A deep learning framework for efficient pathology image analysis
Nature Communications, vol. 17
Abstract
Artificial intelligence has transformed digital pathology by enabling biomarker prediction from high-resolution whole-slide images. However, current methods are computationally inefficient, processing thousands of redundant tiles per slide and requiring complex aggregation models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE combines task-agnostic tile selection with detailed feature extraction and is benchmarked against leading slide- and tile-level foundation models across 43 tasks from nine cancer types spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperforms patch aggregation methods by up to 23% and achieves the highest overall classification performance. It processes one slide in 2.27 s, reducing computational time by more than 99% compared with existing models. This efficiency supports rapid and auditable workflows by enabling review of the exact tiles used for each prediction and reducing dependence on high-performance computing. By reliably identifying informative regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide search, integration into multi-omics pipelines and emerging clinical foundation models.
Authors 26
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University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Pathology, University Medical Center Mainz, Mainz, Germany
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University Hospital Carl Gustav Carus · Nationales Centrum für Tumorerkrankungen Dresden · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
National Center for Tumor Diseases Dresden (NCT/UCC), Dresden, Germany
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Universitätsklinikum Aachen · University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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Johannes Kepler University of Linz · Kepler Universitätsklinikum
Affiliation as printed
Institute of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
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Affiliation as printed
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
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Affiliation as printed
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Affiliation as printed
Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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Affiliation as printed
Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA
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Affiliation as printed
Center for Cancer Research, Medical University of Vienna, Vienna, Austria
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Affiliation as printed
Center for Cancer Research, Medical University of Vienna, Vienna, Austria
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Centre international de recherche sur le cancer · Imperial College London
Affiliation as printed
Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, UK
Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
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Affiliation as printed
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany
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University of Washington · Fred Hutch Cancer Center
Affiliation as printed
Department of Epidemiology, University of Washington, Seattle, WA, USA
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
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University of Washington · Fred Hutch Cancer Center
Affiliation as printed
Department of Epidemiology, University of Washington, Seattle, WA, USA
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
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University of Milan · European Institute of Oncology
Affiliation as printed
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy
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University of Milan · European Institute of Oncology
Affiliation as printed
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy
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European Institute of Oncology
Affiliation as printed
Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy
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Affiliation as printed
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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German Cancer Research Center · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Jakob Nikolas Kather corresponding
University of Leeds · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany. jakob-nikolas.kather@alumni.dkfz.de
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany. jakob-nikolas.kather@alumni.dkfz.de
Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany. jakob-nikolas.kather@alumni.dkfz.de
Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK. jakob-nikolas.kather@alumni.dkfz.de
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