Deep topographic proteomics of a human brain tumour

Abstract

Cellular protein expression profiles within tissues are key to understanding disease pathology, and their spatial organisation determines cellular function. To precisely define molecular phenotypes in the spatial context of tissue, there is a need for unbiased, quantitative technology capable of mapping the expression of many hundreds to thousands of proteins within tissue structures. Here, we present a workflow for spatially resolved, quantitative proteomics of tissue that generates maps of protein expression across a tissue slice derived from a human atypical teratoid-rhabdoid tumour (AT/RT). We employ spatially-aware statistical methods that do not require prior knowledge of tissue structure to highlight proteins and pathways with varying spatial abundance patterns. We identify novel aspects of AT/RT biology that map onto the brain-tumour interface. Overall, this work informs on methods for spatially resolved deep proteo-phenotyping of tissue heterogeneity. Advanced spatially resolved tissue proteomics will push the boundaries of understanding tissue biology and pathology at the molecular level.

Deep topographic proteomics of a human brain tumour

“…The R code used for analysis can be downloaded from https://zenodo. org/record/8341909 104 . Code for the affinity network fusion analysis can be accessed at https://github.com/pdcharles/spatial-proteomics-anf.…”

Crosstalk between Immune Checkpoint Modulators, Metabolic Reprogramming and Cellular Plasticity in Triple-Negative Breast Cancer

“…Combinatorial techniques like immunohistochemistry followed by Matrix assisted laser desorption ionisation–mass spectrometry imaging (MALDI-MSI) to visualise spatial distribution of lipids and metabolites in TNBC patient biospecimens would provide region-specific distribution profiles. This could be coupled with laser capture microdissection (LMD) to cut out specific regions of interest (ROI) from the tissues for proteomics profiling with LC-MS/MS [ 101 ]. Mapping the profiling data to the ROIs can provide vital information about the tumour and TME.…”