An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism
Permanent lenke
https://hdl.handle.net/10037/24321Dato
2021-07-07Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Razzaq, Misbah; Iglesias, Maria Jesus; Ibrahim-Kosta, Manal; Goumidi, Louisa; Soukarieh, Omar; Proust, Carole; Roux, Maguelonne; Suchon, Pierre; Boland, Anne; Daiain, Delphine; Olaso, Robert; Havervall, Sebastian; Thalin, Charlotte; Butler, Lynn; Deleuze, Jean-François; Odeberg, Jacob; Morange, Pierre-Emmanuel; Trégouët, David-AlexandreSammendrag
Venous thromboembolism is the third common cardiovascular disease and is composed of two
entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While
PE is observed in~ 40% of patients with documented DVT, there is limited biomarkers that can help
identifying patients at high PE risk. To fll this need, we implemented a two hidden-layers artifcial
neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT
patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear
approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping
DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected
single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main
fndings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients.
The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing
sets, respectively. A GWAS on the LIME approximate identifed a strong statistical association peak
(rs1424597: p= 5.3 × 10–7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele
were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%,
p= 0.005) and the EOVT (3% vs. 0%, p= 0.013) studies. In a sample of 112 COVID-19 patients known
to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4
levels were associated (p= 0.025) with worsened respiratory function. Using an original integrated
proteomics and genetics strategy, we identifed PLXNA4 as a new susceptibility gene for PE whose
exact role now needs to be further elucidated.
Forlag
NatureSitering
Razzaq, M., Iglesias, M.J., Ibrahim-Kosta, M. et al. An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism. Sci Rep 11, 14015 (2021).Metadata
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