{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:32:29Z","timestamp":1792150349075,"version":"4.4.0"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Slovenian Research and Innovation Agency","award":["P3-0054"],"award-info":[{"award-number":["P3-0054"]}]},{"name":"Slovenian Research and Innovation Agency","award":["P3-0054"],"award-info":[{"award-number":["P3-0054"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Differentiation between adenocarcinomas is sometimes challenging. The promising avenue for discovering new biomarkers lies in bioinformatics using DNA methylation analysis. Utilizing a 2853-sample identification dataset and a 782-sample independent verification dataset, we have identified diagnostic DNA methylation biomarkers that are hypermethylated in cancer and differentiate between breast invasive carcinoma, cholangiocarcinoma, colorectal cancer, hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma and stomach adenocarcinoma. The best panels for cancer type exhibit sensitivity of 77.8\u201395.9%, a specificity of 92.7\u201397.5% for tumors, a specificity of 91.5\u201397.7% for tumors and normal tissues and a diagnostic accuracy of 85.3\u201396.4%. We have shown that the results can be extended from the primary cancers to their liver metastases, as the best panels diagnose and differentiate between pancreatic adenocarcinoma liver metastases and breast invasive carcinoma liver metastases with a sensitivity and specificity of 83.3\u2013100% and a diagnostic accuracy of 86.8\u201391.9%. Moreover, the panels could detect hypermethylation of selected regions in the cell-free DNA of patients with liver metastases. At the same time, these were unmethylated in the cell-free DNA of healthy donors, confirming their applicability for liquid biopsies.<\/jats:p>","DOI":"10.1038\/s41598-024-53754-1","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:02:38Z","timestamp":1707285758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Discovery of novel DNA methylation biomarker panels for the diagnosis and differentiation between common adenocarcinomas and their liver metastases"],"prefix":"10.1038","volume":"14","author":[{"given":"Tina","family":"Dra\u0161kovi\u010d","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hauptman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"53754_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1055\/s-2006-939841","volume":"23","author":"A Ananthakrishnan","year":"2006","unstructured":"Ananthakrishnan, A., Gogineni, V. & Saeian, K. Epidemiology of primary and secondary liver cancers. Semin. Interv. Radiol. 23, 47\u201363. https:\/\/doi.org\/10.1055\/s-2006-939841 (2006).","journal-title":"Semin. Interv. Radiol."},{"key":"53754_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41572-021-00261-6","volume":"7","author":"DI Tsilimigras","year":"2021","unstructured":"Tsilimigras, D. I. et al. Liver metastases. Nat. Rev. Dis. Primers 7, 27. https:\/\/doi.org\/10.1038\/s41572-021-00261-6 (2021).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"53754_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030859","author":"T Dra\u0161kovi\u010d","year":"2023","unstructured":"Dra\u0161kovi\u010d, T., Zidar, N. & Hauptman, N. Circulating tumor DNA methylation biomarkers for characterization and determination of the cancer origin in malignant liver tumors. Cancers (Basel) https:\/\/doi.org\/10.3390\/cancers15030859 (2023).","journal-title":"Cancers (Basel)"},{"key":"53754_CR4","doi-asserted-by":"publisher","first-page":"55368","DOI":"10.18632\/oncotarget.10552","volume":"7","author":"J de Ridder","year":"2016","unstructured":"de Ridder, J. et al. Incidence and origin of histologically confirmed liver metastases: An explorative case-study of 23,154 patients. Oncotarget 7, 55368\u201355376. https:\/\/doi.org\/10.18632\/oncotarget.10552 (2016).","journal-title":"Oncotarget"},{"key":"53754_CR5","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/hmg\/ddq513","volume":"20","author":"D Aran","year":"2011","unstructured":"Aran, D., Toperoff, G., Rosenberg, M. & Hellman, A. Replication timing-related and gene body-specific methylation of active human genes. Hum. Mol. Genet. 20, 670\u2013680. https:\/\/doi.org\/10.1093\/hmg\/ddq513 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"53754_CR6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ccr.2012.11.006","volume":"23","author":"SA Bert","year":"2013","unstructured":"Bert, S. A. et al. Regional activation of the cancer genome by long-range epigenetic remodeling. Cancer Cell 23, 9\u201322. https:\/\/doi.org\/10.1016\/j.ccr.2012.11.006 (2013).","journal-title":"Cancer Cell"},{"key":"53754_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nrg816","volume":"3","author":"PA Jones","year":"2002","unstructured":"Jones, P. A. & Baylin, S. B. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415\u2013428. https:\/\/doi.org\/10.1038\/nrg816 (2002).","journal-title":"Nat. Rev. Genet."