Department of Life Sciences and Centre for Integrative Systems Biology and Bioinformatics, Imperial College, London, United Kingdom.
CRUK Beatson Institute, Glasgow, G61 1BD, Scotland, UK.
Sci Rep. 2019 Jun 19;9(1):8784. doi: 10.1038/s41598-019-45305-w.
Stereotyped behaviors are series of postures that show very little variability between repeats. They have been used to classify the dynamics of individuals, groups and species without reference to the lower-level mechanisms that drive them. Stereotypes are easily identified in animals due to strong constraints on the number, shape, and relative positions of anatomical features, such as limbs, that may be used as landmarks for posture identification. In contrast, the identification of stereotypes in single cells poses a significant challenge as the cell lacks these landmark features, and finding constraints on cell shape is a non-trivial task. Here, we use the maximum caliber variational method to build a minimal model of cell behavior during migration. Without reference to biochemical details, we are able to make behavioral predictions over timescales of minutes using only changes in cell shape over timescales of seconds. We use drug treatment and genetics to demonstrate that maximum caliber descriptors can discriminate between healthy and aberrant migration, thereby showing potential applications for maximum caliber methods in automated disease screening, for example in the identification of behaviors associated with cancer metastasis.
刻板行为是指一系列姿势,在重复之间表现出很小的可变性。它们被用于对个体、群体和物种的动态进行分类,而无需参考驱动它们的低级机制。由于肢体等解剖特征的数量、形状和相对位置受到强烈限制,因此动物中的刻板行为很容易识别,这些特征可用作姿势识别的标志。相比之下,由于细胞缺乏这些标志特征,因此在单细胞中识别刻板行为具有很大的挑战性,并且找到对细胞形状的限制是一项非平凡的任务。在这里,我们使用最大口径变分方法构建细胞在迁移过程中行为的最小模型。无需参考生化细节,我们仅使用秒级时间尺度上的细胞形状变化,就能够在分钟级时间尺度上进行行为预测。我们使用药物处理和遗传学来证明最大口径描述符可以区分健康和异常的迁移,从而表明最大口径方法在自动疾病筛查中的潜在应用,例如在识别与癌症转移相关的行为方面。