Bottom-up shotgun proteomics is extremely sensitive and allows researcher to mine deep into the proteome. However important biological information such as the effects of alternative splicing or of endogenous protein proteolysis remains a significant challenge. However, directly profiling the undigested proteoforms can overcome many of these limitations and constitutes a very powerful tool for biomarker candidate discovery. Bruker’s UHR-Q-TOFs have the capacity to deal with very complex mixtures of intact proteins with no resolution loss, accuracy or dynamic range making them particularly suited to this task.
The complex mixtures of intact proteins in top down proteomics represent a significant challenge for many mass spectrometers. This has been somewhat overcome by the use of extensive pre-fractionation before MS analysis. Despite its effectiveness, pre-fractionation leads to issues with reproducibility when comparing large sample cohorts. Bruker’s UHR-Q-TOF systems deliver highly reproducible and accurate information from complex mixtures of proteoforms, and require less pre-fractionation of the sample resulting in improved reproducibility and making them compatible with the large sample cohorts that are required for clinical research.
