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Background Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD. Methods RNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database. Results Five differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched. Conclusion A novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.

Multiple sclerosis (MS) is one of the most common neurological disabilities of the central nervous system. Immune-modulatory therapy with Interferon-β (IFN-β) is a commonly used first-line treatment to prevent MS patients from relapses. Nevertheless, a large proportion of MS patients on IFN-β therapy experience their first relapse within 2 years of treatment initiation. Feature selection, a machine learning strategy, is routinely used in the fields of bioinformatics and computational biology to determine which subset of genes is most relevant to an outcome of interest. The majority of feature selection methods focus on alterations in gene expression levels. In this study, we sought to determine which genes are most relevant to relapse of MS patients on IFN-β therapy. Rather than the usual focus on alterations in gene expression levels, we devised a feature selection method based on alterations in gene-to-gene interactions. In this study, we applied the proposed method to a longitudinal microarray dataset and evaluated the IFN-β effect on MS patients to identify gene pairs with differentially correlated edges that are consistent over time in the responder group compared to the non-responder group. The resulting gene list had a good predictive ability on an independent validation set and explicit biological implications related to MS. To conclude, it is anticipated that the proposed method will gain widespread interest and application in personalized treatment research to facilitate prediction of which patients may respond to a specific regimen.