A method of determining a density of a first epitope of a core histone at a genomic locus in chromatin of a cell, the method comprising: preparing a library of native nucleosomes from the chromatin, wherein the library comprises nucleosomes each comprising the core histone and a nucleosome nucleotide sequence indicative of the genomic locus and at least one nucleosome comprising the core histone having the first epitope; adding a standard to the library to create a doped library; wherein the standard comprises a reconstituted nucleosome comprising (i) a standard histone or standard histone fragment having the first epitope and (ii) a standard molecule comprising a double stranded polynucleotide having a standard nucleotide sequence linking to a barcode molecule comprising a barcode sequence, the barcode molecule being selected from the group consisting of a nucleotide barcode sequence molecule, a locked nucleic acid sequence and a DNA sequence; wherein the standard histone or standard histone fragment and the standard nucleotide sequence form a stable protein-DNA association; adding a first affinity reagent directed to the first epitope and selected from the group consisting of an antibody, a monobody, an aptamer, a Fab, and a binding peptide, to the doped library to capture an amount of native nucleosomes and standard comprising the first epitope; determining a relative genomic abundance for the first epitope by comparing the amount of a given nucleotide sequence associated with the captured native nucleosomes comprising the first epitope and the amount of a given nucleotide sequence associated with the native nucleosome in an input amount from the doped library; determining a standard capture efficiency for the first epitope by comparing the amount of a barcode sequence associated with the captured standard and the amount of a given nucleotide sequence associated with the standard in an input amount from the doped library; and determining the density of the first epitope of the core histone at the genomic locus by comparing the relative genomic abundance to the standard capture efficiency; wherein said first epitope is a post-translational modification or a protein isoform. preparing a library of native nucleosomes from the chromatin, wherein the library comprises nucleosomes each comprising the core histone and a nucleosome nucleotide sequence indicative of the genomic locus and at least one nucleosome comprising the core histone having the first epitope; adding a standard to the library to create a doped library; wherein the standard comprises a reconstituted nucleosome comprising (i) a standard histone or standard histone fragment having the first epitope and (ii) a standard molecule comprising a double stranded polynucleotide having a standard nucleotide sequence linking to a barcode molecule comprising a barcode sequence, the barcode molecule being selected from the group consisting of a nucleotide barcode sequence molecule, a locked nucleic acid sequence and a DNA sequence; wherein the standard histone or standard histone fragment and the standard nucleotide sequence form a stable protein-DNA association; (i) a standard histone or standard histone fragment having the first epitope and (ii) a standard molecule comprising a double stranded polynucleotide having a standard nucleotide sequence linking to a barcode molecule comprising a barcode sequence, the barcode molecule being selected from the group consisting of a nucleotide barcode sequence molecule, a locked nucleic acid sequence and a DNA sequence; wherein the standard histone or standard histone fragment and the standard nucleotide sequence form a stable protein-DNA association; adding a first affinity reagent directed to the first epitope and selected from the group consisting of an antibody, a monobody, an aptamer, a Fab, and a binding peptide, to the doped library to capture an amount of native nucleosomes and standard comprising the first epitope; determining a relative genomic abundance for the first epitope by comparing the amount of a given nucleotide sequence associated with the captured native nucleosomes comprising the first epitope and the amount of a given nucleotide sequence associated with the native nucleosome in an input amount from the doped library; determining a standard capture efficiency for the first epitope by comparing the amount of a barcode sequence associated with the captured standard and the amount of a given nucleotide sequence associated with the standard in an input amount from the doped library; and determining the density of the first epitope of the core histone at the genomic locus by comparing the relative genomic abundance to the standard capture efficiency; wherein said first epitope is a post-translational modification or a protein isoform.