Methods for enriching and sequencing nucleic acids for non- invasive cancer testing

A method of processing a nucleic acid sample useful for cancer monitoring, the method comprising:

• (a) isolating cell-free DNA (cfDNA) from a nucleic acid sample of a human subject;
• (b) generating a barcoded sequencing library by tagging the isolated cfDNA with a plurality of molecular barcodes and amplifying the tagged cfDNA;
• (c) selectively enriching the barcoded sequencing library using at least 500 different target-specific oligonucleotides that specifically hybridize to at least 500 different target loci in the barcoded sequencing library;
• and
• (d) sequencing the enriched barcoded sequencing library to generate sequence reads, and identifying from the sequence reads one or more genetic or epigenetic features associated with cancer.