{"doi":"10.1101/2021.11.02.466753","title":"Proteomics of spatially identified tissues in whole organs","abstract":"<h4>SUMMARY</h4> Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from uncleared samples in both rodent and human tissues. Using DISCO-MS, we investigated microglia activation locally along axonal tracts after brain injury and revealed known and novel biomarkers. Furthermore, we identified initial individual amyloid-beta plaques in the brains of a young familial Alzheimer’s disease mouse model, characterized the core proteome of these aggregates, and highlighted their compositional heterogeneity. Thus, DISCO-MS enables quantitative, unbiased proteome analysis of target tissues following unbiased imaging of entire organs, providing new diagnostic and therapeutic opportunities for complex diseases, including neurodegeneration. <h4>Graphical Abstract</h4> <h4>Highlights</h4> DISCO-MS combines tissue clearing, whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometry DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from fresh tissues DISCO-MS enables identification of rare pathological regions & their subsequent molecular analysis DISCO-MS revealed core proteome of plaques in 6 weeks old Alzheimer‘s disease mouse model Supplementary Video can be seen at: http://discotechnologies.org/DISCO-MS/","journal":null,"year":2021,"id":12368,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0508,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-11-04","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":20986,"name":"Andreas-David Brunner","orcid":"0000-0002-2733-7899","position":1,"is_corresponding":false},{"id":64849,"name":"Zhouyi Rong","orcid":"0000-0003-4849-1278","position":2,"is_corresponding":false},{"id":64850,"name":"Hongcheng Mai","orcid":"0000-0001-6615-0157","position":3,"is_corresponding":false},{"id":20977,"name":"Marvin Thielert","orcid":"0000-0003-3639-2221","position":4,"is_corresponding":false},{"id":94922,"name":"Rami Al-Maskari","orcid":"0000-0001-8256-3795","position":5,"is_corresponding":false},{"id":64853,"name":"Florian Kofler","orcid":"0000-0003-0642-7884","position":7,"is_corresponding":false},{"id":64854,"name":"Mihail Ivilinov Todorov","orcid":"0000-0002-8627-1260","position":8,"is_corresponding":false},{"id":35695,"name":"Mayar Ali","orcid":"0000-0002-0398-5699","position":9,"is_corresponding":false},{"id":64856,"name":"Zeynep Ilgin Kolabas","orcid":"0000-0002-0672-681X","position":11,"is_corresponding":false},{"id":64857,"name":"Doris Kaltenecker","orcid":"0000-0002-4110-1006","position":12,"is_corresponding":false},{"id":64859,"name":"Stefan Frieder Lichtenthaler","orcid":"0000-0003-2211-2575","position":14,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":16,"is_corresponding":false},{"id":2937,"name":"Matthias Mann","orcid":"0000-0003-1292-4799","position":17,"is_corresponding":false},{"id":38433,"name":"Ali Ertürk","orcid":"0000-0001-5163-5100","position":18,"is_corresponding":false},{"id":64852,"name":"Johannes C. Paetzold","orcid":"0000-0002-4844-6955","position":20,"is_corresponding":false},{"id":64855,"name":"Müge Molbay","orcid":"0000-0001-6546-4322","position":21,"is_corresponding":false},{"id":64858,"name":"Stephan A. Müller","orcid":"0000-0003-3414-307X","position":22,"is_corresponding":false},{"id":51419,"name":"Bjoern Menze","orcid":"0000-0003-4136-5690","position":23,"is_corresponding":false},{"id":64847,"name":"Harsharan Singh Bhatia","orcid":"0000-0001-9912-8263","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}