Principal Components Analysis Based Unsupervised Feature Extraction Applied to Gene Expression Analysis of Blood from Dengue Haemorrhagic Fever Patients

Dengue haemorrhagic fever (DHF) sometimes occurs after recovery from the disease caused by Dengue virus (DENV), and is often fatal. However, the mechanism of DHF has not been determined, possibly because no suitable methodologies are available to analyse this disease. Therefore, more innovative methods are required to analyse the gene expression profiles of DENV-infected patients. Principal components analysis (PCA)-based unsupervised feature extraction (FE) was applied to the gene expression profiles of DENV-infected patients, and an integrated analysis of two independent data sets identified 46 genes as critical for DHF progression. PCA using only these 46 genes rendered the two data sets highly consistent. The application of PCA to the 46 genes of an independent third data set successfully predicted the progression of DHF. A fourth in vitro data set confirmed the identification of the 46 genes. These 46 genes included interferon-and heme-biosynthesis-related genes. The former are enriched in binding sites for STAT1, STAT2, and IRF1, which are associated with DHF-promoting antibody-dependent enhancement, whereas the latter are considered to be related to the dysfunction of spliceosomes, which may mediate haemorrhage. These results are outcomes that other type of bioinformatic analysis could hardly achieve.