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The aim of this paper is to identify key genes in lung adenocarcinoma (LUAD) through weighted gene co-expression network analysis (WGCNA), and to further understand the molecular mechanism of LUAD. 107 gene expression profiles were downloaded from GSE10072 in the GEO database. We performed rigorous processing of the initial gene expression profile data. Subsequently, we used WGCNA to identify disease-driven modules and enforced functional enrichment analysis. The key genes were defined as the most connected genes in the driver module and were validated using the GSE75037 and TCGA database. GSE10072 removed 41 unpaired lung samples and 4 outliers. By analyzing the 62 samples using WGCNA, we obtained 26 modules and identified the brown and magenta modules as the driving modules for the LUAD. We found that the “Cell cycle”, “Oocyte meiosis” and “Progesterone-mediated oocyte maturation” pathways may be related to the occurrence of LUAD. GSE75037 removed 8 outlier and obtained 2909 differentially expressed genes (DEGs), 26 genes (9 genes in the brown module, 17 genes in the magenta module) overlap with key genes in the driver module. The results of the survival analysis suggest that 19 genes were significantly correlated with the patient’s survival time, including KPNA2, FEN1, RRM2, TOP2A, CENPF, MCM4, BIRC5, MELK, MAD2L1, CCNB1, CCNA2, KIF11, CDKN3, NUSAP1, CEP55, AURKA, NEK2, KIF14 and CDCA8, which may be potential biomarkers or therapeutic targets for LUAD. In this study, we provide a theoretical basis for further understanding the biological mechanism of LUAD through bioinformatics analysis of LUAD.

Due to its high dimensionality and high noise levels, analysis of a large brain functional network may not be powerful and easy to interpret; instead, decomposition of a large network into smaller subcomponents called modules may be more promising as suggested by some empirical evidence. For example, alteration of brain modularity is observed in patients suffering from various types of brain malfunctions. Although several methods exist for estimating brain functional networks, such as the sample correlation matrix or graphical lasso for a sparse precision matrix, it is still difficult to extract modules from such network estimates. Motivated by these considerations, we adapt a weighted gene co-expression network analysis (WGCNA) framework to resting-state fMRI (rs-fMRI) data to identify modular structures in brain functional networks. Modular structures are identified by using topological overlap matrix (TOM) elements in hierarchical clustering. We propose applying a new adaptive test built on the proportional odds model (POM) that can be applied to a high-dimensional setting, where the number of variables (p) can exceed the sample size (n) in addition to the usual p < n setting. We applied our proposed methods to the ADNI data to test for associations between a genetic variant and either the whole brain functional network or its various subcomponents using various connectivity measures. We uncovered several modules based on the control cohort, and some of them were marginally associated with the APOE4 variant and several other SNPs; however, due to the small sample size of the ADNI data, larger studies are needed.