Proteoform Mapping Calls for a Combined Effort From Bottom‐Up and Top‐Down Proteomics

Proteomics has demonstrated that each protein consists of various proteoforms that provide an additional layer of biological data next to gene-, transcript-, or protein expression levels. As a result, proteome analyses are increasingly being complemented with proteoform maps. Identification and quantification of the type, site, and dynamics of a proteoform modification contribute to a better understanding of human biology. Testing the hypothesis that proteoform-resolved data can provide novel tools in precision medicine requires robust and high-throughput proteoform measurements. The prime candidate for this purpose is top-down proteomics (TDP), commonly performed with mass spectrometry. In this Special Issue: Top-Down Proteomics, Fornelli et al. report a comparative analysis of various SDS-removal methods that are needed for proteoform mapping in TDP experiments. Their work provides technical guidance on an important aspect of the TDP sample preparation process.