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

Grobecker, P.; Berri, S.; Peden, J. F.; Chow, K.-J.; Fielding, C.; Armogida, I.; Northen, H.; McBride, D. J.; Campbell, P. J.; Becq, J.; Ryan, S. L.; Bentley, D. R.; Harrison, C. J.; Moorman, A. V.; Ross, M. T.; Mijuskovic, M.

2024-05-24 bioinformatics
10.1101/2024.05.23.595509 bioRxiv
Show abstract

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.

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