space. Extensive experiments demonstrated the effectiveness of our approach in integrating multimodal data to significantly improve the diagnosis accuracy without high computational costs, highlighting the potential to enhance real-world diagnostic workflows.

Jing Zhang, Xiaowei Yu, Tong Chen et al.

The Lewy body dementia (LBD) is the second most common neurodegenerative dementia after Alzheimer's disease (AD). Early differentiation between AD and LBD is crucial because they require different treatment approaches, but this is challenging due to significant clinical overlap, heterogeneity, complex pathogenesis, and the rarity of LBD. While recent advances in artificial intelligence (AI) demonstrate powerful learning capabilities and offer new hope for accurate diagnosis, existing methods primarily focus on designing "neural-level networks". Our work represents a pioneering effort in modeling system-level artificial neural network called BrainNet-MoE for brain modeling and diagnosing. Inspired by the brain's hierarchical organization of bottom-up sensory integration and top-down control, we design a set of disease-specific expert groups to process brain sub-network under different condition, A disease gate mechanism guides the specializa-tion of expert groups, while a transformer layer enables communication be-tween all sub-networks, generating a comprehensive whole-brain represen-tation for downstream disease classification. Experimental results show superior classification accuracy with interpretable insights into how brain sub-networks contribute to different neurodegenerative conditions.

Jing Zhang, Yanjun Lyu, Xiaowei Yu et al.

Dynamic functional connectivity (dFC) using resting-state functional magnetic resonance imaging (rs-fMRI) is an advanced technique for capturing the dynamic changes of neural activities, and can be very useful in the studies of brain diseases such as Alzheimer's disease (AD). Yet, existing studies have not fully leveraged the sequential information embedded within dFC that can potentially provide valuable information when identifying brain conditions. In this paper, we propose a novel framework that jointly learns the embedding of both spatial and temporal information within dFC based on the transformer architecture. Specifically, we first construct dFC networks from rs-fMRI data through a sliding window strategy. Then, we simultaneously employ a temporal block and a spatial block to capture higher-order representations of dynamic spatio-temporal dependencies, via mapping them into an efficient fused feature representation. To further enhance the robustness of these feature representations by reducing the dependency on labeled data, we also introduce a contrastive learning strategy to manipulate different brain states. Experimental results on 345 subjects with 570 scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate the superiority of our proposed method for MCI (Mild Cognitive Impairment, the prodromal stage of AD) prediction, highlighting its potential for early identification of AD.

Minheng Chen, Xiaowei Yu, Jing Zhang et al.

Understanding the organization of human brain networks has become a central focus in neuroscience, particularly in the study of functional connectivity, which plays a crucial role in diagnosing neurological disorders. Advances in functional magnetic resonance imaging and machine learning techniques have significantly improved brain network analysis. However, traditional machine learning approaches struggle to capture the complex relationships between brain regions, while deep learning methods, particularly Transformer-based models, face computational challenges due to their quadratic complexity in long-sequence modeling. To address these limitations, we propose a Core-Periphery State-Space Model (CP-SSM), an innovative framework for functional connectome classification. Specifically, we introduce Mamba, a selective state-space model with linear complexity, to effectively capture long-range dependencies in functional brain networks. Furthermore, inspired by the core-periphery (CP) organization, a fundamental characteristic of brain networks that enhances efficient information transmission, we design CP-MoE, a CP-guided Mixture-of-Experts that improves the representation learning of brain connectivity patterns. We evaluate CP-SSM on two benchmark fMRI datasets: ABIDE and ADNI. Experimental results demonstrate that CP-SSM surpasses Transformer-based models in classification performance while significantly reducing computational complexity. These findings highlight the effectiveness and efficiency of CP-SSM in modeling brain functional connectivity, offering a promising direction for neuroimaging-based neurological disease diagnosis.

Xiaowei Yu, Jing Zhang, Tong Chen et al.

Lewy Body Disease (LBD) is a common yet understudied form of dementia that imposes a significant burden on public health. It shares clinical similarities with Alzheimer's disease (AD), as both progress through stages of normal cognition, mild cognitive impairment, and dementia. A major obstacle in LBD diagnosis is data scarcity, which limits the effectiveness of deep learning. In contrast, AD datasets are more abundant, offering potential for knowledge transfer. However, LBD and AD data are typically collected from different sites using different machines and protocols, resulting in a distinct domain shift. To effectively leverage AD data while mitigating domain shift, we propose a Transferability Aware Transformer (TAT) that adapts knowledge from AD to enhance LBD diagnosis. Our method utilizes structural connectivity (SC) derived from structural MRI as training data. Built on the attention mechanism, TAT adaptively assigns greater weights to disease-transferable features while suppressing domain-specific ones, thereby reducing domain shift and improving diagnostic accuracy with limited LBD data. The experimental results demonstrate the effectiveness of TAT. To the best of our knowledge, this is the first study to explore domain adaptation from AD to LBD under conditions of data scarcity and domain shift, providing a promising framework for domain-adaptive diagnosis of rare diseases.

