Charité Center for Basic Sciences, Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Biology, Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Sci Rep. 2024 Jul 14;14(1):16238. doi: 10.1038/s41598-024-66694-7.
Healthy 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.
健康的哺乳动物细胞有一个生物钟，这是一个基因调控网络，使它们能够将生理过程安排在一天中的最佳时间。当健康细胞变成癌细胞时，生物钟通常会受到特别的干扰，因此人们对从癌症的基因表达数据中提取生物钟特征很感兴趣。这是具有挑战性的，因为癌症的临床基因表达样本是类似快照的，而生物钟最好通过基因表达时间序列来检查。在这项研究中，我们从公共的小鼠和狒狒肺组织的基因表达时间序列数据中获得了相交的生物钟基因列表。我们的生物钟基因列表基于生物钟基因的表达水平的相关性，这些相关性与它们之间的相位差异密切相关。结合不同年龄的昼夜物种的生物钟基因表达模式，为健康和癌变的人类肺组织提供了同样重要的生物钟基因。我们通过基于 PCA 的老鼠和狒狒样本的生物钟时间重建来测试我们基因列表中生物钟表示的质量。然后，我们为人类肺组织样本分配潜在的生物钟时间，发现健康的人类肺组织中存在完整的生物钟，而相邻的癌变肺组织中的生物钟则发生了改变，变得微弱。
