A method for estimating abundance of a target nucleic acid present in a cell-free nucleic acid (CFNA) sample comprising the target nucleic acid and non-target nucleic acids, the method comprising: (a) quantifying copy number of the target nucleic acid in the CFNA sample to obtain an observed abundance of the target nucleic acid, wherein the target nucleic acid and the non-target nucleic acid in the CFNA sample are subjected to a ligation reaction; (b) generating a calibration scheme by correlating an observed abundance of a reference nucleic acid present in a CFNA standard to an expected abundance of the reference nucleic acid present in the CFNA standard, which CFNA standard comprises a plurality of genomic polynucleotides generated by contacting chromatin of nuclei isolated from cells to an endonuclease, individual members of the plurality having a 5' terminal end and a 3' terminal end, wherein: (i) at least a subset of the plurality of genomic polynucleotides of the CFNA standard have a length ranging from about 100-300 bases; (ii) a majority of the plurality of genomic polynucleotides of the CFNA standard have a phosphate group at a 5' terminal end and a hydroxyl group at a 3' terminal end, which majority of genomic polynucleotides are ligatable without generating a phosphate group at a 5' terminal end and/or generating a hydroxyl group at a 3' terminal end; and (iii) the plurality of genomic polynucleotides are subjected to a ligation reaction; and (c) estimating abundance of the target nucleic acid in the CFNA sample by adjusting the observed abundance of the target nucleic acid using the calibration scheme. (a) quantifying copy number of the target nucleic acid in the CFNA sample to obtain an observed abundance of the target nucleic acid, wherein the target nucleic acid and the non-target nucleic acid in the CFNA sample are subjected to a ligation reaction; (b) generating a calibration scheme by correlating an observed abundance of a reference nucleic acid present in a CFNA standard to an expected abundance of the reference nucleic acid present in the CFNA standard, which CFNA standard comprises a plurality of genomic polynucleotides generated by contacting chromatin of nuclei isolated from cells to an endonuclease, individual members of the plurality having a 5' terminal end and a 3' terminal end, wherein: (i) at least a subset of the plurality of genomic polynucleotides of the CFNA standard have a length ranging from about 100-300 bases; (ii) a majority of the plurality of genomic polynucleotides of the CFNA standard have a phosphate group at a 5' terminal end and a hydroxyl group at a 3' terminal end, which majority of genomic polynucleotides are ligatable without generating a phosphate group at a 5' terminal end and/or generating a hydroxyl group at a 3' terminal end; and (iii) the plurality of genomic polynucleotides are subjected to a ligation reaction; and (i) at least a subset of the plurality of genomic polynucleotides of the CFNA standard have a length ranging from about 100-300 bases; (ii) a majority of the plurality of genomic polynucleotides of the CFNA standard have a phosphate group at a 5' terminal end and a hydroxyl group at a 3' terminal end, which majority of genomic polynucleotides are ligatable without generating a phosphate group at a 5' terminal end and/or generating a hydroxyl group at a 3' terminal end; and (iii) the plurality of genomic polynucleotides are subjected to a ligation reaction; and (c) estimating abundance of the target nucleic acid in the CFNA sample by adjusting the observed abundance of the target nucleic acid using the calibration scheme.