Machine learning assisted real-time deformability cytometry of CD34+ cells allows to identify patients with myelodysplastic syndromes.

Journal: Scientific reports
PMID:

Abstract

Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations. Hence, quantitative image analysis could improve the accuracy and reproducibility of MDS diagnosis. We used real-time deformability cytometry (RT-DC) to measure bone marrow biopsy samples of MDS patients and age-matched healthy individuals. RT-DC is a high-throughput (1000 cells/s) imaging flow cytometer capable of recording morphological and mechanical properties of single cells. Properties of single cells were quantified using automated image analysis, and machine learning was employed to discover morpho-mechanical patterns in thousands of individual cells that allow to distinguish healthy vs. MDS samples. We found that distribution properties of cell sizes differ between healthy and MDS, with MDS showing a narrower distribution of cell sizes. Furthermore, we found a strong correlation between the mechanical properties of cells and the number of disease-determining mutations, inaccessible with current diagnostic approaches. Hence, machine-learning assisted RT-DC could be a promising tool to automate sample analysis to assist experts during diagnosis or provide a scalable solution for MDS diagnosis to regions lacking sufficient medical experts.

Authors

  • Maik Herbig
    Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.
  • Angela Jacobi
    Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.
  • Manja Wobus
    Medical Department I, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
  • Heike Weidner
    Medical Department III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
  • Anna Mies
    Medical Department I, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
  • Martin Kräter
    Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.
  • Oliver Otto
    Zentrum für Innovationskompetenz: Humorale Immunreaktionen in Kardiovaskulären Erkrankungen, Universität Greifswald, Greifswald, Germany.
  • Christian Thiede
    Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
  • Marie-Theresa Weickert
    Department of Medicine III: Hematology and Oncology, School of Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.
  • Katharina S Götze
    Department of Medicine III: Hematology and Oncology, School of Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.
  • Martina Rauner
    Department of Medicine III, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
  • Lorenz C Hofbauer
    Medical Department III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
  • Martin Bornhäuser
    Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  • Jochen Guck
    Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, Dresden, 01307, Germany.
  • Marius Ader
    Center for Regenerative Therapies Dresden (CRTD), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany. marius.ader@tu-dresden.de.
  • Uwe Platzbecker
    Medical Clinic and Polyclinic I, University Hospital, Technical University Dresden, Dresden, Germany.
  • Ekaterina Balaian
    Medical Department I, University Hospital Carl Gustav Carus Dresden, Dresden, Germany. Ekaterina.Balaian@uniklinikum-dresden.de.