噪声环境下细胞凋亡时间的鲁棒性研究

A. Mencattini, P. Casti, J. Filippi, M. D’Orazio, Sara Cardarelli, G. Antonelli, E. Martinelli
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引用次数: 0

摘要

程序性细胞死亡,即细胞凋亡,在生理上发生在发育和衰老过程中,并作为一种维持组织细胞群的稳态机制。在免疫反应或细胞受到疾病或外部刺激(药物)损伤时,细胞凋亡也作为一种防御机制发生。由于其复杂性和细胞凋亡的命运在很短的时间内(通常是几个小时)解决的事实,细胞凋亡机制直到最近才随着先进的延时显微镜的出现而得到广泛研究。与凋亡阶段相关的时间与许多因素密切相关,包括细胞类型、药物剂量、细胞微环境和相关的交叉对话,但我们对这些因素的了解太少,无法预测细胞凋亡的持续时间。这些时间是至关重要的,因为它们与药物疗效、免疫疗法治疗、癌症免疫相互作用的有效性有关。鉴于此,通过利用视频分析,深度学习算法和多元线性回归,我们提出了一个平台,以非常高的准确度和精度水平检查细胞凋亡和起泡时间。更详细地说,我们通过计算机视觉分析平台人工生成了具有随机变化的细胞凋亡时间曲线的合成细胞凋亡视频。通过在所谓的迁移学习过程中使用预训练的卷积神经网络(CNN)架构,我们将视频的每一帧编码为数字描述符列表。然后通过训练多元线性回归(MLR)模型来完成细胞凋亡时间谱的自动检测。这项工作的扩展版本将考虑到死亡细胞的真实视频和额外的混淆效应,从而展示这项研究的进一步进展。
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Robust examination of cell apoptosis timing in presence of noisy environment
The process of programmable cell death, i.e., apoptosis, physiologically occurs during development and aging and as a homeostatic mechanism to maintain cell populations in tissues. Apoptosis also happens as a defense mechanism in immune reactions or when cells are damaged by disease or external stimuli (drugs). Due to its complexity and the fact that apoptosis fate resolves in a very short time (a few hours in general), apoptosis mechanisms have been extensively studied only recently with the advent of advanced time-lapse microscopy. Timing related to apoptosis stages is strongly correlated to many factors including cell type, drug dose, cell microenvironment, and related cross-talks whose knowledge is too little to predict apoptosis duration. Such times are of fundamental importance since they linked with drug efficacy, immunotherapy treatment, cancer-immune interaction effectiveness. In light of this, by exploiting video analysis, deep learning algorithms, and multiple linear regression, we presented a platform to examine the apoptosis and blebbing times with very high accuracy and precision levels. More in detail, we artificially generated, through a computer vision analysis platform, synthetic apoptosis videos with randomly variated apoptosis timing profiles. By using a pre-trained Convolutional Neural Network (CNN) architecture within the so-called transfer learning procedure, we encoded each frame of the video into a list of numerical descriptors. Automatic examination of apoptosis timing profiles was then accomplished by training a multivariate linear regression (MLR) model. An extended version of the work will present further advancement of this research by considering real videos of dying cells and additional confounding effects.
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