title: Automated identification of abnormal respiratory ciliary motion in nasal biopsies.
abstract: Motile cilia lining the nasal and bronchial passages beat synchronously to clear mucus and foreign matter from the respiratory tract. This mucociliary defense mechanism is essential for pulmonary health, because respiratory ciliary motion defects, such as those in patients with primary ciliary dyskinesia (PCD) or congenital heart disease, can cause severe sinopulmonary disease necessitating organ transplant. The visual examination of nasal or bronchial biopsies is critical for the diagnosis of ciliary motion defects, but these analyses are highly subjective and error-prone. Although ciliary beat frequency can be computed, this metric cannot sensitively characterize ciliary motion defects. Furthermore, PCD can present without any ultrastructural defects, limiting the use of other detection methods, such as electron microscopy. Therefore, an unbiased, computational method for analyzing ciliary motion is clinically compelling. We present a computational pipeline using algorithms from computer vision and machine learning to decompose ciliary motion into quantitative elemental components. Using this framework, we constructed digital signatures for ciliary motion recognition and quantified specific properties of the ciliary motion that allowed high-throughput classification of ciliary motion as normal or abnormal. We achieved >90% classification accuracy in two independent data cohorts composed of patients with congenital heart disease, PCD, or heterotaxy, as well as healthy controls. Clinicians without specialized knowledge in machine learning or computer vision can operate this pipeline as a "black box" toolkit to evaluate ciliary motion.
authors.affiliation: Joint Carnegie Mellon-University of Pittsburgh Ph.D. Program in Computational Biology, Department of Computation and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA. Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Quinn
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
authors.forename: Maliha J
authors.initials: MJ
authors.lastname: Zahid
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Durkin
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Francis
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA. cel36@pitt.edu chakracs@pitt.edu.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. cel36@pitt.edu chakracs@pitt.edu.
authors.forename: S Chakra
authors.initials: SC
authors.lastname: Chennubhotla
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001706:Biopsy; D002648:Child; D002923:Cilia / Q000473:pathology; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006801:Humans; D007619:Kartagener Syndrome / Q000175:diagnosis*; D009666:Nose / Q000473:pathology*