A Markov Random Field Model for Network-based Differential Expression Analysis of Single-cell RNA-seq Data

Published: Nov. 12, 2020, 10:04 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378976v1?rss=1 Authors: Li, H., Xu, Z., Adams, T., Kaminski, N., Zhao, H. Abstract: Recent development of single cell sequencing technologies has made it possible to identify genes with different expression (DE) levels at the cell type level between different groups of samples. However, the often-low sample size of single cell data limits the statistical power to identify DE genes. In this paper, we propose to borrow information through known biological networks. Our approach is based on a Markov Random Field (MRF) model to appropriately accommodate gene network information as well as dependencies among cells to identify cell-type specific DE genes. We implement an Expectation-Maximization (EM) algorithm with mean field-like approximation to estimate model parameters and a Gibbs sampler to infer DE status. Simulation study shows that our method has better power to detect cell-type specific DE genes than conventional methods while appropriately controlling type I error rate. The usefulness of our method is demonstrated through its application to study the pathogenesis and biological processes of idiopathic pulmonary fibrosis (IPF) using a single-cell RNA-sequencing (scRNA-seq) data set, which contains 18,150 protein-coding genes across 38 cell types on lung tissues from 32 IPF patients and 28 normal controls. Copy rights belong to original authors. Visit the link for more info