Pharmacogenomics Guided Spaceflight: the intersection between space-flown drugs and space genes

Ten years ago, it was predicted that the multi-omics revolution would also revolutionize space pharmacogenomics. Current barriers related to the findable, accessible, interoperable, and reproducible use of space-flown pharmaceutical data have contributed to a lack of progress beyond application of earth-based principles. To directly tackle these challenges, we have produced a novel database of all the drugs flown into space, compiled from publicly available ontological and spaceflight-related datasets, to exemplify analyses for describing significant spaceflight-related targets. By focusing on mechanisms perturbed by spaceflight, we have provided a novel avenue for identifying the most relevant changes within the drug absorption, distribution, metabolism, and excretion pathways. We suggest a set of space genes, by necessity limited to available tissue types, that can be expanded and modified based on future tissue-specific and mechanistic-specific high-throughput assays. In sum, we provide the justification and a definitive starting point for pharmacogenomics guided spaceflight as a foundation of precision medicine, which will enable long-term human habitation of the Moon, Mars, and beyond. Graphical Abstract