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

IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Siran Li, Joan Alexander, Jude Kendall, Peter Andrews, Elizabeth Rose, Hope Orjuela, Sarah Park, Craig Podszus, Liam Shanley, Nissim Ranade, Patrick Morris, Danielle Stauder, Daniel Bradford, Zachary Laster, Michael Ronemus, Arvind Rishi, Marina Frimer, Rong Ma, David L. Donoho, Gary L. Goldberg, Michael Wigler, Dan Levy
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引用次数: 0

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.
混合BAG-seq:来自同一细胞核的DNA和RNA揭示了人类肿瘤样本中基因组和转录组景观之间的相互作用
我们介绍了杂交BAG-seq:一种高通量、多组学方法,可以同时从单个细胞核中捕获DNA和RNA。我们将这一方案应用于5例子宫癌患者的65,499个单核样本,并使用来自同一组织的rna和dna单独方案验证了聚类。患者体内通常存在多个肿瘤基因组或表达簇,不同的肿瘤克隆投射到不同或共享的表达状态,显示了几乎所有可能的基因组-转录组相关性。我们还鉴定了在各种细胞类型和具有异常表达模式的患者特异性基质亚型中具有显著X染色体丢失的突变基质。
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来源期刊
Genome Biology
Genome Biology Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
21.00
自引率
3.30%
发文量
241
审稿时长
2 months
期刊介绍: Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens. With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category. Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.
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