A machine-learning-based approach to predict early hallmarks of progressive hearing loss

Machine learning (ML) techniques are increasingly being used to improve disease diagnosis and treatment. However, the application of these computational approaches to the early diagnosis of age-related hearing loss (ARHL), the most common sensory deficit in adults, remains underexplored. Here, we demonstrate the potential of ML for identifying early signs of ARHL in adult mice. We used auditory brainstem responses (ABRs), which are non-invasive electrophysiological recordings that can be performed in both mice and humans, as a readout of hearing function. We recorded ABRs from C57BL/6N mice (6N), which develop early-onset ARHL due to a hypomorphic allele of Cadherin23 (Cdh23^ahl), and from co-isogenic C57BL/6NTac^Cdh23+ mice (6N-Repaired), which do not harbour the Cdh23^ahl allele and maintain good hearing until later in life. We evaluated several ML classifiers across different metrics for their ability to distinguish between the two mouse strains based on ABRs. Remarkably, the models accurately identified mice carrying the Cdh23^ahl allele even in the absence of obvious signs of hearing loss at 1 month of age, surpassing the classification accuracy of human experts. Feature importance analysis using Shapley values indicated that subtle differences in ABR wave 1 were critical for distinguishing between the two genotypes. This superior performance underscores the potential of ML approaches in detecting subtle phenotypic differences that may elude manual classification. Additionally, we successfully trained regression models capable of predicting ARHL progression rate at older ages from ABRs recorded in younger mice. We propose that ML approaches are suitable for the early diagnosis of ARHL and could potentially improve the success of future treatments in humans by predicting the progression of hearing dysfunction.