Using Reactome, a curated Internet database, noise-induced hearing loss studies were aggregated into cellular pathways for organization of the emerging genomic and epigenetic data in the literature.Data Sources:
PubMed and Reactome.org, a relational data base program systematizing biological processes into interactive pathways and subpathways based on ontology, cellular constituents, gene expression, and molecular components.Study Selection:
Peer-reviewed population and laboratory studies for the previous 15 years relating genomics and noise and hearing loss were identified in PubMed. Criteria included p values <0.05 with correction for multiple genes, a fold change of >1.5, or duplicated studies.Data Extraction and Synthesis:
One-hundred fifty-eight unique HGNC identifiers from 77 articles met the selection criteria, and were uploaded into the analysis program at http://reactome.org. These genes participated in a total of 621 cellular interactions in 21 of 23 pathways. Cellular response to stress with its attenuation phase, particularly in response to heat stress, detoxification of ROS, and specific areas of the immune system are predominant pathways identified as significantly "overrepresented" (p values <0.1e-5 and false discovery rates <0.01).Conclusion:
Twenty-one of 23 of the designated pathways in Reactome have significant influence on noise-induced hearing loss, signifying a confluence of molecular pathways in reaction to acoustic trauma; however, cellular response to stress, including heat shock response, and other small areas of immune response were highly overrepresented. Yet-to-be-explored genomics areas include miRNA, lncRNA, copy number variations, RNA sequencing, and human genome-wide association study.