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Various methods have been proposed for ctDNA detection, but low-allelic-fraction (AF) variants are still a great challenge. In addition, no panel-wide calling algorithm is available, which hiders the full usage of ctDNA based \u2018liquid biopsy\u2019. Thus, we developed the VBCALAVD (Virtual Barcode-based Calling Algorithm for Low Allelic Variant Detection) in silico to overcome these limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Based on the understanding of the nature of ctDNA fragmentation, a novel platform-independent virtual barcode strategy was established to eliminate random sequencing errors by clustering sequencing reads into virtual families. Stereotypical mutant-family-level background artifacts were polished by constructing AF distributions. Three additional robust fine-tuning filters were obtained to eliminate stochastic mutant-family-level noises. The performance of our algorithm was validated using cell-free DNA reference standard samples (cfDNA RSDs) and normal healthy cfDNA samples (cfDNA controls). For the RSDs with AFs of 0.1, 0.2, 0.5, 1 and 5%, the mean F1 scores were 0.43 (0.25~0.56), 0.77, 0.92, 0.926 (0.86~1.0) and 0.89 (0.75~1.0), respectively, which indicates that the proposed approach significantly outperforms the published algorithms. Among controls, no false positives were detected. Meanwhile, characteristics of mutant-family-level noise and quantitative determinants of divergence between mutant-family-level noises from controls and RSDs were clearly depicted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Due to its good performance in the detection of low-AF variants, our algorithm will greatly facilitate the noninvasive panel-wide detection of ctDNA in research and clinical settings. The whole pipeline is available at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/zhaodalv\/VBCALAVD\">https:\/\/github.com\/zhaodalv\/VBCALAVD<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12859-020-3412-2","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T06:07:53Z","timestamp":1585894073000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel virtual barcode strategy for accurate panel-wide variant calling in circulating tumor DNA"],"prefix":"10.1186","volume":"21","author":[{"given":"Leilei","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinfang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"3412_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/sj.bjc.6601894","volume":"91","author":"S Bamford","year":"2004","unstructured":"Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, et al. 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All cfDNA samples were obtained under the approval of the Medical Ethics Committee of Shanghai Pulmonary Hospital. The study was approved by Medical Ethics Committee of Shanghai Pulmonary Hospital.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This manuscript contains no individual person\u2019s data in any form.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests. ZX and CL are employed by Smartquerier Co., Ltd. The company would not gain or lose financially or non-financially through publication of this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"127"}}