GestaltMatcher facilitates rare disease matching using facial phenotype descriptors.

Journal: Nature genetics
Published Date: Feb 10, 2022

Abstract

Many monogenic disorders cause a characteristic facial morphology. Artificial intelligence can support physicians in recognizing these patterns by associating facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this 'supervised' approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we developed GestaltMatcher, an encoder for portraits that is based on a deep convolutional neural network. Photographs of 17,560 patients with 1,115 rare disorders were used to define a Clinical Face Phenotype Space, in which distances between cases define syndromic similarity. Here we show that patients can be matched to others with the same molecular diagnosis even when the disorder was not included in the training set. Together with mutation data, GestaltMatcher could not only accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism but also enable the delineation of new phenotypes.

Authors

  • Tzung-Chien Hsieh
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Aviram Bar-Haim
    FDNA Inc., Boston, MA, USA.
  • Shahida Moosa
    Division of Molecular Biology and Human Genetics, Stellenbosch University and Medical Genetics, Tygerberg Hospital, Tygerberg, South Africa.
  • Nadja Ehmke
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Karen W Gripp
    Division of Medical Genetics, A. I. du Pont Hospital for Children/Nemours, Wilmington, DE, USA.
  • Jean Tori Pantel
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Magdalena Danyel
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Martin Atta Mensah
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Denise Horn
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Stanislav Rosnev
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Nicole Fleischer
    FDNA Inc., Boston, MA, USA.
  • Guilherme Bonini
    FDNA Inc., Boston, MA, USA.
  • Alexander Hustinx
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Alexander Schmid
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Alexej Knaus
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Behnam Javanmardi
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Hannah Klinkhammer
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Hellen Lesmann
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Sugirthan Sivalingam
    Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Tom Kamphans
    GeneTalk, Bonn, Germany.
  • Wolfgang Meiswinkel
    GeneTalk, Bonn, Germany.
  • Frédéric Ebstein
    Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany.
  • Elke Krüger
    Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany.
  • Sébastien Küry
    CHU Nantes, Service de Génétique Médicale, Nantes, France.
  • Stéphane Bézieau
    CHU Nantes, Service de Génétique Médicale, Nantes, France.
  • Axel Schmidt
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Sophia Peters
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Hartmut Engels
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Elisabeth Mangold
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Martina Kreiß
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Kirsten Cremer
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Claudia Perne
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Regina C Betz
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Tim Bender
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Kathrin Grundmann-Hauser
    Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
  • Tobias B Haack
    Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
  • Matias Wagner
    Institute of Human Genetics, School of Medicine, Technical University Munich, Munich, Germany.
  • Theresa Brunet
    Institute of Human Genetics, School of Medicine, Technical University Munich, Munich, Germany.
  • Heidi Beate Bentzen
    Norwegian Research Center for Computers and Law, Faculty of Law, University of Oslo, Oslo, Norway.
  • Luisa Averdunk
    Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital, Heinrich-Heine-University, Düsseldorf, Germany.
  • Kimberly Christine Coetzer
    Division of Molecular Biology and Human Genetics, Stellenbosch University and Medical Genetics, Tygerberg Hospital, Tygerberg, South Africa.
  • Gholson J Lyon
    Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, NY 11797, USA.
  • Malte Spielmann
    Institute of Human Genetics, University of Lübeck, Lübeck, Germany.
  • Christian P Schaaf
    Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
  • Stefan Mundlos
    Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Markus M Nöthen
    Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, Bonn, Germany.
  • Peter M Krawitz
    Institute for Genomic Statistic and Bioinformatics, University Hospital Bonn, Rheinische-Friedrich-Wilhelms University, Bonn, Germany.

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