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Updated: Sep 9, 2025
06:24
Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
Published on: March 12, 2021
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Functional phenotyping of genomic variants using joint multiomic single-cell DNA-RNA sequencing
Dominik Lindenhofer1,2, Julia R Bauman3, John A Hawkins1,4
1Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Nature Methods
|September 1, 2025
Summary
We developed single-cell DNA-RNA sequencing (SDR-seq) to link genetic variants to gene expression. This method reveals how genetic variations influence gene activity and disease, like cancer progression.
Area of Science:
- Genomics
- Molecular Biology
- Biotechnology
Background:
- Genetic variants significantly impact gene function and expression, contributing to diseases like cancer.
- Studying endogenous genetic variants is challenging due to limitations in gene editing tools and genotype-to-gene expression linkage at single-cell resolution.
Purpose of the Study:
- To develop a method for simultaneously profiling genetic variants and gene expression at single-cell resolution.
- To accurately link coding and noncoding genetic variants to their effects on gene expression.
Main Methods:
- Development of single-cell DNA-RNA sequencing (SDR-seq).
- Simultaneous profiling of up to 480 genomic DNA loci and genes in thousands of single cells.
- Determination of variant zygosity and associated gene expression changes.
Main Results:
- SDR-seq accurately determines coding and noncoding variant zygosity and associated gene expression.
- Distinct gene expression patterns were associated with coding and noncoding variants in human induced pluripotent stem cells.
- Increased mutational burden in B cell lymphoma correlated with elevated B cell receptor signaling and tumorigenic gene expression.
Conclusions:
- SDR-seq is a powerful platform for dissecting regulatory mechanisms of genetic variants.
- The study advances understanding of gene expression regulation and its role in disease.
- This method enables linking genotypes to gene expression at single-cell resolution for disease research.
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