A Human Cochlear Atlas on Protein Expression: A new path to molecular treatment strategies.

Introduction Despite rapid progress, the underlying cellular and molecular mechanisms of hearing loss are still poorly understood. Sampling and molecular analysis of perilymph may not only improve the understanding of the pathological processes within the inner ear but may also enable novel molecular treatment strategies.

Methods To this aim, analysis of the perilymph proteome from patients undergoing cochlear implantation was performed. For initial cluster analysis, label-free quantification (LFQ) data for each identified protein were uploaded into the Qlucore Omics Explorer and a principal component analysis (PCA) was carried out. Variance filtering using the standard deviation was done to identify a subset of proteins that maximized the PCA projection allowing assessment of relatedness of the individual samples. These data were then converted to a heat map. Individual groups of patient data could then be selected to identify the protein data that characterizes the particular selected group.

Results A multitude of proteins and patterns of protein expression that allow the characterization of patients into subgroups were revealed with the herein presented approach. Expression of single proteins were related to individual cells within the cochlea allowing the generation of a cochlear atlas of protein expression.

Conclusion A human cochlear atlas of protein expression may allow an improved understanding and the modulation of the human perilymph proteome could open novel diagnostic and treatment avenues for targeting inner ear diseases at a molecular level.

Deutschen Forschungsgemeinschaft (DFG) im Rahmen der deutschen Exzellenzstrategie – EXC 2177/1 – Projekt-ID 390895286

Publication History

Article published online:
24 May 2022