Identification of Chronic Hypersensitivity Pneumonitis Biomarkers with Machine Learning and Differential Co-expression Analysis

This study aims to identify the biomarkers for chronic hypersensitivity pneumonitis (CHP) and facilitate the precise gene therapy of CHP.Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease caused by hypersensitive reactions to inhaled antigens. Clinically, the task of differentiating CHP and other interstitial lung diseases, especially idiopathic pulmonary fibrosis (IPF), was challenging.In this study, we analyzed the publically available gene expression profile of 82 CHP patients, 103 IPF patients, and 103 control samples to identify the CHP biomarkers.The CHP biomarkers were selected with advanced feature selection methods: Monte Carlo Feature Selection (MCFS) and Incremental Feature Selection (IFS). A Support Vector Machine (SVM) classifier was built. Then, we analyzed these CHP biomarkers through functional enrichment analysis and differential co-expression analysis.There were 674 identified CHP biomarkers. The co-expression network of these biomarkers in CHP included more negative regulations and the network structure of CHP was quite different from the network of IPF and control.The SVM classifier may serve as an important clinical tool to address the challenging task of differentiating between CHP and IPF. Many of the biomarker genes on the differential coexpression network showed great promise in revealing the underlying mechanisms of CHP.