论文标题

基于细胞力学的计算分类通过机器智能应用于形态得分标记

Cell Mechanics Based Computational Classification of Red Blood Cells Via Machine Intelligence Applied to Morpho-Rheological Markers

论文作者

Ge, Yan, Rosendahl, Philipp, Durán, Claudio, Töpfner, Nicole, Ciucci, Sara, Guck, Jochen, Cannistraci, Carlo Vittorio

论文摘要

尽管荧光细胞标记广泛用于生物医学研究,但其某些缺点是不可避免的,不合适的荧光探针或探针引起了功能变化,这是主要局限性。因此,对细胞进行分类的无标签方法的需求和开发是强大的,并且对精度医学的影响很重要。为此,已经提出了用于细胞机械表型的高通量技术,以获得单个细胞的多维生物物理表征。有了这一动机,我们的目标是研究无监督的机器学习方法的程度,该方法专门应用于通过实时变形和荧光细胞仪(RT-FDC)获得的形态 - 河流学标记物,可以解决从成熟的红细胞提供reticulocytes的无标记区分的困难任务。我们专注于这个问题,因为在血液中的网状细胞(其百分比和细胞特征)的表征在多种人类疾病状况中至关重要,尤其是骨髓疾病,例如贫血和白血病。我们的方法报告有希望的无标签会导致对成熟的红细胞的网状细胞分类,这代表了开发基于高通量形态的基于形态学的方法,用于单细胞的计算分类。此外,我们的方法可以是与现有细胞标签技术集成的替代方法,但也可以是补充方法。

Despite fluorescent cell-labelling being widely employed in biomedical studies, some of its drawbacks are inevitable, with unsuitable fluorescent probes or probes inducing a functional change being the main limitations. Consequently, the demand for and development of label-free methodologies to classify cells is strong and its impact on precision medicine is relevant. Towards this end, high-throughput techniques for cell mechanical phenotyping have been proposed to get a multidimensional biophysical characterization of single cells. With this motivation, our goal here is to investigate the extent to which an unsupervised machine learning methodology, which is applied exclusively on morpho-rheological markers obtained by real-time deformability and fluorescence cytometry (RT-FDC), can address the difficult task of providing label-free discrimination of reticulocytes from mature red blood cells. We focused on this problem, since the characterization of reticulocytes (their percentage and cellular features) in the blood is vital in multiple human disease conditions, especially bone-marrow disorders such as anemia and leukemia. Our approach reports promising label-free results in the classification of reticulocytes from mature red blood cells, and it represents a step forward in the development of high-throughput morpho-rheological-based methodologies for the computational categorization of single cells. Besides, our methodology can be an alternative but also a complementary method to integrate with existing cell-labelling techniques.

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