Enhancing Variant Prioritization in VarFish through On-Premise Computational Facial Analysis

Genes, vol. 15, pp. 370

Abstract

Genomic variant prioritization is crucial for identifying disease-associated genetic variations. Integrating facial and clinical feature analyses into this process enhances performance. This study demonstrates the integration of facial analysis (GestaltMatcher) and Human Phenotype Ontology analysis (CADA) within VarFish, an open-source variant analysis framework. Challenges related to non-open-source components were addressed by providing an open-source version of GestaltMatcher, facilitating on-premise facial analysis to address data privacy concerns. Performance evaluation on 163 patients recruited from a German multi-center study of rare diseases showed PEDIA's superior accuracy in variant prioritization compared to individual scores. This study highlights the importance of further benchmarking and future integration of advanced facial analysis approaches aligned with ACMG guidelines to enhance variant classification.

Authors 8

1. Meghna Ahuja Bhasin

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany

2. Alexej Knaus

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany

3. Pietro Incardona

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Core Unit for Bioinformatics Data Analysis, Medical Faculty, University of Bonn, 53127 Bonn, Germany

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany

4. Alexander Schmid

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany

5. Manuel Holtgrewe

   Berlin Institute of Health at Charité - Universitätsmedizin Berlin

   Affiliation as printed

   CUBI—Core Unit Bioinformatics, Berlin Institute of Health, 10117 Berlin, Germany

6. Miriam Elbracht Aachen Institute for Human Genetics and Genomic Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52062 Aachen, Germany

7. Peter Michael Krawitz

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany

8. Tzung‐Chien Hsieh corresponding

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany