Detergent Screening with Hybrid Detergents Increases Observable Number of Protein Identities in Bottom-Up Proteomics

Detergents are key reagents in bottom-up proteomics that create an apparent, yet underappreciated bias on observable proteomes. Maximizing the chemical diversity in parallelized detergent screens is supposed to maximize observable proteomes by combining proteomics data sets of different detergents. Herein, we address the question of whether combining proteomics data sets from canonical detergents and related hybrid detergents can increase the observable number of unique protein identities by 35% compared to the standard sodium dodecyl sulphate. Our data indicate that the solubilizing properties of hybrid detergents do not reflect an average of canonical detergents, which increases the observable number of unique protein identities from 1604 to 2169 when proteomics data sets from sodium dodecyl sulphate, dodecyltrimethylammonium bromide, dendritic triglycerol detergent and related hybrid detergents from a screen on Escherichia coli are combined. Our data highlight the utility of cationic detergents and related hybrid detergents for enhancing the observable proteome. Detergent screening-based proteome reconstructions with canonical detergents and hybrid detergents present an interesting research direction towards improved proteome profiling applications.