Centre for Engineering Biology and School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Elife. 2023 Jul 7;12:e79812. doi: 10.7554/eLife.79812.
Much of biochemical regulation ultimately controls growth rate, particularly in microbes. Although time-lapse microscopy visualises cells, determining their growth rates is challenging, particularly for those that divide asymmetrically, like , because cells often overlap in images. Here, we present the Birth Annotator for Budding Yeast (BABY), an algorithm to determine single-cell growth rates from label-free images. Using a convolutional neural network, BABY resolves overlaps through separating cells by size and assigns buds to mothers by identifying bud necks. BABY uses machine learning to track cells and determine lineages and estimates growth rates as the rates of change of volumes. Using BABY and a microfluidic device, we show that bud growth is likely first sizer- then timer-controlled, that the nuclear concentration of Sfp1, a regulator of ribosome biogenesis, varies before the growth rate does, and that growth rate can be used for real-time control. By estimating single-cell growth rates and so fitness, BABY should generate much biological insight.
生物化学调控在很大程度上最终控制着生长速度,尤其是在微生物中。尽管延时显微镜可以观察细胞,但确定其生长速度具有挑战性,特别是对于那些不对称分裂的细胞,如 ,因为细胞在图像中经常重叠。在这里,我们提出了用于出芽酵母的出生标注器(BABY),这是一种从无标记图像中确定单细胞生长速度的算法。BABY 使用卷积神经网络通过大小分离细胞,并通过识别芽颈将芽分配给母细胞,从而解决重叠问题。BABY 使用机器学习来跟踪细胞并确定谱系,并将体积变化率估计为生长速率。使用 BABY 和微流控装置,我们表明芽的生长可能首先是尺寸控制,然后是时间控制,核糖体生物发生调节剂 Sfp1 的核浓度在生长速率之前变化,并且生长速率可用于实时控制。通过估计单细胞生长速度和适应性,BABY 应该会产生更多的生物学见解。