The transcriptomic datasets of the plant model organism Arabidopsis thaliana grown in the International Space Station provided by GeneLab have been mined to isolate the impact of spaceflight microgravity on gene expressions related to root growth. A set of computational tools is used to identify the hub genes that respond differently in spaceflight with controlled lighting compared to on the ground. These computational tools based on graph-theoretic approaches are used to infer gene regulatory networks from the transcriptomic datasets. The three main algorithms used for network analyses are Least Absolute Shrinkage and Selection Operator (LASSO), Pearson correlation, and the Hyperlink-Induced Topic Search (HITS) algorithm. Graph-based spectral analyses reveal distinct properties of the spaceflight microgravity networks for the Wassilewskija (WS), Columbia (Col)-0, and mutant phytochromeD (phyD) ecotypes. The set of hub genes that are significantly altered in spaceflight microgravity are mainly involved in cell wall synthesis, protein transport, response to auxin, stress responses, and catabolic processes. Network analysis highlights five important root growth-regulating hub genes that have the highest outdegree distribution in spaceflight microgravity networks. These concerned genes coding for proteins are identified from the Gene Regulatory Networks (GRNs) corresponding to spaceflight total light environment. Furthermore, network analysis uncovers genes that encode nucleotide-diphospho-sugar interconversion enzymes that have higher transcriptional regulation in spaceflight microgravity and are involved in cell wall biosynthesis.

Spaceflight microgravity affects normal plant growth in several ways. The transcriptional dataset of the plant model organism Arabidopsis thaliana grown in the international space station is mined using graph-theoretic network analysis approaches to identify significant gene transcriptions in microgravity essential for the plant’s survival and growth in altered environments. The photosynthesis process is critical for the survival of the plants in spaceflight under different environmentally stressful conditions such as lower levels of gravity, lesser oxygen availability, low atmospheric pressure, and the presence of cosmic radiation. Lasso regression method is used for gene regulatory network inferencing from gene expressions of four different ecotypes of Arabidopsis in spaceflight microgravity related to the photosynthetic process. The individual behavior of hub-genes and stress response genes in the photosynthetic process and their impact on the whole network is analyzed. Logistic regression on centrality measures computed from the networks, including average shortest path, betweenness centrality, closeness centrality, and eccentricity, and the HITS algorithm is used to rank genes and identify interactor or target genes from the networks. Through the hub and authority gene interactions, several biological processes associated with photosynthesis and carbon fixation genes are identified. The altered conditions in spaceflight have made all the ecotypes of Arabidopsis sensitive to dehydration-and-salt stress. The oxidative and heat-shock stress-response genes regulate the photosynthesis genes that are involved in the oxidation-reduction process in spaceflight microgravity, enabling the plant to adapt successfully to the spaceflight environment.

Skeletal muscle atrophy is a common condition in aging, diabetes, and in long duration spaceflights due to microgravity. This article investigates multi-modal gene disease and disease drug networks via link prediction algorithms to select drugs for repurposing to treat skeletal muscle atrophy. Key target genes that cause muscle atrophy in the left and right extensor digitorum longus muscle tissue, gastrocnemius, quadriceps, and the left and right soleus muscles are detected using graph theoretic network analysis, by mining the transcriptomic datasets collected from mice flown in spaceflight made available by GeneLab. We identified the top muscle atrophy gene regulators by the Pearson correlation and Bayesian Markov blanket method. The gene disease knowledge graph was constructed using the scalable precision medicine knowledge engine. We computed node embeddings, random walk measures from the networks. Graph convolutional networks, graph neural networks, random forest, and gradient boosting methods were trained using the embeddings, network features for predicting links and ranking top gene-disease associations for skeletal muscle atrophy. Drugs were selected and a disease drug knowledge graph was constructed. Link prediction methods were applied to the disease drug networks to identify top ranked drugs for therapeutic treatment of skeletal muscle atrophy. The graph convolution network performs best in link prediction based on receiver operating characteristic curves and prediction accuracies. The key genes involved in skeletal muscle atrophy are associated with metabolic and neurodegenerative diseases. The drugs selected for repurposing using the graph convolution network method were nutrients, corticosteroids, anti-inflammatory medications, and others related to insulin.