Peter Krawitz

Alexander Hustinx, Fabio Hellmann, Ömer Sümer et al.

Rare genetic disorders affect more than 6% of the global population. Reaching a diagnosis is challenging because rare disorders are very diverse. Many disorders have recognizable facial features that are hints for clinicians to diagnose patients. Previous work, such as GestaltMatcher, utilized representation vectors produced by a DCNN similar to AlexNet to match patients in high-dimensional feature space to support "unseen" ultra-rare disorders. However, the architecture and dataset used for transfer learning in GestaltMatcher have become outdated. Moreover, a way to train the model for generating better representation vectors for unseen ultra-rare disorders has not yet been studied. Because of the overall scarcity of patients with ultra-rare disorders, it is infeasible to directly train a model on them. Therefore, we first analyzed the influence of replacing GestaltMatcher DCNN with a state-of-the-art face recognition approach, iResNet with ArcFace. Additionally, we experimented with different face recognition datasets for transfer learning. Furthermore, we proposed test-time augmentation, and model ensembles that mix general face verification models and models specific for verifying disorders to improve the disorder verification accuracy of unseen ultra-rare disorders. Our proposed ensemble model achieves state-of-the-art performance on both seen and unseen disorders.

Ömer Sümer, Fabio Hellmann, Alexander Hustinx et al.

Computer vision-based methods have valuable use cases in precision medicine, and recognizing facial phenotypes of genetic disorders is one of them. Many genetic disorders are known to affect faces' visual appearance and geometry. Automated classification and similarity retrieval aid physicians in decision-making to diagnose possible genetic conditions as early as possible. Previous work has addressed the problem as a classification problem and used deep learning methods. The challenging issue in practice is the sparse label distribution and huge class imbalances across categories. Furthermore, most disorders have few labeled samples in training sets, making representation learning and generalization essential to acquiring a reliable feature descriptor. In this study, we used a facial recognition model trained on a large corpus of healthy individuals as a pre-task and transferred it to facial phenotype recognition. Furthermore, we created simple baselines of few-shot meta-learning methods to improve our base feature descriptor. Our quantitative results on GestaltMatcher Database show that our CNN baseline surpasses previous works, including GestaltMatcher, and few-shot meta-learning strategies improve retrieval performance in frequent and rare classes.

Ali Burak Ünal, Cem Ata Baykara, Peter Krawitz et al.

Machine learning has shown promise in facial dysmorphology, where characteristic facial features provide diagnostic clues for rare genetic disorders. GestaltMatcher, a leading framework in this field, has demonstrated clinical utility across multiple studies, but its reliance on centralized datasets limits further development, as patient data are siloed across institutions and subject to strict privacy regulations. We introduce a federated GestaltMatcher service based on a cross-silo horizontal federated learning framework, which allows hospitals to collaboratively train a global ensemble feature extractor without sharing patient images. Patient data are mapped into a shared latent space, and a privacy-preserving kernel matrix computation framework enables syndrome inference and discovery while safeguarding confidentiality. New participants can directly benefit from and contribute to the system by adopting the global feature extractor and kernel configuration from previous training rounds. Experiments show that the federated service retains over 90% of centralized performance and remains robust to both varying silo numbers and heterogeneous data distributions.

Da Wu, Jingye Yang, Cong Liu et al.

Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible answer over a prolonged period of time. Addressing this "diagnostic odyssey" thus has substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features, which can be used by artificial intelligence algorithms to facilitate clinical diagnosis, in prioritizing candidate diseases to be further examined by lab tests or genetic assays, or in helping the phenotype-driven reinterpretation of genome/exome sequencing data. Existing methods using frontal facial photos were built on conventional Convolutional Neural Networks (CNNs), rely exclusively on facial images, and cannot capture non-facial phenotypic traits and demographic information essential for guiding accurate diagnoses. Here we introduce GestaltMML, a multimodal machine learning (MML) approach solely based on the Transformer architecture. It integrates facial images, demographic information (age, sex, ethnicity), and clinical notes (optionally, a list of Human Phenotype Ontology terms) to improve prediction accuracy. Furthermore, we also evaluated GestaltMML on a diverse range of datasets, including 528 diseases from the GestaltMatcher Database, several in-house datasets of Beckwith-Wiedemann syndrome (BWS, over-growth syndrome with distinct facial features), Sotos syndrome (overgrowth syndrome with overlapping features with BWS), NAA10-related neurodevelopmental syndrome, Cornelia de Lange syndrome (multiple malformation syndrome), and KBG syndrome (multiple malformation syndrome). Our results suggest that GestaltMML effectively incorporates multiple modalities of data, greatly narrowing candidate genetic diagnoses of rare diseases and may facilitate the reinterpretation of genome/exome sequencing data.

Fabio Hellmann, Silvan Mertes, Mohamed Benouis et al.

In recent years, the increasing availability of personal data has raised concerns regarding privacy and security. One of the critical processes to address these concerns is data anonymization, which aims to protect individual privacy and prevent the release of sensitive information. This research focuses on the importance of face anonymization. Therefore, we introduce GANonymization, a novel face anonymization framework with facial expression-preserving abilities. Our approach is based on a high-level representation of a face, which is synthesized into an anonymized version based on a generative adversarial network (GAN). The effectiveness of the approach was assessed by evaluating its performance in removing identifiable facial attributes to increase the anonymity of the given individual face. Additionally, the performance of preserving facial expressions was evaluated on several affect recognition datasets and outperformed the state-of-the-art methods in most categories. Finally, our approach was analyzed for its ability to remove various facial traits, such as jewelry, hair color, and multiple others. Here, it demonstrated reliable performance in removing these attributes. Our results suggest that GANonymization is a promising approach for anonymizing faces while preserving facial expressions.

Yaron Gurovich, Yair Hanani, Omri Bar et al.

Facial analysis technologies have recently measured up to the capabilities of expert clinicians in syndrome identification. To date, these technologies could only identify phenotypes of a few diseases, limiting their role in clinical settings where hundreds of diagnoses must be considered. We developed a facial analysis framework, DeepGestalt, using computer vision and deep learning algorithms, that quantifies similarities to hundreds of genetic syndromes based on unconstrained 2D images. DeepGestalt is currently trained with over 26,000 patient cases from a rapidly growing phenotype-genotype database, consisting of tens of thousands of validated clinical cases, curated through a community-driven platform. DeepGestalt currently achieves 91% top-10-accuracy in identifying over 215 different genetic syndromes and has outperformed clinical experts in three separate experiments. We suggest that this form of artificial intelligence is ready to support medical genetics in clinical and laboratory practices and will play a key role in the future of precision medicine.