Detection of mutant alleles in gold standard positive and negative populations, using assays for EGFR L858R (A), EGFR exon 19 deletion (B), and KRAS G12C (C). Receiver operating characteristic (ROC) curves are also shown (D,E,F). By studying plasma from lung cancer patients with non-overlapping genotypes, a “reference range” for each assay can be identified. Dashed lines indicate one candidate threshold for positive with a very high specificity and acceptable sensitivity