In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
- Karolinska Institute, Sweden
- KTH Royal Institute of Technology, Sweden
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.
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Plasma HiRIEFProteomeXchange, PXD010899.
Article and author information
Author details
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.
Reviewing Editor
- Nir Ben-Tal, Tel Aviv University, Israel
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.
Version history
- Received: August 31, 2018
- Accepted: April 4, 2019
- Accepted Manuscript published: April 8, 2019 (version 1)
- 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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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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