},{"key":"53754_CR8","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrg2341","volume":"9","author":"MM Suzuki","year":"2008","unstructured":"Suzuki, M. M. & Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet. 9, 465\u2013476. https:\/\/doi.org\/10.1038\/nrg2341 (2008).","journal-title":"Nat. Rev. Genet."},{"key":"53754_CR9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/978-3-319-43624-1_7","volume":"945","author":"R Lakshminarasimhan","year":"2016","unstructured":"Lakshminarasimhan, R. & Liang, G. The role of DNA methylation in cancer. Adv. Exp. Med. Biol. 945, 151\u2013172. https:\/\/doi.org\/10.1007\/978-3-319-43624-1_7 (2016).","journal-title":"Adv. Exp. Med. Biol."},{"key":"53754_CR10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1080\/15592294.2019.1568178","volume":"14","author":"W Ding","year":"2019","unstructured":"Ding, W., Chen, G. & Shi, T. Integrative analysis identifies potential DNA methylation biomarkers for pan-cancer diagnosis and prognosis. Epigenetics 14, 67\u201380. https:\/\/doi.org\/10.1080\/15592294.2019.1568178 (2019).","journal-title":"Epigenetics"},{"key":"53754_CR11","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","volume":"31","author":"MC Liu","year":"2020","unstructured":"Liu, M. C. et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann. Oncol. 31, 745\u2013759. https:\/\/doi.org\/10.1016\/j.annonc.2020.02.011 (2020).","journal-title":"Ann. Oncol."},{"key":"53754_CR12","doi-asserted-by":"publisher","first-page":"5068","DOI":"10.1038\/s41467-018-07466-6","volume":"9","author":"J Moss","year":"2018","unstructured":"Moss, J. et al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat. Commun. 9, 5068. https:\/\/doi.org\/10.1038\/s41467-018-07466-6 (2018).","journal-title":"Nat. Commun."},{"key":"53754_CR13","doi-asserted-by":"publisher","unstructured":"Cheishvili, D. et al. <em>epi<\/em>Liver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC). medRxiv, 2021.2002.2007.21251315, https:\/\/doi.org\/10.1101\/2021.02.07.21251315 (2021).","DOI":"10.1101\/2021.02.07.21251315"},{"key":"53754_CR14","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s43018-022-00491-x","volume":"4","author":"S Garcia-Recio","year":"2023","unstructured":"Garcia-Recio, S. et al. Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nat. Cancer 4, 128\u2013147. https:\/\/doi.org\/10.1038\/s43018-022-00491-x (2023).","journal-title":"Nat. Cancer"},{"key":"53754_CR15","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nrclinonc.2017.97","volume":"14","author":"S Moran","year":"2017","unstructured":"Moran, S., Martinez-Card\u00fas, A., Boussios, S. & Esteller, M. Precision medicine based on epigenomics: The paradigm of carcinoma of unknown primary. Nat. Rev. Clin. Oncol. 14, 682\u2013694. https:\/\/doi.org\/10.1038\/nrclinonc.2017.97 (2017).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"53754_CR16","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/S1470-2045(16)30297-2","volume":"17","author":"S Moran","year":"2016","unstructured":"Moran, S. et al. Epigenetic profiling to classify cancer of unknown primary: A multicentre, retrospective analysis. Lancet Oncol. 17, 1386\u20131395. https:\/\/doi.org\/10.1016\/S1470-2045(16)30297-2 (2016).","journal-title":"Lancet Oncol."},{"key":"53754_CR17","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1093\/bioinformatics\/btx622","volume":"34","author":"W Tang","year":"2018","unstructured":"Tang, W., Wan, S., Yang, Z., Teschendorff, A. E. & Zou, Q. Tumor origin detection with tissue-specific miRNA and DNA methylation markers. Bioinformatics 34, 398\u2013406. https:\/\/doi.org\/10.1093\/bioinformatics\/btx622 (2018).","journal-title":"Bioinformatics"},{"key":"53754_CR18","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ygeno.2011.07.007","volume":"98","author":"M Bibikova","year":"2011","unstructured":"Bibikova, M. et al. High density DNA methylation array with single CpG site resolution. Genomics 98, 288\u2013295. https:\/\/doi.org\/10.1016\/j.ygeno.2011.07.007 (2011).","journal-title":"Genomics"},{"key":"53754_CR19","doi-asserted-by":"publisher","first-page":"771","DOI":"10.2217\/epi.11.105","volume":"3","author":"S Dedeurwaerder","year":"2011","unstructured":"Dedeurwaerder, S. et al. Evaluation of the infinium methylation 450K technology. Epigenomics 3, 771\u2013784. https:\/\/doi.org\/10.2217\/epi.11.105 (2011).","journal-title":"Epigenomics"},{"key":"53754_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1756-8935-8-6","volume":"8","author":"TJ Peters","year":"2015","unstructured":"Peters, T. J. et al. De novo identification of differentially methylated regions in the human genome. Epigenetics Chromatin 8, 6. https:\/\/doi.org\/10.1186\/1756-8935-8-6 (2015).","journal-title":"Epigenetics Chromatin"},{"key":"53754_CR21","doi-asserted-by":"publisher","first-page":"389","DOI":"10.2217\/epi.15.114","volume":"8","author":"S Moran","year":"2016","unstructured":"Moran, S., Arribas, C. & Esteller, M. Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. Epigenomics 8, 389\u2013399. https:\/\/doi.org\/10.2217\/epi.15.114 (2016).","journal-title":"Epigenomics"},{"key":"53754_CR22","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ygeno.2019.05.007","volume":"112","author":"O Affinito","year":"2020","unstructured":"Affinito, O. et al. Nucleotide distance influences co-methylation between nearby CpG sites. Genomics 112, 144\u2013150. https:\/\/doi.org\/10.1016\/j.ygeno.2019.05.007 (2020).","journal-title":"Genomics"},{"key":"53754_CR23","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/1756-0500-5-210","volume":"5","author":"J Roessler","year":"2012","unstructured":"Roessler, J. et al. Quantitative cross-validation and content analysis of the 450k DNA methylation array from Illumina Inc. BMC Res. Notes 5, 210. https:\/\/doi.org\/10.1186\/1756-0500-5-210 (2012).","journal-title":"BMC Res. Notes"},{"key":"53754_CR24","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s13059-016-1066-1","volume":"17","author":"R Pidsley","year":"2016","unstructured":"Pidsley, R. et al. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 17, 208. https:\/\/doi.org\/10.1186\/s13059-016-1066-1 (2016).","journal-title":"Genome Biol."},{"key":"53754_CR25","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/bjc.2013.496","volume":"109","author":"CS Wilhelm-Benartzi","year":"2013","unstructured":"Wilhelm-Benartzi, C. S. et al. Review of processing and analysis methods for DNA methylation array data. Br. J. Cancer 109, 1394\u20131402. https:\/\/doi.org\/10.1038\/bjc.2013.496 (2013).","journal-title":"Br. J. Cancer"},{"key":"53754_CR26","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1186\/1471-2105-11-587","volume":"11","author":"P Du","year":"2010","unstructured":"Du, P. et al. Comparison of beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinform. 11, 587. https:\/\/doi.org\/10.1186\/1471-2105-11-587 (2010).","journal-title":"BMC Bioinform."},{"key":"53754_CR27","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3350\/cmh.2018.0067","volume":"25","author":"JH Park","year":"2019","unstructured":"Park, J. H. & Kim, J. H. Pathologic differential diagnosis of metastatic carcinoma in the liver. Clin. Mol. Hepatol. 25, 12\u201320. https:\/\/doi.org\/10.3350\/cmh.2018.0067 (2019).","journal-title":"Clin. Mol. Hepatol."},{"key":"53754_CR28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/s0959-8049(01)00378-1","volume":"38","author":"AJ van de Wouw","year":"2002","unstructured":"van de Wouw, A. J., Janssen-Heijnen, M. L., Coebergh, J. W. & Hillen, H. F. Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984\u20131992. Eur. J. Cancer 38, 409\u2013413. https:\/\/doi.org\/10.1016\/s0959-8049(01)00378-1 (2002).","journal-title":"Eur. J. Cancer"},{"key":"53754_CR29","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1177\/107327480601300103","volume":"13","author":"BA Centeno","year":"2006","unstructured":"Centeno, B. A. Pathology of liver metastases. Cancer Control 13, 13\u201326. https:\/\/doi.org\/10.1177\/107327480601300103 (2006).","journal-title":"Cancer Control"},{"key":"53754_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/path.1024","volume":"196","author":"M Esteller","year":"2002","unstructured":"Esteller, M. & Herman, J. G. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J. Pathol. 196, 1\u20137. https:\/\/doi.org\/10.1002\/path.1024 (2002).","journal-title":"J. Pathol."},{"key":"53754_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/genes10100778","author":"B Liu","year":"2019","unstructured":"Liu, B. et al. DNA methylation markers for pan-cancer prediction by deep learning. Genes (Basel) https:\/\/doi.org\/10.3390\/genes10100778 (2019).","journal-title":"Genes (Basel)"},{"key":"53754_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226461","volume":"15","author":"C Zheng","year":"2020","unstructured":"Zheng, C. & Xu, R. Predicting cancer origins with a DNA methylation-based deep neural network model. PLoS One 15, e0226461. https:\/\/doi.org\/10.1371\/journal.pone.0226461 (2020).","journal-title":"PLoS One"},{"key":"53754_CR33","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1186\/s12859-022-04815-7","volume":"23","author":"NS Eissa","year":"2022","unstructured":"Eissa, N. S., Khairuddin, U. & Yusof, R. A hybrid metaheuristic-deep learning technique for the pan-classification of cancer based on DNA methylation. BMC Bioinform. 23, 273. https:\/\/doi.org\/10.1186\/s12859-022-04815-7 (2022).","journal-title":"BMC Bioinform."},{"key":"53754_CR34","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1002\/1878-0261.13176","volume":"16","author":"J Ibrahim","year":"2022","unstructured":"Ibrahim, J., Op de Beeck, K., Fransen, E., Peeters, M. & Van Camp, G. Genome-wide DNA methylation profiling and identification of potential pan-cancer and tumor-specific biomarkers. Mol. Oncol. 