@article{Elyanow01022020,
author = {Elyanow, Rebecca and Dumitrascu, Bianca and Engelhardt, Barbara E. and Raphael, Benjamin J.}, 
title = {netNMF-sc: leveraging gene–gene interactions for imputation and dimensionality reduction in single-cell expression analysis},
volume = {30}, 
number = {2}, 
pages = {195-204}, 
year = {2020}, 
doi = {10.1101/gr.251603.119}, 
abstract ={Single-cell RNA-sequencing (scRNA-seq) enables high-throughput measurement of RNA expression in single cells. However, because of technical limitations, scRNA-seq data often contain zero counts for many transcripts in individual cells. These zero counts, or dropout events, complicate the analysis of scRNA-seq data using standard methods developed for bulk RNA-seq data. Current scRNA-seq analysis methods typically overcome dropout by combining information across cells in a lower-dimensional space, leveraging the observation that cells generally occupy a small number of RNA expression states. We introduce netNMF-sc, an algorithm for scRNA-seq analysis that leverages information across both cells and genes. netNMF-sc learns a low-dimensional representation of scRNA-seq transcript counts using network-regularized non-negative matrix factorization. The network regularization takes advantage of prior knowledge of gene–gene interactions, encouraging pairs of genes with known interactions to be nearby each other in the low-dimensional representation. The resulting matrix factorization imputes gene abundance for both zero and nonzero counts and can be used to cluster cells into meaningful subpopulations. We show that netNMF-sc outperforms existing methods at clustering cells and estimating gene–gene covariance using both simulated and real scRNA-seq data, with increasing advantages at higher dropout rates (e.g., >60%). We also show that the results from netNMF-sc are robust to variation in the input network, with more representative networks leading to greater performance gains.}, 
URL = {http://genome.cshlp.org/content/30/2/195.abstract}, 
eprint = {http://genome.cshlp.org/content/30/2/195.full.pdf+html}, 
journal = {Genome Research} 
}