Is label‐free LC‐MS/MS ready for biomarker discovery?

Label‐free LC‐MS methods are attractive for high‐throughput quantitative proteomics, as the sample processing is straightforward and can be scaled to a large number of samples. Label‐free methods therefore facilitate biomarker discovery in studies involving dozens of clinical samples. However, despite the increased popularity of label‐free workflows, there is a hesitance in the research community to use it in clinical proteomics studies. Therefore, we here discuss pros and cons of label‐free LC‐MS/MS for biomarker discovery, and delineate the main prerequisites for its successful employment. Furthermore, we cite studies where label‐free LC‐MS/MS was successfully used to identify novel biomarkers, and foresee an increased acceptance of label‐free techniques by the proteomics community in the near future.