Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
X

Publications

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


Dominik Lindenhofer, Julia R. Bauman, John A. Hawkins, Donnacha Fitzgerald, Umut Yildiz, Jan M. Marttinen, Moritz Kueblbeck, Judith B. Zaugg, Kyung-Min Noh, Sascha Dietrich, Wolfgang Huber, Oliver Stegle, Lars M. Steinmetz
BioRxiv Jun 2024
Abstract

Genomic variation ranging from single nucleotide polymorphisms to structural variants can impact gene function and expression, contributing to disease mechanisms such as cancer progression. The systematic study of this variation is hindered by inefficient precision editing tools making it challenging to confidently link genotype and gene expression in pooled screens. Additionally, assessing heterogenous variants in primary tumor samples at scale is difficult with current single-cell technologies. We developed droplet-based multiomic targeted scDNA-scRNAseq (SDR-seq) to precisely link genotypes with gene expression profiles in high-throughput. SDR-seq simultaneously assesses up to 480 RNA and gDNA targets with 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 in primary B-cell lymphoma samples, cells with a higher mutational burden exhibit elevated B-cell receptor signaling and tumorigenic gene expression. SDR-seq has broad potential for gaining 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.

VIEW

Area

Heme

Institution Type

Academia

Indication / Modality

Other

Goal of Study

Clinical Profiling

PAD Project

No

Analytes Assessed

InDels, SNV

Species

Human

Panel Used

Custom

Proof Point Demonstrated

Co-occurrence, Clonality, Multi-omics
REQUEST QUOTE