PNNL

Abstract

This review highlights the application of mass spectrometry (MS), with an emphasis on spatially-resolved MS and MS imaging (MSI), in studying biomolecular processes within the kidney related to health and disease. We illustrate how these are powerful methods that can enable label-free and multiplexed detection of many molecular classes across omics domains (e.g., metabolites, drugs, proteins, protein post-translational modifications). This review discusses how the complexity of the kidney often necessitates multiple scales of analysis for interrogating biofluids, whole organ, tissue functional units, single cell, and subcellular compartments. We provide examples of MS methods generating omics data across these spatial domains. MS assays can facilitate both basic science and pathological assessment of the kidney, and we emphasize recent examples of MSI used to advance the field of nephrology. We discuss sample preparation and handling considerations for different MS assays, additional considerations related to spatial and MSI methods, and cost implications. We also provide insight into emerging technology and methods, improvement of spatial resolution, broader molecular characterization, multimodal and multiomic approaches, and the use of machine learning and artificial intelligence. Overall, spatially-resolved MS and MSI methods have the potential to fill much of the omics gap in systems biology analysis of the kidney to provide functional outputs that genomics and transcriptomic methods cannot provide.