Space Omics and Medical Atlas (SOMA) across orbits https://www.nature.com/immersive/d42859-024-00009-8/index.html New studies on astronauts and space biology bring humanity one step closer to the final frontier Time-lapse video taken by the Expedition 28 crew on board the International Space Station during a night pass over North and South America. Credit: Earth Science and Remote Sensing Unit, NASA Johnson Space Center. The Space Omics and Medical Atlas (SOMA) package of manuscripts, data, protocols, and code represents the largest-ever compendium of data for aerospace medicine and space biology. Over 100 institutions from >25 countries worked together for a coordinated 2024 release of molecular, cellular, physiological, phenotypic, and spaceflight data. Notably, this includes analysis of samples collected from the first all-civilian crew of the Inspiration4 mission, which consisted of commercial astronauts who embarked on a short-term mission to a high-altitude orbit (575 km), farther than the International Space Station (ISS). This data is distinct from the longer-duration missions of ISS-based astronauts, who typically stay 120, 180, or 365 days. While in orbit, the Inspiration4 crew performed an extensive battery of scientific experiments, which have now been processed, sequenced, and analyzed, contributing to most of the 44 papers in the SOMA package, some of which are highlighted below. Embracing the spirit of Open Science at NASA and data accessibility, all raw and processed data acquired from the crew during and after their missions have been made available in NASA’s Open Science Data Repository an expansion of NASA GeneLab. Additionally, four new data portals have been created for browsing results from the mission, which also include linked data from the NASA Twins Study, enhancing our understanding of human health in space. Samples from different orbits (i.e. ISS and Inspiration4) have now been analyzed and integrated. Photo credit: Inspiration4 crew The SOMA package represents a milestone in several other respects. It features a >10-fold increase in the number of next-generation sequencing (NGS) data from spaceflight, a 4-fold increase in the number of single-cells processed from spaceflight, the launch of the first aerospace medicine biobank (Weill Cornell Medicine’s CAMbank), the first-ever direct RNA sequencing data from astronauts, the largest number of processed biological samples from a mission (2,911), and the first ever spatially-resolved transcriptome data from astronauts. Working across borders and teams, between companies and governments, and spanning myriad international laboratories enabled the greatest amount of science and erudition to be gained in this package. These data can serve as a springboard for new experiments, hypotheses, and follow-up studies, as well as guide future mission planning and countermeasure development. Finally, this package shows how the modern tools of molecular biology and precision medicine can help guide humanity into more challenging missions, which will be critical for a permanent presence on the moon, Mars, and beyond. The civillian crew for Inspiration4 and the Dragon spacecraft Resillience atop the Falcon 9 rocket. Credit: Inspiration4 / John Kraus Gene expression responses for DNA damage, immune activation, mitochondrial disruption, frailty, sarcopenia, accelerated health risks in multiple organs, and telomere regulation were observed, consistent with prior missions. Nature: The Space Omics and Medical Atlas (SOMA) and international astronaut biobank Communications Medicine: Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology Preprint: Key genes, altered pathways and potential treatments for muscle loss in astronauts and sarcopenic patients Scientific Reports: Aging and putative frailty biomarkers are altered by spaceflight Nature Communications: Direct RNA sequencing of astronauts reveals spaceflight-associated epitranscriptome changes and stress-related transcriptional responses Nature Communications: Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight Communications Biology: Spaceflight induces changes in gene expression profiles linked to insulin and estrogen Nature Communications: Cosmic kidney disease: An integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction Spatial transcriptome data from the kidney profiles show the impact of spaceflight on the kidney structure and kidney cells’ gene expression. Cell types are shown as colors, and labeled sections of the kidney are highlighted by arrows. Stained cross-section of a mouse kidney 6-month post exposure to radiation, analysed for detection of kidney damage and impact of spaceflight. Zoomed in areas of the cross-section shows labelled structure and different cell types of kidney cells'. Liftoff of Inspiration4 from Kennedy Space Center at 8:02 pm (local time) on 16 September 2021. Credit: Inspiration4 / John Kraus T-cells and monocyte cells showed the largest degree of chromatin changes in the immune system after spaceflight and female crew members had a faster return to baseline across all cell types for their chromatin landscape (ATAC-seq) than male astronauts (Kim et al.). These data can also now be visualized in the SOMA browser. Sian Procter (left) and Hayley Arceneaux enjoying a flowing hair moment in zero gravity, analogous to the unwinding of DNA from chromatin observed in their monocytes. Credit: Inspiration4 crew Scientific Reports: Chromosomal positioning and epigenetic architecture influence DNA methylation patterns triggered by galactic cosmic radiation Nature Communications: Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight Communications Biology: Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing Radiation impacts the genome and epigenome. Average telomere length in all Inspiration4 civilian crew members increased during spaceflight, similar to observations from the NASA Twins Study. Also, RNA-seq data revealed significantly increased telomeric RNA, or TERRA, during spaceflight for all astronauts, highlighing a unique response of telomeres to DNA damage, with protective telomeric DNA:RNA hybrids forming to facilitate RNA templated/HR-directed repair and transient activation of ALT/ALT-like phenotype, which likely contribute to the telomere elongation observed during spaceflight. Diagram summarising the effects of chronic exposure to space radiation on astronauts and the cellular mechanisms involved in repairing telomeres. The presented model suggest a telomere-specific DNA damage response associated with chronic exposure to the space radiation environment and elevated levels of oxidative stress. This acts to continuously damage telomeres, thereby triggering increased transcription of TERRA and hybridization at broken telomeres, forming protective telomeric DNA:RNA hybrids and facilitating RNA templated/HR-directed repair and transient activation of ALT/ALT-like phenotypes that possibly contribute to the telomere elongation observed during spaceflight. The reusable Falcon 9 rocket separates at an altitude of 80 km. Credit: Inspiration4 / John Kraus Each cell type exhibited both conserved and distinct disruptions across cell types, species, and missions, with changes in gene expression, chromatin accessibility, and transcription factor motif accessibility observed after spaceflight and during recovery. Novel, single-cell approaches were used to delineate sex-dependent changes in gene networks, cytokines/chemokines (e.g. fibrinogen and CXCL8/IL-8), and radiation response. npj Microgravity: Influence of the spaceflight environment of macrophage lineages Scientific Reports: Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice npj Women’s Health: Understanding how space travel affects the female reproductive system Nature Communications: Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight Using single-cell analysis of human PBMCs exposed to short-term simulated microgravity, the team identified significant transcriptional alterations in immune cells, with monocytes showing the most pathway changes, including increased retroviral and mycobacterial transcripts, providing insights into microgravity-induced immune dysfunction and potential countermeasures like quercetin. Diagram depicting the steps needed for developing drugs that counter the effects of spaceflight on immune cells. Analysis of human PBMCs exposed to simulated microgravity integrated with analysis of data from flight crew allows the identification of key signature changes such as transcriptional alterations in immune cells. Strategies such as gene-compound enrichment analysis followed by compound validation are utilized for drug discovery purposes. During the 3-day mission, the crew monitored their heart activity, blood oxygen levels and immune function, performed ultrasound exams and took samples for microbiological analysis. Credit: Inspiration4 crew Exposed parts of the body showed more transfer from the Dragon spacecraft (figure below). Signatures of response to viruses and T-cell activation was a consistent trend across the crew, and the microbiomes of the crew became more similar to each other over time, as has been observed before in space and in sports. Nature Communications: Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight Nature Microbiology: Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight Moving microbes: A circos plot shows number of strain-sharing events across time, where an event is defined as the detection of the same strain between two different swabbing locations, between the crew members (C001,2,3,4) or the SpaceX Dragon capsule. The thickness of each line represents the proportional number of species, and the color indicates origin. A circos plot showing number of strains sharing events from sequencing data from a longitudinal, multi-omics sampling study of 4 crew members on the SpaceX Inspiration4 mission. The crew collected environmental swabs from the Dragon capsule, skin, nasal and oral swabs at different timepoints during the mission. The plot shows the extent of microbial cross-contamination between all four crew members and the spacecraft during the mid-flight timepoint. From the thickness of each line representing the proportional number of species and the color indicating the origin, it is possible to observe that most strain sharing occurred between sites on the same individual or the spacecraft, with limited exchange between astronauts. Orbiting at an altitude of 590 km and travelling at over 28,000 kph, the spacecraft circled the planet every 90 minutes. Credit: Inspiration4 crew An in-flight spike in mtDNA and mtRNA has been shown for most crews; however, the 3-day i4 mission did not show the same spike, so this indicates the mtDNA phenotype might be age specific or related to the length of the mission. Brain-associated proteins were found in the plasma of crew members after the I4 mission, confirming the brain signature from the JAXA study and prior work in the Twins Study. Nature Communications: Space radiation damage rescued by inhibition of key spaceflight associated miRNAs Nature