TY  - JOUR
A1  - Chen, Mengjie
A1  - Zhan, Qi
A1  - Mu, Zepeng
A1  - Wang, Lili
A1  - Zheng, Zhaohui
A1  - Miao, Jinlin
A1  - Zhu, Ping
A1  - Li, Yang I.
T1  - Alignment of single-cell RNA-seq samples without overcorrection using kernel density matching
Y1  - 2021/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 698 
EP  - 712 
DO  - 10.1101/gr.261115.120 
VL  - 31 
IS  - 4 
UR  - http://genome.cshlp.org/content/31/4/698.abstract 
N2  - Single-cell RNA sequencing (scRNA-seq) technology is poised to replace bulk cell RNA sequencing for many biological and medical applications as it allows users to measure gene expression levels in a cell type–specific manner. However, data produced by scRNA-seq often exhibit batch effects that can be specific to a cell type, to a sample, or to an experiment, which prevent integration or comparisons across multiple experiments. Here, we present Dmatch, a method that leverages an external expression atlas of human primary cells and kernel density matching to align multiple scRNA-seq experiments for downstream biological analysis. Dmatch facilitates alignment of scRNA-seq data sets with cell types that may overlap only partially and thus allows integration of multiple distinct scRNA-seq experiments to extract biological insights. In simulation, Dmatch compares favorably to other alignment methods, both in terms of reducing sample-specific clustering and in terms of avoiding overcorrection. When applied to scRNA-seq data collected from clinical samples in a healthy individual and five autoimmune disease patients, Dmatch enabled cell type–specific differential gene expression comparisons across biopsy sites and disease conditions and uncovered a shared population of pro-inflammatory monocytes across biopsy sites in RA patients. We further show that Dmatch increases the number of eQTLs mapped from population scRNA-seq data. Dmatch is fast, scalable, and improves the utility of scRNA-seq for several important applications. Dmatch is freely available online. 
ER  -