Accurate and efficient detection of gene fusions from RNA sequencing data
Open accessAbstract
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 ( n = 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 KRAS wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in KRAS . In addition, we confirmed the transforming potential of two novel fusions, RRBP1 - RAF1 and RASGRP1 - ATP1A1 , in cellular assays. These results show Arriba's utility in both basic cancer research and clinical translation.
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“The software Arriba (66) was used and specifically focused on detecting the Etv6-Runx1 fusion.”
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- Authors
- Uhrig, S., Ellermann, J., Walther, T., Burkhardt, P., Fröhlich, M., Hutter, B., Toprak, U. H., Neumann, O., Stenzinger, A., Scholl, C., Fröhling, S., & Brors, B.
- Affiliations
- German Cancer Research Center (DE)
- University Hospital Heidelberg (DE)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2021-01-13
- Volume
- 31
- Issue
- 3
- Pages
- 448-460
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC7919457
- OpenAlex
- W3118238647
- Cited by
- 526
- References
- 65
- Citations by year
- 2026: 105 · 2025: 117 · 2024: 104 · 2023: 91 · 2022: 71 · 2021: 37
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genome Research (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum (015, 021)
- Heidelberg Center for Personalized Oncology
- Nationales Centrum für Tumorerkrankungen Heidelberg
- Dietmar Hopp Foundation
- Ontario Institute for Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- fusion gene detection, Arriba, pancreatic cancer, KRAS wild-type tumors, MAPK signaling, precision oncology, RNA sequencing
- MeSH terms
- Humans, Pancreatic Neoplasms, Proto-Oncogene Proteins, RNA, Oncogene Proteins, Fusion, Sequence Analysis, RNA, Gene Fusion, Precision Medicine
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