Communications: Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response Mitochondrial spikes across tissues. Different tissues (vertical axis) measured for their enrichment of mitochondrial RNA (mtRNA) levels (x-axis) show that the brain, skeletal muscle, and retina are among the most responsive tissues to spaceflight. Fold enrichment is shown in proportion to the size of the circle and the p-value is shown from red to blue for signifiance. Bubble chart showing the enrichment of mitochondrial RNA in various tissues during spaceflight. Brain, skeletal muscle, retina and heart muscle are the most responsive tissues to spaceflight with a greater mitochondrial gene count with fold enrichment between 0.96 and 2.84 and p value <0.05 compared with liver, testis, pituitary gland, choroid plexus, intestine, kidney, tongue, lymphoid tissue, thyroid gland, oesophagus, skin, parathyroid, placenta, pancreas, adipose tissue, bone marrow. The total amount of sequence data in the Open Science Data Repository has increased almost 14-fold with the addition of Inspiration4 data. Credit: Inspiration4 crew As research and missions are extended beyond low Earth orbit, experiments and platforms must be maximally automated, light, agile and intelligent to accelerate knowledge discovery and support mission operations. The integration of artificial intelligence into the fields of space biology and space health has deepened the biological understanding of spaceflight effects. To effectively mitigate health hazards, AI-enabled paradigm shifts in astronaut health systems are necessary to enable Earth-independent healthcare to be predictive, preventative, participatory, and personalized. npj Microgravity: Explainable machine learning identifies multi-omics signatures of muscle response to spaceflight in mice Nature Machine Intelligence: Biological research and self-driving labs in deep space supported by artificial intelligence npj Microgravity: NASA GeneLab derived microarrays studies of Mus musculus and Homo sapiens organisms in altered gravitational conditions npj Microgravity: Harmonizing heterogeneous transcriptomics datasets for machine learning-based analysis to identify spaceflown murine liver-specific changes Preprint: Analyzing the relationship between gene expression and phenotype in space-flown mice using a causal inference machine learning ensemble Nature Machine Intelligence: Biomonitoring and precision health in deep space supported by artificial intelligence Layered and integrated data acquisition and monitoring for deep-space missions. The integrated biological and health monitoring system is shown as a pyramid, with layers of increasingly invasive and granular monitoring, where data flow from both experimental models as well as astronauts, and are put into the context of environmental monitoring via AI/ML algorithms. Diagram summarising a plan for multi-layer monitoring with AI algorithms for deep space missions. The monitoring system is shown as a pyramid. The starting layer of monitoring is a continuous environmental sensing of physical, chemical, and biological components. Going up in the pyramid, layers become more invasive with the usage of wearable and point of care devices. At the top of the pyramid, a third layer, more invasive, entails acquisition of molecular physiological biomarkers including usage of swabs and sampling methods. Monitoring data is to be integrated with data from environmental monitoring via AI/ML algorithms. The data collected on the mission adds to the body of evidence for monitoring countermeasure effectiveness. Credit: Inspiration4 / Hayley Arceneaux To mitigate these reported biological changes and limit the damage caused to the body by spaceflight and space environment, it is key to develop countermeasures. Countermeasures can involve novel drug production, repurposing FDA approved drugs, or genome/epigenome modification systems. Preprint: Countermeasures for cardiac fibrosis in space travel: It takes more than a towel for a hitchhiker's guide to the galaxy Countermeasures mediated by miRNAs. Data from the JAXA astronaut cell-free RNA study (CFE) shows that a wide range of micro RNAs (miRNAs) can be helpful for guiding countermeasures. The miRNA targets are shown (top), as well as the enrichment (scale from red to blue) during flight or post-flight for the astronauts. Heatmap chart showing normalized plasma cell-free RNA expression values for 21 key genes over time for the six astronauts over 120 days in space from JAXA cell-free RNA study. Plotting the changes in several micro RNAs before, during and after spaceflight with three miRNA targets being shown at the top (let-7a-5p, miR-125b-5p, miR-16-5p). Most of the 21 antagomir-rescued genes in the JAXA data were downregulated during the flight. Most of the genes show up-regulation post-flight as compared with pre-flight and during flight. The constellation of Libra (the scales) is a metaphor for the ethical challenges of space exploration. Credit: iStock / Getty Images Plus New spacecraft enable novel missions and a wider array of crews to go into space, but also generate new ethical questions and parameters about data accessibility. Some of these ideas and novel data types are discussed in these perspectives: Nature Communications: Biological horizons: pioneering open science in the cosmos npj Microgravity: Inspiration4 data access through the NASA Open Science Data Repository Nature Communications: Ethical considerations for the age of non-governmental space exploration Human Subjects Research Ethical and Operational Guidelines. The ethical