Next-Generation Morphometry for pathomics-data mining in histopathology

Nature Communications, vol. 14, pp. 470

Abstract

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics.

Authors 16

1. David Laurin Hölscher Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

2. Nassim Bouteldja Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

3. Mehdi Joodaki Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Clinic, Aachen, Germany

4. María Luisa Russo

   Fondazione Ricerca Molinette

   Affiliation as printed

   Fondazione Ricerca Molinette, Torino, Italy

5. Yu-Chia Lan Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

6. Alireza Vafaei Sadr Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

7. Mingbo Cheng Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Clinic, Aachen, Germany

8. Vladimı́r Tesař

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic

9. Saskia Freifrau von Stillfried Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

10. Barbara M. Klinkhammer Aachen Institute of Pathology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

11. Jonathan Barratt

    National Health Service · University of Leicester · University Hospitals of Leicester NHS Trust

    Affiliation as printed

    Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom

    John Walls Renal Unit, University Hospital of Leicester National Health Service Trust, Leicester, United Kingdom

12. Jürgen Floege Aachen Department of Nephrology and Immunology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Nephrology and Immunology, RWTH Aachen University Clinic, Aachen, Germany

13. Rosanna Coppo

    Fondazione Ricerca Molinette · Ospedale Regina Margherita

    Affiliation as printed

    Fondazione Ricerca Molinette, Torino, Italy

    Regina Margherita Children's University Hospital, Torino, Italy

14. Ivan G. Costa Aachen Institute for Computational Genomics

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Computational Genomics, RWTH Aachen University Clinic, Aachen, Germany

15. Roman David Bülow Aachen Institute of Pathology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany

16. Peter Boor corresponding Aachen Department of Nephrology and Immunology Institute of Pathology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Nephrology and Immunology, RWTH Aachen University Clinic, Aachen, Germany. pboor@ukaachen.de

    Institute of Pathology, RWTH Aachen University Clinic, Aachen, Germany. pboor@ukaachen.de

    Department of Nephrology and Immunology, RWTH Aachen University Clinic, Aachen, Germany