One of the major goals of the Chromosome-centric Human Proteome Project (C-HPP) is to catalog and annotate myriads of heterogeneous proteoforms, produced by ca. 20 thousand genes. To achieve deeper and personalized dive into proteome we suggest to use customized RNA-seq library of potential proteoforms, which includes aberrant variants, specific to the certain biological sample. Multidimensional fractionation by means of two-dimensional electrophoresis and high-performance liquid chromatography, allowed us to downgrade the difficulty of biological mixture for the following shotgun mass spectrometry. To benchmark proposed pipeline we examined heterogeneity of the HepG2 hepatoblastome cell line proteome.