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Space biology and health data are critical for the success of deep space missions and sustainable human presence off-world. At the core of effectively managing biomedical risks is the commitment to open science principles, which ensure that data are findable, accessible, interoperable, reusable, reproducible and maximally open. The 2021 integration of the Ames Life Sciences Data Archive with GeneLab to establish the NASA Open Science Data Repository significantly enhanced access to a wide range of life sciences, biomedical-clinical and mission telemetry data alongside existing 'omics data from GeneLab. This paper describes the new database, its architecture and new data streams supporting diverse data types and enhancing data submission, retrieval and analysis. Features include the biological data management environment for improved data submission, a new user interface, controlled data access, an enhanced API and comprehensive public visualization tools for environmental telemetry, radiation dosimetry data and 'omics analyses. By fostering global collaboration through its analysis working groups and training programs, the open science data repository promotes widespread engagement in space biology, ensuring transparency and inclusivity in research. It supports the global scientific community in advancing our understanding of spaceflight's impact on biological systems, ensuring humans will thrive in future deep space missions., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR., (© 2024. The Author(s).)

The increasing accessibility of commercial and private space travel necessitates a profound understanding of its impact on human health. The NASA Open Science Data Repository (OSDR) provides transparent and FAIR access to biological studies, notably the SpaceX Inspiration4 (I4) mission, which amassed extensive data from civilian astronauts. This dataset encompasses omics and clinical assays, facilitating comprehensive research on space-induced biological responses. These data allow for multi-modal, longitudinal assessments, bridging the gap between human and model organism studies. Crucially, community-driven data standards established by NASA's OSDR Analysis Working Groups empower artificial intelligence and machine learning to glean invaluable insights, guiding future mission planning and health risk mitigation. This article presents a concise guide to access and analyze I4 data in OSDR, including programmatic access through GLOpenAPI. This pioneering effort establishes a precedent for post-mission health monitoring programs within space agencies, propelling research in the burgeoning field of commercial space travel's impact on human physiology., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

NASA's space life sciences research programs established a decades-long legacy of enhancing our ability to safely explore the cosmos. From Skylab and the Space Shuttle Program to the NASA Balloon Program and the International Space Station National Lab, these programs generated priceless data that continue to paint a vibrant picture of life in space. These data are available to the scientific community in various data repositories, including the NASA Ames Life Sciences Data Archive (ALSDA) and NASA GeneLab. Here we recognize the 30-year anniversary of data access through ALSDA and the 10-year anniversary of GeneLab., (Published by Oxford University Press on behalf of GigaScience 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

While fruit flies ( Drosophila melanogaster ) and humans exhibit immune system dysfunction in space, studies examining their immune systems' interactions with natural parasites in space are lacking. Drosophila parasitoid wasps modify blood cell function to suppress host immunity. In this study, naive and parasitized ground and space flies from a tumor-free control and a blood tumor-bearing mutant strain were examined. Inflammation-related genes were activated in space in both fly strains. Whereas control flies did not develop tumors, tumor burden increased in the space-returned tumor-bearing mutants. Surprisingly, control flies were more sensitive to spaceflight than mutant flies; many of their essential genes were downregulated. Parasitoids appeared more resilient than fly hosts, and spaceflight did not significantly impact wasp survival or the expression of their virulence genes. Previously undocumented mutant wasps with novel wing color and wing shape were isolated post-flight and will be invaluable for host-parasite studies on Earth., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection., Competing Interests: Dr. Mason is a cofounder for Aevum (acquired by Onegevity), Biotia, BridgeOmics, Onegevity (acquired by Thorne HealthTech), as well as a current advisor, shareholder, or compensated speaker for Acuamark Diagnostics, Allen and Company, ArcBio, BGI/MGI, Bumrungrad International Hospital, Carverr, Color Genomics, Cowen, DNA Genotek, EdenRoc, Enzymetrics, Element Bio, Foresite Capital, F!nd Genomics, Genialis, GenPro, Ginger Network, Google, Homo Deus, iCareDx, JP Morgan, Illumina, Infectious Economics, Meenta, Merck, MilliporeSigma, Mirimus, Morgan Stanley, Nano-Lit, Nanostring, New England Biolabs, Nooma, Pandemic Response Lab, Promega, Pendulum Health, Poppy Health, QIAGEN, Roche, Seed, Tecan, Tempus Labs, Testing for America, Thermo Fisher, Torus, Twist Biosciences, UBS, Ursa Bio, WorldQuant, and Zymo Research., (© 2022 The Authors.)

Viruses can subvert a number of cellular processes including splicing in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection, datasets from the betacoronaviruses SARS-CoV and MERS, as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification, and have a smaller number of exons as compared with differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by differential alternative splicing and gene expression in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS. The alternative splicing changes observed in betacoronaviruses infection potentially modify a broad range of cellular functions, via changes in the functions of the products of a diverse set of genes involved in different biological processes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Viruses can subvert a number of cellular processes in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection as well as datasets from the betacoronaviruses SARS-CoV and MERS as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification and a smaller number of exons than differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by DAS and DGE in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS, potentially modifying a broad range of cellular functions and affecting a diverse set of genes and biological functions.

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility, and reusability of pipeline data; to provide a template for data processing of future spaceflight-relevant datasets; and to encourage cross-analysis of data from other databases with the data available in GeneLab., Competing Interests: The authors declare no competing interests.

To understand the physiological changes that occur in response to spaceflight, mice are transported to the International Space Station (ISS) and housed for variable periods of time before euthanasia on-orbit or return to Earth. Sample collection under such difficult conditions introduces confounding factors that need to be identified and addressed. We found large changes in the transcriptome of mouse tissues dissected and preserved on-orbit compared with tissues from mice euthanized on-orbit, preserved, and dissected after return to Earth. Changes due to preservation method eclipsed those between flight and ground samples, making it difficult to identify spaceflight-specific changes. Follow-on experiments to interrogate the roles of euthanasia methods, tissue and carcass preservation protocols, and library preparation methods suggested that differences due to preservation protocols are exacerbated when coupled with polyA selection. This has important implications for the interpretation of existing datasets and the design of future experiments., Competing Interests: The authors declare no competing interests.

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. Mouse studies performed on the Space Shuttle showed disruption of lipid metabolism in liver. However, given that these animals were not sacrificed on-orbit and instead returned live to earth, it is unclear if these disruptions were solely induced by space stressors (e.g. microgravity, space radiation) or in part explained by the stress of return to Earth. In this work we analyzed three liver datasets from two different strains of mice (C57BL/6 (Jackson) & BALB/c (Taconic)) flown aboard the International Space Station (ISS). Notably, these animals were sacrificed on-orbit and exposed to varying spaceflight durations (i.e. 21, 37, and 42 days vs 13 days for the Shuttle mice). Oil Red O (ORO) staining showed abnormal lipid accumulation in all space-flown mice compared to ground controls regardless of strain or exposure duration. Similarly, transcriptomic analysis by RNA-sequencing revealed several pathways that were affected in both strains related to increased lipid metabolism, fatty acid metabolism, lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions including Glucagon (GCG) and Insulin (INS). Moreover, quantitative proteomic analysis showed that a number of lipid related proteins were changed in the livers during spaceflight. Taken together, these data indicate that activation of lipotoxic pathways are the result of space stressors alone and this activation occurs in various genetic backgrounds during spaceflight exposures of weeks to months. If similar responses occur in humans, a prolonged change of these pathways may result in the development of liver disease and should be investigated further.