ePrints

A dedicated caller for DUX4 rearrangements from whole-genome sequencing data

Lookup NU author(s): Sarra Ryan, Emerita Professor Christine Harrison, Professor Anthony MoormanORCiD

Downloads

• Published version [.pdf]

Licence

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© The Author(s) 2024.Rearrangements involving the DUX4 gene (DUX4-r) define a subtype of paediatric and adult acute lymphoblastic leukaemia (ALL) with a favourable outcome. Currently, there is no ‘standard of care’ diagnostic method for their confident identification. Here, we present an open-source software tool designed to detect DUX4-r from short-read, whole-genome sequencing (WGS) data. Evaluation on a cohort of 210 paediatric ALL cases showed that our method detects all known, as well as previously unidentified, cases of IGH::DUX4 and rearrangements with other partner genes. These findings demonstrate the possibility of robustly detecting DUX4-r using WGS in the routine clinical setting.

Publication metadata

Author(s): Grobecker P, Berri S, Peden JF, Chow K-J, Fielding C, Armogida I, Northen H, McBride DJ, Campbell PJ, Becq J, Ryan SL, Bentley DR, Harrison CJ, Moorman AV, Ross MT, Mijuskovic M

Publication type: Article

Publication status: Published

Journal: BMC Medical Genomics

Year: 2025

Volume: 18

Issue: 1

Online publication date: 30/01/2025

Acceptance date: 13/12/2024

Date deposited: 24/02/2025

ISSN (electronic): 1755-8794

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s12920-024-02069-1

DOI: 10.1186/s12920-024-02069-1

Data Access Statement: The datasets analysed during the current study are available in the European Genome-phenome Archive (EGA) repository, under the Accession Code EGAS00001006863 (https://ega-archive.org/studies/EGAS00001006863). Pelops is publicly available as a Python package named ilmn-pelops. The results of this paper are based on Pelops version 0.8.0, which is available through the Python Package Index (https://pypi.org/project/ilmn-pelops/0.8 .0/). The source code can also be found at https://github.com/Illumina/Pelop s. The code has extensive unit test coverage (98.1% at commit 6f29f33e) and tests pass on Python 3.7, 3.9, 3.11. Pelops has minimal dependencies on thirdparty packages, with the exception of pysam [[34]. The IGH::DUX4 caller is also implemented in Illumina DRAGEN 4.3.

PubMed id: 39885506

Altmetrics

Funding

Share