[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-371798-105":59,"doc-detail-371798-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","fragmentation-signatures-in-cancer-patients-resemble-those-of-patients-with-vascular-or-autoimmune-diseases","Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases","","Cancer cfDNA studies show fragmentation patterns can separate cancer cases from healthy controls, yet limited work evaluates cfDNA fragmentomics patterns across other diseases. This research develops “fragmentation signatures,” integrating fragment positioning, length, and end-motif distributions. Patients with venous thromboembolism, systemic lupus erythematosus, dermatomyositis, or scleroderma show signatures resembling advanced cancers. These similarities correlate with inflammatory markers, causing false positives under conventional binary MCED classification. A multiclass MCED approach integrating protein biomarkers improves specificity for autoimmune/vascular disease while preserving sensitivity, offering guidance for more interpretable and accurate fragmentomics-based diagnostics.",{"@graph":69,"@context":122},[70,84,105],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fragmentation-signatures-in-cancer-patients-resemble-those-of-patients-with-vascular-or-autoimmune-diseases/371798/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fragmentation-signatures-in-cancer-patients-resemble-those-of-patients-with-vascular-or-autoimmune-diseases/371798.png","ImageObject",300,407,{"name":92,"@type":93},"Aran","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are fragmentation signatures in cfDNA?","Question",{"text":112,"@type":113},"They are a comprehensive statistical framework integrating distributions of fragment positioning, fragment length, and fragment end-motifs in cell-free DNA.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which non-cancer diseases showed fragmentation signatures resembling advanced cancers?",{"text":117,"@type":113},"Venous thromboembolism, systemic lupus erythematosus, dermatomyositis, and scleroderma.",{"name":119,"@type":110,"acceptedAnswer":120},"How do the findings affect multicancer earlier detection (MCED)?",{"text":121,"@type":113},"They indicate high false-positive rates with conventional binary classification, and support using a multiclass MCED approach that adds protein biomarkers to improve specificity while maintaining sensitivity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},371798,1790600408,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},137455076865,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","RESEARCH ARTICLE  \nMEDICAL SCIENCES COMPUTER SCIENCES  \nFragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases  \nSamuel D. Curtisa, b,c,d , Tingshan Liue,f, Yuxin Baie,f, Yuxuan Wangb,c,d, Sambit Pandae,f, Adam Lig , Haoyin Xue,f, Eliza O’Reillyh, Lisa Dobbynb,c,d, Maria Popolib,c,d, Janine Ptakb,c,d, i, Natalie Sillimanb,c,d, h, Chris Thoburnb, Jeanne Tiej, k, l, Peter Gibbsj, l, m, Lan T. Ho-Phamn,o, Bich N. H. Tranp,  \nThach S. Tranp,q, Tuan V. Nguyenp,q, r,s,t, Maximilian F. Konigc, u,v, Michelle Petriu, Antony Rosenu, Christopher A. Mecolib, u, Ami A. Shahu, Frits Mulderw, Nick van Esw, PLATO-VTE Study Group1, Chetan Bettegowdab,c,d,x, Kenneth W. Kinzlerb,c,d, Nickolas Papadopoulosb,c,d, Joshua T. Vogelsteine,f,  \nBert Vogelsteinb,c,d, i,2, and Christopher Douvilleb,c,d,y,z,2 Affiliations are included on p. 11.  \nContributed by Bert Vogelstein; received December 26, 2024; accepted July 9, 2025; reviewed by Dan Landau and Viktor Adalsteinsson  \nMultiple case-controlled studies have shown that analyzing fragmentation patterns in plasma cell-free DNA (cfDNA) can distinguish individuals with cancer from healthy controls. However, there have been few studies that investigate various types of cfDNA fragmentomics patterns in individuals with other diseases. We therefore developed a comprehensive statistic, called fragmentation signatures, that integrates the distributions of fragment positioning, fragment length, and fragment end-motifs in cfDNA. We found that individuals with venous thromboembolism, systemic lupus erythematosus, dermatomyositis, or scleroderma have cfDNA fragmentation signatures that closely resemble those found in individuals with advanced cancers. Furthermore, these signatures were highly correlated with increases in inflammatory markers in the blood. We demonstrate that these similarities in fragmentation signatures lead to high rates of false positives in individuals with autoimmune or vascular disease when evaluated using conventional binary classification approaches for multicancer earlier detection (MCED) . To address this issue, we introduced a multiclass approach for MCED that integrates fragmentation signatures with protein biomarkers and achieves improved specificity in individuals with autoimmune or vascular disease while maintaining high sensitivity. Though these data put substantial limitations on the specificity of fragmentomics-based tests for cancer diagnostics, they also offer ways to improve the interpretability of such tests. Moreover, we expect these results will lead to a better understanding of the process—most likely inflammatory—from which abnormal fragmentation signatures are derived.  \ncell-free DNA | cancer screening | fragmentomics | rheumatology | autoimmune diseases  \nThe use of cell-free DNA (cfDNA) to assist with the diagnosis of cancer has a long and venerable history. More than 40 y ago, researchers showed that the concentration of cfDNAin the blood of cancer patients was higher than in healthy controls (1). Later studies showed that this increase was not specific for cancer, and that elevations in blood cfDNA concentrations occur in other states, including exercise, trauma, cardiovascular disease, sepsis, aseptic inflammation, autoimmune disease, and viral infections (2–5) . However, in the early 90’s, researchers demonstrated that mutations present in cancer cells can provide highly specific biomarkers for cancer (6, 7) . These studies stimulated efforts to use genetic alterations such as mutations and aneuploidy, as well as epigenetic alterations such as DNA methylation, in a variety of clinical samples, including plasma, serum, sputum, Pap Smears, cerebrospinal fluid, saliva, and urine (8–17). Such analyses are referred to as “liquid biopsies,” emphasizing their noninvasive nature compared to conventional biopsies. There are now thousands of examples of the productive use of such liquid biopsies to assist in the diagnosi","cbCaimpOtdaiiJg7","https://ap.wps.com/l/cbCaimpOtdaiiJg7","pdf",4844577,12,"English","# Significance\n## Fragmentation signatures and clinical interpretation\n## Impact on MCED specificity\n## Inflammation-linked mechanisms","[{\"question\":\"What are fragmentation signatures in cfDNA?\",\"answer\":\"They are a comprehensive statistical framework integrating distributions of fragment positioning, fragment length, and fragment end-motifs in cell-free DNA.\"},{\"question\":\"Which non-cancer diseases showed fragmentation signatures resembling advanced cancers?\",\"answer\":\"Venous thromboembolism, systemic lupus erythematosus, dermatomyositis, and scleroderma.\"},{\"question\":\"How do the findings affect multicancer earlier detection (MCED)?\",\"answer\":\"They indicate high false-positive rates with conventional binary classification, and support using a multiclass MCED approach that adds protein biomarkers to improve specificity while maintaining sensitivity.\"}]","Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases | PDF",1790192894]