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Roche's AVENIO ctDNA analysis kits and bioinformatics analysis (the AVENIO system) are accessible to all NGS laboratories. We have developed an approach, namely the Sec-Seq system, and compared the accuracy, sensitivity, repeatability and economic cost between the AVENIO system and the Sec-Seq system. Both methods share the comparable accuracy and sensitivity in detecting the variant allele frequency of 0.0005, while the Sec-Seq system shows better accuracy in detecting the variant allele frequency of 0.001. Furthermore, the Sec-Seq system displays a much better detection sensitivity than the AVENIO system. The Sec-Seq system has satisfactory performance in detecting the rare genetic variants in ctDNA with lower economic cost compared with the AVENIO system.