Quantification of circadian rhythms in mammalian lung tissue snapshot data

Abstract

AbstractHealthy mammalian cells have a circadian clock, a gene regulatory network that allows them to schedule their physiological processes to optimal times of the day. When healthy cells turn into cancer cells, the circadian clock often becomes cancer specifically disturbed, so there is an interest in the extraction of circadian features from gene expression data of cancer. This is challenging, as clinical gene expression samples of cancer are snapshot-like and the circadian clock is best examined using gene expression time series. In this study, we obtained lists of intersecting circadian genes in public gene expression time series data of lung tissue of mouse and baboon. We base our circadian gene lists on correlations of gene expression levels of circadian genes, which are closely associated to the phase differences between them. Combining circadian gene expression patterns of diurnal and nocturnal species of different ages provides circadian genes that are also important in healthy and cancerous human lung tissue. We tested the quality of the representation of the circadian clock in our gene lists by PCA-based reconstructions of the circadian times of the mouse and baboon samples. Then we assigned potential circadian times to the human lung tissue samples and find an intact circadian clock in the healthy human lung tissue, but an altered, weak clock in the adjacent cancerous lung tissue.