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.
Highlights
The accumulation and persistence of scar tissue in fibrotic diseases such as pulmonary fibrosis, liver cirrhosis, and cardiovascular disease is among the most severe clinical issues, causing an estimated 45% of all deaths in the developed world (Cox & Erler, 2011)
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
Most proteins that we found increased in bronchoalveolar lavage fluid (BALF) of patients with high plasma levels for lactate dehydrogenase (pLDH) were associated with lower lung function (Appendix Fig S6A), and top outliers remained significant after accounting for patient age (Appendix Fig S6B–E)
Summary
The accumulation and persistence of scar tissue in fibrotic diseases such as pulmonary fibrosis, liver cirrhosis, and cardiovascular disease is among the most severe clinical issues, causing an estimated 45% of all deaths in the developed world (Cox & Erler, 2011). Interstitial lung diseases (ILDs) are a heterogeneous group of diseases leading to pulmonary fibrosis, which can cause severe destruction of the lung parenchyma and respiratory failure. Addressing the heterogeneity of ILD entities, disease progression and prognosis, and the currently unpredictable occurrence of acute exacerbations of disease, require new molecular approaches for personalized patient monitoring.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
