In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta

Pernemalm, Maria; Sandberg, AnnSofi; Zhu, Yong; Boekel, Jorrit; Tamburro, Davide; Schwenk, Jochen M.; Björk, Albin; Wahren‐Herlenius, Marie; Åmark, Hanna; Östenson, Claes‐Göran; Westgren, Magnus; Lehtiö, Janne

doi:10.7554/elife.41608

Cited by 62 publications

(79 citation statements)

References 52 publications

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“…This is especially important when considering early disease detection is critical for children, especially when trying to limit both short-and longterm sequelae of any disease. Additionally, a recent proteogenomic study revealed that newborns have three times the number of unique proteins as their mothers, further suggesting that differences in plasma proteomes between adults and children could lead to novel biological outcomes 37 . Studies focusing on sick children are critical for understanding underlying population-specific pathophysiologies and may help reduce guesswork in medical interventions currently associated with drug dosage and predicted patient response.…”

Section: Cohort Selection -Age (Adult Vs Pediatric)mentioning

confidence: 99%

Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data

et al. 2019

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The proteomic analyses of human blood and blood-derived products (e.g. plasma) offers an attractive avenue to translate research progress from the laboratory into the clinic. However, due to its unique protein composition, performing proteomics assays with plasma is challenging. Plasma proteomics has regained interest due to recent technological advances, but challenges imposed by both complications inherent to studying human biology (e.g. inter-individual variability), analysis of biospecimen (e.g. sample variability), as well as technological limitations remain. As part of the Human Proteome Project (HPP), the Human Plasma Proteome Project (HPPP) brings together key aspects of the plasma proteomics pipeline. Here, we provide considerations and recommendations concerning study design, plasma collection, quality metrics, plasma processing workflows, mass spectrometry (MS) data acquisition, data processing and bioinformatic analysis. With exciting opportunities in studying human health and disease though this plasma proteomics pipeline, a more informed analysis of human plasma will accelerate interest whilst enhancing possibilities for the incorporation of proteomics-scaled assays into clinical practice.

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Section: Cohort Selection -Age (Adult Vs Pediatric)mentioning

confidence: 99%

Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data

et al. 2019

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“…Application of S‐Trap, SP3 and PAC in serum proteomics could be useful to improve the availability of low‐abundance proteins. With regard to protein discovery in human plasma, resolving proteins by high‐resolution isoelectric focusing coupled to mass spectrometry (HiRIEF LC/MS/MS) successfully identified more than 1500 proteins …”

Section: Resultsmentioning

confidence: 99%

Cytokines in the grass, a lesson learnt: Measuring cytokines in plasma using multiple reaction monitoring mass spectrometry

Mendoza-Porras

Pires

Goswami

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale: Cytokines are cell regulatory molecules of high importance as indicators for homeostasis and pathology in many species. The current method to measure cytokines in body fluids is reagent dependent, requiring highly specific paired antibodies. Methods:A liquid chromatography/multiple reaction monitoring mass spectrometry (LC/MRM-MS)-based approach was developed to simultaneously establish the limits of detection (LODs) and quantification (LOQs) for recombinant cytokines IL-1β, IL-6, IFNγ and TNFα as pure standards and in bovine sera. All experimental LC/MRM-MS data are available at CSIRO Data Access Portal repository under identifier doi.org/ 10.25919/5de8a0232a862. Results:The present method enabled LODs and LOQs as low as 1.05 and 1.12 fmol/ μL in the experiment comprised of pure standards. Comparable results were obtained in the experiment where digested cytokines were mixed with pre-digested sera proteins. The intrinsic matrix effects were evident when intact cytokines were codigested within undiluted and undigested sera decreasing the ability to detect and quantify cytokines by 10,000-fold compared with pure standards and predigested sera. Conclusions:The developed LC/MRM-MS method provided insights into the difficulties in detecting the target peptides when embedded in complex matrices.Nonetheless, the method may potentially be readily applied in biomarker-focused research interrogating fluids of lesser complexity such as synovial fluid, cerebrospinal fluid and tissue culture media.

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“…Seven proteins constitute 85% of the total protein mass in plasma. 87 Peptides from abundant proteins crowd the spectra, hindering comprehensive profiling of the plasma proteome and making in-depth analysis of plasma cohorts challenging. Plasma depletion strategies are available, 88 but the high cost and time-consuming nature of these methods makes them unlikely to be applicable in large cohorts.…”

Section: Potential Application Of Nanomedicine Strategies For Diagnosmentioning

confidence: 99%

COVID-19: Nanomedicine Uncovers Blood-Clot Mystery

Saei

Sharifi

2020

J. Proteome Res.

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Further complications associated with infection by severe acute respiratory syndrome coronavirus 2 (a.k.a. SARS-CoV-2) continue to be reported. Very recent findings reveal that 20–30% of patients at high risk of mortality from COVID-19 infection experience blood clotting that leads to stroke and sudden death. Timely assessment of the severity of blood clotting will be of enormous help to clinicians in determining the right blood-thinning medications to prevent stroke or other life-threatening consequences. Therefore, rapid identification of blood-clotting-related proteins in the plasma of COVID-19 patients would save many lives. Several nanotechnology-based approaches are being developed to diagnose patients at high risk of death due to complications from COVID-19 infections, including blood clots. This Perspective outlines (i) the significant potential of nanomedicine in assessing the risk of blood clotting and its severity in SARS-CoV-2 infected patients and (ii) its synergistic roles with advanced mass-spectrometry-based proteomics approaches in identifying the important protein patterns that are involved in the occurrence and progression of this disease. The combination of such powerful tools might help us understand the clotting phenomenon and pave the way for development of new diagnostics and therapeutics in the fight against COVID-19.

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In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta

Cited by 62 publications

References 52 publications

Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data

Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data

Cytokines in the grass, a lesson learnt: Measuring cytokines in plasma using multiple reaction monitoring mass spectrometry

COVID-19: Nanomedicine Uncovers Blood-Clot Mystery

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