Dataset Information

Longitudinal Plasma Proteomics Analysis of Acute COVID-19

ABSTRACT: The host response to COVID-19 pathophysiology over the first days of infection remains largely unclear especially the mechanisms in the blood compartment. We report here on a longitudinal proteomic analysis of acute phase COVID-19 patients, for which we used blood plasma and MRM proteomics with internal standards as well as DIA. We measured samples on admission for 49 patients, of which 21 with additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline.

INSTRUMENT(S): 6495B Triple Quadrupole LC/MS, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Severe Covid-19

SUBMITTER: Yassene Mohammed

LAB HEAD: Yassene Mohammed

PROVIDER: PXD029437 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19.

Mohammed Yassene Y Goodlett David R DR Cheng Matthew P MP Vinh Donald C DC Lee Todd C TC Mcgeer Allison A Sweet David D Tran Karen K Lee Terry T Murthy Srinivas S Boyd John H JH Singer Joel J Walley Keith R KR Patrick David M DM Quan Curtis C Ismail Sara S Amar Laetitia L Pal Aditya A Bassawon Rayhaan R Fesdekjian Lara L Gou Karine K Lamontagne Francois F Marshall John J Haljan Greg G Fowler Robert R Winston Brent W BW Russell James A JA

Journal of proteome research 20220210 4

The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measu ...[more]

PMID: 35143212

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Project description:The current state of proteomics requires a choice between targeted and discovery methods. The former provides exceptional quantitation and data completeness, but only with few analytes. Discovery proteomics can identify hundreds and thousands of proteins in a sample, but with poor quantitation and data completeness. We have established and optimized a method that combines targeted and data-independent acquisition for absolute quantitation of all plasma proteins in a single sequential window acquisition of all theoretical fragment ions (SWATH) acquisition run using a panel of spike-in standards (SIS). We compared the absolute quantitation (AQ) of SWATH and high-resolution multiple-reaction monitoring (MRM-HR) acquisition methods using the 100 protein PlasmaDive SIS panel spiked into human plasma. SWATH provided equivalent quantitation and differentially abundant protein profiles as MRM-HR. Absolute quantities of the SIS peptides from the SWATH data were used to estimate the absolute quantities (eAQ) for all the proteins in the run. The eAQ values provided similar quantitation and differentially abundant protein profiles as AQ and protein group (PG) values, and the eAQ method was the only scheme where all selected proteins were verified by MRM-HR. We applied the eAQ method to a cohort of 16 non-small cell lung cancer (NSCLC) patients receiving immunotherapeutics and found that fibronectin (FN1) and proteoglycan 4 (PRG4) were useful markers for predicting patients who would stay on these agents for at least 6 months (area under the curve of 0.8438 and 0.6735, respectively). Thirteen additional plasma samples confirmed that FN1 and PRG4 are putative biomarkers (positive predictive value is 100% and 85.7%, respectively) for a prolonged (>6 months) response to immunotherapeutic agents. In conclusion, we describe an optimized method for absolute quantification of all proteins in a SWATH run, and this approach is amenable for the identification of plasma biomarkers.

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