{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:59:16Z","timestamp":1790873956772,"version":"4.1.0"},"reference-count":51,"publisher":"Cold Spring Harbor Laboratory","issue":"10","funder":[{"name":"National Key Research and Development Program of China","award":["2024YFC3405900"],"award-info":[{"award-number":["2024YFC3405900"]}]},{"name":"National Key Research and Development Program of China","award":["2024YFC2510300"],"award-info":[{"award-number":["2024YFC2510300"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371855"],"award-info":[{"award-number":["82371855"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341101"],"award-info":[{"award-number":["82341101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2025-PUMCH-C-015"],"award-info":[{"award-number":["2025-PUMCH-C-015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genome Res."],"accepted":{"date-parts":[[2026,8,17]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with\n                    <jats:italic>k<\/jats:italic>\n                    -mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.\n                  <\/jats:p>","DOI":"10.1101\/gr.281656.125","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:40:13Z","timestamp":1789674013000},"page":"2159-2171","source":"Crossref","is-referenced-by-count":0,"title":["CircExor enables interpretable prediction of circRNA localization into extracellular vesicles"],"prefix":"10.1101","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0538-1542","authenticated-orcid":false,"given":"Yusa","family":"Zhang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, State Key Laboratory of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;"},{"name":"Eight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"},{"name":"Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbo","family":"Lu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, State Key Laboratory of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;"},{"name":"Eight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Bao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, State Key Laboratory of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anhao","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, State Key Laboratory of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;"},{"name":"Eight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-9400","authenticated-orcid":false,"given":"Zhi John","family":"Lu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, State Key Laboratory of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;"},{"name":"Institute for Precision Medicine, Tsinghua University, Beijing 100084, China;"},{"name":"The Center for Regeneration Aging and Chronic Diseases, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026100109051457000_36.10.2159.1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158221"},{"key":"2026100109051457000_36.10.2159.2","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.123"},{"key":"2026100109051457000_36.10.2159.3","unstructured":"Duan T , Anand A , Ding DY , Thai KK , Basu S , Ng A , Schuler A . 2020. 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