Fig. 1.

Model for inferring stoichiometries among proteoforms and paralogous proteins independently from peptide-specific biases. A, One shared (X₂) and three unique (X₁, X₃, and X₄) peptides of H3 proteoforms illustrate a very simple case of HIquant. HIquant models the peptide levels measured across conditions (x) as a supposition of the protein levels (p), scaled by unknown peptide-specific biases/nuisances (z). These coupled equations can be written in a matrix form whose solution infers the methylation stoichiometry independently from the nuisances (z). B, The general form of the model for K proteoforms (or homologous proteins) with M peptides quantified across N conditions can be formulated and solved. In many, albeit not all, cases an optimal and unique solution can be found, even in the absence of unique peptides; see supplemental Fig. S1 and Supplemental Information.