Functional phenotyping of genomic variants using multiomic scDNA-scRNA-seq

ABSTRACT: Genomic variation ranging from single nucleotide polymorphisms to structural variants in both coding and non-coding regions can impact gene function and expression, contributing to disease mechanisms such as cancer progression. Current precision editing tools to study variants systematically have limited efficiency and variable outcomes in mammalian cells. Additionally, assessing heterogenous variants in primary tumor samples at scale is challenging with current single-cell technologies. We developed a droplet-based multiomic targeted scDNA-scRNAseq (SDR-seq) method to precisely link genotypes with gene expression profiles in high-throughput. SDR-seq simultaneously assesses up to 480 RNA and gDNA targets high coverage and sensitivity across thousands of cells. Using SDR-seq, we associate coding and non-coding variants with distinct gene expression profiles in human iPSCs. Furthermore, we demonstrate that cells with a higher mutational burden exhibit elevated B-cell receptor signaling and tumorigenic gene expression in primary B-cell lymphoma samples. SDR-seq has the potential to gain functional insights into regulatory mechanisms encoded by genetic variants at diverse loci, advancing our ability to study gene expression regulation and its implications for disease.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE268646 | GEO | 2025/06/17

REPOSITORIES: GEO