Clinical research 

Clinical biochemistry laboratories worldwide measure millions of samples daily from various body fluids such as blood and urine.

A growing part of these analyses is already performed with LCMS, especially diagnostic niches of laboratory medicine, where the analytical specificity of LCMS is superior to immunoassays.

Technological advancements

Innovation is a community effort and new technology plays a huge role in defining what is possible. Recent technological advancements combined with an increased interest in clinical research has pushed the limits of what is now possible within routine analysis using LCMS.

More robust solutions are a key factor in clinical research, where researchers continuously challenge the sensitivity of their workflows to be able to accurately measure both large and small biological changes across large sample cohorts.

The technology available for clinical research is in rapid development and the future potential for this field is looking very promising. Routine analysis and standardized workflows have already been implemented in many clinical biochemistry labs around the globe.

What is needed to make the transition
to LCMS in a clinical setting? 

In order to add value in a clinical setting, there are a number of key criteria for LCMS workflows to be accepted and approved.

Most importantly, these workflows must be simple, robust and preferably built on automation to limit handling variations. Secondly, all instrumentation used should be standardized and robust for everyday use and provide the same results across laboratories.

With these considerations in mind and instrumentation developed specifically for clinical proteomics, LCMS workflows can successfully be transitioned to the clinic.

 

So what do we mean when we say
clinical proteomics? 

Clinical proteomics is a broad topic from discovery proteomics to clinical diagnostics for informing clinical decision making. 

In this video Founder of Evosep Ole vorm elaborates on our thoughts on clinical proteomics and what is needed to bring LCMS into the clinic.

We believe that the Evosep One is a great asset in routine analysis as it offers a standardized platform with sensitive and reproducible workflows that can be combined with automated sample preparation – all essential for clinical studies in general. 

The Trudel group at Princess Margaret Cancer Centre

A PERSONALIZED MS-BASED ASSAY TO MONITOR MULTIPLE 2 MYELOMA DISEASE ASSESSMENT 

In collaboration with Rapid Novor and University of Waterloo, the Trudel group at Princess Margaret Cancer Centre in Toronto have developed a non-invasive MS-based test to assess minimal residual disease (MRD), a measure of depth of remission to treatment, which has become an important parameter in assessing the disease burden in multiple myeloma.

In conclusion, they have developed and validated a non-invasive, sensitive, personalized assay that is ideal for frequent monitoring of multiple myeloma patients in complete remission. They hope to further develop their assay, allowing to sequence more than one M-protein and improve the sensitivity even further.

Learn more about their results in our blog post here

Odense University hospital and the mann lab

PROTEOMICS OUTPERFORMS ESTABLISHED TESTS FOR DETECTING THREE STAGES OF LIVER DISEASE

In collaboration with Odense University Hospital in Denmark, the Mann group at Novo Nordisk Foundation Center for Protein Research have developed a machine learning model based on their biomarker panel, which for the first time outperforms existing tests, laying the foundation for a generic proteomics liver health assessment.

With ongoing improvements in technology, they expect an increase in performance of their model. Targeted or ‘global targeted’ MS-based assays could be developed to retain the full specificity of this technology. An additional benefit of plasma proteomic profiling is its generic nature, meaning that it provides additional information apart from the targeted panel.

Learn more about their results in our blog post here

Clinical research in the future

With the rapid development and maturing of technologies used in clinical applications in a routine setting we are convinced that we are just in the beginning of what will be possible in this field.

LCMS has the potential to become a more prominent key technology in many fields within the clinical biochemistry laboratory as these workflows, when combined with automation offer 24/7 availability.

In the videos we have asked pioneers from the industry for their 2 minute take on the future of proteomics. Hear from:

  • Professor Matthias Mann, Group Leader at Mann Lab, The Max Planck Institute
  • Professor Phil Robinson, Head of Cell Signalling Unit and Co-Director of ProCan at the Children’s Medical Research Institute
  • Dr. Thomas Conrads, Co-Principal Investigator and Chief Scientific Officer of the Department of Defense Gynecologic Cancer Center of Excellence


“So, when we say clinical, we mean that we designed the Evosep One to be really fast and robust. Once you’re in the clinic you would have hundreds if not thousands of samples that are stacked up and need to be analysed on a very tight schedule. So it is important that the system works every day.”

Ole Vorm, Founder of Evosep

 

ole-vorm

EVOSEP WEBINAR

MEET OUR USERS in clinical research and learn how they have implemented Evosep One for routine analysis

Evosep One in the Clinical Biochemistry Lab

THU February 24  I   4:00 PM CEST

In this webinar, you can meet users working in a clinical biochemistry laboratory and learn about their work and how they have implemented the Evosep One for routine analyses.

More clinical research from our users

Here you can see publications available featuring clinical research with Evosep One. For a full overview of publications published using the Evosep One Technology visit our Literature room here

TitleSubjectMaterialYearSummaryInstituteEvosep methodMS instrumentationLearn More
Unleashing the true power of DIA/SWATH data acquisition with short gradients – Rapid profiling of pre-clinical models and proteome dynamics, , 2019Achieving sufficient statistical power for the analysis of a comprehensive set of target proteins requires processing of a large number of samples. With finite resources, researchers face a difficult choice: should they aim at deeper proteomic coverage or higher sample throughput?

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Standardized workflow for precise mid- and high-throughput proteomics of blood biofluids, , , 2021In this seminar from the Canadian National Proteomics Network (CNPN) meeting 2021, Angela McArdle presents a standardized workflow for precise high-throughput proteomics of blood biofluids. They established optimal conditions for sample preparation and DIA analysis in plasma, then automated and adapted this for depleted plasma and whole blood.

