Using single-sample networks to identify the contrasting patterns of gene interactions and reveal the radiation dose-dependent effects in multiple tissues of spaceflight mice.

Transcriptome profiles are sensitive to space stressors and serve as valuable indicators of the biological effects during spaceflight. Herein, we transformed the expression profiles into gene interaction patterns by single-sample networks (SSNs) and performed the integrated analysis on the 301 spaceflight and 290 ground control samples, which were obtained from the GeneLab platform. Specifically, an individual SSN was established for each sample. Based on the topological structures of 591 SSNs, the differentially interacted genes (DIGs) were identified between spaceflights and ground controls. The results showed that spaceflight disrupted the gene interaction patterns in mice and resulted in significant enrichment of biological processes such as protein/amino acid metabolism and nucleic acid (DNA/RNA) metabolism (P-value < 0.05). We observed that the mice exposed to radiation doses within the three intervals (4.66-7.14, 7.592-8.295, 8.49-22.099 mGy) exhibited similar gene interaction patterns. Low and medium doses resulted in changes to the circadian rhythm, while the damaging effects on genetic material became more pronounced in higher doses. The gene interaction patterns in response to space stressors varied among different tissues, with the spleen, lung, and skin being the most responsive to space radiation (P-value < 0.01). The changes observed in gene networks during spaceflight conditions might contribute to the development of various diseases, such as mental disorders, depression, and metabolic disorders, among others. Additionally, organisms activated specific gene networks in response to virus reactivation. We identified several hub genes that were associated with circadian rhythms, suggesting that spaceflight could lead to substantial circadian rhythm dysregulation.