PO.CL01.14 · 临床研究
CellScape质量控制(CSQC):一种组织和蛋白无关的空间蛋白质组学质量评估平台
CellScape Quality Control (CSQC): A tissue- and protein-agnostic platform for spatial proteomics quality assessment
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言:空间蛋白质组学是一种新兴的精准肿瘤学诊断工具,然而跨组织切片和批次的数据可重复性仍是实现稳健生物标志物发现和临床可操作结果的一大障碍。组织质量、组织制备、抗体性能和成像条件的差异均会引入伪影,损害定量准确性。因此,对成像数据进行人工质量控制至关重要,但这非常耗时且主观。因此,一个标准化、自动化和定量化的质量控制框架对于支持空间蛋白质组学工作流在精准肿瘤学中的切实应用至关重要。
方法:我们开发了CellScape质量控制(CSQC),一种基于机器学习的框架,用于自动化染色质量评估和组织筛选。CSQC在来自跨实验室的十台CellScape™精密空间表型分析仪器的>20种组织类型的>100个样本上进行训练。该数据集包含超过50种生物标志物,代表核、膜和胞质靶点,涵盖多种抗体克隆、染色方案和成像放大倍数(10x和20x)。专家注释被用作模型训练和验证的金标准。
结果:CSQC在背景、伪影和可用组织检测方面实现了平均IoU>0.7,与专家注释显示出强一致性。该系统自动标记出次优染色和批次水平伪影,从而实现跨仪器和跨站点的协调统一。CSQC的部署将每个样本的人工审查时间从数小时缩短至数分钟,从而使单个操作员能够在给定时间范围内将下游分析快速扩展至数十张切片和数十种蛋白。此外,我们观察到经CSQC筛选后下游标志物定量和可重复性有明显改善。
结论:CSQC提供了一种标准化、定量化和可扩展的染色与组织质量控制方法,支持在CellScape精密空间表型分析平台上开展稳健的多站点空间蛋白质组学工作流。该框架促进了检测协调统一、基准化的可重复性以及可靠的空间生物标志物发现,助力临床转化。
查看英文原文 English abstract
Introduction: Spatial proteomics is an emerging diagnostic tool for precision oncology, yet data reproducibility across tissue sections and batches remains a major obstacle towards achieving robust biomarker discovery and clinically actionable results. Variability in tissue quality, tissue preparation, antibody performance, and imaging conditions all introduce artifacts that compromise quantitative accuracy. Manual quality control of imaging data is thus essential, but it is very time consuming and subjective. A standardized, automated, and quantitative quality control framework is therefore essential to support realistic adoption of spatial proteomic workflows in precision oncology.
Methods: We developed CellScape Quality Control (CSQC), a machine learning-based framework for automated stain quality assessment and tissue vetting. CSQC was trained on >100 samples from >20 tissue types from ten CellScape™ precise spatial phenotyping instruments across laboratories. The dataset included more than 50 biomarkers representing nuclear, membrane, and cytoplasmic targets across multiple antibody clones, stain protocols, and imaging magnifications (10x and 20x). Expert annotations were used as ground truth for model training and validation.
Results: CSQC achieved a mean IoU >0.7 for background, artifact, and usable tissue detection, showing strong concordance with expert annotations. The system automatically flagged suboptimal staining and batch-level artifacts, thereby enabling harmonization across instruments and sites. The deployment of CSQC reduced manual review time from several hours to minutes per sample, and thereby allowed rapid scaling of downstream analyses to dozens of slides and proteins analyzed by a single operator in a given time frame. In addition, we observed a noticeable improvement in downstream marker quantification and reproducibility following CSQC vetting.
Conclusion: CSQC provides a standardized, quantitative, and scalable approach to stain and tissue quality control, supporting robust multisite spatial proteomics workflows on the CellScape precise spatial phenotyping platform. This framework facilitates assay harmonization, benchmarked reproducibility, and reliable spatial biomarker discovery for clinical translation.
利益披露 Disclosure
D. Jimenez-Sanchez,
Bruker Spatial Biology Employment.
B. J. Lane,
Bruker Spatial Biology Employment.
M. H. Ingalls,
United States Employment.
C. E. Jackson,
Bruker Spatial Biology Employment.
S. T. Lott,
Bruker Spatial Biology Employment.
A. Northcutt,
Bruker Spatial Biology Employment.
A. Christians,
Bruker Spatial Biology Employment.
A. Brix,
Bruker Spatial Biology Employment.
J. Brooks,
Bruker Spatial Biology Employment.
O. Braubach,
Bruker Spatial Biology Employment.