Proteoform Analysis to Fulfill Unmet Clinical Needs and Reach Global Standardization of Protein Measurands in Clinical Chemistry Proteomics.

In clinical testing of protein markers, structure variants of the measurand are often not taken into account. This heterogeneous character of protein measurands in immunoassays often renders test standardization impossible. Consequently, test results from different methods can lead to underdiagnosis or overdiagnosis and, thus, undertreatment or overtreatment of patients. The systematic structural analysis of protein isoforms has been coined proteoform profiling and is performed through mass spectrometry-based proteomics strategies. Knowledge on proteoforms allows refining existing uni-marker tests and moreover has great potential to contribute to the urgent need for new tests to predict prognosis and severity of diseases.