{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:37:44Z","timestamp":1792622264407,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cell-free DNA (cfDNA) analysis offers an attractive noninvasive means of detecting and monitoring diseases. cfDNA cleavage patterns within a short range (e.g., 11 nucleotides) have been reported to correlate with cytosine-phosphate-guanine (CpG) methylation, allowing fragmentomics-based methylation analysis (FRAGMA). Here, we adopted FRAGMA to the extended region harboring multiple nucleosomes, termed FRAGMAXR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We profiled cfDNA nucleosomal patterns over the genomic regions from \u2212800 to 800\u2005bp surrounding differentially methylated CpG sites, harboring approximately 8 nucleosomes, referred to as CpG-associated cfDNA nucleosomal patterns. Such nucleosomal patterns were analyzed by FRAGMAXR in cancer patients and pregnant women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified distinct cfDNA nucleosomal patterns around differentially methylated CpG sites. Compared with subjects without cancer, patients with hepatocellular carcinoma (HCC) showed reduced amplitude of nucleosomal patterns, with a gradual decrease over tumor stages. Nucleosomal patterns associated with differentially methylated CpG sites could be used to train a machine learning model, resulting in the detection of HCC patients with an area under the receiver operating characteristic curve of 0.93. We further demonstrated the feasibility of multicancer detection using a dataset comprising lung, breast, and ovarian cancers. The tissue-of-origin analysis of plasma cfDNA from pregnant women and cancer patients revealed that the placental DNA and tumoral DNA contributions deduced by FRAGMAXR correlated well with values measured using genetic variants (Pearson r: 0.85 and 0.94, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CpG-associated cfDNA nucleosomal patterns of cfDNA molecules are influenced by DNA methylation and might be useful for biomarker developments for cancer liquid biopsy and noninvasive prenatal testing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae118","type":"journal-article","created":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T18:05:23Z","timestamp":1722189923000},"page":"1355-1365","source":"Crossref","is-referenced-by-count":17,"title":["Methylation-Associated Nucleosomal Patterns of Cell-Free DNA in Cancer Patients and Pregnant Women"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-1666","authenticated-orcid":false,"given":"Guanhua","family":"Zhu","sequence":"first","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-3476","authenticated-orcid":false,"given":"Peiyong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqian","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlei","family":"Peng","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1746-9804","authenticated-orcid":false,"given":"L Y Lois","family":"Choy","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C Y","family":"Yu","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Jane L","family":"Ma","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Kang","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyue","family":"Bai","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Centre for Novostics, Hong Kong Science Park , Hong Kong SAR ,","place":["China"]},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong SAR 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