Journal Article

scReQTL: an approach to correlate SNVs to gene expression from individual scRNA-seq datasets

Słowiński, Piotr, Horvath, Anelia, Tsaneva-Atanasova, Krasimira, Bousounis, Pavlos, Prashant, N. M., Alomran, Nawaf, Ibeawuchi, Helen, Liu, Hongyu, Spurr, Liam F., Sein, Justin

2021

Overview

Background Recently, pioneering expression quantitative trait loci (eQTL) studies on single cell RNA sequencing (scRNA-seq) data have revealed new and cell-specific regulatory single nucleotide variants (SNVs). Here, we present an alternative QTL-related approach applicable to transcribed SNV loci from scRNA-seq data: scReQTL. ScReQTL uses Variant Allele Fraction (VAF RNA ) at expressed biallelic loci, and corelates it to gene expression from the corresponding cell. Results Our approach employs the advantage that, when estimated from multiple cells, VAF RNA can be used to assess effects of SNVs in a single sample or individual. In this setting scReQTL operates in the context of identical genotypes, where it is likely to capture RNA-mediated genetic interactions with cell-specific and transient effects. Applying scReQTL on scRNA-seq data generated on the 10 × Genomics Chromium platform using 26,640 mesenchymal cells derived from adipose tissue obtained from three healthy female donors, we identified 1272 unique scReQTLs. ScReQTLs common between individuals or cell types were consistent in terms of the directionality of the relationship and the effect size. Comparative assessment with eQTLs from bulk sequencing data showed that scReQTL analysis identifies a distinct set of SNV-gene correlations, that are substantially enriched in known gene-gene interactions and significant genome-wide association studies (GWAS) loci. Conclusion ScReQTL is relevant to the rapidly growing source of scRNA-seq data and can be applied to outline SNVs potentially contributing to cell type-specific and/or dynamic genetic interactions from an individual scRNA-seq dataset. Availability: https://github.com/HorvathLab/NGS/tree/master/scReQTL

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adipose tissue / Animal Genetics and Genomics / Biomedical and Life Sciences / Chromium / Chromium plating / Datasets / eQTL, ReQTL, scReQTL, single cell / Female / Gene Expression / Gene Expression Profiling / Gene mapping / Gene sequencing / Genetic research / Genetic variation / Genome-wide association studies / Genome-Wide Association Study / Genomics / Genotypes / Humans / Life Sciences / Mesenchyme / Methodology / Methodology Article / Methods / Microarrays / Microbial Genetics and Genomics / Neutrophils / Nucleotides / Plant Genetics and Genomics / Proteomics / Quantitative trait loci / Regression analysis / Ribonucleic acid / RNA / RNA sequencing / RNA, Small Cytoplasmic / scRNA-seq / scVAFRNA / Sequence Analysis, RNA / Single-Cell Analysis / SNV / Software / Transcriptomic methods / VAFRNA