Towards an Unsupervised Spatiotemporal Representation of Cilia Video Using A Modular Generative Pipeline

Motile cilia are a highly conserved organelle found on the exterior of many human cells. Cilia beat in rhythmic patterns to transport substances or generate signaling gradients. Disruption of these patterns is often indicative of diseases known as ciliopathies, whose consequences can include dysfunction of macroscopic structures within the lungs, kidneys, brain, and other organs. Characterizing ciliary motion phenotypes as healthy or diseased is an essential step towards diagnosing and differentiating ciliopathies. We propose a modular generative pipeline for the analysis of cilia video data so that expert labor may be supplemented for this task. Our proposed model is divided into three modules: preprocessing, appearance, and dynamics. The preprocessing module augments the initial data, and its output is fed frame-by-frame into the generative appearance model which learns a compressed latent representation of the cilia. The frames are then embedded into the latent space as a low-dimensional path. This path is fed into the generative dynamics module, which focuses only on the motion of the cilia. Since both the appearance and dynamics modules are generative, the pipeline itself serves as an end-to-end generative model. This thorough and versatile model allows experts to spend less time caught in the minutiae of cilia biopsy analysis, while also enabling new insights by quantifying subtle patterns that would be otherwise difficult to categorize.

[1]  Jürgen Schmidhuber,et al.  Learning to Forget: Continual Prediction with LSTM , 2000, Neural Computation.

[2]  Steven S. Beauchemin,et al.  The computation of optical flow , 1995, CSUR.

[3]  Gunnar Farnebäck,et al.  Two-Frame Motion Estimation Based on Polynomial Expansion , 2003, SCIA.

[4]  Joel Nothman,et al.  SciPy 1.0-Fundamental Algorithms for Scientific Computing in Python , 2019, ArXiv.

[5]  L. Leatherbury,et al.  Airway ciliary dysfunction and sinopulmonary symptoms in patients with congenital heart disease. , 2014, Annals of the American Thoracic Society.

[6]  Max Welling,et al.  VAE with a VampPrior , 2017, AISTATS.

[7]  Diederik P. Kingma,et al.  An Introduction to Variational Autoencoders , 2019, Found. Trends Mach. Learn..

[8]  Kilian Q. Weinberger,et al.  Densely Connected Convolutional Networks , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[9]  Yoshua Bengio,et al.  The One Hundred Layers Tiramisu: Fully Convolutional DenseNets for Semantic Segmentation , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[10]  Anthony A. Hyman,et al.  Mitosis : a subject collection from Cold Spring Harbor Perspectives in biology , 2015 .

[11]  M. Decramer,et al.  Regulation of mucociliary clearance in health and disease. , 1999, The European respiratory journal.

[12]  Gaël Varoquaux,et al.  The NumPy Array: A Structure for Efficient Numerical Computation , 2011, Computing in Science & Engineering.

[13]  A. Bush,et al.  Diagnosing primary ciliary dyskinesia , 2007, Thorax.

[14]  Berthold K. P. Horn,et al.  Determining Optical Flow , 1981, Other Conferences.

[15]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[16]  Stefano Soatto,et al.  Dynamic Textures , 2003, International Journal of Computer Vision.

[17]  C. Chennubhotla,et al.  Novel use of differential image velocity invariants to categorize ciliary motion defects , 2011, Proceedings of the 2011 Biomedical Sciences and Engineering Conference: Image Informatics and Analytics in Biomedicine.

[18]  John D. Hunter,et al.  Matplotlib: A 2D Graphics Environment , 2007, Computing in Science & Engineering.

[19]  L. Ostrowski,et al.  Cilia and Mucociliary Clearance. , 2017, Cold Spring Harbor perspectives in biology.

[20]  A. Catana,et al.  The determination factors of left-right asymmetry disorders- a short review , 2017, Clujul medical.

[21]  Alexander Lerchner,et al.  Spatial Broadcast Decoder: A Simple Architecture for Learning Disentangled Representations in VAEs , 2019, ArXiv.

[22]  Takeo Kanade,et al.  An Iterative Image Registration Technique with an Application to Stereo Vision , 1981, IJCAI.

[23]  Javier Sánchez Pérez,et al.  TV-L1 Optical Flow Estimation , 2013, Image Process. Line.

[24]  M. Chilvers,et al.  Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy Subjects , 2017, Chest.

[25]  Peter Kovesi,et al.  Extracting Differential Invariants of Motion Directly From Optical Flow , 2004 .

[26]  T. Ferkol,et al.  Ciliopathies: the central role of cilia in a spectrum of pediatric disorders. , 2012, The Journal of pediatrics.

[27]  Natalia Gimelshein,et al.  PyTorch: An Imperative Style, High-Performance Deep Learning Library , 2019, NeurIPS.

[28]  Charles Lu,et al.  Stacked Neural Networks for end-to-end ciliary motion analysis , 2018, ArXiv.

[29]  Yoshua Bengio,et al.  Learning Phrase Representations using RNN Encoder–Decoder for Statistical Machine Translation , 2014, EMNLP.

[30]  H. Omran,et al.  Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia , 2014, European Respiratory Journal.

[31]  P. Satir,et al.  The physiology of cilia and mucociliary interactions. , 1990, Annual review of physiology.

[32]  S. Chennubhotla,et al.  Automated identification of abnormal respiratory ciliary motion in nasal biopsies , 2015, Science Translational Medicine.