{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:59:23Z","timestamp":1775523563820,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62225109"],"award-info":[{"award-number":["62225109"]}],"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":["62472120"],"award-info":[{"award-number":["62472120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3406303"],"award-info":[{"award-number":["2024YFC3406303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gene fusions are critical oncogenic drivers and therapeutic targets in diverse cancers. Long-read ribonucleic acid sequencing (RNA-seq) offers an unprecedented opportunity to resolve the full-length structure of fusion isoforms, but its high intrinsic error rates pose significant challenges to the precise identification of true fusion events. Here, we developed GFSeeker, an innovative splicing-graph-based computational framework for accurate gene fusion detection from long-read RNA-seq. GFSeeker employs a unique pipeline based on a splicing graph reference and a dual re-alignment validation to effectively overcome data noise from high error rates. Benchmarking across simulated, non-tumor, and cancer cell line datasets demonstrated GFSeeker\u2019s state-of-the-art performance, achieving 6%\u201315% higher F1 score compared to existing methods. Notably, GFSeeker successfully identified the known fusion event, MATN2\u2013POP1, in the MCF-7 cancer cell line, missed by other tools, highlighting its superior sensitivity in resolving complex fusion events. These results validate GFSeeker as a powerful and reliable tool for gene fusion discovery, heralding its significant potential to advance cancer research and precision diagnostics.<\/jats:p>","DOI":"10.1093\/bib\/bbaf702","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:50:29Z","timestamp":1765889429000},"source":"Crossref","is-referenced-by-count":1,"title":["GFSeeker: a splicing-graph-based approach for accurate gene fusion detection from long-read RNA sequencing data"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9535-6578","authenticated-orcid":false,"given":"Bingyan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , Harbin 150040 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-4049","authenticated-orcid":false,"given":"Heng","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University , Harbin 150040 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0870-6693","authenticated-orcid":false,"given":"Runtian","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University , Harbin 150040 ,","place":["China"]}]},{"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , Harbin 150040 ,","place":["China"]},{"name":"College of Life Sciences, Northeast Forestry University , Harbin 150040 ,","place":["China"]},{"name":"School of Computer Science and Technology, Harbin Institute of Technology , Harbin 150001 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-8503","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , Harbin 150001 ,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"2026010711361295400_ref1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1002\/path.2632","article-title":"Fusion genes and chromosome translocations in the common epithelial cancers","volume":"220","author":"Edwards","year":"2010","journal-title":"J Pathol"},{"key":"2026010711361295400_ref2","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nrc3947","article-title":"The emerging complexity of gene fusions in cancer","volume":"15","author":"Mertens","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"2026010711361295400_ref3","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1038\/s41467-020-16434-y","article-title":"Evolution and structure of clinically relevant gene fusions in multiple myeloma","volume":"11","author":"Foltz","year":"2020","journal-title":"Nat Commun"},{"key":"2026010711361295400_ref4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/ncrna7010010","article-title":"Fusion genes and RNAs in cancer development","volume":"7","author":"Taniue","year":"2021","journal-title":"Noncoding RNA"},{"key":"2026010711361295400_ref5","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/s41591-019-0434-2","article-title":"Immunogenic neoantigens derived from gene fusions stimulate T cell responses","volume":"25","author":"Yang","year":"2019","journal-title":"Nat Med"},{"key":"2026010711361295400_ref6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/(SICI)1097-4644(1998)72:30\/31+&lt;264::AID-JCB32&gt;3.3.CO;2-L","article-title":"Translocations, fusion genes, and acute leukemia","volume":"72","author":"Saha","year":"1998","journal-title":"J Cell Biochem"},{"key":"2026010711361295400_ref7","doi-asserted-by":"publisher","first-page":"107325","DOI":"10.1016\/j.leukres.2023.107325","article-title":"Genetic alterations in the BCR-ABL1 fusion gene related to imatinib resistance in chronic myeloid leukemia","volume":"131","author":"Mart\u00ednez-Castillo","year":"2023","journal-title":"Leuk Res"},{"key":"2026010711361295400_ref8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/path.2154","article-title":"Morphological features of TMPRSS2\u2013ERGgene fusion prostate cancer","volume":"212","author":"Mosquera","year":"2007","journal-title":"J Pathol"},{"key":"2026010711361295400_ref9","doi-asserted-by":"publisher","first-page":"5450","DOI":"10.3892\/mmr.2017.7281","article-title":"Significance of the TMPRSS2:ERG gene fusion in prostate cancer","volume":"16","author":"Wang","year":"2017","journal-title":"Mol Med Rep"},{"key":"2026010711361295400_ref10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.canlet.2008.03.035","article-title":"PAX3\u2013FOXO1 fusion gene in rhabdomyosarcoma","volume":"270","author":"Linardic","year":"2008","journal-title":"Cancer