Systems-based approaches to study immunometabolism

Abstract

Technical advances at the interface of biology and computation, such as single-cell RNA-sequencing (scRNA-seq), reveal new layers of complexity in cellular systems. An emerging area of investigation using the systems biology approach is the study of the metabolism of immune cells. The diverse spectra of immune cell phenotypes, sparsity of immune cell numbers in vivo, limitations in the number of metabolites identified, dynamic nature of cellular metabolism and metabolic fluxes, tissue specificity, and high dependence on the local milieu make investigations in immunometabolism challenging, especially at the single-cell level. In this review, we define the systemic nature of immunometabolism, summarize cell- and system-based approaches, and introduce mathematical modeling approaches for systems interrogation of metabolic changes in immune cells. We close the review by discussing the applications and shortcomings of, and challenges faced by metabolic modeling techniques. With systems-oriented studies of metabolism expected to become a mainstay of immunological research, an understanding of current approaches toward systems immunometabolism will help investigators make the best use of current resources and push the boundaries of the discipline.

MEBOCOST: Metabolite-mediated Cell Communication Modeling by Single Cell Transcriptome

“…We designed MEBOCOST to take the output of these FBA analysis algorithms as its input data. Whereas flux balance analysis is popular for conventional metabolic analysis, the drawback is that it relies on some assumptions that might not be valid in many applications 24 . Also, flux balance analysis is computation-intensive and currently cannot be conducted at genome-scale for large single-cell datasets without massive parallelization of the computational task.…”

Innate metabolic responses against viral infections

“…Single-cell immunometabolic analysis should clarify the heterogeneity of the metabolic programmes within tissue compartments. Integrative technologies such as metabolic-based flow cytometry 9,192 , flow cytometric-based mitochondrial dynamics analysis 193 , mass-spectrometry coupled with liquid or gas chromatography 194,195 , single-cell RNA sequencing 196,197 , mass cytometry 198 and single-cell energetic metabolism by profiling translation inhibition 199,200 can be adapted to investigate these questions. Comparative studies of metabolic responses across animal models will also improve predictive clinical significance in humans.…”

Tumor-immune metaphenotypes orchestrate an evolutionary bottleneck that promotes metabolic transformation

“…The effect of metabolic processes on the immune system is multifaceted and complex, involving both intracellular metabolism of many varied cell types and the impact of this metabolic activity on the surrounding microenvironment. Immunometabolism is a growing area of study 9 and systems biology and modeling approaches are being applied to the field 10 . Mathematical models are highly suited to studying tumor-immune dynamics [11][12][13][14][15][16] , whether using non-spatial continuum approaches (recently reviewed in 17) or spatial agentbased models (recently reviewed in 18).…”