Systems and methods for monitoring of cancer using minimal residual disease analysis

A method for detecting a presence or an absence of minimal residual disease (MRD) in a subject, comprising:

• (a) assaying deoxyribonucleic acid (DNA) molecules from a first biological sample obtained or derived from said subject at a first time point;
• (b) detecting a set of biomarkers from said DNA molecules based at least in part on said assaying of (a), wherein said set of biomarkers comprise differentially expressed markers or variants;
• (c) generating a plurality of probe nucleic acids that are customized for said subject, wherein said probe nucleic acids comprises sequences of at least a subset of said set of biomarkers;
• (d) using said plurality of probe nucleic acids, sequencing cell free deoxynucleic acids (cfDNA) from a second biological sample obtained or derived from said subject at a second time point to detect the presence or absence of said subset of said set of biomarkers, wherein said sequencing is performed at a depth of at least about 80×;
• (e) sequencing nucleic acids obtained or derived from said subject at least part by using whole genome sequencing to determine a copy number of at least one region of a genome of a subject;
• and
• (f) computer processing said subset of said set of biomarkers and said copy number of said at least one region of a genome to detect said presence or absence of minimal residual disease (MRD) in a subject.