Evidence map›Paper›PMID 36891577›Full record

ArticleProteomics. Clinical applications2023

Optimised plasma sample preparation and LC-MS analysis to support large-scale proteomic analysis of clinical trial specimens: Application to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.

Matthew B O'Rourke, Andrzej S Januszewski, David R Sullivan, Imre Lengyel, Alan J Stewart, Swati Arya, Ronald C Ma, Sanjeev Galande, Anandwardhan A Hardikar, Mugdha V Joglekar and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Proteomics. Clinical applications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 4 countries.

Matthew B O'RourkeBowel Cancer & Biomarker Lab, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Andrzej S JanuszewskiNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
David R SullivanNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Imre LengyelWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, Belfast, UK.
Alan J StewartSchool of Medicine, University of St Andrews, St Andrews, Fife, UK.
Swati AryaSchool of Medicine, University of St Andrews, St Andrews, Fife, UK.
Ronald C MaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Sanjeev GalandeIndian Institute of Science Education and Research, Pune, India.
Anandwardhan A HardikarNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Mugdha V JoglekarNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Anthony C KeechNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Alicia J JenkinsNHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Mark P MolloyBowel Cancer & Biomarker Lab, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
The University of Sydney · AUNational Health and Medical Research Council · AUUniversity of St Andrews · GBCancer Australia · AUChinese University of Hong Kong · HKIndian Institute of Science Education and Research Pune · INQueen's University Belfast · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeRobust, affordable plasma proteomic biomarker workflows are needed for large-scale clinical studies. We evaluated aspects of sample preparation to allow liquid chromatography-mass spectrometry (LC-MS) analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes.

methodsUsing LC-MS with data-independent acquisition we evaluated four variables: plasma protein depletion, EDTA or citrated anti-coagulant blood collection tubes, plasma lipid depletion strategies and plasma freeze-thaw cycles. Optimised methods were applied in a pilot study of FIELD participants.

resultsLC-MS of undepleted plasma conducted over a 45 min gradient yielded 172 proteins after excluding immunoglobulin isoforms. Cibachrome-blue-based depletion yielded additional proteins but with cost and time expenses, while immunodepleting albumin and IgG provided few additional identifications. Only minor variations were associated with blood collection tube type, delipidation methods and freeze-thaw cycles. From 65 batches involving over 1500 injections, the median intra-batch quantitative differences in the top 100 proteins of the plasma external standard were less than 2%. Fenofibrate altered seven plasma proteins. CONCLUSIONS AND CLINICAL RELEVANCE: A robust plasma handling and LC-MS proteomics workflow for abundant plasma proteins has been developed for large-scale biomarker studies that balance proteomic depth with time and resource costs.

Indexed as

Diabetes Mellitus, Type 2FenofibrateAdultBiomarkersBlood ProteinsChromatography, LiquidHumansPilot ProjectsProteomicsTandem Mass SpectrometryBiomarkersBlood ProteinsFenofibrateBiomarkerdiabetesfenofibratemass spectrometryplasmaproteomics

Identifiers

PMID36891577
PMCPMC10909541
OpenAlexW4323653511

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.