The present invention provides a computer-implemented method for detecting
cell-
free DNA (cfDNA), such as circulating tumour
DNA, in
a DNA-containing sample obtained from a patient, the method comprising: (a) providing loci of interest comprising at least 2
mutation-containing loci representative of a tumour of the patient (“patient-specific loci”); (b) providing sequence data comprising sequence reads of a plurality of
polynucleotide fragments from
a DNA-containing sample from the patient, wherein said sequence reads span said at least 2
mutation-containing loci of step (a); (c) optionally, performing reads collapsing to group the sequence reads into read families; (d) calculating the
mutant allele fraction across some or all of said at least 2 patient-specific loci, optionally wherein the
mutant allele fraction is calculated by aggregating
mutant reads and total reads; (e) classifying the sample as containing or not containing the target cfDNA based on the calculated
mutant allele fraction. Also provided a related methods and systems.