Hybrid BAG-seq: DNA and RNA from the same single nucleus reveals interactions between genomic and transcriptomic landscapes in human tumor samples

Li, Siran, Alexander, Joan, Kendall, Jude, Andrews, Peter, Rose, Elizabeth, Orjuela, Hope, Park, Sarah, Podszus, Craig, Shanley, Liam, Ranade, Nissim, Morris, Patrick, Stauder, Danielle, Bradford, Daniel, Laster, Zachary, Ronemus, Michael, Rishi, Arvind, Frimer, Marina, Ma, Rong, Donoho, David L, Goldberg, Gary L, Wigler, Michael, Levy, Dan (September 2025) Hybrid BAG-seq: DNA and RNA from the same single nucleus reveals interactions between genomic and transcriptomic landscapes in human tumor samples. Genome Biology, 26 (1). p. 314. ISSN 1474-760X (Public Dataset)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/41015771

DOI: 10.1186/s13059-025-03790-5

Abstract

We introduce hybrid BAG-seq: a high-throughput, multi-omic method that simultaneously captures DNA and RNA from single nuclei. We apply this protocol to 65,499 single nuclei from samples of five uterine cancer patients and validate the clustering using RNA-only and DNA-only protocols from the same tissues. Multiple tumor genome or expression clusters are often present within a patient, with different tumor clones projecting into distinct or shared expression states, demonstrating nearly all possible genome-transcriptome correlations. We also identify mutant stroma with significant X chromosome loss in various cell types and patient-specific stromal subtypes exhibiting aberrant expression patterns.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Li, Siran Alexander, Joan Kendall, Jude T. Andrews, Peter Park, Sarah Ranade, Nissim Ronemus, Michael Wigler, Michael H. Levy, Dan Morris, Patrick Rose, Elizabeth Orjuela, Hope Podszus, Craig Shanley, Liam Stauder, Danielle Bradford, Daniel Laster, Zachary Goldberg, Gary
Communities:	CSHL labs > Beyaz lab CSHL labs > Levy lab CSHL labs > Wigler lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	27 September 2025
Date Deposited:	29 Sep 2025 13:36
Last Modified:	30 Sep 2025 17:17
PMCID:	PMC12476631
Related URLs:	Publisher
Dataset ID:	SRA: PRJNA773107 https://github.com/levycshl/bag-pipe https://doi.org/10.5281/zenodo.17048209 https://github.com/siranli01/DNA_RNA https://doi.org/10.5281/zenodo.17051405
URI:	https://repository.cshl.edu/id/eprint/41972

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