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

Elife. 2019 Apr 8;8:e41608. doi: 10.7554/eLife.41608.

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.

Keywords: biomarker discovery; computational biology; human; human biology; mass spectrometry; medicine; plasma; proteogenomics; proteomics; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / analysis*
  • Chromatography, Liquid
  • Female
  • Healthy Volunteers
  • Humans
  • Isoelectric Focusing
  • Male
  • Maternal-Fetal Exchange*
  • Plasma / chemistry*
  • Pregnancy
  • Protein Transport
  • Proteome / analysis*
  • Tandem Mass Spectrometry

Substances

  • Blood Proteins
  • Proteome

Grant support

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