
@article {120169,
	title = {Functional analysis of structural variants in single cells using Strand-seq.},
	journal = {Nat Biotechnol},
	volume = {41},
	year = {2023},
	month = {2022 Nov 24},
	pages = {832-844},
	chapter = {6},
	abstract = {<p>Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations.</p>
},
	issn = {1546-1696},
	doi = {10.1038/s41587-022-01551-4},
	author = {Jeong, Hyobin and Grimes, Karen and Rauwolf, Kerstin K and Bruch, Peter-Martin and Rausch, Tobias and Hasenfeld, Patrick and Benito, Eva and Roider, Tobias and Sabarinathan, Radhakrishnan and Porubsky, David and Herbst, Sophie A and Erarslan-Uysal, B{\"u}{\c s}ra and Jann, Johann-Christoph and Marschall, Tobias and Nowak, Daniel and Bourquin, Jean-Pierre and Kulozik, Andreas E and Dietrich, Sascha and Bornhauser, Beat and Sanders, Ashley D and Korbel, Jan O}
}