principles currently in place for human subject research and the challenges and new ethical principles and challenges that have to be considered during the second space age. Diagram showing 14 items that constitute the ethical framework in space human subject research. It is split into three areas: first, the existing ethical principles and regulations, which includes the US Code of Regulations for informed consent, respecting autonomy, the declaration of Helsinki, avoiding harm, risk–benefit balance, Fairness, and the Genetic Information Non-discrimination Act; second, the implementation of ethical standards, which includes the Institutional Review Board, Informed consent, and Genetic Data Protection; and third, the Emerging ethical challenges in space research, which includes secure drug storage, violating favourable risk–benefit balance, participant’s autonomy: withdrawing from research, and avoiding the increased health risks of space. Nose cone of Dragon spacecraft against a sliver of light on Earth at sunrise for the Inspiration4 crew. Credit: Inspiration4 crew Nature: A second space age spanning omics, platforms, and medicine across orbits The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions planned to enter space. Such rapid advancement into space from many new companies, countries, and space-related entities has ushered humanity into “The Second Space Age.” This era is poised to leverage, for the first time, modern tools and methods of molecular biology, which is enabling precision aerospace medicine for the crews, new technological and computational methods for modeling life, new heavy-lift spacecraft for enabling inter-planetary missions (e.g. Crocco flyby), and systems for the detection, deployment, and protection of life on other worlds. Number of objects launched into space (1957–2023). Data taken from the United Nations Outer Space Objects Index, which shows the exponential increase in launches into space in the past few years. Countries are shown for the USA (blue), Russia/USSR (purple), and a breakdown of all other countries (green). Two pie charts and a histogram showing the total and yearly number of objects launched into space by countries between 1957 and 2023 according to data taken from the United Nations Catalog. The histogram shows an exponential increase in launches into space in the most recent years with USA contributing to more than half of the grand total of launches (USA= 9,632, USSR/Russia= 3,732, China = 1,051, and 2,877 launches being shared by a number of other countries including UK, Japan, France, India, Germany, Canada. New missions enabled by modern spacecraft. The orbital trajectory for a three-planet mission (Crocco Flyby) in 2033 that would fly by Mars twice and also Venus within about 18 months on a SpaceX Starship (calculations validated by Try Lam at Jet Propulsion Laboratory, editing with Brent West). The launch dates and approximate orbital timings are shown around the planetary orbits (dotted line circles) and the flight path. The sun is shown in the middle of the figure. Concentric circles of Mars, Earth, and Venus around the sun, and the planned spiral course that a rocket to Mars will take. The launch dates and approximate orbital timings are shown around the planetary orbits for the three-planet mission departing from Earth 18th April 2033, then flying by Mars twice between November and December 2033 and Venus on 6th June 2034. A visual summary of the 44 papers in the SOMA package is also available as a PDF version. All papers can be accessed in the collection page. Chris Mason, Weill Cornell Medicine, Mason Lab Afshin Beheshti, Blue Marble Space Institute of Science at NASA Ames Research Center, Beheshti Lab Mathias Basner, University of Pennsylvannia, Basner Lab Eliah G. Overbey, The University of Austin, Overbey Lab Cem Meydan, Weill Cornell Medicine, Meydan Lab Masafumi Muratani, University of Tsukuba/JAXA, Muratani Lab Susan Bailey, Colorado State University, Bailey Lab Eric Bershad, Baylor College of Medicine, Center for Space Medicine Joseph Borg, University of Malta, Borg Lab Sylvain Costes, NASA Ames Research Center, Costes Lab and NASA OSDR: Open Science for Life in Space David Furman, The Buck Institute, Furman Lab; Stanford University, 1000 Immunomes Project Stefania Giacomello, SciLifeLab, Giacomello Lab Christopher Jones, University of Pennsylvannia, Jones Lab Begum Mathyk, University of South Florida, Begum Lab Amber Paul, Embry-Riddle Aeronautical University, Paul Lab Jonathan Schisler, University of North Carolina, Schisler Lab Mark Shelhamer, Johns Hopkins University, Human Spaceflight Lab Keith Siew, University College London, Siew Lab Scott Smith, Nutritional Biochemistry Laboratory, Smith Lab Emmanuel Urquieta, University of Central Florida, Urquieta Lab Stephen (Ben) Walsh, University College London, Walsh Lab Fredric Zenhausern, University of Arizona, Zenhausern Lab Sara Zwart, Nutritional Biochemistry Laboratory, Johnson Space Center NASA Artificial Intelligence for Life in Space (AI4LS) Working Group, Sylvain V. Costes, Lauren M. Sanders NASA GeneLab Sample Processing Lab, Valery Boyko NASA Open Science Data Repository, Sylvain V. Costes, Samrawit G. Gebre, Danielle K. Lopez, Lauren M. Sanders, Ryan T. Scott, Amanda M. Saravia-Butler, San-huei Lai Polo, Rachel Gilbert Thanks to funding, logistical, and mission support from NASA/TRISH, JAXA, ESA, WorldQuant, and SpaceX, as well as thanks to the crews, their families, and all mission support staff and teams. Thanks to all OSDR Analysis Working Group members.