Ziyu Liu, Lintao Tang, Zeliang Sun et al.

Large language models (LLMs) have emerged as powerful tools for medical information retrieval, yet their accuracy and depth remain limited in specialized domains such as Alzheimer's disease (AD), a growing global health challenge. To address this gap, we introduce AD-GPT, a domain-specific generative pre-trained transformer designed to enhance the retrieval and analysis of AD-related genetic and neurobiological information. AD-GPT integrates diverse biomedical data sources, including potential AD-associated genes, molecular genetic information, and key gene variants linked to brain regions. We develop a stacked LLM architecture combining Llama3 and BERT, optimized for four critical tasks in AD research: (1) genetic information retrieval, (2) gene-brain region relationship assessment, (3) gene-AD relationship analysis, and (4) brain region-AD relationship mapping. Comparative evaluations against state-of-the-art LLMs demonstrate AD-GPT's superior precision and reliability across these tasks, underscoring its potential as a robust and specialized AI tool for advancing AD research and biomarker discovery.

Minheng Chen, Chao Cao, Tong Chen et al.

The 3-hinge gyrus (3HG) is a newly defined folding pattern, which is the conjunction of gyri coming from three directions in cortical folding. Many studies demonstrated that 3HGs can be reliable nodes when constructing brain networks or connectome since they simultaneously possess commonality and individuality across different individual brains and populations. However, 3HGs are identified and validated within individual spaces, making it difficult to directly serve as the brain network nodes due to the absence of cross-subject correspondence. The 3HG correspondences represent the intrinsic regulation of brain organizational architecture, traditional image-based registration methods tend to fail because individual anatomical properties need to be fully respected. To address this challenge, we propose a novel self-supervised framework for anatomical feature embedding of the 3HGs to build the correspondences among different brains. The core component of this framework is to construct a structural similarity-enhanced multi-hop feature encoding strategy based on the recently developed Kolmogorov-Arnold network (KAN) for anatomical feature embedding. Extensive experiments suggest that our approach can effectively establish robust cross-subject correspondences when no one-to-one mapping exists.

Jing Zhang, Xiaowei Yu, Minheng Chen et al.

Integrating brain imaging data with clinical reports offers a valuable opportunity to leverage complementary multimodal information for more effective and timely diagnosis in practical clinical settings. This approach has gained significant attention in brain disorder research, yet a key challenge remains: how to effectively link objective imaging data with subjective text-based reports, such as doctors' notes. In this work, we propose a novel framework that aligns brain connectomes with clinical reports in a shared cross-modal latent space at both the subject and connectome levels, thereby enhancing representation learning. The key innovation of our approach is that we treat brain subnetworks as tokens of imaging data, rather than raw image patches, to align with word tokens in clinical reports. This enables a more efficient identification of system-level associations between neuroimaging findings and clinical observations, which is critical since brain disorders often manifest as network-level abnormalities rather than isolated regional alterations. We applied our method to mild cognitive impairment (MCI) using the ADNI dataset. Our approach not only achieves state-of-the-art predictive performance but also identifies clinically meaningful connectome-text pairs, offering new insights into the early mechanisms of Alzheimer's disease and supporting the development of clinically useful multimodal biomarkers.

Yan Zhuang, Minheng Chen, Chao Cao et al.

Understanding the structural and functional organization of the human brain requires a detailed examination of cortical folding patterns, among which the three-hinge gyrus (3HG) has been identified as a key structural landmark. GyralNet, a network representation of cortical folding, models 3HGs as nodes and gyral crests as edges, highlighting their role as critical hubs in cortico-cortical connectivity. However, existing methods for analyzing 3HGs face significant challenges, including the sub-voxel scale of 3HGs at typical neuroimaging resolutions, the computational complexity of establishing cross-subject correspondences, and the oversimplification of treating 3HGs as independent nodes without considering their community-level relationships. To address these limitations, we propose a fully differentiable subnetwork partitioning framework that employs a spectral modularity maximization optimization strategy to modularize the organization of 3HGs within GyralNet. By incorporating topological structural similarity and DTI-derived connectivity patterns as attribute features, our approach provides a biologically meaningful representation of cortical organization. Extensive experiments on the Human Connectome Project (HCP) dataset demonstrate that our method effectively partitions GyralNet at the individual level while preserving the community-level consistency of 3HGs across subjects, offering a robust foundation for understanding brain connectivity.