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.

doi:10.1101/2024.05.23.595509

bioRxiv · 10.1101/2024.05.23.595509

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.

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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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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. Pelops: A dedicated caller for DUX4 rearrangements from whole-genome sequencing data. https://doi.org/10.1101/2024.05.23.595509

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