Identification of a unique temporal signature in blood and BAL associated with IPF progression.

Scientific Reports
Katy C NormanKelly B Arnold

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and heterogeneous interstitial lung disease of unknown origin with a low survival rate. There are few treatment options available due to the fact that mechanisms underlying disease progression are not well understood, likely because they arise from dysregulation of complex signaling networks spanning multiple tissue compartments. To better characterize these networks, we used systems-focused data-driven modeling approaches to identify cross-tissue compartment (blood and bronchoalveolar lavage) and temporal proteomic signatures that differentiated IPF progressors and non-progressors. Partial least squares discriminant analysis identified a signature of 54 baseline (week 0) blood and lung proteins that differentiated IPF progression status by the end of 80 weeks of follow-up with 100% cross-validation accuracy. Overall we observed heterogeneous protein expression patterns in progressors compared to more homogenous signatures in non-progressors, and found that non-progressors were enriched for proteomic processes involving regulation of the immune/defense response. We also identified a temporal signature of blood proteins that was significantly different at early and late progre...Continue Reading

References

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Nov 14, 2019·Cellular and Molecular Bioengineering·Katy C NormanKelly B Arnold

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Methods Mentioned

BETA
bronchoalveolar lavage
blood draws
blood draw
ELISA
bronchoalveolar
lavage
genotyping
PCA
biopsy
Protein Assay

Clinical Trials Mentioned

NCT01071707

Software Mentioned

GraphPad
SOMAmers ©
DAVID database for integrated discovery
LASSO
SomaLogic
PLSDA
SOMAlogic ©
DAVID
R
Prism

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