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Deep topographic proteomics of a human brain tumour

Significant step forward in spatial proteomics, providing invaluable insights into tissue biology and disease mechanisms at the molecular level.

In a groundbreaking study published in Nature Communications, David et al. from the lab of A/Prof Roman Fischer have delved into the intricate world of tissue biology and disease pathology with spatially-resolved proteomics. The spatial organization of proteins within tissues plays a pivotal role in understanding how cells function and how diseases progress. To achieve this, an advanced workflow was developed and used to determine the spatial abundance patterns of proteins from human atypical teratoid-rhabdoid tumour samples.

Traditionally, mapping protein distributions within tissues was challenging, but recent developments in spatially-resolved sequencing and mass spectrometry imaging have opened new horizons. The research highlights the potential of laser capture microdissection (LCM) as a precise tissue sampling method. Unlike previous methods, LCM allows for spatially-resolved sampling, uncovering novel tissue structures and spatial protein expression patterns.

The research aims to redefine our understanding of tissue biology and pathology by using spatially-aware statistical methods to identify proteins and pathways with differential spatial expression. This approach revealed spatial proteo-phenotypes and unveiled correlations between the tumor matrix and immune responses.

The study also explored how protein abundance is influenced by the vascular structure within tumors, shedding light on nutrient and oxygen-dependent spatial proteomes within cancerous tissues. Advanced instrumentation, such as the IonOpticks column, played a crucial role in achieving high-resolution and accurate proteome quantitation within tissues.

This research marks a significant step forward in spatial proteomics, providing invaluable insights into tissue biology and disease mechanisms at the molecular level.


More information

The study used a 15cm IonOpticks column to map protein abundance in tissue at down to 40µm resolution, uncovering spatial markers for tumor boundaries and immune response-driven networks.

Read the study at; Nature Communications, 2023, 14

Authors

S. Davis; C. Scott; J. Oetjen; P. D. Charles; B. M. Kessler; O. Ansorge; R. Fischer

Title

Deep topographic proteomics of a human brain tumour

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