16, 2432\u20132447. https:\/\/doi.org\/10.1002\/1878-0261.13176 (2022).","journal-title":"Mol. Oncol."},{"key":"53754_CR35","doi-asserted-by":"publisher","first-page":"7414","DOI":"10.1073\/pnas.1703577114","volume":"114","author":"X Hao","year":"2017","unstructured":"Hao, X. et al. DNA methylation markers for diagnosis and prognosis of common cancers. Proc. Natl. Acad. Sci. 114, 7414\u20137419. https:\/\/doi.org\/10.1073\/pnas.1703577114 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"53754_CR36","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1080\/15592294.2017.1412907","volume":"13","author":"L Vrba","year":"2018","unstructured":"Vrba, L. & Futscher, B. W. A suite of DNA methylation markers that can detect most common human cancers. Epigenetics 13, 61\u201372. https:\/\/doi.org\/10.1080\/15592294.2017.1412907 (2018).","journal-title":"Epigenetics"},{"key":"53754_CR37","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20201053","author":"X Liu","year":"2020","unstructured":"Liu, X., Peng, Y. & Wang, J. Integrative analysis of DNA methylation and gene expression profiles identified potential breast cancer-specific diagnostic markers. Biosci. Rep. https:\/\/doi.org\/10.1042\/bsr20201053 (2020)."},{"key":"53754_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.742578","author":"C Zhu","year":"2021","unstructured":"Zhu, C. et al. A novel gene prognostic signature based on differential DNA methylation in breast cancer. Front. Genet. https:\/\/doi.org\/10.3389\/fgene.2021.742578 (2021).","journal-title":"Front. Genet."},{"key":"53754_CR39","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/15592294.2021.1890885","volume":"17","author":"L Danilova","year":"2022","unstructured":"Danilova, L., Wrangle, J., Herman, J. G. & Cope, L. DNA-methylation for the detection and distinction of 19 human malignancies. Epigenetics 17, 191\u2013201. https:\/\/doi.org\/10.1080\/15592294.2021.1890885 (2022).","journal-title":"Epigenetics"},{"key":"53754_CR40","doi-asserted-by":"publisher","first-page":"10243","DOI":"10.1007\/s00521-021-06357-0","volume":"34","author":"RD Amor","year":"2022","unstructured":"Amor, R. D., Colomer, A., Monteagudo, C. & Naranjo, V. A deep embedded refined clustering approach for breast cancer distinction based on DNA methylation. Neural Comput. Appl. 34, 10243\u201310255. https:\/\/doi.org\/10.1007\/s00521-021-06357-0 (2022).","journal-title":"Neural Comput. Appl."},{"key":"53754_CR41","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/1471-2407-10-227","volume":"10","author":"PW Ang","year":"2010","unstructured":"Ang, P. W. et al. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer 10, 227. https:\/\/doi.org\/10.1186\/1471-2407-10-227 (2010).","journal-title":"BMC Cancer"},{"key":"53754_CR42","doi-asserted-by":"publisher","first-page":"303","DOI":"10.4067\/S0716-97602008000300007","volume":"41","author":"C Bernal","year":"2008","unstructured":"Bernal, C. et al. DNA methylation profile in diffuse type gastric cancer: Evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis. Biol. Res. 41, 303\u2013315 (2008).","journal-title":"Biol. Res."},{"key":"53754_CR43","doi-asserted-by":"publisher","first-page":"6195","DOI":"10.1158\/0008-5472.Can-11-1630","volume":"71","author":"MJ Fackler","year":"2011","unstructured":"Fackler, M. J. et al. Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence. Cancer Res. 71, 6195\u20136207. https:\/\/doi.org\/10.1158\/0008-5472.Can-11-1630 (2011).","journal-title":"Cancer Res."},{"key":"53754_CR44","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12920-019-0501-z","volume":"12","author":"N Hauptman","year":"2019","unstructured":"Hauptman, N., Jevsinek Skok, D., Spasovska, E., Bostjancic, E. & Glavac, D. Genes CEP55, FOXD3, FOXF2, GNAO1, GRIA4, and KCNA5 as potential diagnostic biomarkers in colorectal cancer. BMC Med. Genom. 12, 54. https:\/\/doi.org\/10.1186\/s12920-019-0501-z (2019).","journal-title":"BMC Med. Genom."},{"key":"53754_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2022.110478","volume":"114","author":"FA Lamare","year":"2022","unstructured":"Lamare, F. A. et al. Genome-wide DNA methylation profiling of stomach cancer in the ethnic population of Mizoram, North East India. Genomics 114, 110478. https:\/\/doi.org\/10.1016\/j.ygeno.2022.110478 (2022).","journal-title":"Genomics"},{"key":"53754_CR46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s13148-020-00940-3","volume":"12","author":"T Li","year":"2020","unstructured":"Li, T., Chen, X., Gu, M., Deng, A. & Qian, C. Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis. Clin. Epigenetics 12, 161. https:\/\/doi.org\/10.1186\/s13148-020-00940-3 (2020).","journal-title":"Clin. Epigenetics"},{"key":"53754_CR47","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.3390\/genes13101913","volume":"13","author":"X Li","year":"1913","unstructured":"Li, X. et al. Classification and prognosis analysis of pancreatic cancer based on DNA methylation profile and clinical information. Genes (Basel) 13, 2022. https:\/\/doi.org\/10.3390\/genes13101913 (1913).","journal-title":"Genes (Basel)"},{"key":"53754_CR48","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1186\/s12935-020-01253-4","volume":"20","author":"Q Lian","year":"2020","unstructured":"Lian, Q. et al. DNA methylation data-based molecular subtype classification and prediction in patients with gastric cancer. Cancer Cell Int. 20, 349. https:\/\/doi.org\/10.1186\/s12935-020-01253-4 (2020).","journal-title":"Cancer Cell Int."},{"key":"53754_CR49","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1186\/s12885-017-3226-4","volume":"17","author":"T McInnes","year":"2017","unstructured":"McInnes, T. et al. Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer. BMC Cancer 17, 228. https:\/\/doi.org\/10.1186\/s12885-017-3226-4 (2017).","journal-title":"BMC Cancer"},{"key":"53754_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e06000","volume":"7","author":"S Roy","year":"2021","unstructured":"Roy, S., Singh, A. P. & Gupta, D. Unsupervised subtyping and methylation landscape of pancreatic ductal adenocarcinoma. Heliyon 7, e06000. https:\/\/doi.org\/10.1016\/j.heliyon.2021.e06000 (2021).","journal-title":"Heliyon"},{"key":"53754_CR51","doi-asserted-by":"publisher","first-page":"21234","DOI":"10.1038\/s41598-020-78228-y","volume":"10","author":"R Xiang","year":"2020","unstructured":"Xiang, R. & Fu, T. Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures. Sci. Rep. 10, 21234. https:\/\/doi.org\/10.1038\/s41598-020-78228-y (2020).","journal-title":"Sci. Rep."},{"key":"53754_CR52","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1093\/carcin\/bgv013","volume":"36","author":"K Yamanoi","year":"2015","unstructured":"Yamanoi, K. et al. Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: Its correlation with tumor aggressiveness and patient outcome. Carcinogenesis 36, 509\u2013520. https:\/\/doi.org\/10.1093\/carcin\/bgv013 (2015).","journal-title":"Carcinogenesis"},{"key":"53754_CR53","doi-asserted-by":"publisher","first-page":"156ra140","DOI":"10.1126\/scitranslmed.3004504","volume":"4","author":"H Zouridis","year":"2012","unstructured":"Zouridis, H. et al. Methylation subtypes and large-scale epigenetic alterations in gastric cancer. Sci. Transl. Med. 4, 156ra140. https:\/\/doi.org\/10.1126\/scitranslmed.3004504 (2012).","journal-title":"Sci. Transl. Med."},{"key":"53754_CR54","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12916-021-02197-w","volume":"20","author":"Z Qiu","year":"2022","unstructured":"Qiu, Z. et al. Common DNA methylation changes in biliary tract cancers identify subtypes with different immune characteristics and clinical outcomes. BMC Med. 20, 64. https:\/\/doi.org\/10.1186\/s12916-021-02197-w (2022).","journal-title":"BMC Med."},{"key":"53754_CR55","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1038\/s41416-022-01738-1","volume":"126","author":"E Loi","year":"2022","unstructured":"Loi, E. et al. HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples. Br. J. Cancer 126, 1783\u20131794. https:\/\/doi.org\/10.1038\/s41416-022-01738-1 (2022).","journal-title":"Br. J. Cancer"},{"key":"53754_CR56","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1158\/2159-8290.Cd-17-0368","volume":"7","author":"A Jusakul","year":"2017","unstructured":"Jusakul, A. et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 7, 1116\u20131135. https:\/\/doi.org\/10.1158\/2159-8290.Cd-17-0368 (2017).","journal-title":"Cancer Discov."},{"key":"53754_CR57","doi-asserted-by":"publisher","first-page":"11512","DOI":"10.1038\/s41598-022-15058-0","volume":"12","author":"E Gon\u00e7alves","year":"2022","unstructured":"Gon\u00e7alves, E., Gon\u00e7alves-Reis, M., Pereira-Leal, J. B. & Cardoso, J. DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies. Sci. Rep. 12, 11512. https:\/\/doi.org\/10.1038\/s41598-022-15058-0 (2022).","journal-title":"Sci. Rep."},{"key":"53754_CR58","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1002\/hep.25569","volume":"55","author":"J Shen","year":"2012","unstructured":"Shen, J. et al. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology 55, 1799\u20131808. https:\/\/doi.org\/10.1002\/hep.25569 (2012).","journal-title":"Hepatology"},{"key":"53754_CR59","doi-asserted-by":"publisher","unstructured":"Wheeler, D. A., Roberts, L. R. & Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 169, 1327-1341.e1323. https:\/\/doi.org\/10.1016\/j.cell.2017.05.046 (2017).","DOI":"10.1016\/j.cell.2017.05.046"},{"key":"53754_CR60","volume-title":"IARC Press","author":"SR Hamilton","year":"2000","unstructured":"Hamilton, S. R. & Aaltonen, L. A. IARC Press (2000)."},{"key":"53754_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104657","volume":"93","author":"MP Dragomir","year":"2023","unstructured":"Dragomir, M. P. et al. DNA methylation-based classifier differentiates intrahepatic pancreato-biliary tumours. EBioMedicine 93, 104657. