Multi-cohort, Pathway-level Analysis of Spaceflight Disorders

It is known that spaceflight can have negative impacts on astronauts’ health and immune systems. As genomics data rapidly populate public repositories, including NIH GEO and GeneLab, we have sufficient data to understand the biological mechanisms in order to provide immune countermeasures to ensure astronaut health. However, conventional analysis methods that focus on a single cohort are prone to study bias and data heterogeneity, leading to inconsistent conclusions. In addition, most analyses focus on differential analysis at the gene level, exacerbating the inconsistency. Our hypothesis is that a phenomenon can be triggered by a number of different events, through different genes, but still involve common mechanism(s). As signals propagate along a pathway, the genes that are differentially expressed (DE) change over time, while the pathway involved remains the same. Therefore, instead of focusing on DE genes, we propose to characterize spaceflight disorders using pathway signatures. The goal of this project is to develop a multi-cohort technique to identify the pathway signatures of spaceflight disorders using transcription profiling. The long-term goal (beyond this project) is to identify treatments that provide immune countermeasures by repurposing existing drugs. If successful, this project has the potential to significantly improve astronaut health, which is the main objective of NASA Space Medicine. To achieve our objective, we will develop an R statistical package that can: i) perform multicohort analysis; and ii) identify and visualize pathway signatures (impacted pathways, signaling cascades, and exit interfaces and statistics). This work will be performed by the Science PI Dr. Tin Nguyen, his Ph.D. student Hung Nguyen, and the co-PI Dr. Hung La, in collaboration with NASA scientists Drs. Jonathan Galazka and Sylvain Costes. The project has been discussed with NASA contact Dr. David Tomko.

This is a mature technology (TRL 7+) — the realistic path in is usually NASA's Technology Transfer Program: licensing an existing NASA patent, or a Space Act Agreement to use NASA facilities/expertise directly. NASA also runs a startup licensing program with no upfront fee for companies formed to commercialize a specific NASA technology.

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