{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:52:29Z","timestamp":1792666349821,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"crossref","award":["21ZR1458200"],"award-info":[{"award-number":["21ZR1458200"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015640","name":"Tongji Hospital","doi-asserted-by":"publisher","award":["2021"],"award-info":[{"award-number":["2021"]}],"id":[{"id":"10.13039\/501100015640","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015640","name":"Tongji Hospital","doi-asserted-by":"publisher","award":["ITJ(ZD)2104"],"award-info":[{"award-number":["ITJ(ZD)2104"]}],"id":[{"id":"10.13039\/501100015640","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["NCI P50CA121974"],"award-info":[{"award-number":["NCI P50CA121974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2024,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 \u00d7 10\n                    <jats:sup>\u22127<\/jats:sup>\n                    , which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents.\n                  <\/jats:p>","DOI":"10.1038\/s44321-024-00115-0","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T05:02:28Z","timestamp":1724130148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9586-327X","authenticated-orcid":false,"given":"Xinxing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Bacchiocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-3813","authenticated-orcid":false,"given":"Wen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Wittkop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-3813","authenticated-orcid":false,"given":"Fernando L","family":"Mendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6662-4321","authenticated-orcid":false,"given":"Yingyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-9994","authenticated-orcid":false,"given":"Qianqian","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus W","family":"Bosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Sznol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-453X","authenticated-orcid":false,"given":"Qin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Faham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6080-7488","authenticated-orcid":false,"given":"Li","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-1964","authenticated-orcid":false,"given":"Ruth","family":"Halaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0430-2834","authenticated-orcid":false,"given":"Hai","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-6280","authenticated-orcid":false,"given":"Zhiqian","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"115_CR1","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature22364","volume":"545","author":"C Abbosh","year":"2017","unstructured":"Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R et al (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545:446\u2013451","journal-title":"Nature"},{"key":"115_CR2","doi-asserted-by":"publisher","unstructured":"Alexandre Pellan C, Adam JW, Anushri A, Itai R, William FH, Rebecca M, Daniel H, Theophile L, Giorgio I, Soren G et al (2022) Whole genome error-corrected sequencing for sensitive circulating tumor DNA cancer monitoring. Preprint at https:\/\/doi.org\/10.1101\/2022.11.17.516904","DOI":"10.1101\/2022.11.17.516904"},{"key":"115_CR3","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Tian Ng AW, Wu Y, Boot A, Covington KR, Gordenin DA, Bergstrom EN et al (2020) The repertoire of mutational signatures in human cancer. Nature 578:94\u2013101","journal-title":"Nature"},{"key":"115_CR4","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/s41588-023-01376-0","volume":"55","author":"JH Bae","year":"2023","unstructured":"Bae JH, Liu R, Roberts E, Nguyen E, Tabrizi S, Rhoades J, Blewett T, Xiong K, Gydush G, Shea D et al (2023) Single duplex DNA sequencing with CODEC detects mutations with high sensitivity. Nat Genet 55:871\u2013879","journal-title":"Nat Genet"},{"key":"115_CR5","doi-asserted-by":"publisher","first-page":"329","DOI":"10.6004\/jnccn.2021.0012","volume":"19","author":"AB