A network-based dynamic criterion for identifying prediction and early diagnosis biomarkers of complex diseases.

Abstract

Lung adenocarcinoma (LUAD) seriously threatens human health and generally results from dysfunction of relevant module molecules, which dynamically change with time and conditions, rather than that of an individual molecule. In this study, a novel network construction algorithm for identifying early warning network signals (IEWNS) is proposed for improving the performance of LUAD early diagnosis. To this end, we theoretically derived a dynamic criterion, namely, the relationship of variation (RV), to construct dynamic networks. RV infers correlation [Formula: see text] statistics to measure dynamic changes in molecular relationships during the process of disease development. Based on the dynamic networks constructed by IEWNS, network warning signals used to represent the occurrence of LUAD deterioration can be defined without human intervention. IEWNS was employed to perform a comprehensive analysis of gene expression profiles of LUAD from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The experimental results suggest that the potential biomarkers selected by IEWNS can facilitate a better understanding of pathogenetic mechanisms and help to achieve effective early diagnosis of LUAD. In conclusion, IEWNS provides novel insight into the initiation and progression of LUAD and helps to define prospective biomarkers for assessing disease deterioration.