Systems and methods to detect rare mutations and copy number variation

Abstract

The present disclosure provides a method for monitoring residual disease in a subject. Generally, the method comprises determining a frequency of cancer mutations from a first sample obtained from a tumor biopsy from the subject; determining a frequency of the cancer mutations discovered in the first sample from a second sample comprising cell-free deoxyribonucleic acid (cfDNA) molecules that is obtained from the subject after the subject has undergone a course of treatment for cancer; and determining a presence or absence of cancer in the subject based on an analysis of the frequency of the cancer mutations from sequence data from the second sample, wherein adapters are ligated to at least 20% of the cfDNA molecules using more than a 10× molar excess of adapters relative to the cfDNA molecules in the population of cfDNA molecules.