Predicting mechanical ventilation effects on six human tissue transcriptomes.

Background: Mechanical ventilation (MV) is a lifesaving therapy used for patients with respiratory failure. Nevertheless, MV is associated with numerous complications and increased mortality. The aim of this study is to define the effects of MV on gene expression of direct and peripheral human tissues.

Methods: Classification models were applied to Genotype-Tissue Expression Project (GTEx) gene expression data of six representative tissues-liver, adipose, skin, nerve-tibial, muscle and lung, for performance comparison and feature analysis. We utilized 18 prediction models using the Random Forest (RF), XGBoost (eXtreme Gradient Boosting) decision tree and ANN (Artificial Neural Network) methods to classify ventilation and non-ventilation samples and to compare their prediction performance for the six tissues. In the model comparison, the AUC (area under receiver operating curve), accuracy, precision, recall, and F1 score were used to evaluate the predictive performance of each model. We then conducted feature analysis per each tissue to detect MV marker genes followed by pathway enrichment analysis for these genes.

Results: XGBoost outperformed the other methods and predicted samples had undergone MV with an average accuracy for the six tissues of 0.951 and average AUC of 0.945. The feature analysis detected a combination of MV marker genes per each tested tissue, some common across several tissues. MV marker genes were mainly related to inflammation and fibrosis as well as cell development and movement regulation. The MV marker genes were significantly enriched in inflammatory and viral pathways.

Conclusion: The XGBoost method demonstrated clear enhanced performance and feature analysis compared to the other models. XGBoost was helpful in detecting the tissue-specific marker genes for identifying transcriptomic changes related to MV. Our results show that MV is associated with reduced development and movement in the tissues and higher inflammation and injury not only in direct tissues such as the lungs but also in peripheral tissues and thus should be carefully considered before being implemented.