Clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease currently limit treatment of severe Covid-19, characterized by hypoxia, with the risk of rapid deterioration that may require intensive care support and, in some patients, progression to acute respiratory distress syndrome, multiorgan failure and death. Currently, opportunities for biomarker-led timed and targeted precision medicine approaches are limited by an incomplete understanding of pathogenesis and heterogeneity among patients with severe disease. To advance this, the COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium, led by the Knight group at University of Oxford presents a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers.
Plasma protein COVID-19 signatures and subphenotypes
They use a comprehensive multi-modal integrated approach, applied to multiple well-defined cohorts of patients and health volunteers, complemented with the analysis of the Covid-19 plasma proteome. They performed high-throughput liquid chromatography using the 100 samples per day method on the Evosep One coupled to a timsTOF Pro mass spectrometer, producing data for 105 proteins on 257 individuals (340 samples) after QC.
Their proteomic analysis has identified specific plasma cytokine and chemokine levels as biomarkers of severe disease with evidence for acute phase inflammation, complement activation/attack, fibrin clots, proteases, serum amyloid, tissue necrosis, receptor mediated endocytosis and cholesterol transport as hallmarks. Moreover, they have discovered plasma protein signatures that can be used to stratify acute hospitalized COVID-19 cases into disease sub-phenotypes, with cluster membership informative for response state and associated with differential 28-day mortality. They have validated their finding in an independent dataset using a predictive set of seven plasma proteins (cytokines IL-6, IL-8; chemokines CCL2, CCL19, CCL20, CXCL10; and C-type lectin CLEC11A, a key growth factor for primitive hematopoietic progenitor cells). Patient stratification is important given the observed clinical heterogeneity within severe Covid-19. Such variability has historically been a major confounder of clinical trials for targeted immune therapy in other severe infections.
Collectively, their multi-omic integrated blood atlas comprehensively delineates the host immune response in COVID-19 from the start of the UK pandemic, prior to clinical trial-led implementation of approved treatments or vaccination. Integrative approaches such as described here will be important as we seek novel therapeutic targets and the opportunity for a precision medicine approach to treatment.
HIGH-THROUGHPUT PLASMA ANALYSIS
Explore how the Evosep One, with high reproducibility and robustness, is ideally suited for analysis of large sample cohorts of blood plasma. Visit our Applications page on plasma analysis here
MORE RESEARCH ON PLASMA
Here you can see publications available on plasma research featuring Evosep One. For a full overview of publications published using the Evosep One Technology visit our Literature room here
|Title||Subject||Material||Year||Summary||Evosep method||MS instrumentation||Learn More|
|Standardized workflow for precise mid- and high-throughput proteomics of blood biofluids||Clinical research, DIA, Plasma||Publication||2021|
The Van Eyk group presents a standardized workflow for precise high-throughput proteomics of blood biofluids using the 60 SPD method. They established optimal conditions for sample preparation and DIA analysis in plasma, then automated and adapted this for depleted plasma and whole blood.
|60 SPD||Thermo Orbitrap Exploris 480|
|The COVIDome Explorer Researcher Portal||Clinical research, Covid-19, DDA, Plasma||Publication||2021|
Researchers from University of Colorado led by Joaquin M. Espinosa, have created a user-friendly researcher portal enabling easy access and real-time analysis of matched multi-omics datasets for COVID-19, termed the COVIDome Explorer. They illustrate the use through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19.
|30 SPD||Bruker timsTOF Pro|
|A robust mass spectrometer for precision medicine – the Orbitrap Exploris 240 mass spectrometer for large-scale plasma protein profiling||DDA, Plasma||Application note||2021|
This application note from Thermo Fisher Scientific Precision Medicine Science Center demonstrates the reliability and robustness of the Evosep One coupled with the Orbitrap Exploris 240 MS for large-scale, untargeted plasma protein profiling. They observed excellent reproducibility of protein and peptide identifications over 100 injections of human serum performed five weeks apart.
|60 SPD||Thermo Orbitrap Exploris 240|
|Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers||Clinical research, DIA, Fibrosis, Plasma||Publication||2021|
In this study, the Theis and Schiller groups at the Helmholtz Zentrum München, investigated the correspondence of cell state changes in diseased organs to peripheral protein signatures in pulmonary fibrosis patient cohorts. From plasma proteome profiling of more than 122 patients, they propose CRTAC1 protein levels in plasma as a novel biomarker.
