WGS_of_AML_during_PARPi_therapy

We will require WGS on Illumina X10 machines of three samples, along with storage and computational power to perform the relevant analysis.

1 Dataset 5 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001005028	Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.	HiSeq X Ten	5

Publications	Citations
A practical guide for mutational signature analysis in hematological malignancies. Maura F, Degasperi A, Nadeu F, Leongamornlert D, Davies H, Moore L, Royo R, Ziccheddu B, Puente XS, Avet-Loiseau H, Campbell PJ, Nik-Zainal S, Campo E, Munshi N, Bolli N. Nat Commun 10: 2019 2969	112
mmsig: a fitting approach to accurately identify somatic mutational signatures in hematological malignancies. Rustad EH, Nadeu F, Angelopoulos N, Ziccheddu B, Bolli N, Puente XS, Campo E, Landgren O, Maura F. Commun Biol 4: 2021 424	18
The evolution of hematopoietic cells under cancer therapy. Pich O, Cortes-Bullich A, Muiños F, Pratcorona M, Gonzalez-Perez A, Lopez-Bigas N. Nat Commun 12: 2021 4803	28
Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma. Maclachlan KH, Rustad EH, Derkach A, Zheng-Lin B, Yellapantula V, Diamond B, Hultcrantz M, Ziccheddu B, Boyle EM, Blaney P, Bolli N, Zhang Y, Dogan A, Lesokhin AM, Morgan GJ, Landgren O, Maura F. Nat Commun 12: 2021 5172	21
Tracking the evolution of therapy-related myeloid neoplasms using chemotherapy signatures. Diamond B, Ziccheddu B, Maclachlan K, Taylor J, Boyle E, Ossa JA, Jahn J, Affer M, Totiger TM, Coffey D, Chandhok N, Watts J, Cimmino L, Lu SX, Bolli N, Bolton K, Landau H, Park JH, Ganesh K, McPherson A, Sekeres MA, Lesokhin A, Chung DJ, Zhang Y, Ho C, Roshal M, Tyner J, Nimer S, Papaemmanuil E, Usmani S, Morgan G, Landgren O, Maura F. Blood 141: 2023 2359-2371	17