First, we created a hypermethylated DIA assay library by DDA acquisitions of 6 SCX fractions from Gnmt -/- mouse livers. We supplemented this library with a DDA acquisition of a methyl-Lys immunoprecipitation from a hepatoma cell line derived from Gnmt -/- mice. This gave us an assay library of 808 methyl Arg and Lys peptides. We further supplemented the library with DDA acquisitions of a ‘one-pot’ acetyl-Lys and succinyl-Lys immunoaffinity enrichment of mitochondrial extract and whole liver lysate isolated from WT mouse liver which provided us with 2428­­ succinylated peptides and 2547 acetylated peptides. We then assayed whole liver cellular lysate from Mat1a -/- and Gnmt -/- and their WT littermates against this hypermethylated Arg and Lys peptide assay library acquired in both 4 Dalton and 12 Dalton precursor mass windows on the Orbitrap Fusion Lumos.