scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs

Single-cell RNA sequencing (scRNA-seq) enables expression quantitative trait locus (eQTL) analysis at cellular resolution, offering new opportunities to uncover regulatory variants with cell-type-specific effects. However, existing tools are often limited in functionality, input compatibility, or sc...

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Main Authors: Xiaofeng Wu, Xin Huang, Pinjing Chen, Jingtong Kang, Jin Yang, Zhanpeng Huang, Siwen Xu
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/7/743
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author Xiaofeng Wu
Xin Huang
Pinjing Chen
Jingtong Kang
Jin Yang
Zhanpeng Huang
Siwen Xu
author_facet Xiaofeng Wu
Xin Huang
Pinjing Chen
Jingtong Kang
Jin Yang
Zhanpeng Huang
Siwen Xu
author_sort Xiaofeng Wu
collection DOAJ
description Single-cell RNA sequencing (scRNA-seq) enables expression quantitative trait locus (eQTL) analysis at cellular resolution, offering new opportunities to uncover regulatory variants with cell-type-specific effects. However, existing tools are often limited in functionality, input compatibility, or scalability for sparse single-cell data. To address these challenges, we developed scQTLtools, a comprehensive R/Bioconductor package that facilitates end-to-end single-cell eQTL analysis, from preprocessing to visualization. The toolkit supports flexible input formats, including Seurat and SingleCellExperiment objects, handles both binary and three-class genotype encodings, and provides dedicated functions for gene expression normalization, SNP and gene filtering, eQTL mapping, and versatile result visualization. To accommodate diverse data characteristics, scQTLtools implements three statistical models—linear regression, Poisson regression, and zero-inflated negative binomial regression. We applied scQTLtools to scRNA-seq data from human acute myeloid leukemia and identified eQTLs with regulatory effects that varied across cell types. Visualization of SNP–gene pairs revealed both positive and negative associations between genotype and gene expression. These results demonstrate the ability of scQTLtools to uncover cell-type-specific regulatory variation that is often missed by bulk eQTL analyses. Currently, scQTLtools supports cis-eQTL mapping; future development will extend to include trans-eQTL detection. Overall, scQTLtools offers a robust, flexible, and user-friendly framework for dissecting genotype–expression relationships in heterogeneous cellular populations.
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spelling doaj-art-8eb8e1cdef5f4849abff4b8d626ec73d2025-08-20T03:58:25ZengMDPI AGBiology2079-77372025-06-0114774310.3390/biology14070743scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLsXiaofeng Wu0Xin Huang1Pinjing Chen2Jingtong Kang3Jin Yang4Zhanpeng Huang5Siwen Xu6School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSingle-cell RNA sequencing (scRNA-seq) enables expression quantitative trait locus (eQTL) analysis at cellular resolution, offering new opportunities to uncover regulatory variants with cell-type-specific effects. However, existing tools are often limited in functionality, input compatibility, or scalability for sparse single-cell data. To address these challenges, we developed scQTLtools, a comprehensive R/Bioconductor package that facilitates end-to-end single-cell eQTL analysis, from preprocessing to visualization. The toolkit supports flexible input formats, including Seurat and SingleCellExperiment objects, handles both binary and three-class genotype encodings, and provides dedicated functions for gene expression normalization, SNP and gene filtering, eQTL mapping, and versatile result visualization. To accommodate diverse data characteristics, scQTLtools implements three statistical models—linear regression, Poisson regression, and zero-inflated negative binomial regression. We applied scQTLtools to scRNA-seq data from human acute myeloid leukemia and identified eQTLs with regulatory effects that varied across cell types. Visualization of SNP–gene pairs revealed both positive and negative associations between genotype and gene expression. These results demonstrate the ability of scQTLtools to uncover cell-type-specific regulatory variation that is often missed by bulk eQTL analyses. Currently, scQTLtools supports cis-eQTL mapping; future development will extend to include trans-eQTL detection. Overall, scQTLtools offers a robust, flexible, and user-friendly framework for dissecting genotype–expression relationships in heterogeneous cellular populations.https://www.mdpi.com/2079-7737/14/7/743single-cell eQTL analysiseQTL identificationRBioconductorsingle-cell RNA-seqcis-regulatory variants
spellingShingle Xiaofeng Wu
Xin Huang
Pinjing Chen
Jingtong Kang
Jin Yang
Zhanpeng Huang
Siwen Xu
scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
Biology
single-cell eQTL analysis
eQTL identification
R
Bioconductor
single-cell RNA-seq
cis-regulatory variants
title scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
title_full scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
title_fullStr scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
title_full_unstemmed scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
title_short scQTLtools: An R/Bioconductor Package for Comprehensive Identification and Visualization of Single-Cell eQTLs
title_sort scqtltools an r bioconductor package for comprehensive identification and visualization of single cell eqtls
topic single-cell eQTL analysis
eQTL identification
R
Bioconductor
single-cell RNA-seq
cis-regulatory variants
url https://www.mdpi.com/2079-7737/14/7/743
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