KRONOS是首个面向空间蛋白质组学的通用基础模型,可高效分析多光谱组织图像。
A Foundation Model for Spatial Proteomics
- 基于4700万图像块自监督训练,适配多通道、高维、异构的成像数据
- 在11个独立队列中实现细胞表型等任务的顶尖性能,数据效率高
- 支持无分割的批量处理,适合跨机构比较与空间模式检索
基础模型已改变图像分析格局,但其在单细胞分辨率的空间蛋白质组学中的应用仍有限。本文提出KRONOS,一种专为该领域设计的基础模型。它在超过4700万图像块上进行自监督训练,覆盖175种蛋白标记、16种组织类型和8种荧光成像平台。通过关键架构改进,有效应对多通道、高维、异构的多重成像挑战。KRONOS学习到从细胞、微环境到组织层级的生物意义表示,可支持细胞表型分类、区域识别及患者分层等多种下游任务。在11个独立队列中评估,其在细胞表型、治疗响应预测和图像检索任务上均达当前最优表现,且数据效率优异。模型还引入无需分割的补丁级处理范式,实现高效可扩展的空间蛋白质组分析,支持跨机构比较,并可作为空间模式反向搜索工具。KRONOS已在GitHub公开:https://github.com/mahmoodlab/KRONOS。
原文摘要 · Abstract (English)
Foundation models have begun to transform image analysis by acting as pretrained generalist backbones that can be adapted to many tasks even when post-training data are limited, yet their impact on spatial proteomics, imaging that maps proteins at single-cell resolution, remains limited. Here, we introduce KRONOS, a foundation model built for spatial proteomics. KRONOS was trained in a self-supervised manner on over 47 million image patches covering 175 protein markers, 16 tissue types, and 8 fluorescence-based imaging platforms. We introduce key architectural adaptations to address the high-dimensional, multi-channel, and heterogeneous nature of multiplex imaging. We demonstrate that KRONOS learns biologically meaningful representations across multiple scales, ranging from cellular and microenvironment to tissue levels, enabling it to address diverse downstream tasks, including cell phenotyping, region classification, and patient stratification. Evaluated across 11 independent cohorts, KRONOS achieves state-of-the-art performance across cell phenotyping, treatment response prediction, and retrieval tasks, and is highly data-efficient. KRONOS also introduces the paradigm of segmentation-free patch-level processing for efficient and scalable spatial proteomics analysis, allowing cross-institutional comparisons, and as an image reverse search engine for spatial patterns. Together, these results position KRONOS as a flexible and scalable tool for spatial proteomics. The model is publicly accessible at https://github.com/mahmoodlab/KRONOS.
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