Sarker Md Mostafa Kamal, Makhlouf Yasmine, Craig Stephanie G, Humphries Matthew P, Loughrey Maurice, James Jacqueline A, Salto-Tellez Manuel, O'Reilly Paul, Maxwell Perry
Precision Medicine Centre of Excellence, The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.
Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK.
Cancers (Basel). 2021 Jul 29;13(15):3825. doi: 10.3390/cancers13153825.
Biomarkers identify patient response to therapy. The potential immune-checkpoint biomarker, Inducible T-cell COStimulator (ICOS), expressed on regulating T-cell activation and involved in adaptive immune responses, is of great interest. We have previously shown that open-source software for digital pathology image analysis can be used to detect and quantify ICOS using cell detection algorithms based on traditional image processing techniques. Currently, artificial intelligence (AI) based on deep learning methods is significantly impacting the domain of digital pathology, including the quantification of biomarkers. In this study, we propose a general AI-based workflow for applying deep learning to the problem of cell segmentation/detection in IHC slides as a basis for quantifying nuclear staining biomarkers, such as ICOS. It consists of two main parts: a simplified but robust annotation process, and cell segmentation/detection models. This results in an optimised annotation process with a new user-friendly tool that can interact with1 other open-source software and assists pathologists and scientists in creating and exporting data for deep learning. We present a set of architectures for cell-based segmentation/detection to quantify and analyse the trade-offs between them, proving to be more accurate and less time consuming than traditional methods. This approach can identify the best tool to deliver the prognostic significance of ICOS protein expression.
生物标志物可识别患者对治疗的反应。潜在的免疫检查点生物标志物——诱导性T细胞共刺激分子(ICOS),表达于调节性T细胞活化过程中并参与适应性免疫反应,备受关注。我们之前已经表明,用于数字病理学图像分析的开源软件可基于传统图像处理技术,利用细胞检测算法来检测和量化ICOS。目前,基于深度学习方法的人工智能(AI)正在对数字病理学领域产生重大影响,包括生物标志物的量化。在本研究中,我们提出了一种基于AI的通用工作流程,将深度学习应用于免疫组化切片中的细胞分割/检测问题,以此作为量化核染色生物标志物(如ICOS)的基础。它由两个主要部分组成:一个简化但稳健的注释过程,以及细胞分割/检测模型。这产生了一个经过优化的注释过程,带有一个新的用户友好型工具,该工具可以与其他开源软件交互,并协助病理学家和科学家创建和导出用于深度学习的数据。我们展示了一组基于细胞的分割/检测架构,以量化和分析它们之间的权衡,结果证明比传统方法更准确且耗时更少。这种方法可以识别出能够揭示ICOS蛋白表达预后意义的最佳工具。