Figure 3.

Top-down versus bottom-up proteomics. This schematic depicts a general description of the workflows for these two discovery approaches. While both rely on final MS analysis for identifications (not to oversimplify the analysis of intact proteoforms), the main differences lie in the up-front analytical approaches. Top-down resolves intact proteoforms prior to MS while bottom-up generally bypasses any initial separation technique. Thus, top-down provides proteoform information while bottom-up can only provide (limited) amino acid sequence information. Nonetheless, perhaps the most important point to immediately emphasize is the critical importance of high quality/high resolution MS to proteomics as an integrative discipline, now and into the future.