Benson","year":"2021","unstructured":"Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Farkas L et al (2021) Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 19:329\u2013359","journal-title":"J Natl Compr Canc Netw"},{"key":"115_CR6","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/s43018-020-0096-5","volume":"1","author":"SV Bratman","year":"2020","unstructured":"Bratman SV, Yang SYC, Iafolla MAJ, Liu Z, Hansen AR, Bedard PL, Lheureux S, Spreafico A, Razak AA, Shchegrova S et al (2020) Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer 1:873\u2013881","journal-title":"Nat Cancer"},{"key":"115_CR7","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1038\/s41588-023-01446-3","volume":"55","author":"DC Bruhm","year":"2023","unstructured":"Bruhm DC, Mathios D, Foda ZH, Annapragada AV, Medina JE, Adleff V, Chiao EJ, Ferreira L, Cristiano S, White JR et al (2023) Single-molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer. Nat Genet 55:1301\u20131310","journal-title":"Nat Genet"},{"key":"115_CR8","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nature10166","volume":"474","author":"N Cancer Genome Atlas Research","year":"2011","unstructured":"Cancer Genome Atlas Research N (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609\u2013615","journal-title":"Nature"},{"key":"115_CR9","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/S0140-6736(21)01206-X","volume":"398","author":"MS Carlino","year":"2021","unstructured":"Carlino MS, Larkin J, Long GV (2021) Immune checkpoint inhibitors in melanoma. Lancet 398:1002\u20131014","journal-title":"Lancet"},{"key":"115_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2","volume":"9","author":"ZR Chalmers","year":"2017","unstructured":"Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, Schrock A, Campbell B, Shlien A, Chmielecki J et al (2017) Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34","journal-title":"Genome Med"},{"key":"115_CR11","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1158\/2159-8290.CD-17-0716","volume":"7","author":"AA Chaudhuri","year":"2017","unstructured":"Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, Khodadoust MS, Esfahani MS, Liu CL, Zhou L et al (2017) Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov 7:1394\u20131403","journal-title":"Cancer Discov"},{"key":"115_CR12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13045-021-01089-z","volume":"14","author":"G Chen","year":"2021","unstructured":"Chen G, Peng J, Xiao Q, Wu H-X, Wu X, Wang F, Li L, Ding P, Zhao Q, Li Y et al (2021) Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. J Hematol Oncol 14:80","journal-title":"J Hematol Oncol"},{"key":"115_CR13","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1214\/aoms\/1177728725","volume":"25","author":"H Chernoff","year":"1954","unstructured":"Chernoff H (1954) On the distribution of the likelihood ratio. Ann Math Statist 25:573\u2013578","journal-title":"Ann Math Statist"},{"key":"115_CR14","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1038\/s41587-021-00900-z","volume":"39","author":"JD Cohen","year":"2021","unstructured":"Cohen JD, Douville C, Dudley JC, Mog BJ, Popoli M, Ptak J, Dobbyn L, Silliman N, Schaefer J, Tie J et al (2021) Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands. Nat Biotechnol 39:1220\u20131227","journal-title":"Nat Biotechnol"},{"key":"115_CR15","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.1158\/1078-0432.CCR-18-3663","volume":"25","author":"RC Coombes","year":"2019","unstructured":"Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, Ali S, Cleator S, Kenny L, Stebbing J et al (2019) Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res 25:4255\u20134263","journal-title":"Clin Cancer Res"},{"key":"115_CR16","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/s41586-019-1272-6","volume":"570","author":"S Cristiano","year":"2019","unstructured":"Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, Jensen SO, Medina JE, Hruban C, White JR et al (2019) Genome-wide