PhenoScore quantifies phenotypic variation for rare genetic diseases by combining facial analysis with other clinical features using a machine-learning framework.

Journal: Nature genetics
PMID: 37550531

Abstract

Several molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other phenotypic data directly from individuals exists. We developed PhenoScore: an open-source, artificial intelligence-based phenomics framework, combining facial recognition technology with Human Phenotype Ontology data analysis to quantify phenotypic similarity. Here we show PhenoScore's ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 37 of 40 investigated syndromes against clinical features observed in individuals with other neurodevelopmental disorders and show it is an improvement on existing approaches. PhenoScore provides predictions for individuals with variants of unknown significance and enables sophisticated genotype-phenotype studies by testing hypotheses on possible phenotypic (sub)groups. PhenoScore confirmed previously known phenotypic subgroups caused by variants in the same gene for SATB1, SETBP1 and DEAF1 and provides objective clinical evidence for two distinct ADNP-related phenotypes, already established functionally.

Authors

  • Alexander J M Dingemans
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Max Hinne
    Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands.
  • Kim M G Truijen
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Lia Goltstein
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Jeroen van Reeuwijk
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Nicole de Leeuw
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Janneke Schuurs-Hoeijmakers
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Rolph Pfundt
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Illja J Diets
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Joery den Hoed
    Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
  • Elke de Boer
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Jet Coenen-van der Spek
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Sandra Jansen
    Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
  • Bregje W van Bon
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Noraly Jonis
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Charlotte W Ockeloen
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Anneke T Vulto-van Silfhout
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Tjitske Kleefstra
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • David A Koolen
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Philippe M Campeau
    Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
  • Elizabeth E Palmer
    Centre of Clinical Genetics, Sydney Children's Hospitals Network, Randwick, NSW 2031, Australia.
  • Hilde Van Esch
    Center for Human Genetics, University Hospitals Leuven, University of Leuven, Leuven, Belgium.
  • Gholson J Lyon
    Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, NY 11797, USA.
  • Fowzan S Alkuraya
    Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Anita Rauch
    Institute of Medical Genetics, University of Zürich, Zürich, Switzerland.
  • Ronit Marom
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Diana Baralle
    Human Development and Health, Faculty of Medicine, University of Southampton, MP808, Tremona Road, Southampton SO16 6YD, UK.
  • Pleuntje J van der Sluijs
    Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • Gijs W E Santen
    Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • R Frank Kooy
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
  • Marcel A J van Gerven
    Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
  • Lisenka E L M Vissers
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands. lisenka.vissers@radboudumc.nl.
  • Bert B A de Vries
    Department of Human Genetics, Radboud University, University Medical Centre, Nijmegen, The Netherlands.

Keywords

External Resources

Popular Topics
Recent Journals