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Single-cell analysis of structural variations and complex rearrangements with tri-channel processing

Item Type:Article
Title:Single-cell analysis of structural variations and complex rearrangements with tri-channel processing
Creators Name:Sanders, A.D. and Meiers, S. and Ghareghani, M. and Porubsky, D. and Jeong, H. and van Vliet, M.A.C.C. and Rausch, T. and Richter-Pechańska, P. and Kunz, J.B. and Jenni, S. and Bolognini, D. and Longo, G.M.C. and Raeder, B. and Kinanen, V. and Zimmermann, J. and Benes, V. and Schrappe, M. and Mardin, B.R. and Kulozik, A.E. and Bornhauser, B. and Bourquin, J.P. and Marschall, T. and Korbel, J.O.
Abstract:Structural variation (SV), involving deletions, duplications, inversions and translocations of DNA segments, is a major source of genetic variability in somatic cells and can dysregulate cancer-related pathways. However, discovering somatic SVs in single cells has been challenging, with copy-number-neutral and complex variants typically escaping detection. Here we describe single-cell tri-channel processing (scTRIP), a computational framework that integrates read depth, template strand and haplotype phase to comprehensively discover SVs in individual cells. We surveyed SV landscapes of 565 single cells, including transformed epithelial cells and patient-derived leukemic samples, to discover abundant SV classes, including inversions, translocations and complex DNA rearrangements. Analysis of the leukemic samples revealed four times more somatic SVs than cytogenetic karyotyping, submicroscopic copy-number alterations, oncogenic copy-neutral rearrangements and a subclonal chromothripsis event. Advancing current methods, single-cell tri-channel processing can directly measure SV mutational processes in individual cells, such as breakage-fusion-bridge cycles, facilitating studies of clonal evolution, genetic mosaicism and SV formation mechanisms, which could improve disease classification for precision medicine.
Keywords:Cell Line, Chromothripsis, Clonal Evolution, Computational Biology, Gene Rearrangement, Genetic Translocation, Genomic Structural Variation, INDEL Mutation, Leukemia, Sequence Inversion, Single-Cell Analysis
Source:Nature Biotechnology
Publisher:Nature Publishing Group
Page Range:343-354
Date:March 2020
Official Publication:https://doi.org/10.1038/s41587-019-0366-x
PubMed:View item in PubMed

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