cell-free DNA fragmentation in patients with cancer. Nature 570:385\u2013389","journal-title":"Nature"},{"key":"115_CR17","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nbt.3820","volume":"35","author":"P Di Tommaso","year":"2017","unstructured":"Di Tommaso P, Chatzou M, Floden EW, Barja PP, Palumbo E, Notredame C (2017) Nextflow enables reproducible computational workflows. Nat Biotechnol 35:316\u2013319","journal-title":"Nat Biotechnol"},{"key":"115_CR18","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.annonc.2022.02.007","volume":"33","author":"D Gale","year":"2022","unstructured":"Gale D, Heider K, Ruiz-Valdepenas A, Hackinger S, Perry M, Marsico G, Rundell V, Wulff J, Sharma G, Knock H et al (2022) Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer. Ann Oncol 33:500\u2013510","journal-title":"Ann Oncol"},{"key":"115_CR19","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13045-022-01342-z","volume":"15","author":"A Hallermayr","year":"2022","unstructured":"Hallermayr A, Wohlfrom T, Steinke-Lange V, Benet-Pages A, Scharf F, Heitzer E, Mansmann U, Haberl C, de Wit M, Vogelsang H et al (2022) Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients. J Hematol Oncol 15:125","journal-title":"J Hematol Oncol"},{"key":"115_CR20","doi-asserted-by":"publisher","first-page":"5364","DOI":"10.3390\/cancers13215364","volume":"13","author":"N Honore","year":"2021","unstructured":"Honore N, Galot R, van Marcke C, Limaye N, Machiels JP (2021) Liquid biopsy to detect minimal residual disease: methodology and impact. Cancers 13:5364","journal-title":"Cancers"},{"key":"115_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2906","volume":"13","author":"M Ignatiadis","year":"2011","unstructured":"Ignatiadis M, Reinholz M (2011) Minimal residual disease and circulating tumor cells in breast cancer. Breast Cancer Res 13:222","journal-title":"Breast Cancer Res"},{"key":"115_CR22","unstructured":"Illumina (2023) Sequencing accuracy with unique molecular identifiers. https:\/\/www.illumina.com\/techniques\/sequencing\/ngs-library-prep\/multiplexing\/unique-molecular-identifiers.html"},{"key":"115_CR24","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1016\/j.ccell.2022.10.022","volume":"40","author":"A Jamshidi","year":"2022","unstructured":"Jamshidi A, Liu MC, Klein EA, Venn O, Hubbell E, Beausang JF, Gross S, Melton C, Fields AP, Liu Q et al (2022) Evaluation of cell-free DNA approaches for multi-cancer early detection. Cancer Cell 40:1537\u20131549.e1512","journal-title":"Cancer Cell"},{"key":"115_CR25","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434\u2013443","journal-title":"Nature"},{"key":"115_CR26","doi-asserted-by":"publisher","first-page":"9530","DOI":"10.1073\/pnas.1105422108","volume":"108","author":"I Kinde","year":"2011","unstructured":"Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B (2011) Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci USA 108:9530\u20139535","journal-title":"Proc Natl Acad Sci USA"},{"key":"115_CR27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41591-022-02115-4","volume":"29","author":"D Kotani","year":"2023","unstructured":"Kotani D, Oki E, Nakamura Y, Yukami H, Mishima S, Bando H, Shirasu H, Yamazaki K, Watanabe J, Kotaka M et al (2023) Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med 29:127\u2013134","journal-title":"Nat Med"},{"key":"115_CR28","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1038\/s41587-021-00981-w","volume":"39","author":"DM Kurtz","year":"2021","unstructured":"Kurtz DM, Soo J, Co Ting Keh L, Alig S, Chabon JJ, Sworder BJ, Schultz A, Jin MC, Scherer F, Garofalo A et al (2021) Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat Biotechnol 39:1537\u20131547","journal-title":"Nat Biotechnol"},{"key":"115_CR29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nature12213","volume":"499","author":"MS Lawrence","year":"2013","unstructured":"Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214\u2013218","journal-title":"Nature"},{"key":"115_CR30","unstructured":"Li H (2013) Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at https:\/\/arxiv.org\/abs\/1303.3997"},{"key":"115_CR31","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.1097\/CM9.0000000000001097","volume":"133","author":"RY Li","year":"2020","unstructured":"Li RY, Liang ZY (2020) Circulating tumor DNA in lung cancer: real-time monitoring of disease evolution and treatment response. Chin Med J 133:2476\u20132485","journal-title":"Chin Med J"},{"key":"115_CR32","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1158\/1078-0432.CCR-21-1242","volume":"28","author":"S Li","year":"2022","unstructured":"Li S, Zeng W, Ni X, Zhou Y, Stackpole ML, Noor ZS, Yuan Z, Neal A, Memarzadeh S, Garon EB et al (2022) cfTrack: a method of exome-wide mutation analysis of cell-free DNA to simultaneously monitor the full spectrum of cancer treatment outcomes including MRD, recurrence, and evolution. Clin Cancer Res 28:1841\u20131853","journal-title":"Clin Cancer Res"},{"key":"115_CR33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40425-014-0042-0","volume":"2","author":"EJ Lipson","year":"2014","unstructured":"Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, Diaz Jr LA (2014) Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunother Cancer 2:42","journal-title":"J Immunother Cancer"},{"key":"115_CR34","doi-asserted-by":"crossref","unstructured":"Liu MH, Costa BM, Bianchini EC, Choi U, Bandler RC, Lassen E, Gro\u0144ska-P\u0119ski M, Schwing A, Murphy ZR, Rosenkj\u00e6r D et al (2024) DNA mismatch and damage patterns revealed by single-molecule DNA sequencing. Nature 630:752\u2013761","DOI":"10.1038\/s41586-024-07532-8"},{"key":"115_CR35","doi-asserted-by":"publisher","first-page":"eaax7392","DOI":"10.1126\/scitranslmed.aax7392","volume":"11","author":"BR McDonald","year":"2019","unstructured":"McDonald BR, Contente-Cuomo T, Sammut SJ, Odenheimer-Bergman A, Ernst B, Perdigones N, Chin SF, Farooq M, Mejia R, Cronin PA et al (2019) Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer. Sci Transl Med 11:eaax7392","journal-title":"Sci Transl Med"},{"key":"115_CR36","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s43018-019-0011-0","volume":"1","author":"EJ Moding","year":"2020","unstructured":"Moding EJ, Liu Y, Nabet BY, Chabon JJ, Chaudhuri AA, Hui AB, Bonilla RF, Ko RB, Yoo CH, Gojenola L et al (2020) Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small cell lung cancer. Nat Cancer 1:176\u2013183","journal-title":"Nat Cancer"},{"key":"115_CR23","doi-asserted-by":"crossref","unstructured":"Nordentoft I, Lindskrog SV, Birkenkamp-Demtr\u00f6der K, Gonzalez S, Kuzman M, Levatic J, Glavas D, Ptashkin R, Smadbeck J, Afterman D et al (2024) Whole-genome mutational analysis for tumor-informed detection of circulating tumor dna in patients with urothelial carcinoma. Eur Urol S0302\u20132838(24)02384-4","DOI":"10.1016\/j.eururo.2024.05.014"},{"key":"115_CR37","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrclinonc.2017.53","volume":"14","author":"K Pantel","year":"2017","unstructured":"Pantel K, Alix-Panabieres C (2017) Tumour microenvironment: informing on minimal residual disease in solid tumours. Nat Rev Clin Oncol 14:325\u2013326","journal-title":"Nat Rev Clin Oncol"},{"key":"115_CR38","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41571-019-0187-3","volume":"16","author":"K Pantel","year":"2019","unstructured":"Pantel K, Alix-Panabieres C (2019) Liquid biopsy and minimal residual disease\u2014latest advances and implications for cure. Nat Rev Clin Oncol 16:409\u2013424","journal-title":"Nat Rev Clin Oncol"},{"key":"115_CR39","doi-asserted-by":"publisher","first-page":"5586","DOI":"10.1158\/1078-0432.CCR-21-0410","volume":"27","author":"AR Parikh","year":"2021","unstructured":"Parikh AR, Van Seventer EE, Siravegna G, Hartwig AV, Jaimovich A, He Y, Kanter K, Fish MG, Fosbenner KD, Miao B et al (2021) Minimal residual disease detection using a plasma-only circulating tumor DNA assay in patients with colorectal cancer. Clin Cancer Res 27:5586\u20135594","journal-title":"Clin Cancer