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104657 (2023).","journal-title":"EBioMedicine"},{"key":"53754_CR62","doi-asserted-by":"publisher","first-page":"642","DOI":"10.3389\/fonc.2020.00642","volume":"10","author":"GC Kim","year":"2020","unstructured":"Kim, G. C. et al. ETS1 suppresses tumorigenesis of human breast cancer via trans-activation of canonical tumor suppressor genes. Front. Oncol. 10, 642. https:\/\/doi.org\/10.3389\/fonc.2020.00642 (2020).","journal-title":"Front. Oncol."},{"key":"53754_CR63","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s13148-022-01361-0","volume":"14","author":"P Song","year":"2022","unstructured":"Song, P. et al. Genome-wide screening for differentially methylated long noncoding RNAs identifies LIFR-AS1 as an epigenetically regulated lncRNA that inhibits the progression of colorectal cancer. Clin. Epigenetics 14, 138. https:\/\/doi.org\/10.1186\/s13148-022-01361-0 (2022).","journal-title":"Clin. Epigenetics"},{"key":"53754_CR64","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.752511","volume":"11","author":"X Wang","year":"2021","unstructured":"Wang, X. et al. RNF135 promoter methylation is associated with immune infiltration and prognosis in hepatocellular carcinoma. Front. Oncol. 11, 752511. https:\/\/doi.org\/10.3389\/fonc.2021.752511 (2021).","journal-title":"Front. Oncol."},{"key":"53754_CR65","doi-asserted-by":"publisher","first-page":"3497810","DOI":"10.1155\/2020\/3497810","volume":"2020","author":"S Gong","year":"2020","unstructured":"Gong, S., Ye, W., Liu, T., Jian, S. & Liu, W. The development of three-DNA methylation signature as a novel prognostic biomarker in patients with colorectal cancer. BioMed. Res. Int. 2020, 3497810. https:\/\/doi.org\/10.1155\/2020\/3497810 (2020).","journal-title":"BioMed. Res. Int."},{"key":"53754_CR66","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/hep.31659","volume":"74","author":"G Hernandez-Meza","year":"2021","unstructured":"Hernandez-Meza, G. et al. DNA methylation profiling of human hepatocarcinogenesis. Hepatology 74, 183\u2013199. https:\/\/doi.org\/10.1002\/hep.31659 (2021).","journal-title":"Hepatology"},{"key":"53754_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60796-8","author":"L Erichsen","year":"2020","unstructured":"Erichsen, L. et al. Basic hallmarks of urothelial cancer unleashed in primary uroepithelium by interference with the epigenetic master regulator ODC1. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-020-60796-8 (2020).","journal-title":"Sci. Rep."},{"key":"53754_CR68","doi-asserted-by":"publisher","first-page":"R14","DOI":"10.1186\/bcr2233","volume":"11","author":"S Tommasi","year":"2009","unstructured":"Tommasi, S., Karm, D. L., Wu, X., Yen, Y. & Pfeifer, G. P. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res. 11, R14. https:\/\/doi.org\/10.1186\/bcr2233 (2009).","journal-title":"Breast Cancer Res."},{"key":"53754_CR69","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13073-018-0548-z","volume":"10","author":"J Cheng","year":"2018","unstructured":"Cheng, J. et al. Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers. Genome Med. 10, 42. https:\/\/doi.org\/10.1186\/s13073-018-0548-z (2018).","journal-title":"Genome Med."},{"key":"53754_CR70","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1158\/1078-0432.Ccr-11-1007","volume":"18","author":"S Matsumura","year":"2012","unstructured":"Matsumura, S. et al. Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor suppressor in hepatocellular carcinoma. Clin. Cancer Res. 18, 3541\u20133551. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-11-1007 (2012).","journal-title":"Clin. Cancer Res."},{"key":"53754_CR71","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.3892\/ijo.2012.1397","volume":"40","author":"E Moravcikova","year":"2012","unstructured":"Moravcikova, E. et al. Down-regulated expression of apoptosis-associated genes APIP and UACA in non-small cell lung carcinoma. Int. J. Oncol. 40, 2111\u20132121. https:\/\/doi.org\/10.3892\/ijo.2012.1397 (2012).","journal-title":"Int. J. Oncol."},{"key":"53754_CR72","doi-asserted-by":"publisher","first-page":"e79898","DOI":"10.1371\/journal.pone.0079898","volume":"8","author":"AA Dihal","year":"2013","unstructured":"Dihal, A. A. et al. The homeobox gene MEIS1 is methylated in BRAF (p.V600E) mutated colon tumors. PLoS One 8, e79898. https:\/\/doi.org\/10.1371\/journal.pone.0079898 (2013).","journal-title":"PLoS One"},{"key":"53754_CR73","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1053\/j.gastro.2013.08.055","volume":"145","author":"K Revill","year":"2013","unstructured":"Revill, K. et al. Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma. Gastroenterology 145, 1424-1435.e1421-1425. https:\/\/doi.org\/10.1053\/j.gastro.2013.08.055 (2013).","journal-title":"Gastroenterology"},{"key":"53754_CR74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055761","volume":"8","author":"MA Song","year":"2013","unstructured":"Song, M. A. et al. Elucidating the landscape of aberrant DNA methylation in hepatocellular carcinoma. PLoS One 8, e55761. https:\/\/doi.org\/10.1371\/journal.pone.0055761 (2013).","journal-title":"PLoS One"},{"key":"53754_CR75","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41366-018-0065-6","volume":"43","author":"AB Crujeiras","year":"2019","unstructured":"Crujeiras, A. B. et al. Identification of an episignature of human colorectal cancer associated with obesity by genome-wide DNA methylation analysis. Int. J. Obes. (Lond) 43, 176\u2013188. https:\/\/doi.org\/10.1038\/s41366-018-0065-6 (2019).","journal-title":"Int. J. Obes. (Lond)"},{"key":"53754_CR76","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20204370","author":"Q Zheng","year":"2021","unstructured":"Zheng, Q., Min, S. & Zhou, Q. Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases. Biosci. Rep. https:\/\/doi.org\/10.1042\/bsr20204370 (2021)."},{"key":"53754_CR77","doi-asserted-by":"publisher","first-page":"131","DOI":"10.21037\/tcr.2016.03.07","volume":"5","author":"P Yuan","year":"2016","unstructured":"Yuan, P. et al. OSMR and SEPT9: Promising biomarkers for detection of colorectal cancer based on blood-based tests. Transl. Cancer Res. 5, 131\u2013139 (2016).","journal-title":"Transl. Cancer Res."},{"key":"53754_CR78","doi-asserted-by":"publisher","first-page":"1065693","DOI":"10.3389\/fgene.2022.1065693","volume":"13","author":"W Liang","year":"2022","unstructured":"Liang, W. et al. Circulating tumour cell combined with DNA methylation for early detection of hepatocellular carcinoma. Front. Genet. 13, 1065693. https:\/\/doi.org\/10.3389\/fgene.2022.1065693 (2022).","journal-title":"Front. Genet."},{"key":"53754_CR79","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1002\/hep.30244","volume":"69","author":"JB Kisiel","year":"2019","unstructured":"Kisiel, J. B. et al. Hepatocellular carcinoma detection by plasma methylated DNA: Discovery, phase I pilot, and phase II clinical validation. Hepatology (Baltimore, Md.) 69, 1180\u20131192. https:\/\/doi.org\/10.1002\/hep.30244 (2019).","journal-title":"Hepatology (Baltimore, Md.)"},{"key":"53754_CR80","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","volume":"44","author":"A Colaprico","year":"2015","unstructured":"Colaprico, A. et al. TCGAbiolinks: An R\/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 44, e71\u2013e71. https:\/\/doi.org\/10.1093\/nar\/gkv1507 (2015).","journal-title":"Nucleic Acids Res."},{"key":"53754_CR81","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nature08987","volume":"464","author":"TJ Hudson","year":"2010","unstructured":"Hudson, T. J. et al. International network of cancer genome projects. Nature 464, 993\u2013998. https:\/\/doi.org\/10.1038\/nature08987 (2010).","journal-title":"Nature"},{"key":"53754_CR82","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1186\/1471-2105-9-365","volume":"9","author":"EA Houseman","year":"2008","unstructured":"Houseman, E. A. et al. Model-based clustering of DNA methylation array data: A recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions. BMC Bioinform. 9, 365. https:\/\/doi.org\/10.1186\/1471-2105-9-365 (2008).","journal-title":"BMC Bioinform."},{"key":"53754_CR83","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/j.1525-1497.2004.30091.x","volume":"19","author":"AJ Alberg","year":"2004","unstructured":"Alberg, A. J., Park, J. W., Hager, B. W., Brock, M. V. & Diener-West, M. The use of \u201coverall accuracy\u201d to evaluate the validity of screening or diagnostic tests. J. Gen. Intern. Med. 19, 460\u2013465. https:\/\/doi.org\/10.1111\/j.1525-1497.2004.30091.x (2004).","journal-title":"J. Gen. Intern. Med."},{"key":"53754_CR84","unstructured":"Carstensen Bendix, Plummer Martyn , Laara Esa & Michael, H. (2022)."},{"key":"53754_CR85","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ebiom.2018.12.058","volume":"40","author":"S Shimada","year":"2019","unstructured":"Shimada, S. et al. Comprehensive molecular and immunological characterization of hepatocellular carcinoma. EBioMedicine 40, 457\u2013470. https:\/\/doi.org\/10.1016\/j.ebiom.2018.12.058 (2019).","journal-title":"EBioMedicine"},{"key":"53754_CR86","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1002\/hep.30493","volume":"69","author":"B Goeppert","year":"2019","unstructured":"Goeppert, B. et al. Integrative analysis defines distinct prognostic subgroups of intrahepatic cholangiocarcinoma. Hepatology 69, 2091\u20132106. https:\/\/doi.org\/10.1002\/hep.30493 (2019).","journal-title":"Hepatology"},{"key":"53754_CR87","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1038\/ng.2806","volume":"45","author":"W Chan-On","year":"2013","unstructured":"Chan-On, W. et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat. Genet. 45, 1474\u20131478. https:\/\/doi.org\/10.1038\/ng.2806 (2013).","journal-title":"Nat. Genet."