Patent ID: 11959134
Assignee: BIONANO GENOMICS, INC.
Field: Computer technology (Electrical engineering)
Classification: CPC C  G | IPC C  G

Claim 13:
14. A method of analyzing nucleic acid molecules without compromising strand phosphodiester bond integrity, comprising:
providing a plurality of nucleic acid molecules comprising a plurality of occurrences of a first DNA repeated motif and a second DNA repeated motif, wherein an input coverage is 50-fold or less, wherein the first DNA repeated motif, the second DNA repeated motif, or both have an average repeat frequency of about 5 sites to about 35 sites per 100 Kb in the plurality of nucleic acid molecules;
covalently labeling the plurality of nucleic acid molecules in a sequence-specific and CpG-methylation-insensitive fashion at the first DNA repeated motif with a first label, wherein the first DNA repeated motif comprises a first methyltransferase recognition sequence and the covalent labeling is effected with a CpG-methylation-insensitive methyltransferase in the presence of a first modified cofactor,
covalently labeling the plurality of nucleic acid molecules in a sequence-specific and CpG-methylation-dependent fashion at the second DNA repeated motif with a second label, wherein the second DNA repeated motif comprises a second methyltransferase recognition sequence and the covalent labeling is effected with a CpG-methylation-dependent methyltransferase in the presence of a second modified cofactor; and
detecting the first label and the second label to identify patterns of the first DNA repeated motif and the second DNA repeated motif of the plurality of nucleic acid molecules, respectively,
wherein the covalently labeled nucleic acid molecules have a length of at least 150 kb and the strand phosphodiester bonds of the plurality of nucleic acid molecules are intact.