Netrias, LLC, Annapolis, USA.
Department of Biology, Duke University, Durham, NC, USA.
Sci Rep. 2024 Oct 9;14(1):23581. doi: 10.1038/s41598-024-66936-8.
Flow cytometry is a useful and efficient method for the rapid characterization of a cell population based on the optical and fluorescence properties of individual cells. Ideally, the cell population would consist of only healthy viable cells as dead cells can confound the analysis. Thus, separating out healthy cells from dying and dead cells, and any potential debris, is an important first step in analysis of flow cytometry data. While gating of debris can be conducted using measured optical properties, identifying dead and dying cells often requires utilizing fluorescent stains (e.g. Sytox, a nucleic acid stain that stains cells with compromised cell membranes) to identify cells that should be excluded from downstream analyses. These stains prolong the experimental preparation process and use a flow cytometer's fluorescence channels that could otherwise be used to measure additional fluorescent markers within the cells (e.g. reporter proteins). Here we outline a stain-free method for identifying viable cells for downstream processing by gating cells that are dying or dead. AutoGater is a weakly supervised deep learning model that can separate healthy populations from unhealthy and dead populations using only light-scatter channels. In addition, AutoGater harmonizes different measurements of dead cells such as Sytox and CFUs.
流式细胞术是一种快速基于单个细胞的光学和荧光特性来对细胞群体进行特征分析的有效方法。理想情况下,细胞群体应仅由健康的存活细胞组成,因为死亡细胞会使分析复杂化。因此,将健康细胞与死亡和濒死细胞以及任何潜在的碎片分离开来,是分析流式细胞术数据的重要第一步。虽然可以使用测量的光学特性来对碎片进行门控,但通常需要使用荧光染料(例如 Sytox,一种染色受损细胞膜的核酸染料)来识别应从下游分析中排除的细胞。这些染料延长了实验准备过程,并使用流式细胞仪的荧光通道,否则这些通道可用于测量细胞内的其他荧光标记物(例如报告蛋白)。在这里,我们概述了一种无需染色的方法,通过对正在死亡或死亡的细胞进行门控,来识别可用于下游处理的存活细胞。AutoGater 是一种弱监督深度学习模型,仅使用光散射通道即可将健康群体与不健康和死亡群体分开。此外,AutoGater 还协调了 Sytox 和 CFUs 等不同的死亡细胞测量方法。