A peptidoform based proteomic strategy for studying functions of post-translational modifications

Protein post-translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the produced proteoforms. In this Viewpoint, we firstly reviewed the concepts of proteoform and peptidoform. We show that many of the current PTM biological investigation and annotation studies largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular "modified peptidoform" is matched to the corresponding "unmodified peptidoform" as a reference for the quantitative analysis between samples and conditions. We suggest this strategy has the potential to provide more directly relevant information to learn the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature "peptidoform" in future bottom-up proteomic studies.