Panel 3: Genomics, precision medicine and targeted therapies

Abstract

Objective: To review the most recent advances in human and bacterial genomics as applied to pathogenesis and clinical management of otitis media. DataSources: PubMed articles published since the last meeting in June 2015 up to June 2019. Review Methods: A panel of experts in human and bacterial genomics of otitis media was formed. Each panel member reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The panel met at the 20th International Symposium on Recent Advances in Otitis Media in June 2019, discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion:Trans-disciplinary approaches applying pan-omic technologies to identify human susceptibility to otitis media and to understand microbial population dynamics, patho-adaptation and virulence mechanisms are crucial to the development of novel, personalized therapeutics and prevention strategies for otitis media.

Multi-omic studies on missense PLG variants in families with otitis media

“…Likewise PLG was network analysis. The PLG variant c.112A > G (p.Lys38Glu) was identified along with 31 other significant loci in a previous GWAS of OM 9,22 . In order to identify common biological processes between PLG and other loci associated with OM, this list of 32 genes was uploaded into NetworkAnalyst 3.0 and mapped (Reactome; Supplementary Figure S3A) [23][24][25] .…”

“…Network analysis of PLG was performed with NetworkAnalyst 3.0 23 – 25 . A list of 32 genes previously found to be associated with OM 22 and the IMEx Interactome generic protein–protein interaction database were used as input. Significant pathways were identified using the databases from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, Gene Ontology (GO), and PANTHER via the Function Explorer tool in NetworkAnalyst.…”

Editorial: Otitis media susceptibility due to genetic variants

“…Cholesteatoma is a cyst-like middle ear lesion that grows insidiously and erodes surrounding temporal bone structures, usually because of long-standing, inadequately treated chronic OM. Previous DNA exome and genome-wide association studies in humans have mostly focused on the common forms of OM, including acute OM, recurrent acute OM, chronic OM with effusion, and chronic suppurative OM ( Santos-Cortez et al, 2019 ; Jamieson et al, 2021 ). Before this study, only two exome sequencing studies on families with cholesteatoma were published by the same group ( Prinsley et al, 2019 ; Cardenas et al, 2023 ), with none of the candidate genes and pathways overlapping with those identified by Lee et al These studies suggest that at least a subset of cholesteatoma patients has a potential genetic basis in their disease etiology.…”

“…Family history is a well-known risk factor for OM in its many forms ( Huyett et al, 2018 ); however, compared to the epidemiology and microbiology of OM, genetic susceptibility to OM is less studied. Much of what we know about OM genetics relies on common variants from a few genome-wide association studies and several candidate gene associations of immune markers, rare variants in a few families, and gene-by-gene experiments in rodent models ( Santos-Cortez et al, 2019 ; Giese et al, 2020 ).…”

Editorial: Otitis Media Genomics and the Middle Ear Microbiome

“…However, the mechanisms by which common acute OM progresses in severity despite treatment are poorly understood. Elucidation of molecular mechanisms of genetic susceptibility in humans, and of host-microbiota interactions are key to understanding OM progression and improving current protocols for prevention, diagnosis and treatment ( Marsh et al, 2020 ; Santos-Cortez et al, 2020 ; Thornton et al, 2020 ).…”