Res"},{"key":"115_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27022-z","volume":"12","author":"B Qiu","year":"2021","unstructured":"Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, Chen X, Bao H, Xu Y, Shao Y et al (2021) Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun 12:6770","journal-title":"Nat Commun"},{"key":"115_CR41","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1038\/s41591-019-0652-7","volume":"25","author":"P Razavi","year":"2019","unstructured":"Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, Abida W, Juluru K, De Bruijn I, Hou C et al (2019) High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med 25:1928\u20131937","journal-title":"Nat Med"},{"key":"115_CR42","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1001\/jamaoncol.2019.0528","volume":"5","author":"T Reinert","year":"2019","unstructured":"Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS et al (2019) Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol 5:1124\u20131131","journal-title":"JAMA Oncol"},{"key":"115_CR43","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1093\/bioinformatics\/bts271","volume":"28","author":"CT Saunders","year":"2012","unstructured":"Saunders CT, Wong WS, Swamy S, Becq J, Murray LJ, Cheetham RK (2012) Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28:1811\u20131817","journal-title":"Bioinformatics"},{"key":"115_CR44","doi-asserted-by":"publisher","first-page":"e006284","DOI":"10.1136\/jitc-2022-006284","volume":"11","author":"NP Semenkovich","year":"2023","unstructured":"Semenkovich NP, Szymanski JJ, Earland N, Chauhan PS, Pellini B, Chaudhuri AA (2023) Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA. J Immunother Cancer 11:e006284","journal-title":"J Immunother Cancer"},{"key":"115_CR45","doi-asserted-by":"publisher","first-page":"5114","DOI":"10.1158\/1538-7445.AM2022-5114","volume":"82","author":"AC Tan","year":"2022","unstructured":"Tan AC, Saw SP, Lai GG, Chua KL, Takano A, Ong B-H, Koh TP, Jain A, Tan WL, Ng QS et al (2022) Abstract 5114: ultra-sensitive detection of minimal residual disease (MRD) through whole genome sequencing (WGS) using an AI-based error suppression model in resected early-stage non-small cell lung cancer (NSCLC). Cancer Res 82:5114\u20135114","journal-title":"Cancer Res"},{"key":"115_CR46","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1093\/annonc\/mdz390","volume":"30","author":"N Tarazona","year":"2019","unstructured":"Tarazona N, Gimeno-Valiente F, Gambardella V, Zuniga S, Rentero-Garrido P, Huerta M, Rosello S, Martinez-Ciarpaglini C, Carbonell-Asins JA, Carrasco F et al (2019) Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer. Ann Oncol 30:1804\u20131812","journal-title":"Ann Oncol"},{"key":"115_CR47","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1515\/cclm-2023-0541","volume":"62","author":"F Wang","year":"2023","unstructured":"Wang F, Li X, Li M, Liu W, Lu L, Li Y, Chen X, Yang S, Liu T, Cheng W et al (2023) Ultra-short cell-free DNA fragments enhance cancer early detection in a multi-analyte blood test combining mutation, protein and fragmentomics. Clin Chem Lab Med 62:168\u2013177","journal-title":"Clin Chem Lab Med"},{"key":"115_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.201900357","volume":"4","author":"L Wang","year":"2020","unstructured":"Wang L, Hu X, Guo Q, Huang X, Lin C-H, Chen X, Li M, Yao Q, Zhou Q, Wang J et al (2020) CLAmp-seq: a novel amplicon-based NGS assay with concatemer error correction for improved detection of actionable mutations in plasma cfDNA from patients with NSCLC. Small Methods 4:1900357","journal-title":"Small Methods"},{"key":"115_CR49","doi-asserted-by":"publisher","first-page":"e87","DOI":"10.1093\/nar\/gkz474","volume":"47","author":"TT Wang","year":"2019","unstructured":"Wang TT, Abelson S, Zou J, Li T, Zhao Z, Dick JE, Shlush LI, Pugh TJ, Bratman SV (2019) High efficiency error suppression for accurate detection of low-frequency variants. Nucleic Acids Res 47:e87","journal-title":"Nucleic Acids