[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-378376-105":59,"doc-detail-378376-en":129},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","multidimensional-fragmentomic-profiling-of-cell-free-dna-released-from-patient-derived-organoids-research-open-access-abstract","Multidimensional fragmentomic profiling of cell-free DNA released from patient-derived organoids - Research Open Access - Abstract","","Fragmentomics studies cfDNA fragmentation patterns for early detection of multiple cancers in liquid biopsy, but clinical use is limited by an incomplete understanding of cfDNA biology and by plasma contamination from hematopoietic cell-derived cfDNA. Conventional two-dimensional cell models poorly reflect in vivo tissue contexts. This study proposes three-dimensional patient-derived organoids as a robust in vitro model, enabling multifaceted fragmentomic analyses of cfDNA released during proliferative versus apoptotic states.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/multidimensional-fragmentomic-profiling-of-cell-free-dna-released-from-patient-derived-organoids-research-open-access-abstract/378376/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/multidimensional-fragmentomic-profiling-of-cell-free-dna-released-from-patient-derived-organoids-research-open-access-abstract/378376.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is fragmentomics and why is it relevant to cancer detection?","Question",{"text":111,"@type":112},"Fragmentomics investigates fragmentation patterns of cell-free DNA and is used as a promising strategy for early detection of multiple cancers through liquid biopsy.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"Why are traditional in vivo samples and 2D cell lines challenging for cfDNA biology studies?",{"text":116,"@type":112},"Plasma cfDNA is predominantly derived from hematopoietic cells, which can obscure tissue-specific tumor signals. In addition, conventional 2D models do not capture in vivo tissue context well.",{"name":118,"@type":109,"acceptedAnswer":119},"How does this study use patient-derived organoids to study cfDNA?",{"text":120,"@type":112},"The study establishes patient-derived organoid lines, extracts cfDNA from organoid culture media in proliferative and apoptotic states, and performs whole-genome sequencing-based fragmentomic analyses of multiple features.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},378376,1790246437,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Kim etal. Human Genomics (2023) 17:96 [https://doi.org/10.1186/s40246-023-00533-0](https://doi.org/10.1186/s40246-023-00533-0)  \nHuman Genomics  \n RESEARCH Open Access  \nMultidimensional fragmentomic profiling  \nof cell-free DNA released from patient-derived organoids  \nJaeryuk Kim1,2,5, Seung‑Pyo Hong 1,2,5, Seyoon Lee1,2,5, Woochan Lee1,2,5, Dakyung Lee 1,2,5, Rokhyun Kim 1,2,5, Young Jun Park1,3,5, Sungji Moon1,4,5, Kyunghyuk Park1,5, Bukyoung Cha1,5 and Jong‑Il Kim 1,2,3,4,5,6*  \nAbstract  \nBackground Fragmentomics, the investigation of fragmentation patterns of cell‑free DNA (cfDNA), has emerged as a promising strategy for the early detection of multiple cancers in the field of liquid biopsy. However, the clinical application of this approach has been hindered by a limited understanding of cfDNA biology. Furthermore, the preva‑ lence of hematopoietic cell‑derived cfDNA in plasma complicates the in vivo investigation of tissue‑specific cfDNA other than that of hematopoietic origin. While conventional two‑dimensional cell lines have contributed to research on cfDNA biology, their limited representation of in vivo tissue contexts underscores the need for more robust models. In this study, we propose three‑dimensional organoids as a novel in vitro model for studying cfDNA biology, focusing on multifaceted fragmentomic analyses.  \nResults We established nine patient‑derived organoid lines from normal lung airway, normal gastric, and gastric cancer tissues. We then extracted cfDNA from the culture medium of these organoids in both proliferative and apop‑ totic states. Using whole‑genome sequencing data from cfDNA, we analyzed various fragmentomic features, includ‑ ing fragment size, footprints, end motifs, and repeat types at the end. The distribution of cfDNA fragment sizes in organoids, especially in apoptosis samples, was similar to that found in plasma, implying occupancy by mononu‑ cleosomes. The footprints determined by sequencing depth exhibited distinct patterns depending on fragment sizes, reflecting occupancy by a variety of DNA‑binding proteins. Notably, we discovered that short fragments (\u003C 118 bp) were exclusively enriched in the proliferative state and exhibited distinct fragmentomic profiles, characterized by 3 bp palindromic end motifs and specific repeats.  \nConclusions In conclusion, our results highlight the utility of in vitro organoid models as a valuable tool for studying cfDNA biology and its associated fragmentation patterns. This, in turn, will pave the way for further enhancements in noninvasive cancer detection methodologies based on fragmentomics.  \nKeywords Cell‑free DNA biology, In vitro models, Fragmentomics, Organoids, Extrachromosomal circular DNA  \n*Correspondence: Jong‑Il Kim [jongil@snu.ac.kr](jongil@snu.ac.kr)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waive","cbCail32efSpwAgd","https://ap.wps.com/l/cbCail32efSpwAgd","pdf",6494106,15,"English","# Background\n## Fragmentomics and multicancer early detection\n## Limits of in vivo and 2D models\n## Challenges from hematopoietic cfDNA “noise”\n# Results\n## Patient-derived organoid lines\n## cfDNA extraction in proliferative vs apoptotic states\n## Whole-genome sequencing fragmentomic feature analyses\n# Conclusions\n## Value of organoid models for fragmentomics-based cancer detection","[{\"question\":\"What is fragmentomics and why is it relevant to cancer detection?\",\"answer\":\"Fragmentomics investigates fragmentation patterns of cell-free DNA and is used as a promising strategy for early detection of multiple cancers through liquid biopsy.\"},{\"question\":\"Why are traditional in vivo samples and 2D cell lines challenging for cfDNA biology studies?\",\"answer\":\"Plasma cfDNA is predominantly derived from hematopoietic cells, which can obscure tissue-specific tumor signals. In addition, conventional 2D models do not capture in vivo tissue context well.\"},{\"question\":\"How does this study use patient-derived organoids to study cfDNA?\",\"answer\":\"The study establishes patient-derived organoid lines, extracts cfDNA from organoid culture media in proliferative and apoptotic states, and performs whole-genome sequencing-based fragmentomic analyses of multiple features.\"}]","Multidimensional fragmentomic profiling of cell-free DNA released from patient-derived organoids - Research Open Access - Abstract | PDF",1790229674,38]