The first data set was obtained from a cohort of 12 healthy individuals and 57 patients with pancreatic cancer. The variant detection results are summarized in the top-half of Table 1. In the samples from healthy individuals, 12 variants were detected (S3 Table). Although variants present in less than 1% of the reads do not affect the analysis in conventional NGS applications, such as whole genome or exome sequencing, they are a serious problem in the detection of ctDNA. In our case, 5 out of 12 healthy individuals were variant-positive (Table 1, top right). Therefore, direct use of variants identified by NOIR-SS is not appropriate for the diagnosis of pancreatic cancer. Therefore, we developed a filter to remove variants present in healthy individuals. To develop our variant filter, we used the first set of 12 healthy individuals and 57 patients with pancreatic cancer as “training data,” as is the norm when solving classification problems in the field of statistics.