Molecular response and progression detection from circulating cell free dna

A method of monitoring a cancer patient for cancer recurrence, the method comprising:

• A) obtaining, in electronic form, a first set of nucleic acid sequences from a methylation sequencing of a plurality of cell-free DNA fragments from a first liquid biopsy sample obtained from the cancer patient, wherein each respective nucleic acid sequence in the first set of nucleic acid sequences comprises a methylation pattern for a corresponding cell-free DNA fragment in the plurality of cell-free DNA fragments;
• B) mapping each respective nucleic acid sequence, in the first set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a first set of mapped nucleic acid sequences;
• C) determining, from the set of mapped nucleic acid sequences, a first set of nucleic acid sequence metrics that is a plurality of methylation metrics for the first liquid biopsy sample, wherein the plurality of methylation metrics comprises a plurality of bin-level methylation metrics, a plurality of fragment-level methylation metrics, or a plurality of CpG-level methylation metrics;
• D) making a minimal residual disease (MRD) status prediction for the cancer patient using the plurality of methylation metric;
• E) obtaining, in electronic form, a second set of nucleic acid sequences from a sequencing of a plurality of cell-free DNA fragments from a second liquid biopsy sample obtained from the cancer patient;
• F) mapping each respective nucleic acid sequence, in the second set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a second set of mapped nucleic acid sequences;
• G) determining, from the second set of mapped nucleic acid sequences, a second set of nucleic acid sequence metrics that comprises a single nucleotide variation (SNV) or insertion/deletion (INDEL) status at each locus in a plurality of loci;
• and
• H) characterizing a cancer status of the cancer patient using the second set of nucleic acid sequence metrics.

A computer system, comprising one or more processors and memory, the memory storing instructions for performing a method of monitoring a cancer patient for cancer recurrence, the method comprising:

• A) obtaining, in electronic form, a first set of nucleic acid sequences from a methylation sequencing of a plurality of cell-free DNA fragments from a first liquid biopsy sample obtained from the cancer patient, wherein each respective nucleic acid sequence in the first set of nucleic acid sequences comprises a methylation pattern for a corresponding cell-free DNA fragment in the plurality of cell-free DNA fragments;
• B) mapping each respective nucleic acid sequence, in the first set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a first set of mapped nucleic acid sequences;
• C) determining, from the set of mapped nucleic acid sequences, a first set of nucleic acid sequence metrics that is a plurality of methylation metrics for the first liquid biopsy sample, wherein the plurality of methylation metrics comprises a plurality of bin-level methylation metrics, a plurality of fragment-level methylation metrics, or a plurality of CpG-level methylation metrics;
• D) making a minimal residual disease (MRD) status prediction for the cancer patient using the plurality of methylation metric;
• E) obtaining, in electronic form, a second set of nucleic acid sequences from a sequencing of a plurality of cell-free DNA fragments from a second liquid biopsy sample obtained from the cancer patient;
• F) mapping each respective nucleic acid sequence, in the second set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a second set of mapped nucleic acid sequences;
• G) determining, from the second set of mapped nucleic acid sequences, a second set of nucleic acid sequence metrics that comprises a single nucleotide variation (SNV) or insertion/deletion (INDEL) status at each locus in a plurality of loci;
• and
• H) characterizing a cancer status of the cancer patient using the second set of nucleic acid sequence metrics.

A non-transitory computer-readable medium storing one or more computer programs, executable by a computer, for making a minimal residual disease (MRD) status prediction for a cancer patient, the computer comprising one or more processors and a memory, the one or more computer programs collectively encoding computer executable instructions that perform a method comprising:

• A) obtaining, in electronic form, a first set of nucleic acid sequences from a methylation sequencing of a plurality of cell-free DNA fragments from a first liquid biopsy sample obtained from the cancer patient, wherein each respective nucleic acid sequence in the first set of nucleic acid sequences comprises a methylation pattern for a corresponding cell-free DNA fragment in the plurality of cell-free DNA fragments;
• B) mapping each respective nucleic acid sequence, in the first set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a first set of mapped nucleic acid sequences;
• C) determining, from the set of mapped nucleic acid sequences, a first set of nucleic acid sequence metrics that is a plurality of methylation metrics for the first liquid biopsy sample, wherein the plurality of methylation metrics comprises a plurality of bin-level methylation metrics, a plurality of fragment-level methylation metrics, or a plurality of CpG-level methylation metrics;
• D) making a minimal residual disease (MRD) status prediction for the cancer patient using the plurality of methylation metric;
• E) obtaining, in electronic form, a second set of nucleic acid sequences from a sequencing of a plurality of cell-free DNA fragments from a second liquid biopsy sample obtained from the cancer patient;
• F) mapping each respective nucleic acid sequence, in the second set of nucleic acid sequences, to a location in a reference construct for the genome of the species of the cancer patient, thereby obtaining a second set of mapped nucleic acid sequences;
• G) determining, from the second set of mapped nucleic acid sequences, a second set of nucleic acid sequence metrics that comprises a single nucleotide variation (SNV) or insertion/deletion (INDEL) status at each locus in a plurality of loci;
• and
• H) characterizing a cancer status of the cancer patient using the second set of nucleic acid sequence metrics.