Investigating the evolution process of lung adenocarcinoma via random walk and dynamic network analysis

Abstract

Lung adenocarcinoma (LUAD) is a typical disease regarded as having multi-stage progression. However, many existing methods often ignore the critical differences among these stages, thereby limiting their effectiveness for discovering key biological molecules and biological functions as signals at each stage. In this study, we propose a method to discover the evolution between biological molecules and biological functions by investigating the multi-stage biological molecules of LUAD. The method is based on the random walk algorithm and the Monte Carlo method to generate clusters as the modules, which were used as subgraphs of the differentiated biological molecules network in each stage. The connection between modules of adjacent stages is based on the measurement of the Jaccard coefficient. The online gene set enrichment analysis tool (DAVID) was used to obtain biological functions corresponding to the individual important modules. The core evolution network was constructed by combining the aforementioned two networks. Since the networks here are all dynamic, we also propose a strategy to visualize the dynamic information together in one network. Eventually, 12 core modules and 11 core biological functions were found through such evolutionary analyses. Among the core biological functions that we obtained, six functions are related to the disease, the biological function of neutrophil chemotaxis is not directly associated with LUAD but can serve as a predictor, two functions may serve as a predictive signal, and two functions need to be verified through more biological evidence. Compared with two alternative design methods, the method proposed in this study performed more efficiently.