JAFFAL: detecting fusion genes with long-read transcriptome sequencing

Nadia M Davidson; Ying Chen; Teresa Sadras; Georgina L Ryland; Piers Blombery; Paul G Ekert; Jonathan Göke; Alicia Oshlack

doi:10.1186/s13059-021-02588-5

JAFFAL: detecting fusion genes with long-read transcriptome sequencing

Genome Biol. 2022 Jan 6;23(1):10. doi: 10.1186/s13059-021-02588-5.

Authors

Nadia M Davidson^{1

2

3}, Ying Chen⁴, Teresa Sadras^{5

6}, Georgina L Ryland^{5

6

7}, Piers Blombery^{5

6}, Paul G Ekert^{5

6

8

9

10}, Jonathan Göke^{4

11}, Alicia Oshlack^{12

13

14}

Affiliations

¹ Peter MacCallum Cancer Centre, Victoria, Australia. davidson.n@wehi.edu.au.
² School of BioSciences, University of Melbourne, Victoria, Australia. davidson.n@wehi.edu.au.
³ The Walter and Eliza Hall Institute, Victoria, Australia. davidson.n@wehi.edu.au.
⁴ Genome Institute of Singapore, Singapore, Singapore.
⁵ Peter MacCallum Cancer Centre, Victoria, Australia.
⁶ Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.
⁷ Centre for Cancer Research, University of Melbourne, Victoria, Australia.
⁸ Children's Cancer Institute, Lowy Cancer Centre, UNSW, Sydney, NSW, Australia.
⁹ School of Women's and Children's Health, UNSW, Sydney, NSW, Australia.
¹⁰ Murdoch Children's Research Institute, Victoria, Australia.
¹¹ National Cancer Centre Singapore, Singapore, Singapore.
¹² Peter MacCallum Cancer Centre, Victoria, Australia. alicia.oshlack@petermac.org.
¹³ School of BioSciences, University of Melbourne, Victoria, Australia. alicia.oshlack@petermac.org.
¹⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia. alicia.oshlack@petermac.org.

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 .

Keywords: Fusions; Long reads; Nanopore; PacBio; RNA sequencing; Translocations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Gene Fusion
High-Throughput Nucleotide Sequencing*
Humans
Sequence Analysis, DNA
Transcriptome*