},{"key":"53754_CR88","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/jnci\/djac183","volume":"115","author":"H Yu","year":"2023","unstructured":"Yu, H. et al. DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer. J. Natl. Cancer Inst. 115, 52\u201361. https:\/\/doi.org\/10.1093\/jnci\/djac183 (2023).","journal-title":"J. Natl. Cancer Inst."},{"key":"53754_CR89","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3390\/biom10050719","volume":"10","author":"M Ishak","year":"2020","unstructured":"Ishak, M. et al. Genome-wide open chromatin methylome profiles in colorectal cancer. Biomolecules 10, 719. https:\/\/doi.org\/10.3390\/biom10050719 (2020).","journal-title":"Biomolecules"},{"key":"53754_CR90","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115657","volume":"427","author":"M Li","year":"2021","unstructured":"Li, M. et al. Genomic methylation variations predict the susceptibility of six chemotherapy related adverse effects and cancer development for Chinese colorectal cancer patients. Toxicol. Appl. Pharmacol. 427, 115657. https:\/\/doi.org\/10.1016\/j.taap.2021.115657 (2021).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"53754_CR91","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.ebiom.2015.06.025","volume":"2","author":"M Wielscher","year":"2015","unstructured":"Wielscher, M. et al. Diagnostic performance of plasma DNA methylation profiles in lung cancer. Pulmonary fibrosis and COPD. EBioMedicine 2, 929\u2013936. https:\/\/doi.org\/10.1016\/j.ebiom.2015.06.025 (2015).","journal-title":"EBioMedicine"},{"key":"53754_CR92","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1158\/2159-8290.Cd-20-1202","volume":"11","author":"E Espinet","year":"2021","unstructured":"Espinet, E. et al. Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin. Cancer Discov. 11, 638\u2013659. https:\/\/doi.org\/10.1158\/2159-8290.Cd-20-1202 (2021).","journal-title":"Cancer Discov."},{"key":"53754_CR93","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s10120-022-01344-3","volume":"26","author":"M Urabe","year":"2023","unstructured":"Urabe, M. et al. Adenocarcinoma of the stomach and esophagogastric junction with low DNA methylation show poor prognoses. Gastric Cancer 26, 95\u2013107. https:\/\/doi.org\/10.1007\/s10120-022-01344-3 (2023).","journal-title":"Gastric Cancer"},{"key":"53754_CR94","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/ijc.31381","volume":"143","author":"HD Woo","year":"2018","unstructured":"Woo, H. D. et al. Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes. Int. J. Cancer 143, 597\u2013609. https:\/\/doi.org\/10.1002\/ijc.31381 (2018).","journal-title":"Int. J. Cancer"},{"key":"53754_CR95","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.yexmp.2017.07.001","volume":"103","author":"Y Chen","year":"2017","unstructured":"Chen, Y. et al. Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS). Exp. Mol. Pathol. 103, 78\u201383. https:\/\/doi.org\/10.1016\/j.yexmp.2017.07.001 (2017).","journal-title":"Exp. Mol. Pathol."},{"key":"53754_CR96","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s13058-017-0873-y","volume":"19","author":"KC Johnson","year":"2017","unstructured":"Johnson, K. C., Houseman, E. A., King, J. E. & Christensen, B. C. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age. Breast Cancer Res. 19, 81. https:\/\/doi.org\/10.1186\/s13058-017-0873-y (2017).","journal-title":"Breast Cancer Res."},{"key":"53754_CR97","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee, M. J. et al. Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30, 1363\u20131369. https:\/\/doi.org\/10.1093\/bioinformatics\/btu049 (2014).","journal-title":"Bioinformatics"},{"key":"53754_CR98","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","volume":"23","author":"S Davis","year":"2007","unstructured":"Davis, S. & Meltzer, P. S. GEOquery: A bridge between the gene expression omnibus (GEO) and BioConductor. Bioinformatics 23, 1846\u20131847. https:\/\/doi.org\/10.1093\/bioinformatics\/btm254 (2007).","journal-title":"Bioinformatics"},{"key":"53754_CR99","doi-asserted-by":"publisher","first-page":"D933","DOI":"10.1093\/nar\/gkac958","volume":"51","author":"FJ Martin","year":"2022","unstructured":"Martin, F. J. et al. Ensembl 2023. Nucleic Acids Res. 51, D933\u2013D941. https:\/\/doi.org\/10.1093\/nar\/gkac958 (2022).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53754-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53754-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53754-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:04:30Z","timestamp":1707285870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53754-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53754"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-53754-1","relation":{"references":[{"id-type":"uri","id":"","asserted-by":"subject"},{"id-type":"uri","id":"","asserted-by":"subject"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]},"assertion":[{"value":"25 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3095"}}