GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss

Abstract Effective research and clinical application in audiology and hearing loss (HL) require the integration of diverse data, yet the absence of a dedicated database impedes understanding and insight extraction in HL. To address this, the Genetic Deafness Commons (GDC) is developed by consolidati...

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Main Authors: Hui Cheng, Xuegang Wang, Mingjun Zhong, Jia Geng, Wenjian Li, Kanglu Pei, Jing Wang, Lanchen Wang, Yu Lu, Jing Cheng, Fengxiao Bu, Huijun Yuan
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202408891
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author Hui Cheng
Xuegang Wang
Mingjun Zhong
Jia Geng
Wenjian Li
Kanglu Pei
Jing Wang
Lanchen Wang
Yu Lu
Jing Cheng
Fengxiao Bu
Huijun Yuan
author_facet Hui Cheng
Xuegang Wang
Mingjun Zhong
Jia Geng
Wenjian Li
Kanglu Pei
Jing Wang
Lanchen Wang
Yu Lu
Jing Cheng
Fengxiao Bu
Huijun Yuan
author_sort Hui Cheng
collection DOAJ
description Abstract Effective research and clinical application in audiology and hearing loss (HL) require the integration of diverse data, yet the absence of a dedicated database impedes understanding and insight extraction in HL. To address this, the Genetic Deafness Commons (GDC) is developed by consolidating extensive genetic and genomic data from 51 public databases and the Chinese Deafness Genetics Consortium. This repository comprises 5 983 613 variants across 201 HL genes, revealing the genetic landscape of HL and identifying six novel mutational hotspots within the DNA‐binding domains of transcription factors. Comparative phenotypic analyses highlighted considerable disparities between human and mouse models. Among the 201 human HL genes, 133 exhibit hearing abnormalities in mice; 35 have been tested in mice without exhibiting a hearing loss phenotype; and 33 lack auditory testing data. Moreover, gene expression analyses in the cochleae of mice, humans, and rhesus macaques demonstrated a notable correlation (R2 0.718–0.752). Utilizing gene expression, function, pathway, and phenotype data, a SMOTE‐Random Forest model identified 18 candidate HL genes, including TBX2, newly confirmed as an HL gene. As a comprehensive and unified repository, the GDC advances audiology research and practice by improving data accessibility and usability, ultimately fostering deeper insights into hearing disorders.
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spelling doaj-art-b48ec0b1b018484ab7ebccd024a32e5a2025-08-20T03:41:08ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202408891GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing LossHui Cheng0Xuegang Wang1Mingjun Zhong2Jia Geng3Wenjian Li4Kanglu Pei5Jing Wang6Lanchen Wang7Yu Lu8Jing Cheng9Fengxiao Bu10Huijun Yuan11Department of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaDepartment of Oto‐Rhino‐LaryngologyWest China Hospital of Sichuan UniversityChengdu610000ChinaAbstract Effective research and clinical application in audiology and hearing loss (HL) require the integration of diverse data, yet the absence of a dedicated database impedes understanding and insight extraction in HL. To address this, the Genetic Deafness Commons (GDC) is developed by consolidating extensive genetic and genomic data from 51 public databases and the Chinese Deafness Genetics Consortium. This repository comprises 5 983 613 variants across 201 HL genes, revealing the genetic landscape of HL and identifying six novel mutational hotspots within the DNA‐binding domains of transcription factors. Comparative phenotypic analyses highlighted considerable disparities between human and mouse models. Among the 201 human HL genes, 133 exhibit hearing abnormalities in mice; 35 have been tested in mice without exhibiting a hearing loss phenotype; and 33 lack auditory testing data. Moreover, gene expression analyses in the cochleae of mice, humans, and rhesus macaques demonstrated a notable correlation (R2 0.718–0.752). Utilizing gene expression, function, pathway, and phenotype data, a SMOTE‐Random Forest model identified 18 candidate HL genes, including TBX2, newly confirmed as an HL gene. As a comprehensive and unified repository, the GDC advances audiology research and practice by improving data accessibility and usability, ultimately fostering deeper insights into hearing disorders.https://doi.org/10.1002/advs.202408891databasegene expressionhearing lossmouse phenotypemachine learning
spellingShingle Hui Cheng
Xuegang Wang
Mingjun Zhong
Jia Geng
Wenjian Li
Kanglu Pei
Jing Wang
Lanchen Wang
Yu Lu
Jing Cheng
Fengxiao Bu
Huijun Yuan
GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
Advanced Science
database
gene expression
hearing loss
mouse phenotype
machine learning
title GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
title_full GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
title_fullStr GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
title_full_unstemmed GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
title_short GDC: Integration of Multi‐Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss
title_sort gdc integration of multi omic and phenotypic resources to unravel the genetic pathogenesis of hearing loss
topic database
gene expression
hearing loss
mouse phenotype
machine learning
url https://doi.org/10.1002/advs.202408891
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