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Inferring time-dependent population growth rates in cell cultures undergoing adaptation
BMC Bioinformatics ( IF 2.9 ) Pub Date : 2020-12-17 , DOI: 10.1186/s12859-020-03887-7
H. Jonathan G. Lindström , Ran Friedman

The population growth rate is an important characteristic of any cell culture. During sustained experiments, the growth rate may vary due to competition or adaptation. For instance, in presence of a toxin or a drug, an increasing growth rate indicates that the cells adapt and become resistant. Consequently, time-dependent growth rates are fundamental to follow on the adaptation of cells to a changing evolutionary landscape. However, as there are no tools to calculate the time-dependent growth rate directly by cell counting, it is common to use only end point measurements of growth rather than tracking the growth rate continuously. We present a computer program for inferring the growth rate over time in suspension cells using nothing but cell counts, which can be measured non-destructively. The program was tested on simulated and experimental data. Changes were observed in the initial and absolute growth rates, betraying resistance and adaptation. For experiments where adaptation is expected to occur over a longer time, our method provides a means of tracking growth rates using data that is normally collected anyhow for monitoring purposes. The program and its documentation are freely available at https://github.com/Sandalmoth/ratrack under the permissive zlib license.

中文翻译:

推断经历适应的细胞培养中的时间依赖性种群增长率

人口增长率是任何细胞培养的重要特征。在持续的实验过程中,生长速率可能会因竞争或适应而变化。例如,在存在毒素或药物的情况下,生长速率的增加表明细胞可以适应并具有抗性。因此,随时间变化的生长速率对于细胞适应不断变化的进化格局至关重要。但是,由于没有工具可以直接通过细胞计数直接计算随时间变化的生长速率,因此通常仅使用生长的终点测量值,而不是连续跟踪生长速率。我们提出了一种计算机程序,用于推断悬浮细胞随时间的生长速率,仅使用细胞计数即可,该计数可以无损测量。该程序已在模拟和实验数据上进行了测试。观察到了初始和绝对增长率,背叛能力和适应能力的变化。对于预期将在更长的时间内发生适应性的实验,我们的方法提供了一种方法,该方法使用通常出于监视目的而通常收集的数据来跟踪增长率。该程序及其文档可通过许可的zlib许可在https://github.com/Sandalmoth/ratrack上免费获得。
更新日期:2020-12-17
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