Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets.

Autor: Matharu SS; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Nordmann CS; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Ottman KR; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Akkem R; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Palumbo D; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Cruz DRD; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Campbell K; Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA., Sievert G; Center for Clinical Translational Science, University of Kentucky College of Medicine, Lexington, KY, USA., Sturgill J; Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA., Porterfield JZ; Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA., Joshi S; Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA., Alfar HR; Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA., Peng C; Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA., Pokrovskaya ID; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Kamykowski JA; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Wood JP; Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA., Garvy B; Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA., Aronova MA; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Whiteheart SW; Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA., Leapman RD; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA., Storrie B; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jazyk: angličtina
Zdroj: Platelets [Platelets] 2023 Dec; Vol. 34 (1), pp. 2264978. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1080/09537104.2023.2264978
Abstrakt: Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/mitochondrion-to-plateletvolume ratio is significantly greater in COVID-19 patient platelets indicating a denser packing of organelles, and a more compact platelet. The COVID-19 patient platelets were significantly smaller -by 35% in volume - with most of the difference in organelle packing density being due to decreased platelet size. There was little to no 3D ultrastructural evidence for differential activation of the platelets from COVID-19 patients. Though limited by sample size, our studies suggest that factors outside of the platelets themselves are likely responsible for COVID-19 complications. Our studies show how deep learning 3D methodology can become the gold standard for 3D ultrastructural studies of platelets.
Databáze: MEDLINE
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