METHODS AND SYSTEMS FOR REFINING COPY NUMBER VARIATION IN A LIQUID BIOPSY ASSAY

Methods, systems, and software are provided for validating a copy number variation in a test subject. A first dataset is obtained comprising bin-level sequence ratios, segment-level sequence ratios and segment-level measures of dispersion. Bins representing regions of a human reference genome are determined from sequencing cell-free nucleic acids in a liquid biopsy sample and reference samples. Segments encompass subsets of adjacent bins, where segment-level sequence ratios and measures of dispersion are determined using bin-level sequence ratios. A copy number status annotation for a segment is validated by applying the first dataset to a plurality of filters comprising a measure of central tendency bin-level sequence ratio filter, a confidence filter, and a measure of central tendency-plus-deviation bin-level sequence ratio filter. When a filter is fired, the copy number status annotation of the segment is rejected; and when no filter is fired, the copy number status annotation of the segment is validated.