@article{Chen01042021,
author = {Chen, Mengjie and Zhan, Qi and Mu, Zepeng and Wang, Lili and Zheng, Zhaohui and Miao, Jinlin and Zhu, Ping and Li, Yang I.}, 
title = {Alignment of single-cell RNA-seq samples without overcorrection using kernel density matching},
volume = {31}, 
number = {4}, 
pages = {698-712}, 
year = {2021}, 
doi = {10.1101/gr.261115.120}, 
abstract ={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.}, 
URL = {http://genome.cshlp.org/content/31/4/698.abstract}, 
eprint = {http://genome.cshlp.org/content/31/4/698.full.pdf+html}, 
journal = {Genome Research} 
}