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bioRxiv · 10.1101/2025.11.02.686130

Machine Learning Analysis of Cilia-Driven Particle Transport Distinguishes Primary Ciliary Dyskinesia Cilia from Normal Cilia

Hadas, N.·Xu, H.·Neupane, S.·Twan, W. K.·Elgamal, A.·Horani, A.
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Abstract

RationalPrimary ciliary dyskinesia (PCD) is a genetic condition that results in dysmotile cilia and abnormal mucociliary clearance. Despite advances in understanding the pathogenesis of PCD, diagnosis continues to be challenging. Here we used feature-based machine learning and image-based deep learning to objectively quantify the directed particle transport of motile cilia and detect PCD-related cilia dysfunction. MethodsFluorescent microspheres were captured on cultured multiciliated cells using high-speed video microscopy as a proxy for motile cilia function. An interactive Jython script was designed to automatically detect, track and extract raw track metrics from videos. Data was subsequently analyzed to approximate a quantifiable and visual signature of ciliary transport through a custom-built Python Package, CiliaTracks. ResultsAirway epithelial cells were obtained from 14 individuals with genetically confirmed PCD, 10 healthy donors, and 2 patients with cystic fibrosis. A total of 602 videos (301 PCD and 301 non-PCD) were captured. Quantitative and visual analyses of fluorescent microsphere trajectories, including kinematic metrics and trajectory plots, revealed distinct motility profiles between PCD and non-PCD samples. Classical machine learning models and a convolutional neural network were employed to classify PCD using both modalities, demonstrating excellent accuracy of 95-97%, and the capacity to differentiate PCD from normal cells or cystic fibrosis. ConclusionCilia-propelled microsphere transport exhibits unique trajectory patterns in PCD, enabling differentiation from non-PCD samples. Machine learning provides an objective and accurate framework for characterizing ciliary dysfunction, offering potential as a diagnostic tool for PCD.

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Hadas, N., Xu, H., Neupane, S., Twan, W. K., Elgamal, A., Horani, A.. 2025-11-04. Machine Learning Analysis of Cilia-Driven Particle Transport Distinguishes Primary Ciliary Dyskinesia Cilia from Normal Cilia. https://doi.org/10.1101/2025.11.02.686130

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