Single-cell network biology for resolving cellular heterogeneity in human diseases

Abstract

Understanding cellular heterogeneity is the holy grail of biology and medicine. Cells harboring identical genomes show a wide variety of behaviors in multicellular organisms. Genetic circuits underlying cell-type identities will facilitate the understanding of the regulatory programs for differentiation and maintenance of distinct cellular states. Such a cell-type-specific gene network can be inferred from coregulatory patterns across individual cells. Conventional methods of transcriptome profiling using tissue samples provide only average signals of diverse cell types. Therefore, reconstructing gene regulatory networks for a particular cell type is not feasible with tissue-based transcriptome data. Recently, single-cell omics technology has emerged and enabled the capture of the transcriptomic landscape of every individual cell. Although single-cell gene expression studies have already opened up new avenues, network biology using single-cell transcriptome data will further accelerate our understanding of cellular heterogeneity. In this review, we provide an overview of single-cell network biology and summarize recent progress in method development for network inference from single-cell RNA sequencing (scRNA-seq) data. Then, we describe how cell-type-specific gene networks can be utilized to study regulatory programs specific to disease-associated cell types and cellular states. Moreover, with scRNA data, modeling personal or patient-specific gene networks is feasible. Therefore, we also introduce potential applications of single-cell network biology for precision medicine. We envision a rapid paradigm shift toward single-cell network analysis for systems biology in the near future. Systems biology: A single-cell, network-driven approach to disease Gene regulatory networks reconstructed from single-cell RNA sequencing datasets are allowing researchers to better understand the molecular circuits and cell states that contribute to complex human disease. Junha Cha and Insuk Lee from Yonsei University in Seoul, South Korea, review the concept of 'single-cell network biology', which involves using computational algorithms on genetic expression data from thousands of cells to infer functional interactions in various biological contexts. This systems biology approach to analyzing the profiles of messenger RNA in single cells is helping researchers discover new signaling pathways that could serve as disease biomarkers or therapeutic targets. In the future, patient-specific models of personal gene networks could explain why certain genetic variants affect disease risk. This research could also eventually lead to new types of individualized medical treatments.