Refinement of computational identification of somatic copy number alterations using DNA methylation microarrays illustrated in cancers of unknown primary
Blecua, Pedro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Davalos, Veronica (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
De Villasante, Izar (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Merkel, Angelika (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Musulén, Eva (Hospital Universitari General de Catalunya)
Coll-Sanmartin, Laia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2022
Abstract:	High-throughput genomic technologies are increasingly used in personalized cancer medicine. However, computational tools to maximize the use of scarce tissues combining distinct molecular layers are needed. Here we present a refined strategy, based on the R-package 'conumee', to better predict somatic copy number alterations (SCNA) from deoxyribonucleic acid (DNA) methylation arrays. Our approach, termed hereafter as 'conumee-KCN', improves SCNA prediction by incorporating tumor purity and dynamic thresholding. We trained our algorithm using paired DNA methylation and SNP Array 6. 0 data from The Cancer Genome Atlas samples and confirmed its performance in cancer cell lines. Most importantly, the application of our approach in cancers of unknown primary identified amplified potentially actionable targets that were experimentally validated by Fluorescence in situ hybridization and immunostaining, reaching 100% specificity and 93. 3% sensitivity.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1080 "la Caixa" Foundation LCF/PR/GN18/51140001 Agencia Estatal de Investigación RTI2018-094049-B-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Somatic copy number alterations ; DNA methylation ; Gene amplification ; Actionable target identification ; Cancers of unknown primary
Published in:	Briefings in Bioinformatics, Vol. 23 Núm. 5 (september 2022) , p. bbac161, ISSN 1477-4054

DOI: 10.1093/bib/bbac161
PMID: 35524475

9 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles