An alternative to standard sequence database searching and open modification searching that allows the identification of novel or unexpected peptides is de novo peptide sequencing. Rather than searching for peptides in a database, the peptide sequence is directly determined from the MS/MS spectrum . This provides some advantages in immunopeptidomics, where it is challenging to construct a complete database accounting for genetic variation, unannotated open reading frames, and the presence of pathogens. However, because spectra might not contain a complete fragmentation pattern, as well as the presence of noise peaks, de novo peptide sequencing is a challenging task .