Integrating multiomics longitudinal data to reconstruct networks underlying lung development

Academic Article

Abstract

  • A comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. To construct such a model, we profiled mRNA, microRNA, DNA methylation, and proteomics of developing murine alveoli isolated by laser capture microdissection at 14 predetermined time points. We developed a detailed comprehensive and interactive model that provides information about the major expression trajectories, the regulators of specific key events, and the impact of epigenetic changes. Intersecting the model with single-cell RNA-Seq data led to the identification of active pathways in multiple or individual cell types. We then constructed a similar model for human lung development by profiling time-series human omics data sets. Several key pathways and regulators are shared between the reconstructed models. We experimentally validated the activity of a number of predicted regulators, leading to new insights about the regulation of innate immunity during lung development.
  • Digital Object Identifier (doi)

    Author List

  • Ding J; Ahangari F; Espinoza CR; Chhabra D; Nicola T; Yan X; Lal CV; Hagood JS; Kaminski N; Bar-Joseph Z
  • Start Page

  • L556
  • End Page

  • L568
  • Volume

  • 317
  • Issue

  • 5