Construction of Anatomical Structure-specific Developmental Dynamic Networks for Human Brain on Multiple Omics Levels

Abstract

Background: Human brain development is a series of complex processes exhibiting profound changes from gestation to adulthood. Objective: We aimed to construct dynamic developmental networks for each anatomical structure of the human brain based on omics’ levels in order to gain a new systematical brain map on the molecular level. Methods: We performed the brain development analyses by constructing dynamical networks between adjacent time points on different grouping levels of anatomical structures. The gene-time networks were first built to obtain the developing brain dynamical maps on transcriptome level. Then miRNA-mRNA networks and protein-protein networks were constructed by integrating the information from miRNomics and proteomics. The time and structure-specific biomarkers were filtered based on analyses of topological characters. Results: The most dramatic developmental time and structure were fetal-infancy and telencephalon, respectively. Cortex was the key developmental region in ‘late fetal and neonatal’ and ‘early infancy’. The development of the temporal lobe was different from other lobes since the significant changes of molecules were found only in the comparison pair ‘early fetal-early mid-fetal’ and ‘adolescence-young adulthood’. Interestingly, the changes among different brain structures inside adolescence and adulthood were bigger than other time points. hsa-miR-548c-3p and H3C2 may be new brain development indicators considering their key roles in networks. Conclusion: To our knowledge, this study is the first report of dynamical brain development maps for different anatomical structures on multiple omics. The results provide a new sight of brain development in a systematical way which may provide a more accurate understanding of the human brain.