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

Genome biology
Authors
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.

Year of Publication
2025
Journal
Genome biology
Volume
26
Issue
1
Pages
314
Date Published
09/2025
ISSN
1474-760X
DOI
10.1186/s13059-025-03790-5
PubMed ID
41015771
Links