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

HC Lee, ST Cherng, R Miotto…�- Machine Learning for�…, 2019 - proceedings.mlr.press
Machine Learning for Healthcare Conference, 2019proceedings.mlr.press
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�…
Abstract
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.
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