title: Accurate Detection of Dysmorphic Nuclei Using Dynamic Programming and Supervised Classification.
abstract: A vast array of pathologies is typified by the presence of nuclei with an abnormal morphology. Dysmorphic nuclear phenotypes feature dramatic size changes or foldings, but also entail much subtler deviations such as nuclear protrusions called blebs. Due to their unpredictable size, shape and intensity, dysmorphic nuclei are often not accurately detected in standard image analysis routines. To enable accurate detection of dysmorphic nuclei in confocal and widefield fluorescence microscopy images, we have developed an automated segmentation algorithm, called Blebbed Nuclei Detector (BleND), which relies on two-pass thresholding for initial nuclear contour detection, and an optimal path finding algorithm, based on dynamic programming, for refining these contours. Using a robust error metric, we show that our method matches manual segmentation in terms of precision and outperforms state-of-the-art nuclear segmentation methods. Its high performance allowed for building and integrating a robust classifier that recognizes dysmorphic nuclei with an accuracy above 95%. The combined segmentation-classification routine is bound to facilitate nucleus-based diagnostics and enable real-time recognition of dysmorphic nuclei in intelligent microscopy workflows.
authors.affiliation: Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Marlies
authors.initials: M
authors.lastname: Verschuuren
authors.affiliation: Department of Telecommunication and Information Processing, IPI, iMinds, Ghent University, Ghent, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: De Vylder
authors.affiliation: Institute for Agricultural and Fisheries Research (ILVO), Melle, Belgium.
authors.forename: Hannes
authors.initials: H
authors.lastname: Catrysse
authors.affiliation: Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Robijns
authors.affiliation: Department of Telecommunication and Information Processing, IPI, iMinds, Ghent University, Ghent, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Philips
authors.affiliation: Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.|Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Winnok H
authors.identifier: http://orcid.org/0000-0003-0960-6781
authors.initials: WH
authors.lastname: De Vos
mesh_terms: D000465:Algorithms; D000818:Animals; D019985:Benchmarking; D002467:Cell Nucleus / Q000145:classification / Q000473:pathology / Q000648:ultrastructure*; D020405:Dermis / Q000473:pathology / Q000648:ultrastructure; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure*; D005354:Fibrosarcoma / Q000175:diagnosis / Q000473:pathology / Q000648:ultrastructure*; D006130:Growth Disorders / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods / Q000706:statistics & numerical data*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods / Q000706:statistics & numerical data*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010363:Pattern Recognition, Automated / Q000706:statistics & numerical data*; D061251:Primary Cell Culture; D011371:Progeria / Q000175:diagnosis / Q000473:pathology