Confident assignment of proteoforms bearing PTMs or sequence variations becomes more challenging as query proteoforms get larger and the search databases contain more candidate PTM sites. Unambiguous level 1 proteoform assignments are particularly troublesome when seeking proteoforms specific to a particular biological context (e.g., tissue types), but this can be significantly mitigated with the inclusion of fragment-ion data quality standards. Even at current levels of proteoform characterization quality, organ-specific proteoforms achieve robust tissue type identification.