We next compared the scans that yielded unambiguous PrSMs from each deconvolution tool. In total, 2160 scans across the six files yielded a PrSM with every algorithm (Figure ). From these unambiguous PrSMs, we compared the proteoforms identified using a strict definition of matching that required the same charge in the same scan on the same proteoform, defined as having the same sequence with the same set of post-translational modifications (PTMs) on the same specific residues. Of the 2160 scans that produced PrSMs in all three searches, 1754 (81%) produced the same proteoform identification (Figure ), showing remarkable agreement. If we allowed less strict matching criteria where the PTMs could vary, 2015 (93%) common PrSMs were found (Figure ). However, as previously observed, there is still significant variability from each deconvolution tool because only about half of the unique scans that yielded PrSMs in a particular search were shared between all three (Figure ). To further characterize the performance of the three algorithms in a search context, we dug deeper into the cases where all three tools (IsoDec 8-bin, FLASHDeconv, and TopFD) produced the same proteoform identification. The sequence coverage and percentage of fragments matched were computed for each matched PrSM (see SM9), and the difference in these two parameters between IsoDec 8-bin and both FLASHDeconv and TopFD were calculated. IsoDec produced approximately 10% greater sequence coverage than FLASHDeconv and TopFD (Figure ), but FLASHDeconv had a higher percentage of fragments matched (Figure ). Manually inspecting three representative MS2 spectra revealed that this decrease in fragments matched with IsoDec is likely due to the detection of more low-abundance clusters that are real but do not correspond to a terminal fragment that would be matched in a traditional search. Overall, as observed with the individual spectra, TopFD tends to assign more clusters with lower accuracy, FLASHDeconv tends to assign fewer clusters with higher accuracy, and IsoDec tends to fall in the middle, balancing depth of coverage with accuracy of assignment.