Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Genome research Pub Date : 2025-03-14 DOI:10.1101/gr.279200.124
Qian Qin, Victoria Popic, Kirsty Wienand, Houlin Yu, Emily White, Akanksha Khorgade, Asa Shin, Christophe Georgescu, Catarina D. Campbell, Arthur Dondi, Niko Beerenwinkel, Francisca Vazquez, Aziz M. Al'Khafaji, Brian J. Haas
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引用次数: 0

Abstract

Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics and prognostics and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short-read sequences. Recent advances in long-read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single-cell samples. Here, we developed a new computational tool, CTAT-LR-Fusion, to detect fusion transcripts from long-read RNA-seq with or without companion short reads, with applications to bulk or single-cell transcriptomes. We demonstrate that CTAT-LR-Fusion exceeds the fusion detection accuracy of alternative methods as benchmarked with simulated and genuine long-read RNA-seq. Using short- and long-read RNA-seq, we further apply CTAT-LR-Fusion to bulk transcriptomes of nine tumor cell lines and to tumor single cells derived from a melanoma sample and three metastatic high-grade serous ovarian carcinoma samples. In both bulk and single-cell RNA-seq, long isoform reads yield higher sensitivity for fusion detection than short reads with notable exceptions. By combining short and long reads in CTAT-LR-Fusion, we are able to further maximize the detection of fusion splicing isoforms and fusion-expressing tumor cells.
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来源期刊
Genome research
Genome research 生物-生化与分子生物学
CiteScore
12.40
自引率
1.40%
发文量
140
审稿时长
6 months
期刊介绍: Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies. New data in these areas are published as research papers, or methods and resource reports that provide novel information on technologies or tools that will be of interest to a broad readership. Complete data sets are presented electronically on the journal''s web site where appropriate. The journal also provides Reviews, Perspectives, and Insight/Outlook articles, which present commentary on the latest advances published both here and elsewhere, placing such progress in its broader biological context.
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