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bioRxiv · 10.1101/2024.01.24.577100

Systemic Genome Correlation Loss as a Central Characteristic of Spaceflight

Sakharkar, A.·Lukong, K. E.·Sanders, L. M.·Costes, S. V.·Yang, J.·Taghibiglou, C.
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Abstract

Spaceflight exposes the human body to a unique combination of stressors--microgravity, radiation, and confinement--that induces multisystemic physiological dysregulation. Traditional transcriptomic analyses have focused on differential expression to identify key genes, yet this approach fails to explain why astronauts experience systemic fragility despite often subtle changes in gene abundance. Here, we present a comprehensive meta-analysis of 10 independent transcriptomic and genomic datasets (N = 136) from the NASA Open Science Data Repository. By shifting focus from gene abundance to gene-gene correlation topology, we identify Systemic Genome Correlation Loss as a central biosignature of spaceflight. We show that the regulatory architecture of the transcriptome undergoes a profound decoherence in microgravity, shifting the global correlation distribution toward stochasticity (p < 10-15). This phenomenon is universal across tissues and independent of gene variance. We identify a massive population of 760 genes that maintain stable expression levels but lose over 500 regulatory connections each, outnumbering canonical differentially expressed genes by three-to-one. Finally, we demonstrate that cells preserve the connectivity of survival-critical DNA repair networks preferentially while allowing mitochondrial and synaptic networks to shatter. These findings suggest that astronaut health risks are driven by the entropic decay of regulatory synchronization, proposing a new paradigm for countermeasure development focused on network stabilization rather than pathway inhibition.

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Sakharkar, A., Lukong, K. E., Sanders, L. M., Costes, S. V., Yang, J., Taghibiglou, C.. 2024-01-27. Systemic Genome Correlation Loss as a Central Characteristic of Spaceflight. https://doi.org/10.1101/2024.01.24.577100

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