Accurate and efficient detection of gene fusions from RNA sequencing data

The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally...

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Bibliographic Details
Published in:Genome research 2021-03, Vol.31 (3), p.448-460
Main Authors: Uhrig, Sebastian, Ellermann, Julia, Walther, Tatjana, Burkhardt, Pauline, Fröhlich, Martina, Hutter, Barbara, Toprak, Umut H, Neumann, Olaf, Stenzinger, Albrecht, Scholl, Claudia, Fröhling, Stefan, Brors, Benedikt
Format: Article
Language:English
Subjects:
Cancer
Computer applications
Fibroblast growth factor receptor 2
Gene Fusion - genetics
Humans
K-Ras protein
MAP kinase
Medical research
Method
Oncogene Proteins, Fusion - genetics
Pancreatic cancer
Pancreatic Neoplasms - genetics
Precision Medicine
Proto-Oncogene Proteins - genetics
Ribonucleic acid
RNA
RNA - genetics
Sequence Analysis, RNA
Signal transduction
Tumors
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Summary:The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples ( = 803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated with wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in In addition, we confirmed the transforming potential of two novel fusions, - and - , in cellular assays. These results show Arriba's utility in both basic cancer research and clinical translation.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.257246.119