Polygenic regression uncovers trait-relevant cellular contexts through pathway activation transformation of single-cell RNA sequencing data
Polygenic regression uncovers trait-relevant cellular contexts through pathway activation transformation of single-cell RNA sequencing data
Summary Advances in single-cell RNA sequencing (scRNA-seq) techniques have accelerated functional interpretation of disease-associated variants discovered from genome-wide association studies (GWASs). However, identification of trait-relevant cell populations is often impeded by inherent technical noise and high sparsity in scRNA-seq data. Here, we developed scPagwas, a computational approach that uncovers trait-relevant cellular context by integrating pathway activation transformation of scRNA-seq data and GWAS summary statistics. scPagwas effectively prioritizes trait-relevant genes, which facilitates identification of trait-relevant cell types/populations with high accuracy in extensive simulated and real datasets. Cellular-level association results identified a novel subpopulation of na?ve CD8+ T cells related to COVID-19 severity, and oligodendrocyte progenitor cell and microglia subsets with critical pathways by which genetic variants influence Alzheimer’s disease. Overall, our approach provides new insights for the discovery of trait-relevant cell types and improves the mechanistic understanding of disease variants from a pathway perspective.
Deng Chunyu、Zhou Yijun、Qiu Fei、Yang Jian、Jiang Dingping、Ma Yunlong、Zhang Yan、Su Jianzhong、Shuai Jianwei、Li Jingjing、Zheng Gongwei、Zhang Yaru
School of Life Science and Technology, Harbin Institute of TechnologySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University||Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain HealthSchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Life Sciences, Westlake University||Westlake Laboratory of Life Sciences and BiomedicineSchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University||Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain HealthSchool of Life Science and Technology, Harbin Institute of TechnologySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University||Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain HealthOujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain HealthSchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University||Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health
生物科学研究方法、生物科学研究技术基础医学细胞生物学
GWASSingle-cell RNA sequencingGenetic variantsRisk genesTrait-relevant cell types
Deng Chunyu,Zhou Yijun,Qiu Fei,Yang Jian,Jiang Dingping,Ma Yunlong,Zhang Yan,Su Jianzhong,Shuai Jianwei,Li Jingjing,Zheng Gongwei,Zhang Yaru.Polygenic regression uncovers trait-relevant cellular contexts through pathway activation transformation of single-cell RNA sequencing data[EB/OL].(2025-03-28)[2025-05-15].https://www.medrxiv.org/content/10.1101/2023.03.04.23286805.点此复制
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