Figure 1.

Schematic of the integrated top-down and bottom-up strategy. Protein mixtures are fractionated to a level at which their reduced complexity allows the inference of proteins from peptide-level characterization of the same fraction. Accurate intact protein mass and time measurements facilitate protein abundance profiling that incorporates protein modifications, as well as high-throughput selection of biologically relevant targets for subsequent offline gas-phase fragmentation using only an aliquot of the original fraction used for bottom-up analysis.