In mass spectrometry-based protein quantification, peptides that are shared across different protein sequences are often discarded as being uninformative with respect to each of the parent proteins. We investigate the use of shared peptides which are ubiquitous (∼50% of peptides) in mass spectrometric data-sets for accurate protein identification and quantification. Different from existing approaches, we show how shared peptides can help compute the relative amounts of the proteins that contain them. Also, proteins with no unique peptide in the sample can still be analyzed for relative abundance. Our article uses shared peptides in protein quantification and makes use of combinatorial optimization to reduce the error in relative abundance measurements. We describe the topological and numerical properties required for robust estimates, and use them to improve our estimates for ill-conditioned systems. Extensive simulations validate our approach even in the presence of experimental error. We apply our method to a model of Arabidopsis thaliana root knot nematode infection, and investigate the differential role of several protein family members in mediating host response to the pathogen. Supplementary Material is available at www.liebertonline.com/cmb.