Discovering single-cell eQTLs from scRNA-seq data only.

Tianxing Ma, Haochen Li, Xuegong Zhang
Author Information
  1. Tianxing Ma: MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRIST and Department of Automation, Tsinghua University, Beijing 100084, China.
  2. Haochen Li: School of Medicine, Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China.
  3. Xuegong Zhang: MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRIST and Department of Automation, Tsinghua University, Beijing 100084, China; School of Medicine, Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China. Electronic address: zhangxg@tsinghua.edu.cn.

Abstract

eQTL studies are essential for understanding genomic regulation. The effects of genetic variations on gene regulation are cell-type-specific and cellular-context-related, so studying eQTLs at a single-cell level is crucial. The ideal solution is to use both mutation and expression data from the same cells. However, the current technology of such paired data in single cells is still immature. We present a new method, eQTLsingle, to discover eQTLs only with single-cell RNA-seq (scRNA-seq) data, without genomic data. It detects mutations from scRNA-seq data and models gene expression of different genotypes with the zero-inflated negative binomial (ZINB) model to find associations between genotypes and phenotypes at the single-cell level. On a glioblastoma and gliomasphere scRNA-seq dataset, eQTLsingle discovered hundreds of cell-type-specific tumor-related eQTLs, most of which cannot be found in bulk eQTL studies. Detailed analyses on examples of the discovered eQTLs revealed important underlying regulatory mechanisms. eQTLsingle is a uniquely powerful tool for utilizing the vast scRNA-seq resources for single-cell eQTL studies, and it is available for free academic use at https://github.com/horsedayday/eQTLsingle.

Keywords

MeSH Term

Gene Expression Profiling
Gene Expression Regulation
Sequence Analysis, RNA
Single-Cell Analysis
Software
Exome Sequencing

Word Cloud

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