Traditional omics (transcriptomics, proteomics, metabolomics) provide a 'mixture inventory' that loses spatial information; spatial omics anchors this inventory back to tissue coordinates. According to the molecular level measured, the main branches include: spatial transcriptomics (measuring in-situ mRNA distribution), spatial proteomics (measuring in-situ protein expression), and spatial metabolomics (measuring in-situ metabolite distribution). The three characterize tissue from the three levels of gene expression, protein function, and metabolic end products respectively.
Different branches use different technical means: spatial transcriptomics mostly relies on in-situ sequencing/probe hybridization (such as barcode-array-based methods); spatial proteomics includes both antibody-based imaging and mass-spectrometry-driven approaches; spatial metabolomics mainly relies on mass spectrometry imaging (MSI). Understanding branch differences helps select the right tool for the scientific question.
Mass spectrometry imaging is the core method for spatial metabolomics and also an important tool for spatial proteomics (especially at the protein/peptide level). Compared with antibody-dependent methods, MSI requires no prior targets and can simultaneously present the in-situ distribution of hundreds to thousands of metabolites/lipids/drugs, representing 'discovery-type' spatial analysis. It is also frequently integrated with spatial transcriptomics data, using 'gene expression changes' to correspond to 'metabolite/lipid end-product changes', forming a complete mechanistic picture.
In the spatial proteomics direction, MALDI imaging can present the tissue distribution of proteins/peptides; in the single-cell/subcellular direction, matrix-free sources such as Neo-Source LDPI (2–3 μm) provide new tools for single-cell maps at the metabolic level. It can be said that MSI is a key bridge connecting metabolic end products with spatial heterogeneity.
Spatial transcriptomics: based on in-situ sequencing or probe hybridization, resolution can reach subcellular to single-cell, excels at gene expression profiles, but requires known/designed probes and does not directly give metabolic information. Spatial proteomics: antibody imaging has high resolution but limited throughput; mass-spectrometry routes (MALDI) cover broadly but require sample preparation. Spatial metabolomics: MSI is label-free and parallel across multiple molecules, but quantification and molecular-weight annotation still need methodological support.
| Branch | Main technology | Advantage | Limitation |
|---|---|---|---|
| Spatial transcriptomics | In-situ sequencing / probes | Gene expression, single-cell | Requires probes, no metabolic info |
| Spatial proteomics | Antibody imaging / MALDI | Functional protein level | Antibody throughput / sample prep |
| Spatial metabolomics | Mass spectrometry imaging (MSI) | Label-free, multi-molecule parallel | Hard to quantify and annotate |
A single omics can only see one link in the mechanistic chain, whereas real biological processes involve multi-layer linkage of transcription—protein—metabolism. Multi-omics integration (continuous sections of the same tissue or multi-modal on the same platform) has become the frontier of spatial omics: for example, overlaying spatial transcriptomics with spatial metabolomics can explain 'which genes are up-regulated corresponding to which metabolites accumulate'.
The bottleneck in achieving integration lies in registration (coordinate alignment of different sections/modalities), data volume, and analysis tool chains. Standard formats output by mass spectrometry imaging such as imzML are gradually being connected with transcriptomics and proteomics analysis workflows. As domestic matrix-free imaging sources (such as Neo-Source LDPI/DPI) lower the MSI barrier, the participation of spatial metabolomics in multi-omics integration will continue to rise.
To obtain detailed specifications, compatible models, or a quotation for the MSI LDPI / DPI full series imaging ion sources, visit the Neo-Source official website, or contact the official team for compatibility advice tailored to your mass spectrometer (Agilent / SCIEX / Thermo and other mainstream MS).