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

Nelson, T. M.; Rose, J. K.; Walter, C. E.; Cervantes-Navarro, G. L.; Schmidt, C. M.; Lin, R.; Alexander, E.; Zheng, J. T.; Glicksberg, B. S.; Schmidt, J. C.; Overbey, E.; Rana, B.; Patel, H.; Schmidt, M. A.; Mason, C. E.

doi:10.1101/2024.01.16.575951

bioRxiv · 10.1101/2024.01.16.575951

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

Nelson, T. M.·Rose, J. K.·Walter, C. E.·Cervantes-Navarro, G. L.·Schmidt, C. M.·Lin, R.·Alexander, E.·Zheng, J. T.·Glicksberg, B. S.·Schmidt, J. C.·Overbey, E.·Rana, B.·Patel, H.·Schmidt, M. A.·Mason, C. E.

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Abstract

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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/575951v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@48f739org.highwire.dtl.DTLVardef@5ecdb0org.highwire.dtl.DTLVardef@121c93org.highwire.dtl.DTLVardef@1122b3f_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Nelson, T. M., Rose, J. K., Walter, C. E., Cervantes-Navarro, G. L., Schmidt, C. M., Lin, R., Alexander, E., Zheng, J. T., Glicksberg, B. S., Schmidt, J. C., Overbey, E., Rana, B., Patel, H., Schmidt, M. A., Mason, C. E.. 2024-01-20. Pharmacogenomics Guided Spaceflight: the intersection between space-flown drugs and space genes. https://doi.org/10.1101/2024.01.16.575951

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