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Estimating the Allele-Specific Expression of SNVs From 10× Genomics Single-Cell RNA-Sequencing Data. | LitMetric

AI Article Synopsis

Article Abstract

With the recent advances in single-cell RNA-sequencing (scRNA-seq) technologies, the estimation of allele expression from single cells is becoming increasingly reliable. Allele expression is both quantitative and dynamic and is an essential component of the genomic interactome. Here, we systematically estimate the allele expression from heterozygous single nucleotide variant (SNV) loci using scRNA-seq data generated on the 10×Genomics Chromium platform. We analyzed 26,640 human adipose-derived mesenchymal stem cells (from three healthy donors), sequenced to an average of 150K sequencing reads per cell (more than 4 billion scRNA-seq reads in total). High-quality SNV calls assessed in our study contained approximately 15% exonic and >50% intronic loci. To analyze the allele expression, we estimated the expressed variant allele fraction (VAF) from SNV-aware alignments and analyzed its variance and distribution (mono- and bi-allelic) at different minimum sequencing read thresholds. Our analysis shows that when assessing positions covered by a minimum of three unique sequencing reads, over 50% of the heterozygous SNVs show bi-allelic expression, while at a threshold of 10 reads, nearly 90% of the SNVs are bi-allelic. In addition, our analysis demonstrates the feasibility of scVAF estimation from current scRNA-seq datasets and shows that the 3'-based library generation protocol of 10×Genomics scRNA-seq data can be informative in SNV-based studies, including analyses of transcriptional kinetics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140866PMC
http://dx.doi.org/10.3390/genes11030240DOI Listing

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