Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

Oh, Soo-Jin; Choi, Young-Ki; Shin, Ok Sarah

Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. 10 Systems biology tools enable us to develop and validate predictive models of infectious disease initiation, progression, and outcomes. These models can be derived from the study of the architecture and dynamics of systems-wide host/pathogen molecular interaction networks during infection. Ideally, integrated datasets generated from a combination of high-throughput multi-omics data (transcriptomics, proteomics, metabolomics, lipidomics, etc.) can be used to construct predictive models of the networks and dynamic interactions between the biological components of the complex pathogen-host system. 59 In particular, through years of dedicated effort, high-throughput RNA sequencing (RNA-seq) technology, which is a powerful way to profile the transcriptome with great efficiency and high accuracy, has been employed in various viral infections and diseases. [60] [61] [62] [63] [64] [65] [66] These studies proved that RNA-seq technology has the potential to reveal the dynamics of pathogen genome alteration and systemic changes in host and pathogen gene expression during the process of infection. Thus, if this approach is applied to EID research, information can help to accelerate uncovering the pathogenesis of novel infections and the interaction mechanism of emerging pathogens. As a notable example, several groups have taken advantage of RNAseq technology to provide novel insights into how ZIKV infection may cause microcephaly in a short period of time. Nowakowki, et al. 67 using single-cell RNA-seq and immunohistochemistry, first reported that AXL, a viral receptor for ZIKV, is highly expressed in human radial glial cells, astrocytes, endothelial cells, and microglia in the developing human cortex and in progenitor cells in the developing retina. Additionally, Onorati, et al. 68 analyzed ZIKV-infected neuronal progenitor cells to identify transcriptional changes caused by the virus. Using techniques including single-cell RNA-seq, they described the derivation and characterization of neocortical and spinal cord neuroepithelial stem cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. These data may lead to significant advances in efforts to develop a vaccine against ZIKV.