Systems Biology Approaches to Understanding the Human Immune System

Abstract

Systems biology is an approach to interrogate complex biological systems through large-scale quantification of numerous biomolecules. The immune system involves >1,500 genes/proteins in many interconnected pathways and processes, and a systems-level approach is critical in broadening our understanding of the immune response to vaccination. Changes in molecular pathways can be detected using high-throughput omics datasets (e.g., transcriptomics, proteomics, and metabolomics) by using methods such as pathway enrichment, network analysis, machine learning, etc. Importantly, integration of multiple omic datasets is becoming key to revealing novel biological insights. In this perspective article, we highlight the use of protein-protein interaction (PPI) networks as a multi-omics integration approach to unravel information flow and mechanisms during complex biological events, with a focus on the immune system. This involves a combination of tools, including: InnateDB, a database of curated interactions between genes and protein products involved in the innate immunity; NetworkAnalyst, a visualization and analysis platform for InnateDB interactions; and MetaBridge, a tool to integrate metabolite data into PPI networks. The application of these systems techniques is demonstrated for a variety of biological questions, including: the developmental trajectory of neonates during the first week of life, mechanisms in host-pathogen interaction, disease prognosis, biomarker discovery, and drug discovery and repurposing. Overall, systems biology analyses of omics data have been applied to a variety of immunology-related questions, and here we demonstrate the numerous ways in which PPI network analysis can be a powerful tool in contributing to our understanding of the immune system and the study of vaccines.

MetaNetX/MNXref: unified namespace for metabolites and biochemical reactions in the context of metabolic models

“…Beyond popular applications, such as metabolic flux prediction with flux balance analysis and prediction of the gene essentiality, GSMNs have been used in numerous applications ( 29 ), e.g. chemicals and materials production ( 30–33 ), drug targeting ( 34 , 35 ), human metabolism, disease understanding ( 36 , 37 ) and, multi-organism interaction modeling ( 38 , 39 ). MNXref is now used within tools for testing GSMNs such as MEMOTE ( 40 ), and has been proposed as a reference for minimal standard content for metabolic network reconstruction ( 41 ).…”

Rhizosphere Tripartite Interactions and PGPR-Mediated Metabolic Reprogramming towards ISR and Plant Priming: A Metabolomics Review

“…Over the years, scientists exploring systems biology approaches have made advances to seamlessly integrate multiple omics fields to quantitatively and qualitatively measure and track the intricate molecular mechanisms in organisms. The combination of various omics approaches has helped to unravel the functional dynamics of cell biology in the growth, development, adaptation and survival of organisms, as well as how the organisms interact with their surrounding environment and the underlying global biological changes [28,29].…”

Immune age and biological age as determinants of vaccine responsiveness among elderly populations: the Human Immunomics Initiative research program

“…The human immune system involves more than 1500 genes/proteins in many interconnected pathways and processes [ 43 ]. The last decade has seen an explosion in high-throughput technologies that allow us to study the human immune system in small volumes of blood based on the detection of multi-level changes in molecular immune pathways and networks.…”