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分析三维组织学样本中的DNA损伤。

Profiling DNA damage in 3D Histology Samples.

作者信息

Peñas Kristofer E Delas, Haeusler Ralf, Feng Sally, Magidson Valentin, Dmitrieva Mariia, Wink David, Lockett Stephen, Kinders Robert, Rittscher Jens

机构信息

Department of Engineering Science, University of Oxford, United Kingdom.

Big Data Institute, University of Oxford, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK.

出版信息

Med Opt Imaging Virtual Microsc Image Anal (2022). 2022 Sep 15:84-93. doi: 10.1007/978-3-031-16961-8_9.

DOI:10.1007/978-3-031-16961-8_9
PMID:39899002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7617225/
Abstract

The morphology of individual cells can reveal much about the underlying states and mechanisms in biology. In tumor environments, the interplay among different cell morphologies in local neighborhoods can further improve this characterization. In this paper, we present an approach based on representation learning to capture similarities and subtle differences in cells positive for H2AX, a common marker for DNA damage. We demonstrate that texture representations using GLCM and VAE-GAN enable profiling of cells in both singular and local neighborhood contexts. Additionally, we investigate a possible quantification of immune and DNA damage response interplay by enumerating CD8+ and H2AX+ on different scales. Using our profiling approach, regions in treated tissues can be differentiated from control tissue regions, demonstrating its potential in aiding quantitative measurements of DNA damage and repair in tumor contexts.

摘要

单个细胞的形态可以揭示许多关于生物学潜在状态和机制的信息。在肿瘤环境中,局部区域内不同细胞形态之间的相互作用可以进一步完善这种特征描述。在本文中,我们提出了一种基于表征学习的方法,以捕捉H2AX(一种常见的DNA损伤标记物)阳性细胞中的相似性和细微差异。我们证明,使用灰度共生矩阵(GLCM)和变分自编码器-生成对抗网络(VAE-GAN)的纹理表征能够在单个细胞和局部区域环境中对细胞进行分析。此外,我们通过在不同尺度上枚举CD8+和H2AX+来研究免疫与DNA损伤反应相互作用的一种可能的量化方法。使用我们的分析方法,可以将处理过的组织区域与对照组织区域区分开来,证明了其在辅助肿瘤环境中DNA损伤和修复的定量测量方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/142c3f1568e4/EMS198647-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/77eae02c6795/EMS198647-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/8e0134e71e94/EMS198647-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/142c3f1568e4/EMS198647-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/77eae02c6795/EMS198647-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/8e0134e71e94/EMS198647-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c3/7617225/142c3f1568e4/EMS198647-f003.jpg

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本文引用的文献

1
Analysis of Ionizing Radiation Induced DNA Damage by Superresolution dSTORM Microscopy.超分辨率 dSTORM 显微镜分析电离辐射诱导的 DNA 损伤。
Pathol Oncol Res. 2021 Nov 8;27:1609971. doi: 10.3389/pore.2021.1609971. eCollection 2021.
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DNA Repair Pathways in Cancer Therapy and Resistance.癌症治疗与耐药中的DNA修复途径
Front Pharmacol. 2021 Feb 8;11:629266. doi: 10.3389/fphar.2020.629266. eCollection 2020.
3
A robust unsupervised machine-learning method to quantify the morphological heterogeneity of cells and nuclei.
一种强大的无监督机器学习方法,用于量化细胞和细胞核的形态异质性。
Nat Protoc. 2021 Feb;16(2):754-774. doi: 10.1038/s41596-020-00432-x. Epub 2021 Jan 11.
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Cellpose: a generalist algorithm for cellular segmentation.Cellpose:一种通用的细胞分割算法。
Nat Methods. 2021 Jan;18(1):100-106. doi: 10.1038/s41592-020-01018-x. Epub 2020 Dec 14.
5
DeepCycle reconstructs a cyclic cell cycle trajectory from unsegmented cell images using convolutional neural networks.DeepCycle 使用卷积神经网络从未分割的细胞图像中重建循环细胞周期轨迹。
Mol Syst Biol. 2020 Oct;16(10):e9474. doi: 10.15252/msb.20209474.
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DNA Damage/Repair Management in Cancers.癌症中的DNA损伤/修复管理
Cancers (Basel). 2020 Apr 23;12(4):1050. doi: 10.3390/cancers12041050.
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Disentangled representation learning in cardiac image analysis.心脏影像分析中的解缠表示学习。
Med Image Anal. 2019 Dec;58:101535. doi: 10.1016/j.media.2019.101535. Epub 2019 Jul 18.
8
Quantification of DNA damage induced repair focus formation via super-resolution dSTORM localization microscopy.通过超分辨率 dSTORM 定位显微镜定量分析 DNA 损伤诱导修复焦点的形成。
Nanoscale. 2019 Aug 1;11(30):14226-14236. doi: 10.1039/c9nr03696b.
9
Evaluation of Pharmacodynamic Responses to Cancer Therapeutic Agents Using DNA Damage Markers.利用 DNA 损伤标志物评估癌症治疗药物的药效反应。
Clin Cancer Res. 2019 May 15;25(10):3084-3095. doi: 10.1158/1078-0432.CCR-18-2523. Epub 2019 Feb 21.
10
Development of a quantitative pharmacodynamic assay for apoptosis in fixed tumor tissue and its application in distinguishing cytotoxic drug-induced DNA double strand breaks from DNA double strand breaks associated with apoptosis.固定肿瘤组织中细胞凋亡定量药效学检测方法的建立及其在区分细胞毒性药物诱导的DNA双链断裂与凋亡相关的DNA双链断裂中的应用。
Oncotarget. 2018 Mar 30;9(24):17104-17116. doi: 10.18632/oncotarget.24936.