|100 SPD, 60 SPD||Thermo Q Exactive HF|
|Seroconversion stages COVID19 into distinct pathophysiological states||Clinical research, Covid-19, Plasma||Publication||2020|
In this study, researchers from University of Colorado led by Joaquin M. Espinosa, found highly variable seroconversion status among hospitalized Covid-19 patients. Their results support the existence of distinct pathophysiological states, with seroconversion status being potentially useful as a surrogate marker of underlying processes.
|30 SPD||Bruker timsTOF Pro|
|Gradient off-set focusing HPLC insturment for robust and high throughput clinical proteomics||Clinical research, Plasma, Technology||Application note||2017|
Evosep One for clinical analysis
|A Novel LC System Embeds Analytes in Pre-formed Gradients for Rapid, Ultra-Robust Proteomics||DDA, DIA, Plasma, Technology||Publication||2018|
Description of Evosep
|60 SPD||Thermo Q Exactive HF-X|
|Robust and Reprodusible Protein Quantification in Plasma Using the Evosep One and the Agilent 6495 Triple Quadrupole LC/MS||Plasma, Targeted workflow, Technology||Application note||2020|
Agilent feasibility study
|60 SPD||Agilent 6495 Triple Quadrupole|
|High dynamic range proteome analysis with BoxCar DIA and super-resolution Orbitrap mass spectrometry||DIA, Plasma, Technology||Poster||2020|
|100 SPD, 30 SPD||Thermo Orbitrap Exploris 480|
|Clinical proteomics||Clinical research, Plasma||Poster||2018|
Clinical proteomics poster
|Development of a Novel LC Concept for Clinical Proteomics||DDA, Plasma, Technology||Poster||2018|
Description of Evosep One
|MaxQuant software for ion moiblity enhanced shotgun proteomics||DDA, Plasma, Technology||Publication||2020|
MaxQuant for timsTOF analysis
|100 SPD||Bruker timsTOF Pro|
|Plasma proteomics goes high-throughput – timsTOF Pro with PASEF and 4D feature alignment to quantify 500 plasma proteins in 11.5 min||Clinical research, DDA, Plasma||Application note||2019|
The timsTOF Pro with PASEF and the Evosep One for biomarker discovery in large sample cohorts of human blood plasma (blood plasma from 192 severe infection patients).
|100 SPD||Bruker timsTOF Pro|
|Consistency, consistency – Automated Sample Prep for Translational Proteomics||Clinical research, Plasma||Video||2020|
In this webinar, Emily Chen, Sr. Director at the Thermo Fisher Precision Medicine Science Center presents an automated, robust and scalable sample preparation pipeline for large-scale clinical research samples.
|An Ultra High-Throughput Plasma Protein Profiling (uHTPPP) Workflow Using a Modified Quadrupole-Orbitrap Mass Spectrometer||Clinical research, DDA, Lung, Plasma, Serum, Tissue||Application note||2020|
In this application note, the group of Emily Chen at the Thermo Fisher Precision Medicine Science Center describes a high-throughput plasma and serum proteomics analysis workflow for large population cohort studies that utilizes a standardized sample preparation method, high-throughput data acquisition, and easy to implement QC standard.
|30 SPD, 60 SPD||Thermo Orbitrap Exploris 240|
|Scalable and Automated Plasma Workflow Based on the Thermo Scientific Q Exactive HF-X MS Platform||Clinical research, DDA, Lung, Plasma, Serum||Application note||2019|
In this application note, the group of Emily Chen at PMSC describes a high-throughput plasma and serum proteomics analysis workflow for large population cohort studies that utilizes a standardized sample preparation method, high-throughput data acquisition, and easy to implement QC standard.
|100 SPD, 30 SPD, 60 SPD||Thermo Q Exactive HF-X|
|A paired liver biopsy and plasma proteomics study reveals circulating biomarkers for alcohol-related liver disease||Clinical research, DIA, Liver, Plasma||Publication||2020|
This publication from Matthias Mann groups in Copenhagen and Münich describes a paired liver biopsy and plasma proteomics study, which make use of Boxcar DIA scanning for a large clinical cohort of nearly 600 patients. They have developed a machine learning model based on their biomarker panel, which for the first time outperforms existing tests, …
|30 SPD||Thermo Q Exactive HF-X|
|Fast Confirmatory Analysis of Rhuepos in Plasma for Horseracing Doping Control||Plasma, rHuEPO, Targeted workflow||Application note||2019|
This application note describes a rapid targeted analysis monitoring two tryptic rHuEPO peptides in plasma for horseracing doping control. The results illustrate the promising capabilities of the Evosep One innovative technology for the analysis of protein/peptide-based drugs in the context of drug testing.
|100 SPD||Thermo Q Exactive HF|