The following abstract is drawn from a recently published paper in Nature Cancer. We invite you to read the full paper and join the conversation, become a member of the Pathology News community to share your thoughts, ask questions, and engage with others around this work.

Authors: Darui Jin (晋达睿), Artem Shmatko, Areeba Patel, Samuel Rutz, Lukas Friedrich, Rouzbeh Banan, Ramin Rahmanzade, Philipp Sievers, Stefan Hamelmann, Daniel Schrimpf, Kirsten Göbel, Henri Bogumil, Sybren L. N. Maas, Martin Sill, Felix E. Hinz, Abigail K. Suwala, Felix Keller, Antje Habel, Gleb Rukhovich, Ferdinand Zettl, Obada T. Alhalabi, Sebastian Ille, Jannik Sehring, Daniel Amsel, Benedikt Wiestler, Pedro Piovesan Lago, Bogdana Suchorska, Olfat Ahmad, Dominik Sturm, David Reuss, Pieter Wesseling, Adelheid Wöhrer, Frank L. Heppner, Ingmar Blümcke, Claire Delbridge, Martin Jakobs, Christel Herold-Mende, Sandro M. Krieg, Wolfgang Wick, David T. W. Jones, Stefan M. Pfister, Maysa Al-Hussaini, Yanghao Hou, Felipe D’Almeida Costa, Leonille Schweizer, Luca Bertero, Till Acker, Arnault Tauziede-Espariat, Pascale Varlet, Doron Merkler, Kristof Egervari, Hildegard Dohmen, Pablo Zoroquiain, Roger Gejman, Sebastian Brandner, Xiangzhi Bai, Andreas von Deimling, Felix Sahm & Moritz Gerstung

Abstract

Molecular testing is essential for classifying central nervous system (CNS) tumors, with methylation profiling providing the highest diagnostic granularity. However, this requires more resources and time than conventional hematoxylin and eosin (H&E) histopathology, which is widely available globally. Here we propose Hetairos, an artificial intelligence algorithm that predicts 102 methylation-based CNS tumor subtypes from digital H&E slides. Built and validated on 9,606 patients and over 11,000 slides from 11 centers across four continents, Hetairos identified 50–70% of cases with high confidence, achieving an accuracy of 0.87 for its highest-rated predictions. Hetairos outperformed five board-certified neuropathologists in a direct histology-only comparison (0.68 versus 0.30). Prospective evaluation in routine diagnostics confirmed its performance, reducing turnaround time from 12 days (molecular testing) to 12 min. Hetairos supports diagnostic decision-making across the full spectrum of pediatric and adult CNS tumors by narrowing differential diagnoses and guiding efficient testing.

Read the full article: Hetairos is a histology-based artificial intelligence model for predicting central nervous system tumor methylation subtypes | Nature Cancer

1. Division of AI in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

   Darui Jin  (晋达睿), Artem Shmatko, Areeba Patel, Samuel Rutz, Gleb Rukhovich & Moritz Gerstung

2. Image Processing Center, Beihang University, Beijing, China

   Darui Jin  (晋达睿) & Xiangzhi Bai

3. Faculty of Biosciences, Heidelberg University, Heidelberg, Germany

   Artem Shmatko

4. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany

   Areeba Patel, Lukas Friedrich, Rouzbeh Banan, Ramin Rahmanzade, Philipp Sievers, Stefan Hamelmann, Daniel Schrimpf, Kirsten Göbel, Henri Bogumil, Felix E. Hinz, Abigail K. Suwala, Felix Keller, Antje Habel, Ferdinand Zettl, David Reuss, Andreas von Deimling & Felix Sahm

5. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

   Areeba Patel, Lukas Friedrich, Rouzbeh Banan, Ramin Rahmanzade, Philipp Sievers, Stefan Hamelmann, Daniel Schrimpf, Kirsten Göbel, Henri Bogumil, Felix E. Hinz, Abigail K. Suwala, Felix Keller, Antje Habel, Ferdinand Zettl, David Reuss, Andreas von Deimling & Felix Sahm

6. Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany

   Areeba Patel, Martin Sill, Olfat Ahmad, Dominik Sturm, David T. W. Jones, Stefan M. Pfister & Felix Sahm

7. Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg, Germany

   Samuel Rutz, Felix Keller & Moritz Gerstung

8. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

   Sybren L. N. Maas

9. Department of Pathology, Brain Tumor Center, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

   Sybren L. N. Maas

10. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany

    Martin Sill & Stefan M. Pfister

11. Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

    Obada T. Alhalabi, Sebastian Ille, Bogdana Suchorska, Martin Jakobs, Christel Herold-Mende & Sandro M. Krieg

12. Institute of Neuropathology, Justus Liebig University Giessen, Giessen, Germany

    Jannik Sehring, Daniel Amsel, Till Acker & Hildegard Dohmen

13. AI for Image-Guided Diagnosis and Therapy, School of Medicine and Health, Technical University of Munich, Munich, Germany

    Benedikt Wiestler

14. Munich Center for Machine Learning (MCML), Munich, Germany

    Benedikt Wiestler

15. AC Camargo Cancer Center, São Paulo, Brazil

    Pedro Piovesan Lago & Felipe D’Almeida Costa

16. Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Dominik Sturm & David T. W. Jones

17. Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg, Germany

    Dominik Sturm & Stefan M. Pfister

18. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Pieter Wesseling

19. Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, The Netherlands

    Pieter Wesseling

20. Division of Neuropathology and Neurochemistry, Department of Neurology, Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria

    Adelheid Wöhrer

21. Institute of Neuropathology and Neuromolecular Pathology, Medical University of Innbruck, Innsbruck, Austria

    Adelheid Wöhrer

22. Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany

    Frank L. Heppner

23. German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association, Berlin, Germany

    Frank L. Heppner

24. Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

    Ingmar Blümcke

25. Institute of Pathology, School of Medicine and Health, Technical University of Munich, Munich, Germany

    Claire Delbridge

26. Division for Stereotactic Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

    Martin Jakobs

27. Neurology Clinic, University Hospital Heidelberg, Heidelberg, Germany

    Wolfgang Wick

28. Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Wolfgang Wick

29. National Center for Tumor Diseases (NCT), Heidelberg, Germany

    David T. W. Jones & Stefan M. Pfister

30. Department of Cell Therapy and Applied Genomics, King Hussein Cancer Center, Amman, Jordan

    Maysa Al-Hussaini

31. Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan

    Maysa Al-Hussaini

32. Department of Pathology, Center for Molecular Medicine Testing, College of Basic Medicine, Chongqing Medical University, Chongqing, China

    Yanghao Hou

33. Center for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China

    Yanghao Hou

34. DASA Laboratories, São Paulo, Brazil

    Felipe D’Almeida Costa

35. Edinger Institute, Institute of Neurology, University of Frankfurt am Main, Frankfurt am Main, Germany

    Leonille Schweizer

36. German Cancer Consortium (DKTK) Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Leonille Schweizer

37. Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany

    Leonille Schweizer

38. Department of Medical Sciences, University of Turin, Turin, Italy

    Luca Bertero

39. Department of Neuropathology, Sainte-Anne Hospital, Paris, France

    Arnault Tauziede-Espariat & Pascale Varlet

40. Inserm, UMR 1266, IMA-Brain, Institut de Psychiatrie et Neurosciences de Paris, Paris, France

    Arnault Tauziede-Espariat & Pascale Varlet

41. Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland

    Doron Merkler & Kristof Egervari

42. Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland

    Doron Merkler & Kristof Egervari

43. Pathology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    Pablo Zoroquiain & Roger Gejman

44. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK

    Sebastian Brandner