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A practical guide for mutational signature analysis in hematological malignancies

UID: 11266

Publisher(s): European Genome-phenome Archive

Description
Description from EGA:

"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."
Subject(s)
OncoTree Cancer Type(s)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Access via EGA


Accession #: EGAD00001005028

Access Restrictions
Application Required
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Associated Publications
Equipment Used
Illumina HiSeq X Ten
Dataset Format(s)
CRAM
Dataset Size
206.2 GB
Data Catalog Record Updated
2024-05-30