Another challenge the field faces is deciding when to use database searching versus de novo sequencing methods, or perhaps some combination thereof. Principled methods for estimating what proportion of spectra in a given dataset are foreign would be helpful. We also need to better characterize the tradeoff inherent in increasing the size of the protein database, between potentially reducing the proportion of foreign spectra versus losing some detections due to (implicit) multiple testing correction. More generally, a principled method for FDR control that could take into account database search and de novo analysis of a single dataset would be very beneficial to the field.