Constructing an Integrated Genetic and Epigenetic Cellular Network by Systems Biology Method for Investigating Whole Cellular Mechanism Using NGS Omics Data

Epigenetics is the mechanism that leads to heritable changes in the genetic function without affecting the genome’s sequence. Since the appearance of epigenomics, epigenetics has been widely investigated in cancer initiation and development. These epigenetic mechanisms could explain how individuals who have the same genotype may produce phenotypic differences in response to environmental stimuli. Recently, through the accumulation of high-throughput next-generation sequencing (NGS) data, the primary purpose of systems biology is to construct genetic and epigenetic networks for different cellular levels to investigate whole cellular mechanisms. This chapter introduces a systems biology method to build an integrated genetic and epigenetic cellular network (IGECN) using NGS omics data. We have successfully constructed IGECNs of several diseases and validated them using the literature search evidence. For example, the dysregulation of mir7 leads to the initiation and progression of inflammation-induced gastric cancer; the dysregulation of mir9 leads to HIV-1 infection to hijack CD4+ T cells via dysfunction of the immune and hormone pathways; the dysregulation of mir139-5p, mirLET7i, and mir10a leads to the HIV-1 integration/replication process; the dysregulation of mir101, mir141, and mir152 contributes to the HIV-1 virus assembly and budding mechanisms; dysregulation of mir302a leads to not only the microvesicle-mediated transfer of miRNAs but also the dysfunction of NF-κB signaling pathway in hepatocarcinogenesis. Hence, the coupling dynamic systems of the whole IGECN can permit us to investigate genetic and epigenetic cellular mechanisms via omics data and extensive database mining and are helpful for further experiments from the perspective of systems and synthetic biology.