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The COVIDome Explorer Researcher Portal, , , 2021Researchers 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.

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Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers, , , 2021In 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.,

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Global proteomic analysis of extracellular matrix in mouse and human brain highlights relevance to cerebrovascular disease, , 2021In this study, the Cader group from University of Oxford, presents a global proteomic analysis of the extracellular matrix (ECM) in mouse and human brains. They report the identification of 147 core ECM proteins of the human brain vascular matrisome, including collagens, laminins, fibronectin and nidogens. Network analysis revealed the connection between the ECM proteins …

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High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion, , 2021This publication from OmicEra Diagnostics, describes alterations of the serum proteome during COVID-19 using a scalable plasma proteome profiling workflow. It comprises the most detailed longitudinal protein trajectories during hospitalization, based on one of the largest MS-based body fluid proteomics efforts with a total of 720 plasma serum samples.

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The Host Interactome of Spike Expands the Tropism of SARS-CoV-2, , 2021This publication from the Yates lab, investigates the host interactome determining whether a SARS-CoV-2 infection is productive. They find an “S2 only” dependent, alternative infection of additional cell types with SARS-CoV-2 may impact vaccination strategies and provide a molecular explanation for a severe or prolonged progression of disease in select COVID-19 patients.

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Molecular origin of blood-based infrared fingerprints, , 2021This publication led by the Zigman group describes the molecular understanding of infrared molecular fingerprints (IMFs) by examining a prospective clinical study with both IR spectroscopy ad MS-based proteomics. They find the disease-related differences in IMFs of blood sera are dominated by contributions from the protein fractions, rather than metabolites.

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R1441G but not G201S Mutation Enhances LRRK2 Mediated Rab10 phosporylation in human Peripheral blood neutrophils, , 2021This publication from University of Dundee led by Esther Sammler, describes that in vivo LRRK2 dependent

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Fluvastatin mitigates SARS-CoV-2 infection in human lung cells, 2020Clinical data of patients suffering from COVID-19 have indicated that statin therapy, used to treat high cholesterol, is associated with a better clinical outcome. A collaboration led by Gisa Gerold investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that fluvastatin inhibited coronavirus infection, while other tested statins did not.

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Seroconversion stages COVID19 into distinct pathophysiological states, , 2020In 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.

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Development of a multiplexed targeted mass spectrometry assay for LRRK2-phosphorylated Rabs and Ser910/Ser935 biomarker sites, , 2020This publication from University of Dundee led by Dario R Alessi, describes the validation and development of a new, multiplexed targeted assay that enables the relative quantification of the key components of the LRRK2 pathway, defining the impact of LRRK2 inhibitors and Parkinson’s disease causing mutations.,

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Peptidomic analysis of urine from youths with early type 1 diabetes reveals novel bioactivity of uromodulin peptides in vitro, , , 2019Urinary peptidomics in early type 1 diabetes

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Gradient off-set focusing HPLC insturment for robust and high throughput clinical proteomics, , 2017Evosep One for clinical analysis

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Clinical proteomics, 2018Clinical proteomics poster

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Using Artificial Intelligence on Ultrafast LC-MSMS-DIA runs for Bacterial Identification in Urine, , 2019View the recording of our HUPO 2019 lunch seminar, where Florence Roux-Dalvai from Québec Research Center, Canada presents a new strategy for bacterial species identification in urinary tract infection using artificial intelligence on ultrafast LCMS DIA runs.  , ,

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Plasma proteomics goes high-throughput – timsTOF Pro with PASEF and 4D feature alignment to quantify 500 plasma proteins in 11.5 min, , 2019The 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).

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Consistency, consistency – Automated Sample Prep for Translational Proteomics, 2020In 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.

Watch webinar

An Ultra High-Throughput Plasma Protein Profiling (uHTPPP) Workflow Using a Modified Quadrupole-Orbitrap Mass Spectrometer, , , , , 2020In 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.,

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Scalable and Automated Plasma Workflow Based on the Thermo Scientific Q Exactive HF-X MS Platform, , , , 2019In 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., ,

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Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients, , 2020In this study, researchers from University of Colorado led by Angelo D’Alessandro, performed proteomics analysis of Covid-19 patients and healthy control individuals. They measured the proteomes of red blood cells (RBC) and identified increased glycolysis in RBCs from COVID-19 patients, accompanied by increased oxidation of key structural proteins.

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Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens, , , 2020This publication by the Akhilesh Pandey group describes a targeted FAIMS-PRM assay on an Orbitrap Exploris 480 MS. More than 700 nasopharyngeal swab samples were analyzed with high specificity and comparable sensitivity to the gold standard RT-PCR method for the diagnosis of SARS-CoV-2.,

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Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV, , , 2020This publication describes the molecular functions of viral proteins and their interactions with the host proteome of SARS-CoV-2. The impact of viral infection on the proteome and phosphoproteome were analyzed in a time-resolved manner by DIA. The analysis revealed key pathways perturbed during the infection identifying potential vulnerable points of SARS-CoV-2.,

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Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level, , , 2020This publication describes a serum proteomics analysis of COVID-19 patients, stratified by the degree of inflammation, represented by IL-6 levels. It highlights an increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential therapeutic interventions, such as the use of pro-fibrinolytic agents.

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A paired liver biopsy and plasma proteomics study reveals circulating biomarkers for alcohol-related liver disease, , , 2020This 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, …

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HOW FAR WILL YOU GO? THE FIVE STANDARD METHODS FOR THE EVOSEP ONE
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The proteomics dilemma – High throughput analysis versus proteome depth
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PAVING THE WAY TO CLINICAL PROTEOMICS
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