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A practical guide for mutational signature analysis in hematological malignancies
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019), Dipòsit Digital de la UB, Universidad de Barcelona, Scopus, RUO. Repositorio Institucional de la Universidad de Oviedo, instname, Recercat. Dipósit de la Recerca de Catalunya, UPCommons. Portal del coneixement obert de la UPC, Universitat Politècnica de Catalunya (UPC)
- Publication Year :
- 2019
-
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.<br />Mutational signature analysis provides important information about the mutational processes underpinning different stages of tumorigenesis. Here, the authors compare publicly available signature extraction tools and suggest a framework for the generation of accurate and reproducible signature data.
- Subjects :
- 0301 basic medicine
Computer science
Chronic lymphocytic leukemia
ADN
DNA Mutational Analysis
General Physics and Astronomy
Datasets as Topic
Myeloma
02 engineering and technology
Cancer--Immunological aspects
Hematological malignancies
Cancer genomics
Leukaemia
lcsh:Science
45/70
Multidisciplinary
BRCA1 Protein
article
Myeloid leukemia
High-Throughput Nucleotide Sequencing
Genomics
021001 nanoscience & nanotechnology
Signature (logic)
3. Good health
Leukemia
Leukemia, Myeloid, Acute
631/208/212
Practice Guidelines as Topic
0210 nano-technology
Multiple Myeloma
631/67/1990/804
Leucèmia mieloide
Science
Mutational signatures
45/23
631/67/69
Computational biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
631/67/1990/283
631/67/1990
medicine
Humans
Càncer -- Aspectes immunològics
BRCA2 Protein
Haematological cancer
Whole Genome Sequencing
Mutació (Biologia)
Computational Biology
General Chemistry
DNA
Mutation (Biology)
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
030104 developmental biology
Mutation
lcsh:Q
Treatment decision making
Analysis tools
Homologous Recombination Deficiency
Ciències de la salut [Àrees temàtiques de la UPC]
Subjects
Details
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....83fc151ad8809d65370630f5b832efd8
- Full Text :
- https://doi.org/10.1038/s41467-019-11037-8