Single-cell genome and transcriptome sequencing without upfront whole-genome amplification reveals cell state plasticity of melanoma subclones

Theunis, K; Vanuytven, S; Claes, I; Geurts, J; Rambow, F; Brown, D; Van Der Haegen, M; Marin-Bejar, O; Rogiers, A; Van Raemdonck, N; Leucci, E; Demeulemeester, J; Sifrim, A; Marine, JC; Voet, T

Author(s): Theunis, K; Vanuytven, S; Claes, I; Geurts, J; Rambow, F; Brown, D; Van Der Haegen, M; Marin-Bejar, O; Rogiers, A; Van Raemdonck, N; Leucci, E; Demeulemeester, J; Sifrim, A; Marine, JC; Voet, T;
Details: Publication Year 2025-03-20,Volume 53,Issue #6,Page gkaf173
Journal Title: Nucleic Acids Research
Abstract: Single-cell multi-omics methods enable the study of cell state diversity, which is largely determined by the interplay of the genome, epigenome, and transcriptome. Here, we describe Gtag&T-seq, a genome-and-transcriptome sequencing (G&T-seq) protocol of the same single cells that omits whole-genome amplification (WGA) by using direct genomic tagmentation (Gtag). Gtag drastically decreases the cost and improves coverage uniformity at single-cell and pseudo-bulk levels compared to WGA-based G&T-seq. We also show that transcriptome-based DNA copy number inference has limited resolution and accuracy, underlining the importance of affordable multi-omic approaches. Applying Gtag&T-seq to a melanoma xenograft model before treatment and at minimal residual disease revealed differential cell state plasticity and treatment response between cancer subclones. In summary, Gtag&T-seq is a low-cost and accurate single-cell multi-omics method that explores genetic alterations and their functional consequences in single cells at scale.
Publisher: Oxford Academic
Keywords: *Single-Cell Analysis/methods; Humans; *Melanoma/genetics/pathology; Animals; *Transcriptome/genetics; Mice; DNA Copy Number Variations/genetics; Cell Line, Tumor; Genomics/methods; Cell Plasticity/genetics; Gene Expression Profiling/methods; Whole Genome Sequencing/methods; Genome, Human/genetics
Research Division(s): Advanced Technology And Biology
PubMed ID: 40138718
Publisher's Version: https://doi.org/10.1093/nar/gkaf173
Open Access at Publisher's Site: https://doi.org/10.1093/nar/gkaf173
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-04-08 03:06:11

Last Modified: 2025-04-08 03:12:24