Lett"},{"key":"2026010711361295400_ref11","doi-asserted-by":"publisher","first-page":"35445","DOI":"10.18632\/oncotarget.16367","article-title":"Pathogenesis ofETV6\/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"2026010711361295400_ref12","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1038\/s41467-019-09374-9","article-title":"Diagnosis of fusion genes using targeted RNA sequencing","volume":"10","author":"Heyer","year":"2019","journal-title":"Nat Commun"},{"key":"2026010711361295400_ref13","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/diagnostics10080521","article-title":"Next generation sequencing for gene fusion analysis in lung cancer: a literature review","volume":"10","author":"Bruno","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"2026010711361295400_ref14","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s13059-019-1842-9","article-title":"Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods","volume":"20","author":"Haas","year":"2019","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13073-015-0167-x","article-title":"JAFFA: high sensitivity transcriptome-focused fusion gene detection","volume":"7","author":"Davidson","year":"2015","journal-title":"Genome Med"},{"key":"2026010711361295400_ref16","doi-asserted-by":"publisher","first-page":"21597","DOI":"10.1038\/srep21597","article-title":"Comparative assessment of methods for the fusion transcripts detection from RNA-seq data","volume":"6","author":"Kumar","year":"2016","journal-title":"Sci Rep"},{"key":"2026010711361295400_ref17","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv1234","article-title":"Comprehensive evaluation of fusion transcript detection algorithms and a meta-caller to combine top performing methods in paired-end RNA-seq data","volume":"44","author":"Liu","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2026010711361295400_ref18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2013-14-7-405","article-title":"The advantages of SMRT sequencing","volume":"14","author":"Roberts","year":"2013","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref19","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1111\/1755-0998.12324","article-title":"A first look at the Oxford nanopore MinION sequencer","volume":"14","author":"Mikheyev","year":"2014","journal-title":"Mol Ecol Resour"},{"key":"2026010711361295400_ref20","doi-asserted-by":"publisher","first-page":"5935","DOI":"10.1038\/s41467-023-41649-0","article-title":"TAGET: a toolkit for analyzing full-length transcripts from long-read sequencing","volume":"14","author":"Xia","year":"2023","journal-title":"Brief Bioinform"},{"key":"2026010711361295400_ref21","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1038\/s41592-024-02298-3","article-title":"Systematic assessment of long-read RNA-seq methods for transcript identification and quantification","author":"Pardo-Palacios","year":"2024"},{"key":"2026010711361295400_ref22","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41587-023-01815-7","article-title":"High-throughput RNA isoform sequencing using programmed cDNA concatenation","volume":"42","author":"Al\u2019Khafaji","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026010711361295400_ref23","doi-asserted-by":"publisher","first-page":"9726","DOI":"10.1073\/pnas.1806447115","article-title":"Improving nanopore read accuracy with the R2C2 method enables the sequencing of highly multiplexed full-length single-cell cDNA","volume":"115","author":"Volden","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026010711361295400_ref24","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and challenges in long-read sequencing data analysis","volume":"21","author":"Amarasinghe","year":"2020","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13059-021-02588-5","article-title":"JAFFAL: detecting fusion genes with long-read transcriptome sequencing","volume":"23","author":"Davidson","year":"2022","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref26","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1186\/s12864-020-07207-4","article-title":"LongGF: computational algorithm and software tool for fast and accurate detection of gene fusions by long-read transcriptome sequencing","volume":"21","author":"Liu","year":"2020","journal-title":"BMC Genomics"},{"key":"2026010711361295400_ref27","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1158\/0008-5472.CAN-22-1628","article-title":"Gene fusion detection and characterization in long-read cancer transcriptome sequencing data with FusionSeeker","volume":"83","author":"Chen","year":"2023","journal-title":"Cancer Res"},{"key":"2026010711361295400_ref28","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1101\/gr.279200.124","article-title":"Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution","volume-title":"Genome research","author":"Qin","year":"2025"},{"key":"2026010711361295400_ref29","doi-asserted-by":"publisher","DOI":"10.1101\/2025.02.23.639788","article-title":"GFHunter enables accurate and efficient gene fusion detection in long-read cancer transcriptomes","volume-title":"bioRxiv","author":"Liu","year":"2025"},{"key":"2026010711361295400_ref30","doi-asserted-by":"publisher","first-page":"S181","DOI":"10.1093\/bioinformatics\/18.suppl_1.S181","article-title":"Splicing graphs and EST assembly problem","volume":"18","author":"Heber","year":"2002","journal-title":"Bioinformatics"},{"key":"2026010711361295400_ref31","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nbt.4227","article-title":"Variation graph toolkit improves read mapping by representing genetic variation in the