Hierarchical Classification via Cascading Feature Elimination: Application to Human Phenotype Ontology-Aligned Facial Phenotyping (FaceMesh2HPO)
Organizations: 1*Chair for Human-centered Artificial Intelligence, University of Augsburg, Universitätsstr. 6a, Augsburg, 86159, Bavaria, Germany. · Institute for Genomic Statistics and Bioinformatics, University of Bonn, Venusberg-Campus 1, Bonn, 53127, North Rhine-Westphalia, Germany. · 3National Human Genome Research Institute, National Institutes of2026 Health, 10 Center Dr, Bethesda, 20892, MD, United States of America.
Abstract
FaceMesh2HPO is a framework for classifying facial phenotypic descriptors aligned with the Human Phenotype Ontology (HPO) to support clinical diagnosis. Using annotations from 124 clinicians across 10 disorders (107 HPO terms) combined with non-syndromic controls, we generated 3D facial meshes (478 landmarks) from 2D images and trained a hierarchical PointNet-based pipeline with cascading classification and feature elimination. The best models, incorporating 3D meshes, facial outline, and demographic metadata, achieved AUROCs between ~0.55 and ~0.89, with higher performance at parent nodes than leaf terms. External validation showed variable generalizability across disorders. Results demonstrate that hierarchical modeling of 3D facial geometry enables interpretable, ontology-linked phenotype classification, though performance on rare leaf terms remains limited. Improved data diversity and feature selection strategies are needed to enhance robustness and clinical utility.