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Enhancing high-content imaging for studying microtubule networks at large-scale

机译:提高大含量成像,用于以大规模研究微管网络

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Given the crucial role of microtubules for cell survival, many researchers have found success using microtubule-targeting agents in the search for effective cancer therapeutics. Understanding microtubule responses to targeted interventions requires that the microtubule network within cells can be consistently observed across a large sample of images. However, fluorescence noise sources captured simultaneously with biological signals while using wide-held microscopes can obfuscate fine microtubule structures. Such requirements are particularly challenging for high-throughput imaging, where researchers must make decisions related to the trade-off between imaging quality and speed. Here, we propose a computational framework to enhance the quality of high-throughput imaging data to achieve fast speed and high quality simultaneously. Using CycleGAN, we learn an image model from low-throughput, high-resolution images to enhance features, such as microtubule networks in high-throughput low-resolution images. We show that CycleGAN is effective in identifying microtubules with 0.93+ AUC-ROC and that these results are robust to different kinds of image noise. We further apply CycleGAN to quantify the changes in microtubule density as a result of the application of drug compounds, and show that the quantified responses correspond well with known drug effects.
机译:鉴于微管对细胞存活的关键作用,许多研究人员在寻求有效癌症治疗中使用微管靶向剂已经找到了成功。了解对靶向干预的微管反应要求在大型图像样本中可以始终观察细胞内的微管网络。然而,在使用宽带显微镜的同时与生物信号同时捕获的荧光噪声源可以混淆细微的微管结构。这些要求对于高通量成像尤其具有挑战性,研究人员必须做出与成像质量和速度之间的权衡相关的决策。在这里,我们提出了一种计算框架来提高高通量成像数据的质量,同时实现快速和高质量。使用Cryscan,我们学习从低吞吐量,高分辨率图像的图像模型来增强特征,例如高吞吐量低分辨率图像中的微管网络。我们表明Conscargan在识别具有0.93+ AUC-ROC的微管中有效,并且这些结果对不同种类的图像噪声具有鲁棒性。我们进一步应用Cycleangan以量化药物化合物的结果量化微管密度的变化,并表明定量的反应与已知的药物效应相当良好。

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