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bioRxiv · 10.1101/2024.08.19.608726

GDC: An Integrated Resource to Explore the Pathogenesis of Hearing Loss through Genetics and Genomics

Cheng, H.·Wang, X.·Zhong, M.·Geng, J.·Li, W.·Pei, K.·Lu, Y.·Cheng, J.·Bu, F.·Yuan, H.
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Abstract

Effective research and clinical application in audiology and hearing loss (HL) often require the integration of diverse data. However, the absence of a dedicated database impeded understanding and insight extraction in HL. To address this, the Genetic Deafness Commons (GDC) was developed by consolidating extensive genetic and genomic data from 51 public databases and the Chinese Deafness Genetics Consortium, encompassing 5,983,613 variants across 201 HL genes. This comprehensive dataset detailed the genetic landscape of HL, identifying six novel mutational hotspots within DNA binding domains of transcription factor genes, which were eligible for evidence-based variant pathogenicity classification. Comparative phenotypic analyses highlighted considerable disparities between human and mouse models, with only 130 human HL genes exhibiting hearing abnormality in mice. Moreover, gene expression analyses in the cochleae of mice and rhesus macaques demonstrated a notable correlation (R2 = 0.76). Utilizing gene expression, function, pathway, and phenotype data, a SMOTE-Random Forest model identified 18 candidate HL genes, including TBX2 and ERCC2, newly confirmed as HL genes. The GDC, as a comprehensive and unified repository, significantly advances audiology research and clinical practice by enhancing data accessibility and usability, thereby facilitating deeper insights into hearing disorders.

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Cheng, H., Wang, X., Zhong, M., Geng, J., Li, W., Pei, K., Lu, Y., Cheng, J., Bu, F., Yuan, H.. 2024-08-20. GDC: An Integrated Resource to Explore the Pathogenesis of Hearing Loss through Genetics and Genomics. https://doi.org/10.1101/2024.08.19.608726

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