Methods for computer processing sequence reads to detect molecular residual disease

A method for detecting molecular residual disease in a subject, the method comprising:

• (a) obtaining a plurality of cell-free deoxyribonucleic acid (cfDNA) molecules obtained or derived from the subject to generate amplified cfDNA molecules;
• (b) enriching a plurality of the cfDNA molecules for a sequencing panel of no more than twenty genomic regions to generate an enriched set of cfDNA molecules, wherein the sequencing panel of no more than twenty genomic regions is selected using information derived from a cancer tumor biopsy of the subject;
• (c) sequencing a plurality of the enriched set of amplified cfDNA molecules at a sequence read depth of at least about fifty thousand sequence reads per base to generate sequence reads;
• (d) computer processing a plurality of the sequence reads at least in part by aligning a plurality of the sequence reads to a reference genome to generate aligned sequence reads;
• (e) computer processing a plurality of the aligned sequence reads to detect a variant, thereby determining the molecular residual disease in the subject.