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

Abstract

Here we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy.

Data availability

MS raw data are available via ProteomeXchange with identifier PXD010899.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Maria Pernemalm

    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4624-031X
  2. AnnSofi Sandberg

    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Yafeng Zhu

    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Jorrit Boekel

    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Davide Tamburro

    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Jochen M Schwenk

    Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8141-8449
  7. Albin Björk

    Rheumatology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Marie Wahren-Herlenius

    Rheumatology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Hanna Åmark

    Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  10. Claes-Göran Östenson

    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  11. Magnus Westgren

    Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  12. Janne Lehtiö

    Department of oncology and pathology, Karolinska Institute, Stockholm, Sweden
    For correspondence
    janne.lehtio@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8100-9562

Funding

Vetenskapsrådet

  • Maria Pernemalm
  • AnnSofi Sandberg
  • Yafeng Zhu
  • Jorrit Boekel
  • Claes-Göran Östenson
  • Janne Lehtiö

Stiftelsen Olle Engkvist Byggmästare

  • Claes-Göran Östenson

Cancerfonden

  • Maria Pernemalm
  • Janne Lehtiö

Stiftelsen för Strategisk Forskning

  • Maria Pernemalm
  • AnnSofi Sandberg
  • Yafeng Zhu
  • Janne Lehtiö

Horizon 2020 Framework Programme

  • Maria Pernemalm
  • Janne Lehtiö

Familjen Erling-Perssons Stiftelse

  • Janne Lehtiö

Barncancerfonden

  • Janne Lehtiö

Stockholms Läns Landsting

  • Claes-Göran Östenson

the Swedish Council for Working Life and Social Research

  • Claes-Göran Östenson

Swedish Diabetes Foundation

  • Claes-Göran Östenson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The plasma collections were approved by local ethics boards and all participants signed informed consent. The approval identifiers for the corresponding studies are as follows; Healthy normals Dnr 91:164 for men and Dnr 95:298 for women, mother/child 2014/1622-31/2 and female longitudinal 2008/915-31/4.

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Publication history

  1. Received: August 31, 2018
  2. Accepted: April 4, 2019
  3. Accepted Manuscript published: April 8, 2019 (version 1)
  4. Version of Record published: May 15, 2019 (version 2)

Copyright

© 2019, Pernemalm et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Maria Pernemalm
  2. AnnSofi Sandberg
  3. Yafeng Zhu
  4. Jorrit Boekel
  5. Davide Tamburro
  6. Jochen M Schwenk
  7. Albin Björk
  8. Marie Wahren-Herlenius
  9. Hanna Åmark
  10. Claes-Göran Östenson
  11. Magnus Westgren
  12. Janne Lehtiö
(2019)
In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
eLife 8:e41608.
https://doi.org/10.7554/eLife.41608

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