Res"},{"key":"115_CR50","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1200\/JCO.21.02229","volume":"40","author":"JD Wolchok","year":"2022","unstructured":"Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R et al (2022) Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol 40:127\u2013137","journal-title":"J Clin Oncol"},{"key":"115_CR51","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.7150\/thno.16558","volume":"7","author":"T Xu","year":"2017","unstructured":"Xu T, Kang X, You X, Dai L, Tian D, Yan W, Yang Y, Xiong H, Liang Z, Zhao GQ et al (2017) Cross-platform comparison of four leading technologies for detecting EGFR mutations in circulating tumor DNA from non-small cell lung carcinoma patient plasma. Theranostics 7:1437\u20131446","journal-title":"Theranostics"},{"key":"115_CR52","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/hep.32308","volume":"76","author":"X Zhang","year":"2022","unstructured":"Zhang X, Wang Z, Tang W, Wang X, Liu R, Bao H, Chen X, Wei Y, Wu S, Bao H et al (2022) Ultrasensitive and affordable assay for early detection of primary liver cancer using plasma cell-free DNA fragmentomics. Hepatology 76:317\u2013329","journal-title":"Hepatology"},{"issue":"6","key":"115_CR53","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s40291-023-00670-1","volume":"27","author":"J Zhao","year":"2023","unstructured":"Zhao J, Reuther J, Scozzaro K, Hawley M, Metzger E, Emery M, Chen I, Barbosa M, Johnson L, O\u2019Connor A et al (2023) Personalized cancer monitoring assay for the detection of ctDNA in patients with solid tumors. Mol Diagn Ther 27(6):753\u2013768","journal-title":"Mol Diagn Ther"},{"key":"115_CR54","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/s41591-020-0915-3","volume":"26","author":"A Zviran","year":"2020","unstructured":"Zviran A, Schulman RC, Shah M, Hill STK, Deochand S, Khamnei CC, Maloney D, Patel K, Liao W, Widman AJ et al (2020) Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Nat Med 26:1114\u20131124","journal-title":"Nat Med"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44321-024-00115-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/s44321-024-00115-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44321-024-00115-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T14:32:46Z","timestamp":1786026766000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/s44321-024-00115-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9,12]]}},"alternative-id":["115"],"URL":"https:\/\/doi.org\/10.1038\/s44321-024-00115-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.13.24301070","asserted-by":"object"}]},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"assertion":[{"value":"22 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"QQY is an employee of Shanghai YunSheng Medical Laboratory Co., Ltd. LW, PT, FM, YYW, TW, and MF are employees or consultant of AccuraGen Inc. QY received research funding and speaker fee from AstraZeneca and is a Scientific Advisory Board member of AccuraGen, Inc. MWB received research funding from AstraZeneca. MS disclosed the following: stock options: Actym, Adaptive Biotechnologies, Amphivena, Asher, Evolveimmune, Intensity, Nextcure, Normunity, Oncohost, Thetis; Stock: Johnson and Johnson, Glaxo-Smith Kline; consulting fees: Adagene, Adaptimmune, Agenus, Alkermes, Alligator, Anaptys, Asher, Astra Zeneca, Biond, Biontech, Boston Pharmaceuticals, Bristol-Myers, Dragonfly, Evaxion, Evolveimmune, Genentech-Roche, Gilead, Glaxo Smith Kline, Ichnos, Idera, Immunocore, Incyte, Innate pharma, Iovance, iTEOS, Jazz Pharmaceuticals, Kadmon-Sanofi, Kanaph, Merck, Molecular Partners, Nextcure, Nimbus, Normunity, Numab, Ocellaris-Lilly, Oncohost, Ontario Institute for Cancer Research, Partner Therapeutics, Pfizer, Pierre-Fabre, PIO Therapeutics, Pliant, Regeneron, Rootpath, Rubius, Sapience, Simcha, Stcube, Sumitomo, Targovax, Teva, Turnstone, Verastem, Xilio, all these companies are unrelated to this study. Other authors have no conflict of interest to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"12"}}