The AudioGene Translational Dashboard for Diagnosing Autosomal Dominant Nonsyndromic Hearing Loss: Phenotypic Data Visualization and Analysis Study.

Abstract

Background: Autosomal dominant nonsyndromic hearing loss (ADNSHL) is highly heterogeneous, with more than 64 genes implicated in its etiology. This complexity limits the diagnostic power of clinical examinations and audiometry alone, while existing computational approaches have achieved only moderate accuracy and often lack interpretability. As precision medicine increasingly emphasizes genotype-phenotype correlations, there is a recognized need for diagnostic tools that provide clinicians with transparent, interpretable outputs.

Objective: This study aimed to develop and evaluate the AudioGene Translational Dashboard, an interpretable clinical informatics tool that integrates machine learning models and interactive visualizations to enhance genotype-phenotype correlations and support diagnostic decision-making in ADNSHL.

Methods: We developed the AudioGene Translational Dashboard, integrating 2 machine learning models (AudioGene version 4 and AudioGene version 9.1) with 6 interactive visualization tools. AudioGene version 4 uses a multi-instance support vector machine classifier for patients with multiple audiograms, while AudioGene version 9.1 combines adaptive boosting, k-nearest neighbors, random forest models, and logistic regression for patients with a single audiogram. Visualizations include audiometric profile plots, audioprofile surfaces, clustering analyses, and data distribution charts designed to facilitate clinical interpretation.

Results: The AudioGene Translational Dashboard was developed to address the "70/30" phenomenon, indicating a 74% likelihood that the causative gene is among the top 3 predicted genes, thereby providing clinicians with a clear confidence indicator ("green flag") or a caution alert ("red flag") during diagnosis. While this level of performance is well suited for hypothesis generation, the remaining uncertainty underscores the need for interpretive context in clinical decision-making. Visualization tools enhanced clinicians' ability to interpret and correlate phenotypic data with predicted genetic outcomes, improving diagnostic confidence and interpretability.

Conclusions: The AudioGene Translational Dashboard advances clinical informatics in genetic diagnosis of ADNSHL by integrating explainable artificial intelligence with interactive visualizations, enhancing clinical interpretability and diagnostic accuracy. This approach facilitates informed clinical decision-making, highlights the translational potential of genotype-phenotype computational models, and supports precision medicine in hearing loss diagnostics. Future enhancements will target improving class balance and incorporating additional user-customizable features to further optimize clinical applicability.