Abstract:Foundation models, first introduced in 2021, are large-scale pre-trained models (e.g., large language models (LLMs) and vision-language models (VLMs)) that learn from extensive unlabeled datasets through unsupervised methods, enabling them to excel in diverse downstream tasks. These models, like GPT, can be adapted to various applications such as question answering and visual understanding, outperforming task-specific AI models and earning their name due to broad applicability across fields. The development of biomedical foundation models marks a significant milestone in leveraging artificial intelligence (AI) to understand complex biological phenomena and advance medical research and practice. This survey explores the potential of foundation models across diverse domains within biomedical fields, including computational biology, drug discovery and development, clinical informatics, medical imaging, and public health. The purpose of this survey is to inspire ongoing research in the application of foundation models to health science.
Abstract:Ordinal regression refers to classifying object instances into ordinal categories. Ordinal regression is crucial for applications in various areas like facial age estimation, image aesthetics assessment, and even cancer staging, due to its capability to utilize ordered information effectively. More importantly, it also enhances model interpretation by considering category order, aiding the understanding of data trends and causal relationships. Despite significant recent progress, challenges remain, and further investigation of ordinal regression techniques and applications is essential to guide future research. In this survey, we present a comprehensive examination of advances and applications of ordinal regression. By introducing a systematic taxonomy, we meticulously classify the pertinent techniques and applications into three well-defined categories based on different strategies and objectives: Continuous Space Discretization, Distribution Ordering Learning, and Ambiguous Instance Delving. This categorization enables a structured exploration of diverse insights in ordinal regression problems, providing a framework for a more comprehensive understanding and evaluation of this field and its related applications. To our best knowledge, this is the first systematic survey of ordinal regression, which lays a foundation for future research in this fundamental and generic domain.
Abstract:Clinical trials are pivotal in cardiac drug development, yet they often fail due to inadequate efficacy and unexpected safety issues, leading to significant financial losses. Using in-silico trials to replace a part of physical clinical trials, e.g., leveraging advanced generative models to generate drug-influenced electrocardiograms (ECGs), seems an effective method to reduce financial risk and potential harm to trial participants. While existing generative models have demonstrated progress in ECG generation, they fall short in modeling drug reactions due to limited fidelity and inability to capture individualized drug response patterns. In this paper, we propose a Drug-Aware Diffusion Model (DADM), which could simulate individualized drug reactions while ensuring fidelity. To ensure fidelity, we construct a set of ordinary differential equations to provide external physical knowledge (EPK) of the realistic ECG morphology. The EPK is used to adaptively constrain the morphology of the generated ECGs through a dynamic cross-attention (DCA) mechanism. Furthermore, we propose an extension of ControlNet to incorporate demographic and drug data, simulating individual drug reactions. We compare DADM with the other eight state-of-the-art ECG generative models on two real-world databases covering 8 types of drug regimens. The results demonstrate that DADM can more accurately simulate drug-induced changes in ECGs, improving the accuracy by at least 5.79% and recall by 8%.
Abstract:Healthcare systems worldwide face persistent challenges in efficiency, accessibility, and personalization. Powered by modern AI technologies such as multimodal large language models and world models, Embodied AI (EmAI) represents a transformative frontier, offering enhanced autonomy and the ability to interact with the physical world to address these challenges. As an interdisciplinary and rapidly evolving research domain, "EmAI in healthcare" spans diverse fields such as algorithms, robotics, and biomedicine. This complexity underscores the importance of timely reviews and analyses to track advancements, address challenges, and foster cross-disciplinary collaboration. In this paper, we provide a comprehensive overview of the "brain" of EmAI for healthcare, wherein we introduce foundational AI algorithms for perception, actuation, planning, and memory, and focus on presenting the healthcare applications spanning clinical interventions, daily care & companionship, infrastructure support, and biomedical research. Despite its promise, the development of EmAI for healthcare is hindered by critical challenges such as safety concerns, gaps between simulation platforms and real-world applications, the absence of standardized benchmarks, and uneven progress across interdisciplinary domains. We discuss the technical barriers and explore ethical considerations, offering a forward-looking perspective on the future of EmAI in healthcare. A hierarchical framework of intelligent levels for EmAI systems is also introduced to guide further development. By providing systematic insights, this work aims to inspire innovation and practical applications, paving the way for a new era of intelligent, patient-centered healthcare.
