Robust analysis of allele-specific copy number alterations from scRNA-seq data with XClone.

Autor: Huang R; School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China., Huang X; School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.; Center for Translational Stem Cell Biology, Hong Kong Science and Technology Park, Hong Kong SAR, China., Tong Y; Department of Pathology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.; Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China., Yan HYN; Department of Pathology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.; Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China., Leung SY; Department of Pathology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.; Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China.; The Jockey Club Centre for Clinical Innovation and Discovery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.; Centre for PanorOmic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Stegle O; Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Huang Y; School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China. yuanhua@hku.hk.; Center for Translational Stem Cell Biology, Hong Kong Science and Technology Park, Hong Kong SAR, China. yuanhua@hku.hk.; Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong SAR, China. yuanhua@hku.hk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 06; Vol. 15 (1), pp. 6684. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1038/s41467-024-51026-0
Abstrakt: Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.
(© 2024. The Author(s).)
Databáze: MEDLINE
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