This project developed a proteomic methodology that deepens the detectable and quantifiable proteome from limited proteomes where abundant proteins pose interference. As proof-of-principle, this study used Xenopus laevis, where ~90% of the proteome is dominated by abundant yolk proteins in the early developing embryo. We pooled Xenopus embryos and depleted the proteome to ~30% yolk protein content to prepare a carrier proteome. This yolk-depleted carrier proteome digest was spiked into isobarically tagged proteome digests that were prepared from limited tissues and cells isolated by fluorescence-activated cell sorting (FACS). The resulting samples were analyzed using liquid chromatography (LC) high resolution mass spectrometry (HRMS). We demonstrated that the yolk depleted carrier dilutes abundant yolk peptides and boosts the overall depth of proteome coverage, including many biologically important non-yolk proteins present in low abundance.