Abstract:Multi-modality pre-training paradigm that aligns protein sequences and biological descriptions has learned general protein representations and achieved promising performance in various downstream applications. However, these works were still unable to replicate the extraordinary success of language-supervised visual foundation models due to the ineffective usage of aligned protein-text paired data and the lack of an effective function-informed pre-training paradigm. To address these issues, this paper curates a large-scale protein-text paired dataset called ProtAnno with a property-driven sampling strategy, and introduces a novel function-informed protein pre-training paradigm. Specifically, the sampling strategy determines selecting probability based on the sample confidence and property coverage, balancing the data quality and data quantity in face of large-scale noisy data. Furthermore, motivated by significance of the protein specific functional mechanism, the proposed paradigm explicitly model protein static and dynamic functional segments by two segment-wise pre-training objectives, injecting fine-grained information in a function-informed manner. Leveraging all these innovations, we develop ProtCLIP, a multi-modality foundation model that comprehensively represents function-aware protein embeddings. On 22 different protein benchmarks within 5 types, including protein functionality classification, mutation effect prediction, cross-modal transformation, semantic similarity inference and protein-protein interaction prediction, our ProtCLIP consistently achieves SOTA performance, with remarkable improvements of 75% on average in five cross-modal transformation benchmarks, 59.9% in GO-CC and 39.7% in GO-BP protein function prediction. The experimental results verify the extraordinary potential of ProtCLIP serving as the protein multi-modality foundation model.
Abstract:Deep learning models are widely used to process Computed Tomography (CT) data in the automated screening of pulmonary diseases, significantly reducing the workload of physicians. However, the three-dimensional nature of CT volumes involves an excessive number of voxels, which significantly increases the complexity of model processing. Previous screening approaches often overlook this issue, which undoubtedly reduces screening efficiency. Towards efficient and effective screening, we design a hierarchical approach to reduce the computational cost of pulmonary disease screening. The new approach re-organizes the screening workflows into three steps. First, we propose a Computed Tomography Volume Compression (CTVC) method to select a small slice subset that comprehensively represents the whole CT volume. Second, the selected CT slices are used to detect pulmonary diseases coarsely via a lightweight classification model. Third, an uncertainty measurement strategy is applied to identify samples with low diagnostic confidence, which are re-detected by radiologists. Experiments on two public pulmonary disease datasets demonstrate that our approach achieves comparable accuracy and recall while reducing the time by 50%-70% compared with the counterparts using full CT volumes. Besides, we also found that our approach outperforms previous cutting-edge CTVC methods in retaining important indications after compression.
Abstract:Antibodies safeguard our health through their precise and potent binding to specific antigens, demonstrating promising therapeutic efficacy in the treatment of numerous diseases, including COVID-19. Recent advancements in biomedical language models have shown the great potential to interpret complex biological structures and functions. However, existing antibody specific models have a notable limitation that they lack explicit consideration for antibody structural information, despite the fact that both 1D sequence and 3D structure carry unique and complementary insights into antibody behavior and functionality. This paper proposes Sequence-Structure multi-level pre-trained Antibody Language Model (S$^2$ALM), combining holistic sequential and structural information in one unified, generic antibody foundation model. We construct a hierarchical pre-training paradigm incorporated with two customized multi-level training objectives to facilitate the modeling of comprehensive antibody representations. S$^2$ALM's representation space uncovers inherent functional binding mechanisms, biological evolution properties and structural interaction patterns. Pre-trained over 75 million sequences and 11.7 million structures, S$^2$ALM can be adopted for diverse downstream tasks: accurately predicting antigen-antibody binding affinities, precisely distinguishing B cell maturation stages, identifying antibody crucial binding positions, and specifically designing novel coronavirus-binding antibodies. Remarkably, S$^2$ALM outperforms well-established and renowned baselines and sets new state-of-the-art performance across extensive antibody specific understanding and generation tasks. S$^2$ALM's ability to model comprehensive and generalized representations further positions its potential to advance real-world therapeutic antibody development, potentially addressing unmet academic, industrial, and clinical needs.
