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. 2022 Jun 2:12:765985.
doi: 10.3389/fgene.2021.765985. eCollection 2021.

Protein Network Analysis of Whole Exome Sequencing of Severe Preeclampsia

Jessica Schuster  1   2 , George A Tollefson  1 , Valeria Zarate  1 , Anthony Agudelo  1 , Joan Stabila  1 , Ashok Ragavendran  3   4 , James Padbury  1   2   5 , Alper Uzun  1   2   4   5
Affiliations

Protein Network Analysis of Whole Exome Sequencing of Severe Preeclampsia

Jessica Schuster et al. Front Genet. .

Abstract

Preeclampsia is a hypertensive disorder of pregnancy, which complicates up to 15% of US deliveries. It is an idiopathic disorder associated with several different phenotypes. We sought to determine if the genetic architecture of preeclampsia can be described by clusters of patients with variants in genes in shared protein interaction networks. We performed a case-control study using whole exome sequencing on early onset preeclamptic mothers with severe clinical features and control mothers with uncomplicated pregnancies between 2016 and 2020. A total of 143 patients were enrolled, 61 women with early onset preeclampsia with severe features based on ACOG criteria, and 82 control women at term, matched for race and ethnicity. A network analysis and visualization tool, Proteinarium, was used to confirm there are clusters of patients with shared gene networks associated with severe preeclampsia. The majority of the sequenced patients appear in two significant clusters. We identified one case dominant and one control dominant cluster. Thirteen genes were unique to the case dominated cluster. Among these genes, LAMB2, PTK2, RAC1, QSOX1, FN1, and VCAM1 have known associations with the pathogenic mechanisms of preeclampsia. Using bioinformatic analysis, we were able to identify subsets of patients with shared protein interaction networks, thus confirming our hypothesis about the genetic architecture of preeclampsia.

Keywords: complex diseases; computational biology; network biology; preeclampsia; protein protein interaction (PPI).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Figure shows the univariate work flow for analysis of the whole exome sequencing results.
FIGURE 2
FIGURE 2
(A) Dendrogram shows statistically significant (p < 0.05) clusters of patients. Case dominated cluster (Cluster A) and control dominated cluster (Cluster B) are presented by dashed lines. Cases are represented in red and controls are represented in blue color. (B) Layered network graphs for the case dominated cluster A are presented. 13 unique genes of cluster A are in red color. (C) Layered network graphs for the control dominated cluster B are presented. 11 unique genes of cluster B are in blue color.
See this image and copyright information in PMC

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