Cellular morphological features are predictive markers of cancer cell state
Cellular morphological features are predictive markers of cancer cell state
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DOI：
10.1016/j.compbiomed.2020.104044
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发表时间：
2020-11-01
影响因子：
7.7
通讯作者：
Prasad, Ashok
中科院分区：
文献类型：
--
作者：
Alizadeh, Elaheh;Castle, Jordan;Prasad, Ashok
由于基因或蛋白质表达的随机性，即使遗传上相同的细胞也具有异质性。分析异质性的单细胞技术对于基础科学和癌症等疾病将是有价值的，其中准确估计肿瘤特性对于准确诊断和分级至关重要。细胞形态是许多细胞过程的紧急结果，可能携带有关单细胞水平细胞特性的信息。在这里，我们研究是否形态参数是足够的单细胞分类，使用一组15个细胞系，代表三个过程：（i）正常细胞的转化使用特定的基因突变;（ii）乳腺癌的转移和（iii）骨肉瘤的转移。细胞形态被定义为细胞形状和肌动蛋白结构的定量测量。我们使用一个工具箱，计算细胞图像的定量形态参数，并将其应用于数百个属于不同细胞系的细胞图像。使用降维和机器学习的组合，我们测试这些不同的过程是否具有特定的形态特征，以及单细胞是否可以单独基于形态进行分类。使用形态参数，我们可以高准确度地将细胞准确分类为属于正确的类别。形态学特征可以区分仅仅因为亲本系上不同突变而不同的细胞。此外，肿瘤发生和转移似乎以刻板的形态学变化为特征。因此，细胞形态是单细胞水平上细胞表型或状态的标志。
Even genetically identical cells have heterogeneous properties because of stochasticity in gene or protein expression. Single cell techniques that assay heterogeneous properties would be valuable for basic science and diseases like cancer, where accurate estimates of tumor properties is critical for accurate diagnosis and grading. Cell morphology is an emergent outcome of many cellular processes, potentially carrying information about cell properties at the single cell level. Here we study whether morphological parameters are sufficient for classification of single cells, using a set of 15 cell lines, representing three processes: (i) the transformation of normal cells using specific genetic mutations; (ii) metastasis in breast cancer and (iii) metastasis in osteosarcomas. Cellular morphology is defined as quantitative measures of the shape of the cell and the structure of the actin. We use a toolbox that calculates quantitative morphological parameters of cell images and apply it to hundreds of images of cells belonging to different cell lines. Using a combination of dimensional reduction and machine learning, we test whether these different processes have specific morphological signatures and whether single cells can be classified based on morphology alone. Using morphological parameters we could accurately classify cells as belonging to the correct class with high accuracy. Morphological signatures could distinguish between cells that were different only because of a different mutation on a parental line. Furthermore, both oncogenesis and metastasis appear to be characterized by stereotypical morphology changes. Thus, cellular morphology is a signature of cell phenotype, or state, at the single cell level.