Genomic Analysis of Cardiovascular Diseases Utilizing Space Omics and Medical Atlas

The Space Omics and Medical Atlas (SOMA) is an extensive database containing gene expression information from samples collected during the short-duration Inspiration4 spaceflight mission in 2021. Given our prior understanding of the genetic basis for cardiovascular diseases in spaceflight, including orthostatic intolerance and cardiac deconditioning, we aimed to characterize changes in differential gene expression among astronauts using SOMA-derived data and curated cardiovascular pathways.

Using the KEGG 2021 database, we curated a list of genes related to cardiovascular adaptations in spaceflight, focusing on pathways such as fluid shear stress and atherosclerosis, lipid metabolism, arrhythmogenic ventricular hypertrophy, and cardiac muscle contraction. Genes were cross-matched to spaceflight-relevant datasets from the Open Science Data Repository (OSDR). Differential expression analysis was performed using DESeq2 (v1.40.2, R) with normalization by median-of-ratios, paired pre-/post-flight covariates, and log2 fold change shrinkage using apeglm. Differentially expressed genes (DEGs) were defined as |log2FC| ≥ 1 and FDR < 0.05 (Benjamini-Hochberg correction). Module score analyses were conducted across SOMA cell types to confirm conserved cardiac adaptation genes.

A total of 185 spaceflight-relevant genes were analyzed. Statistically significant changes were observed in immune-related cardiovascular pathways, particularly within monocytes and T cells. Persistent upregulation of arrhythmogenic genes such as GJA1 was noted at post-flight day 82. WikiPathways enrichment revealed additional pathways, including focal adhesion, insulin signaling, and heart development.

Short-duration spaceflight induces significant gene expression changes that are relevant to cardiovascular disease risk. These changes are mediated largely through immune signaling and transcriptional regulation in peripheral blood mononuclear cells. Findings highlight the need for tailored countermeasures and longitudinal monitoring in future long-duration missions.