Abstract:Modeling disease progression is crucial for improving the quality and efficacy of clinical diagnosis and prognosis, but it is often hindered by a lack of longitudinal medical image monitoring for individual patients. To address this challenge, we propose the first Medical Video Generation (MVG) framework that enables controlled manipulation of disease-related image and video features, allowing precise, realistic, and personalized simulations of disease progression. Our approach begins by leveraging large language models (LLMs) to recaption prompt for disease trajectory. Next, a controllable multi-round diffusion model simulates the disease progression state for each patient, creating realistic intermediate disease state sequence. Finally, a diffusion-based video transition generation model interpolates disease progression between these states. We validate our framework across three medical imaging domains: chest X-ray, fundus photography, and skin image. Our results demonstrate that MVG significantly outperforms baseline models in generating coherent and clinically plausible disease trajectories. Two user studies by veteran physicians, provide further validation and insights into the clinical utility of the generated sequences. MVG has the potential to assist healthcare providers in modeling disease trajectories, interpolating missing medical image data, and enhancing medical education through realistic, dynamic visualizations of disease progression.
Abstract:Electrocardiogram (ECG), a non-invasive and affordable tool for cardiac monitoring, is highly sensitive in detecting acute heart attacks. However, due to the lengthy nature of ECG recordings, numerous machine learning methods have been developed for automated heart disease detection to reduce human workload. Despite these efforts, performance remains suboptimal. A key obstacle is the inherent complexity of ECG data, which includes heterogeneity (e.g., varying sampling rates), high levels of noise, demographic-related pattern shifts, and intricate rhythm-event associations. To overcome these challenges, this paper introduces AnyECG, a foundational model designed to extract robust representations from any real-world ECG data. Specifically, a tailored ECG Tokenizer encodes each fixed-duration ECG fragment into a token and, guided by proxy tasks, converts noisy, continuous ECG features into discrete, compact, and clinically meaningful local rhythm codes. These codes encapsulate basic morphological, frequency, and demographic information (e.g., sex), effectively mitigating signal noise. We further pre-train the AnyECG to learn rhythmic pattern associations across ECG tokens, enabling the capture of cardiac event semantics. By being jointly pre-trained on diverse ECG data sources, AnyECG is capable of generalizing across a wide range of downstream tasks where ECG signals are recorded from various devices and scenarios. Experimental results in anomaly detection, arrhythmia detection, corrupted lead generation, and ultra-long ECG signal analysis demonstrate that AnyECG learns common ECG knowledge from data and significantly outperforms cutting-edge methods in each respective task.
Abstract:Protein function prediction is a pivotal task in drug discovery, significantly impacting the development of effective and safe therapeutics. Traditional machine learning models often struggle with the complexity and variability inherent in predicting protein functions, necessitating more sophisticated approaches. In this work, we introduce Protein-Mamba, a novel two-stage model that leverages both self-supervised learning and fine-tuning to improve protein function prediction. The pre-training stage allows the model to capture general chemical structures and relationships from large, unlabeled datasets, while the fine-tuning stage refines these insights using specific labeled datasets, resulting in superior prediction performance. Our extensive experiments demonstrate that Protein-Mamba achieves competitive performance, compared with a couple of state-of-the-art methods across a range of protein function datasets. This model's ability to effectively utilize both unlabeled and labeled data highlights the potential of self-supervised learning in advancing protein function prediction and offers a promising direction for future research in drug discovery.