Mass Spectrometry—based Metabolomics, Analysis of Metabolite-Protein Interactions, and imaging

Abstract

Our understanding of biology has been greatly improved through recent developments in mass spectrometry, which is providing detailed information on protein and metabolite composition as well as protein-metabolite interactions. The high sensitivity and resolution of mass spectrometry achieved with liquid or gas chromatography allows for detection and quantification of hundreds to thousands of molecules in a single measurement. Where homogenization-based sample preparation and extraction methods result in a loss of spatial information, mass spectrometry imaging technologies provide the in situ distribution profiles of metabolites and proteins within tissues. Mass spectrometry–based analysis of metabolite abundance, protein-metabolite interactions, and spatial distribution of compounds facilitates the high-throughput screening of biochemical reactions, the reconstruction of metabolic networks, biomarker discovery, determination of tissue compositions, and functional annotation of both proteins and metabolites.

Microscope mode secondary ion mass spectrometry imaging with a Timepix detector

“…[8][9][10] Disease studies such as the fundamental understanding of the biochemistry of neurodegenerative diseases 11,12 or cancer, 13 drug distribution studies 10,14 and forensics, 15,16 among others, also benefit from the information revealed by MSI.…”

Functional Genomics, Proteomics, Metabolomics and Bioinformatics for Systems Biology

“…DNA and associated proteins, which play an important role in gene regulation, gene- [44], IMS [144,147] Metabolomics tools MetabolomeExpress [150], metaP [151], KEGG [145], human metabolome project [142] Lipidomics methods MS [44,161], orbitraps [160], IMS [144,147] Lipidomics tools LIPID MAPS [165], XCMS [162], MZmine2 [163] environment interactions, development and in diseases such as inflammation and cancer [60,61]. Such modifications involve the DNA itself but not its sequence, i.e.…”

“…Targeted strategies are specific and sensitive, allow absolute quantification and thus widely used in clinical diagnostics and drug development. Targeted approaches based on stable isotopes and models of metabolic networks allow estimation of the flux through biochemical pathways [145]. In contrast, untargeted approaches harbour a high coverage, though any metabolite identification is less specific and sensitive, and requires more intensive computational analysis.…”

“…Metabolomics also include identification of substrate in in vitro assays of three types: (1) the protein is fixed onto a surface and ligands screened, (2) the metabolite is fixed and serve as bait for interacting proteins, or (3) activity-based protein profiling using chemical probes and beads. Last but not least, location of metabolites within cells, tissues or bodies can be studied by coupling MALDI or matrix-free MS and imaging techniques (imaging mass spectrometry, IMS) to obtain spectra by scanning the biological sample with the laser and then compiling a map of metabolite content across that sample [145,148].…”

“…Major lipidomics intiatives include the 'Lipid Metabolites And Pathways Strategy' (LIPID MAPS) which has established standards and enabled absolute rather than relative quantification [166], and the Mouse Macrophage Lipidome [167]. Absolute quantities for proteomics and lipidomics will help characterise complexes comprising both proteins and lipids [145].…”