Identifying peptides with unlimited post-translational modifications(PTMs)is a challenging task in the database searching based framework.The search space expands very fast with respect to the number of considered PTMs since the traditional database searching methods need to score all possible theoretical spectra with different PTM patterns.There are two approaches trying to address this problem.The first one uses the alignment-based algorithms to avoid enumerating all PTM patterns.Tools,such as MS-Alignment and MODa,use this approach.The second one compares each experimental spectrum with the theoretical spectra from the unmodified peptide sequences within a large precursor mass window.Tools,such as MSFragger and Open-pFind,use this approach.Although these tools use brilliant algorithms to achieve remarkable performance,there are still issues unaddressed.We proposed a PTM-invariant peptide identification(PIPI)concept in identifying peptides with unlimited PTMs.We transform the PTM-variant spectra and peptide sequences into PTM-invariant ones with a novel coding method.After such a transformation,we can perform a fast and simple database search just like there is no PTM but still get the correct results.Finally,we used data sets to demonstrate the power of our method.