Differential gene regulatory networks in development and disease

Cell Mol Life Sci. 2018 Mar;75(6):1013-1025. doi: 10.1007/s00018-017-2679-6. Epub 2017 Oct 10.

Abstract

Gene regulatory networks, in which differential expression of regulator genes induce differential expression of their target genes, underlie diverse biological processes such as embryonic development, organ formation and disease pathogenesis. An archetypical systems biology approach to mapping these networks involves the combined application of (1) high-throughput sequencing-based transcriptome profiling (RNA-seq) of biopsies under diverse network perturbations and (2) network inference based on gene-gene expression correlation analysis. The comparative analysis of such correlation networks across cell types or states, differential correlation network analysis, can identify specific molecular signatures and functional modules that underlie the state transition or have context-specific function. Here, we review the basic concepts of network biology and correlation network inference, and the prevailing methods for differential analysis of correlation networks. We discuss applications of gene expression network analysis in the context of embryonic development, cancer, and congenital diseases.

Keywords: Coexpression networks; Correlation; Systems biology; Transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Congenital Abnormalities / genetics*
  • Congenital Abnormalities / metabolism
  • Congenital Abnormalities / pathology
  • Embryo, Mammalian
  • Embryonic Development / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Signal Transduction
  • Single-Cell Analysis
  • Systems Biology
  • Transcriptome