PhenoScore: AI-based phenomics to quantify rare disease and genetic variation
Abstract
Abstract While both molecular and phenotypic data are essential when interpreting genetic variants, prediction scores (CADD, PolyPhen, and SIFT) have focused on molecular details to evaluate pathogenicity — omitting phenotypic features. To unlock the full potential of phenotypic data, we developed PhenoScore: an open source, artificial intelligence-based phenomics framework. PhenoScore combines facial recognition technology with Human Phenotype Ontology (HPO) data analysis to quantify phenotypic similarity at both the level of individual patients as well as of cohorts. We prove PhenoScore’s ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 25 out of 26 investigated genetic syndromes against clinical features observed in individuals with other neurodevelopmental disorders. Moreover, PhenoScore was able to provide objective clinical evidence for two distinct ADNP -related phenotypes, that had already been established functionally, but not yet phenotypically. Hence, PhenoScore will not only be of use to unbiasedly quantify phenotypes to assist genomic variant interpretation at the individual level, such as for reclassifying variants of unknown clinical significance, but is also of importance for detailed genotype-phenotype studies.
Authors 31
-
Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Artificial Intelligence, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Artificial Intelligence, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD Nijmegen, the Netherlands
Department of Artificial Intelligence, Donders Institute for Brain, Cognition and Behaviour, Radboud University
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Max Planck Institute for Psycholinguistics
Affiliation as printed
Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, the Netherlands
Language and Genetics Department, Max Planck Institute for Psycholinguistics
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Department of Human Genetics, Amsterdam UMC, University of Amsterdam
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Center for Human Genetics, University Hospitals Leuven, University of Leuven, Leuven, Belgium
Center for Human Genetics, University Hospitals Leuven, University of Leuven
-
The Graduate Center, CUNY · City University of New York
Affiliation as printed
Biology PhD Program, The Graduate Center, The City University of New York, New York, United States of America
Department of Human Genetics and George A. Jervis Clinic, Institute for Basic Research in Developmental Disabilities (IBR), Staten Island, New York, USA
Biology PhD Program, The Graduate Center, The City University of New York
Department of Human Genetics and George A. Jervis Clinic, Institute for Basic Research in Developmental Disabilities (IBR)
-
King Faisal Specialist Hospital & Research Centre
Affiliation as printed
Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
-
Affiliation as printed
Institute of Medical Genetics, University of Zurich, Schlieren, 8952, Zurich, Switzerland
Institute of Medical Genetics, University of Zurich
-
Affiliation as printed
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Department of Molecular and Human Genetics, Baylor College of Medicine
-
Affiliation as printed
Faculty of Medicine, University of Southampton, University Rd, Southampton, SO17 1BJ, UK
Faculty of Medicine, University of Southampton
-
Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Department of Clinical Genetics, Leiden University Medical Center
-
Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Department of Clinical Genetics, Leiden University Medical Center
-
Affiliation as printed
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
Department of Medical Genetics, University of Antwerp
-
Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Artificial Intelligence, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD Nijmegen, the Netherlands
Department of Artificial Intelligence, Donders Institute for Brain, Cognition and Behaviour, Radboud University
-
Lisenka E.L.M. Vissers corresponding
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
-
Bert B A De Vries corresponding
Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, P.O. Box 9101, Nijmegen, the Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
Cited by 6 stored of 6
6 results
No patents citing this paper on Lens.org (checked 2026-10-11).