Approaching complexity: systems biology and ms-based techniques to address immune signaling

ABSTRACT

Introduction

Studying immune signaling has been critical for our understanding of immunology, pathogenesis, cancer, and homeostasis. To enhance the breadth of the analysis, high throughput methods have been developed to survey multiple areas simultaneously, including transcriptomics, reporter assays, and ELISAs. While these techniques have been extremely informative, mass-spectrometry-based technologies have been gaining momentum and starting to be widely used in the studies of immune signaling and systems immunology.

Areas covered

We present established proteomic methods that have been used to address immune signaling and discuss the new mass-spectrometry- based techniques of interest to the expanding field of systems immunology. Established and new proteomic methods and their applications discussed here include post-translational modification analysis, protein quantification, secretome analysis, and interactomics. In addition, we present developments in small molecule and metabolite analysis, mass spectrometry imaging, and single cell analysis. Finally, we discuss the role of multi-omic integration in aiding leading edge investigation.

Expert opinion

In science, available techniques enhance the breadth and depth of the studies. By incorporating proteomic techniques and their innovative use, it will be possible to expand the current studies and to address novel questions at the forefront of scientific discovery.

KEYWORDS:

• Proteomics
• immunology
• post-translational modifications
• protein quantification
• secretome
• extracellular signaling
• interactomics
• metabolites
• mass spectrometry imaging
• single cell proteomics
• multi-omics

Article highlights

• Combining proteomic techniques with systems biology approaches offers new tools for the analysis of immune signaling.

• Current proteomic techniques used to address immune signaling:○ Post-translational modification screens (phosphorylation and ubiquitination), Protein quantification, secretome analysis, and interactomics.

• Future mass spectrometry–based techniques to use in immune signaling:○ Small molecule and metabolite analysis, mass spectrometry imaging, single cell analysis.

• Expanding our use of these established and developing techniques will lead to an improved understanding of immune signaling.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer declarations

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was supported by the Intramural Research Program of NIAID, NIH.