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http://hdl.handle.net/2445/147244
Title: | A practical guide for mutational signature analysis in hematological malignancies |
Author: | Maura, Francesco Degasperi, Andrea Nadeu, Ferran Leongamornlert, Daniel Davies, Helen Moore, Luiza Royo, Romina Ziccheddu, Bachisio Puente, Xose S. Avet-Loiseau, Hervé Campbell, Peter J. Nik-Zainal, Serena Campo Güerri, Elias Munshi, Nikhil Bolli, Niccolò |
Keywords: | Leucèmia mieloide Mutació (Biologia) ADN Myeloid leukemia Mutation (Biology) DNA |
Issue Date: | 5-Jul-2019 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-11037-8 |
It is part of: | Nature Communications, 2019, vol. 10, p. 2969 |
URI: | http://hdl.handle.net/2445/147244 |
Related resource: | https://doi.org/10.1038/s41467-019-11037-8 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Fonaments Clínics) |
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693579.pdf | 2.19 MB | Adobe PDF | View/Open | |
693579_Correction.pdf | Author Correction | 338.88 kB | Adobe PDF | View/Open |
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