JAFFAL: Detecting Fusion Genes with Long-read Transcriptome Sequencing

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2022 Jan 7

PMID 34991664

Citations 23

Authors

Nadia M Davidson

Ying Chen

Teresa Sadras

Georgina L Ryland

Piers Blombery

Paul G Ekert

Jonathan Goke

Alicia Oshlack

Affiliations

Soon will be listed here.

Abstract

In cancer, fusions are important diagnostic markers and targets for therapy. Long-read transcriptome sequencing allows the discovery of fusions with their full-length isoform structure. However, due to higher sequencing error rates, fusion finding algorithms designed for short reads do not work. Here we present JAFFAL, to identify fusions from long-read transcriptome sequencing. We validate JAFFAL using simulations, cell lines, and patient data from Nanopore and PacBio. We apply JAFFAL to single-cell data and find fusions spanning three genes demonstrating transcripts detected from complex rearrangements. JAFFAL is available at https://github.com/Oshlack/JAFFA/wiki .

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References

Gao Q, Liang W, Foltz S, Mutharasu G, Jayasinghe R, Cao S . Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Rep. 2018; 23(1):227-238.e3. PMC: 5916809. DOI: 10.1016/j.celrep.2018.03.050. View

Kumar S, Vo A, Qin F, Li H . Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data. Sci Rep. 2016; 6:21597. PMC: 4748267. DOI: 10.1038/srep21597. View

White R, Pellefigues C, Ronchese F, Lamiable O, Eccles D . Investigation of chimeric reads using the MinION. F1000Res. 2017; 6:631. PMC: 5600009. DOI: 10.12688/f1000research.11547.2. View

Cmero M, Schmidt B, Majewski I, Ekert P, Oshlack A, Davidson N . MINTIE: identifying novel structural and splice variants in transcriptomes using RNA-seq data. Genome Biol. 2021; 22(1):296. PMC: 8532352. DOI: 10.1186/s13059-021-02507-8. View

Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F . GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22(9):1760-74. PMC: 3431492. DOI: 10.1101/gr.135350.111. View

Kangaspeska S, Hultsch S, Edgren H, Nicorici D, Murumagi A, Kallioniemi O . Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms. PLoS One. 2012; 7(10):e48745. PMC: 3485361. DOI: 10.1371/journal.pone.0048745. View

Liu H, Begik O, Lucas M, Ramirez J, Mason C, Wiener D . Accurate detection of mA RNA modifications in native RNA sequences. Nat Commun. 2019; 10(1):4079. PMC: 6734003. DOI: 10.1038/s41467-019-11713-9. View

Jeck W, Lee J, Robinson H, Le L, Iafrate A, Nardi V . A Nanopore Sequencing-Based Assay for Rapid Detection of Gene Fusions. J Mol Diagn. 2018; 21(1):58-69. DOI: 10.1016/j.jmoldx.2018.08.003. View

Workman R, Tang A, Tang P, Jain M, Tyson J, Razaghi R . Nanopore native RNA sequencing of a human poly(A) transcriptome. Nat Methods. 2019; 16(12):1297-1305. PMC: 7768885. DOI: 10.1038/s41592-019-0617-2. View

10.

Sadedin S, Pope B, Oshlack A . Bpipe: a tool for running and managing bioinformatics pipelines. Bioinformatics. 2012; 28(11):1525-6. DOI: 10.1093/bioinformatics/bts167. View

11.

Maher C, Palanisamy N, Brenner J, Cao X, Kalyana-Sundaram S, Luo S . Chimeric transcript discovery by paired-end transcriptome sequencing. Proc Natl Acad Sci U S A. 2009; 106(30):12353-8. PMC: 2708976. DOI: 10.1073/pnas.0904720106. View

12.

Haas B, Dobin A, Li B, Stransky N, Pochet N, Regev A . Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 2019; 20(1):213. PMC: 6802306. DOI: 10.1186/s13059-019-1842-9. View

13.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A, Kim S . The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7. PMC: 3320027. DOI: 10.1038/nature11003. View

14.

Liu Q, Hu Y, Stucky A, Fang L, Zhong J, Wang K . LongGF: computational algorithm and software tool for fast and accurate detection of gene fusions by long-read transcriptome sequencing. BMC Genomics. 2020; 21(Suppl 11):793. PMC: 7771079. DOI: 10.1186/s12864-020-07207-4. View

15.

Tian L, Jabbari J, Thijssen R, Gouil Q, Amarasinghe S, Voogd O . Comprehensive characterization of single-cell full-length isoforms in human and mouse with long-read sequencing. Genome Biol. 2021; 22(1):310. PMC: 8582192. DOI: 10.1186/s13059-021-02525-6. View

16.

Inaki K, Hillmer A, Ukil L, Yao F, Woo X, Vardy L . Transcriptional consequences of genomic structural aberrations in breast cancer. Genome Res. 2011; 21(5):676-87. PMC: 3083084. DOI: 10.1101/gr.113225.110. View

17.

Vellichirammal N, Albahrani A, Banwait J, Mishra N, Li Y, Roychoudhury S . Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts. Mol Ther Nucleic Acids. 2020; 19:1379-1398. PMC: 7044684. DOI: 10.1016/j.omtn.2020.01.023. View

18.

Jia W, Qiu K, He M, Song P, Zhou Q, Zhou F . SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data. Genome Biol. 2013; 14(2):R12. PMC: 4054009. DOI: 10.1186/gb-2013-14-2-r12. View

19.

Rang F, Kloosterman W, de Ridder J . From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy. Genome Biol. 2018; 19(1):90. PMC: 6045860. DOI: 10.1186/s13059-018-1462-9. View

20.

Uhrig S, Ellermann J, Walther T, Burkhardt P, Frohlich M, Hutter B . Accurate and efficient detection of gene fusions from RNA sequencing data. Genome Res. 2021; 31(3):448-460. PMC: 7919457. DOI: 10.1101/gr.257246.119. View