PhagoStat a scalable and interpretable end to end framework for efficient quantification of cell phagocytosis in neurodegenerative disease studies

Abstract

Quantifying the phagocytosis of dynamic, unstained cells is essential for evaluating neurodegenerative diseases. However, measuring rapid cell interactions and distinguishing cells from background make this task very challenging when processing time-lapse phase-contrast video microscopy. In this study, we introduce an end-to-end, scalable, and versatile real-time framework for quantifying and analyzing phagocytic activity. Our proposed pipeline is able to process large data-sets and includes a data quality verification module to counteract potential perturbations such as microscope movements and frame blurring. We also propose an explainable cell segmentation module to improve the interpretability of deep learning methods compared to black-box algorithms. This includes two interpretable deep learning capabilities: visual explanation and model simplification. We demonstrate that interpretability in deep learning is not the opposite of high performance, by additionally providing essential deep learning algorithm optimization insights and solutions. Besides, incorporating interpretable modules results in an efficient architecture design and optimized execution time. We apply this pipeline to quantify and analyze microglial cell phagocytosis in frontotemporal dementia (FTD) and obtain statistically reliable results showing that FTD mutant cells are larger and more aggressive than control cells. The method has been tested and validated on several public benchmarks by generating state-of-the art performances. To stimulate translational approaches and future studies, we release an open-source end-to-end pipeline and a unique microglial cells phagocytosis dataset for immune system characterization in neurodegenerative diseases research. This pipeline and the associated dataset will consistently crystallize future advances in this field, promoting the development of efficient and effective interpretable algorithms dedicated to the critical domain of neurodegenerative diseases’ characterization. https://github.com/ounissimehdi/PhagoStat.