Gene fusions are not uncommon causes of cancer. Gene fusions can be detected in short-read RNA sequencing with the help of additional algorithms. These gene fusions can be queried against databases such as OncoKB or ChimerDB to identify known fusions and possible drug interventions.
Detecting fusions in RNA-seq data can be tricky as these transcripts are often under-expressed. It may be prudent to have deeper sequencing than for general RNA-seq experiments focused on differential gene expression to improve detection and support for subtle findings.
From the p22162 manuscript:
Fusion detection was performed with Arriba [37]. Raw reads were mapped to Ensembl v107 Homo sapiens GRCh38 [38] reference by Star 2.7.9a [21] using the parameters suggested by Arriba. Fusion processing was performed using the hg38 reference databases provided by the Arriba helper script download_references.sh. Processed fusions were queried against ChimerDB v4.0 [39]. Fusions with at least 2 valid supporting reads were reported as present in ChimerDB if they were in ChimerKB, in ChimerPub with a prediction score >= 0.8, or in ChimerSeq-Plus. Drug targets were identified by querying OncoKB [36]. Novel fusions were reported only if they had a ‘high’ confidence rating from Arriba’s algorithm and were not deletion/read-through events due to high false positive rate [37].
21. Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21.
36. Chakravarty D, Gao J, Phillips SM, et al. OncoKB: A Precision Oncology Knowledge Base. JCO Precis Oncol. 2017;2017.
37. Uhrig S, Ellermann J, Walther T, et al. Accurate and efficient detection of gene fusions from RNA sequencing data. Genome Res. 2021;31(3):448-460.
38. Cunningham F, Allen JE, Allen J, et al. Ensembl 2022. Nucleic Acids Res. 2022;50(D1):D988-D995.
39. Jang YE, Jang I, Kim S, et al. ChimerDB 4.0: an updated and expanded database of fusion genes. Nucleic Acids Res. 2020;48(D1):D817-D824.