Spatial-omics goes 3D🤗! Out at Cell Cell 👉🏼 We developed DISCO-MS with Matthias Mann Lab, a spatial proteomics technology for specimens fully imaged in 3D. DISCO-MS is aided by robotics and enables the study of diseases at their early stages.

Summary: DISCO-MS is a spatial proteomics technology: it enables proteomics analysis of cleared tissues imaged in 3D. DISCO-MS is aided by AI and robotics and yields proteome similar to fresh or fixed samples. Have questions? Add them below👇 we will answer📖

DISCO-MS Step 1: We start by rendering a mouse body or human organ optically transparent using robust clearing methods such as vDISCO or SHANEL. Then, after their cell-level light-sheet microscopy scan, we can visualize fluorescently-labeled structures in 3D as complete.

Step 2: Next, we employ deep learning-based image analysis to identify regions associated with illnesses such as Alzheimer’s disease, brain injury, or coronary artery disease in an unbiased manner.

Step 3: Small tissue regions are isolated with the help of a specialized robotic extraction system called DISCO-bot. Samples can currently be as small as 0.014 mm3. Smaller samples (down to 0.0005 mm3 or 60 cells) can be analyzed using laser capture microdissection.

Step 4: Next, the molecular composition of the tissue isolates is analyzed using high-sensitivity mass-spectrometry. The cellular proteome measured in cleared tissue is almost indistinguishable from the one obtained from fresh or fixed tissue controls.

Example application 1: To show the utility of DISCO-MS, we first characterized microglia activation after traumatic brain injury. We identified numerous proteins that were differentially regulated between equivalent regions along the optical tract in damaged and healthy brains.

Example application 2: Our technology enables us to characterize subtle changes, which would be easily missed using standard methods. To this end, we analyzed the first A-beta plaques appearing in the 5xFAD Alzheimer’s disease mouse model from different brain regions.

Example application 3: Next, we studied immune cell heterogeneity in the bone marrow. To this end, we used Lsy-M-EGFP mice (labeling immune cells) and identified regional protein expressions in curvy bones: scapula and cranium.

Example application 4: DISCO-MS works equally well on clinical samples. We used DISCO-bot-aided DISCO-MS to study coronary artery disease. After identifying all atherosclerotic plaques in the human heart, we studied proteome composition related to plaque development.

Conclusions: DISCO-MS combines the complete 3D-imaging data of whole organs and organisms with their unbiased proteome signatures. It works well in preclinical and clinical samples, thus, can be used almost for any biomedical tissue analysis.

Limitations and future developments: Currently we cannot reach single cell resolution as such proteomics methods are limited. We are also working on improving DISCO-bot for smaller tissue isolation.

You want to learn more about DISCO-MS, and/or use it? Let us know!

Authors @HarsharanBhatia @ADBxMPIB @FurkOzturk @Sakethkapoor @zhouyi_rong @Hongcheng_Mai @marvinchth @mayarbali @rami96614090 @MihailMuc @jocpae @Dorie00 @ilginkolabas @MolbayM @moritz_negwer @Lu_h99 @NatalieKrahmer @Farida80168644 @IngoBechmann @fabian_theis @Bjoern @menze_group

Authors @labs_mann @erturklab Non-author acknowledgement @MarkusElsner1 @MarinBralo

Worked done at the @HelmholtzMunich, @MPI_Biochem, @LMU_Muenchen, @LMU_Uniklinikum, @ISD_Research, @TU_Muenchen, @DZNE_de, supported by @SyNergy_Cluster, @ERC_Research, @NOMIS and graduate programs @IMPRS_LS, GSN-LMU, and MMRS-LMU.