reference","volume":"36","author":"Garrison","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2026010711361295400_ref32","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2026010711361295400_ref33","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-genom-120219-080406","article-title":"Pangenome graphs","volume":"21","author":"Eizenga","year":"2020","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2026010711361295400_ref34","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41592-022-01731-9","article-title":"Haplotype-aware pantranscriptome analyses using spliced pangenome graphs","volume":"20","author":"Sibbesen","year":"2023","journal-title":"Nat Methods"},{"key":"2026010711361295400_ref35","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.11.664486","article-title":"SVPG: a pangenome-based structural variant detection approach and rapid augmentation of pangenome graphs with new samples","volume-title":"bioRxiv","author":"Hu","year":"2025"},{"key":"2026010711361295400_ref36","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1186\/s12859-018-2436-3","article-title":"ASGAL: aligning RNA-seq data to a splicing graph to detect novel alternative splicing events","volume":"19","author":"Denti","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"2026010711361295400_ref37","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s13059-020-02168-z","article-title":"The design and construction of reference pangenome graphs with minigraph","volume":"21","author":"Li","year":"2020","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref38","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"2026010711361295400_ref39","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1093\/bioinformatics\/btaa963","article-title":"abPOA: an SIMD-based C library for fast partial order alignment using adaptive band","volume":"37","author":"Gao","year":"2021","journal-title":"Bioinformatics"},{"key":"2026010711361295400_ref40","doi-asserted-by":"publisher","first-page":"lqac092","DOI":"10.1093\/nargab\/lqac092","article-title":"PBSIM3: a simulator for all types of PacBio and ONT long reads","volume":"4","author":"Ono","year":"2022","journal-title":"NAR Genom Bioinformatics"},{"key":"2026010711361295400_ref41","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1093\/nar\/gkw032","article-title":"Recurrent chimeric fusion RNAs in non-cancer tissues and cells","volume":"44","author":"Babiceanu","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2026010711361295400_ref42","doi-asserted-by":"publisher","first-page":"27889","DOI":"10.18632\/oncotarget.8556","article-title":"Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma","volume":"7","author":"Pintarelli","year":"2016","journal-title":"Oncotarget"},{"key":"2026010711361295400_ref43","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/0039-128X(75)90110-5","article-title":"MCF-7: a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors","volume":"26","author":"Horwitz","year":"1975","journal-title":"Steroids"},{"key":"2026010711361295400_ref44","doi-asserted-by":"publisher","first-page":"R6","DOI":"10.1186\/gb-2011-12-1-r6","article-title":"Identification of fusion genes in breast cancer by paired-end RNA-sequencing","volume":"12","author":"Edgren","year":"2011","journal-title":"Genome Biol"},{"key":"2026010711361295400_ref45","doi-asserted-by":"publisher","first-page":"e48745","DOI":"10.1371\/journal.pone.0048745","article-title":"Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms","volume":"7","author":"Kangaspeska","year":"2012","journal-title":"PloS One"},{"key":"2026010711361295400_ref46","doi-asserted-by":"publisher","first-page":"e1002464","DOI":"10.1371\/journal.pcbi.1002464","article-title":"RNA-seq mapping and detection of gene fusions with a suffix array algorithm","volume":"8","author":"Sakarya","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"2026010711361295400_ref47","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1101\/gr.113225.110","article-title":"Transcriptional consequences of genomic structural aberrations in breast cancer","volume":"21","author":"Inaki","year":"2011","journal-title":"Genome Res"},{"key":"2026010711361295400_ref48","doi-asserted-by":"publisher","first-page":"12353","DOI":"10.1073\/pnas.0904720106","article-title":"Chimeric transcript discovery by paired-end transcriptome sequencing","volume":"106","author":"Maher","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026010711361295400_ref49","doi-asserted-by":"publisher","first-page":"e100","DOI":"10.1093\/nar\/gkr362","article-title":"A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines","volume":"39","author":"Asmann","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2026010711361295400_ref50","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-025-02623-4","article-title":"A systematic benchmark of nanopore long-read RNA sequencing for transcript-level analysis in human cell lines","author":"Chen","year":"2025","journal-title":"Nat Methods"},{"key":"2026010711361295400_ref51","doi-asserted-by":"publisher","first-page":"D817","DOI":"10.1093\/nar\/gkz1013","article-title":"ChimerDB 40: an updated and expanded database of fusion genes","volume":"48","author":"Jang","year":"2020","journal-title":"Nucleic Acids Res"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/1\/bbaf702\/66292343\/bbaf702.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/1\/bbaf702\/66292343\/bbaf702.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:36:22Z","timestamp":1767803782000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaf702\/8416442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,7]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaf702","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]},"article-number":"bbaf702"}}