Patent ID: 11926821
Assignee: THE CHINESE UNIVERSITY OF HONG KONG
Field: Computer technology (Electrical engineering)
Classification: CPC C  G | IPC C  G

Claim 0:
1. A method of determining an extent of cfDNA damage in an individual, the method comprising:
receiving a first sample comprising a first set of double-stranded nucleic acid molecules derived from cell-free nucleic acid molecules in a biological sample obtained from the individual, wherein:
one or more double-stranded nucleic acid molecules of the first set of double-stranded nucleic acid molecules each have one or more defects, and
the one or more defects are present in the respective double-stranded nucleic acid molecule at a location at least one nucleotide away from a closest end of the respective double-stranded nucleic acid molecule;

receiving a second sample comprising a second set of double-stranded nucleic acid molecules derived from the cell-free nucleic acid molecules in the biological sample;
adding a first mixture comprising an enzyme to the first sample;
adding a second mixture to the second sample, wherein the second mixture excludes the enzyme;
repairing the one or more defects in each of the one or more double-stranded nucleic acid molecules of the first set of double-stranded nucleic acid molecules using the enzyme to produce a repaired first set of double-stranded nucleic acid molecules, wherein the second set of double-stranded nucleic acid molecules is unrepaired;
sequencing the repaired first set of double-stranded nucleic acid molecules to determine a first set of reads;
sequencing the second set of double-stranded nucleic acid molecules to determine a second set of reads;
determining, based at least on sizes of the first set of reads and the second set of reads, a value of a parameter characterizing a difference in defects between the repaired first set of double-stranded nucleic acid molecules and the second set of double-stranded nucleic acid molecules;
comparing the value of the parameter to a reference value, wherein the reference value is determined using one or more healthy subjects; and
determining an extent of cfDNA damage for the individual based on the comparison of the value of the parameter to the reference value.