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

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.

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Publication Details

Journal
Genome biology
Published
2025-09-27
DOI
https://doi.org/10.1186/s13059-025-03790-5
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
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article

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

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Genome biology
Single-cell and spatial transcriptomics
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Hybrid BAG-seq: DNA and RNA from the same single nucleus reveals interactions between genomic and transcriptomic landscapes in human tumor samples

Michael Wigler, Sarah Park, Michael Ronemus, Arvind Rishi, Nissim Ranade, Marina Frimer, Elizabeth Rose, Rong Ma, David L. Donoho, Dan Levy, Patrick G. Morris, Zvi Laster, Joan Alexander, Hope Orjuela, Craig Podszus, Danielle Stauder, Siran Li, Gary L. Goldberg, Liam Shanley, Daniel W. Bradford, Jude Kendall, Peter M. Andrews
article en

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.

Genome biologyVol. 26(1)
Broad Institute (US), Northwell Health (US), Harvard University (US), Hofstra University (US), Cold Spring Harbor Laboratory (US), Dana-Farber Cancer Institute (US), Stanford University (US)
Openalex Percentile: Top 77%
Single-cell and spatial transcriptomics
DOIOpen Access PDFOpenAlex
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