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  Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers

Mayr, C. H., Simon, L. M., Leuschner, G., Ansari, M., Schniering, J., Geyer, P. E., et al. (2021). Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers. Embo Molecular Medicine, 13(4): e12871. doi:10.15252/emmm.202012871.

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EMBO Mol Med - 2021 - Mayr - Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.pdf (Publisher version), 5MB
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EMBO Mol Med - 2021 - Mayr - Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.pdf
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© 2021 The Authors. Open Access funding enabled and organized by Projekt DEAL.
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 Creators:
Mayr, Christoph H.1, Author
Simon, Lukas M.1, Author
Leuschner, Gabriela1, Author
Ansari, Meshal1, Author
Schniering, Janine1, Author
Geyer, Philipp E.2, Author              
Angelidis, Ilias1, Author
Strunz, Maximilian1, Author
Singh, Pawandeep1, Author
Kneidinger, Nikolaus1, Author
Reichenberger, Frank1, Author
Silbernagel, Edith1, Author
Boehm, Stephan1, Author
Adler, Heiko1, Author
Lindner, Michael1, Author
Maurer, Britta1, Author
Hilgendorff, Anne1, Author
Prasse, Antje1, Author
Behr, Jurgen1, Author
Mann, Matthias2, Author              
Eickelberg, Oliver1, AuthorTheis, Fabian J.1, AuthorSchiller, Herbert B.1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: IDIOPATHIC PULMONARY-FIBROSIS; GENE-EXPRESSION ANALYSIS; EXUDATE MACROPHAGES; ACUTE EXACERBATION; DISEASE; INJURY; TRANSCRIPTOMICS; GLUCOCORTICOIDS; DELTA; ATLASResearch & Experimental Medicine; biomarker; data integration; fibrosis; proteomics; single‐ cell RNA‐ seq;
 Abstract: The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type-2 epithelial cell health status in lavage fluid and plasma. Using cross-modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.

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Language(s): eng - English
 Dates: 2021-03-02
 Publication Status: Published online
 Pages: 22
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000624020400001
DOI: 10.15252/emmm.202012871
 Degree: -

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Project name : discovAIR
Grant ID : 874656
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Embo Molecular Medicine
Source Genre: Journal
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Publ. Info: Chichester : Wiley-Blackwell
Pages: - Volume / Issue: 13 (4) Sequence Number: e12871 Start / End Page: - Identifier: ISSN: 1757-4676
CoNE: https://pure.mpg.de/cone/journals/resource/1757-4676