Network Approaches for Dissecting the Immune System

Abstract

The immune system is a complex biological network composed of hierarchically organized genes, proteins, and cellular components that combat external pathogens and monitor the onset of internal disease. To meet and ultimately defeat these challenges, the immune system orchestrates an exquisitely complex interplay of numerous cells, often with highly specialized functions, in a tissue-specific manner. One of the major methodologies of systems immunology is to measure quantitatively the components and interaction levels in the immunologic networks to construct a computational network and predict the response of the components to perturbations. The recent advances in high-throughput sequencing techniques have provided us with a powerful approach to dissecting the complexity of the immune system. Here we summarize the latest progress in integrating omics data and network approaches to construct networks and to infer the underlying signaling and transcriptional landscape, as well as cell-cell communication, in the immune system, with a focus on hematopoiesis, adaptive immunity, and tumor immunology. Understanding the network regulation of immune cells has provided new insights into immune homeostasis and disease, with important therapeutic implications for inflammation, cancer, and other immune-mediated disorders.

Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing

“…The lineage differentiation patterns and transcriptional profiling were well conserved between human and mouse, indicating evolutionary similarity in their hematopoietic systems. Further, we examined the TF activities that may contribute in maintaining differentiation during hematopoiesis and linked those to target genes [ 41 ]. A set of TF regulons, defined by TF-to-target correlation and TF motif analysis, was identified for different cell populations, and the regulons of human and mouse are highly conserved.…”

<p>Identification of Novel Therapeutic Molecular Targets in Inflammatory Bowel Disease by Using Genetic Databases</p>

“…Though these ever-growing database repositories do offer the advantage of high throughput screening, we acknowledge that this information still has to be used in conjunction with wet lab data to advance our understanding of IBD. 31 – 33 …”

Why is Complexity Science valuable for reaching the goals of the UN 2030 Agenda?

“…In the nervous system, the nodes might be the single neurons and the links are the synaptic connections (Telesford et al 2011 ). In the immune system, the basic nodes are the immune cells and the links are the signaling molecules, such as the cell-surface receptors and secreted molecules (Rieckmann et al 2017 ; Shi et al 2020 ). In biological ecosystems, the species are the nodes and their trophic and symbiotic interactions are the edges (Dunne et al 2002 ; Krause et al 2003 ).…”