Simultaneous Estimation of Many Sparse Networks via Hierarchical Poisson Log-Normal Model

TL;DR

This paper introduces a hierarchical Poisson Log-Normal model for the simultaneous estimation of multiple gene expression networks from single-cell RNA-seq data, effectively capturing condition-specific structures.

Contribution

It proposes a novel hierarchical model and an efficient variational EM and ADMM-based estimation method tailored for count data with many zeros.

Findings

Outperforms traditional methods in network recovery

Effectively captures shared and condition-specific gene networks

Provides deeper biological insights from real datasets

Abstract

The advancement of single-cell RNA-sequencing (scRNA-seq) technologies allow us to study the individual level cell-type-specific gene expression networks by direct inference of genes' conditional independence structures. scRNA-seq data facilitates the analysis of gene expression data across different conditions or samples, enabling simultaneous estimation of condition- or sample-specific gene networks. Since the scRNA-seq data are count data with many zeros, existing network inference methods based on Gaussian graphs cannot be applied to such single cell data directly. We propose a hierarchical Poisson Log-Normal model to simultaneously estimate many such networks to effectively incorporate the shared network structures. We develop an efficient simultaneous estimation method that uses the variational EM and alternating direction method of multipliers (ADMM) algorithms, optimized for parallel processing. Simulation studies show this method outperforms traditional methods in network structure recovery and parameter estimation across various network models. We apply the method to two single cell RNA-seq datasets, a yeast single-cell gene expression dataset measured under 11 different environmental conditions, and a single-cell gene expression data from 13 inflammatory bowel disease patients. We demonstrate that simultaneous estimation can uncover a wider range of conditional dependence networks among genes, offering deeper insights into gene expression mechanisms.