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Space Radiation Induces Long Term Impact on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species

Space radiation can damage the cardiovascular system and thus is an important health risk factor for astronauts during long-term space missions. We utilized publicly available transcriptomic data through NASA's GeneLab platform (genelab.nasa.gov) to determine cardiovascular system response to space radiation. GeneLab is an open repository that houses all NASA related omics experiments including on the International Space Station (ISS) and related radiation ground studies. We analyzed 3 datasets from GeneLab: GLDS-117 and GLDS-109, which are ground studies of cardiomyocytes followed-up for 28 days after exposure to 90cGy of proton at 1GeV and 15cGy of 56Fe at 1GeV; and GLDS-52, human endothelial cells (HUVECs) that were cultured for 10 days on the ISS. The ground studies were designed to characterize the long-term impact following space irradiation on cardiomyocytes for 5 different time points up to 28 days after irradiation. Our analysis was guided by the hypothesis that there are common persistent molecules affecting the cardiovascular system due to radiation effects during spaceflight. Endothelial cells are known to directly regulate the development and activity of cardiomyocytes, and thus their response to spaceflight should be highly correlated with cardiomyocytes. To investigate our hypothesis, we identified the molecular pathways that were modified for all time points compared across both radiation on the ground and the pathways found in HUVECs flown in the ISS. We found the following key results related to the cardiovascular systems: 1) space radiation downregulate ROS functions; and 2) the key/driving genes: FYN, LCK, AKT1 are upregulated and LYN and FOS are downregulated with FYN being the central driver/hub for the cardiovascular response to space radiation. It is worth noting the activation of FYN is a key event which prevents cardiac cell death and ROS production. From our study we thus hypothesize that a feedback loop occurs from the oxidative stress caused by space radiation that upregulates FYN which in turn reduces ROS levels and thus ROS pathways, preventing cardiomyocyte and endothelial cell death and thus protecting the cardiovascular systems. We believe that this is a novel mechanism for space radiation induced cardiovascular risk directly linking radiation ground studies to spaceflight

Beheshti, Afshin

Systemic Response to Microgravity: Utilizing GeneLab Datasets to Identify Molecular Targets for Future Hypotheses-Driven Spaceflight Studies

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF(beta)1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF(beta)1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab

Systemic Microgravity Response: Utilizing GeneLab to Develop Hypotheses for Spaceflight Risks

Biological risks associated with microgravity is a major concern for space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. The overall goal of our work is to identify potential master regulators responsible for such responses to microgravity conditions. To do this we utilized the NASA GeneLab database which contains a wide array of omics experiments, including data from: 1) different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); 2) different tissues; and 3) different types of assays that measure epigenetic, transcriptional, and protein expression changes. We have performed meta-analysis identifying potential master regulators involved with systemic responses to microgravity. The analysis used 7 different murine and rat data sets, examining the following tissues: liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius). Using a systems biology approach, we were able to determine that p53 and immune related pathways appear central to pan-tissue microgravity responses. Evidence for a universal response in the form of consistency of change across tissues in regulatory pathways was observed in both STS and ISS experiments with varying durations; while degree of change in expression of these master regulators varied across species and strain, some change in these master regulators was universally observed. Interestingly, certain skeletal muscle (gastrocnemius and soleus) show an overall down-regulation in these genes, while in other types (extensor digitorum longus, tibialis anterior and quadriceps) they are up-regulated, suggesting certain muscle tissues may be compensating for atrophy responses caused by microgravity. Studying these organtissue-specific perturbations in molecular signaling networks, we demonstrate the value of GeneLab in characterizing potential master regulators associated with biological risks for spaceflight.

Microgravity

Cross Kingdom Analysis of Data Within the GeneLab Repository Identifies a Potential Conserved Response of Life to the Stress Associated with Spaceflight

It is important to determine the health risks and potential survival for astronauts associated with long-term space missions. This entails not only understanding the impact the space environment will have on humans, but also how it will affect other organisms needed for humans to survive in space such as plants. In addition, it has been reported in the literature that hundreds of genes seem to be conserved and/or transferred between different organisms from bacteria, archaea, fungi, microorganisms, and plants to animals. Since space travel involves humans in a closed environment over a long period of time, we hypothesize that potential conserved biological factors will occur between the different organisms in that environment possibly due to transfer of genes. Determining the conserved factors that are commonly being regulated in space can shed insight into possible universal master regulators and also determine the symbiotic relationship between the organisms in space. Utilizing NASA's GeneLab Data Repository (a rapidly expanding, curated clustering of spaceflight-related ‘omics-level datasets for all organisms), we were able to uncover a novel pathway and factors that were commonly shared between humans, mice, plants, C. Elegans, and drosophilas. Through ChIP-Seq enrichment analysis techniques utilizing various GeneLab datasets from each species that were flown in space, we found the following factors to be conserved across all species: oxidative stress, DNA damage (through GABPA/NRFs and NFY), SIX5, GTF2B and glutamine synthetase. Such commonalities would likely reflect the effects of factors such as microgravity and the increased radiation exposure inherent in spaceflight on basic physical processes shared by all biological systems at the cellular level. Differences between organismal responses revealed by GeneLab's data should also help understand the unique reactions to life in space that arise from the very different lifestyles of microbes, animals and plants.

Barker, Richard

GL4U: Training the next generation of bioinformaticians, one omics datatype at a time

Spaceflight modifies gene expression in every organism examined to date, including humans. Understanding how these gene expression changes affect physiology is crucial for the development of countermeasures to enable long-duration manned missions. NASA’s GeneLab project provides researchers open access to multi-omics data, including genetic and gene expression data, from spaceflight experiments that can be mined to understand the effects of spaceflight on biological systems. To ensure new knowledge generation through data re-use, it is important to maximize the number of scientists who utilize GeneLab data. Training students on the GeneLab platform is the best way to create long-term adopters of this NASA database and its tools. Turning students into future instructors and advocates will also accelerate the dissemination of these data and tools to the broader scientific community. Therefore, in collaboration with the GeneLab Educational Working Group (EWG), GeneLab has created GeneLab for Colleges and Universities (GL4U). GL4U provides space biology-relevant training in bioinformatics to the next generation of scientists through direct and indirect approaches. The GeneLab team plans to host two annual data processing bootcamps, one for college-level students (direct) and one for college educators (indirect – training of trainers), in which participants learn to analyze GeneLab’s space-relevant omics data. During the bootcamp, educators will receive materials and training to enable them to run the bootcamp at their home institutions or alternatively to adapt the content to implement within existing courses, thereby extending the reach of this initiative. The GL4U direct training pilot program was conducted in June 2021 in collaboration with USRA and San Jose State University (SJSU). During the pilot, SJSU students participated in a week-long bootcamp consisting of space biology-specific lectures and hands-on instruction using Jupyter Notebooks to analyze RNA sequence data. This pilot demonstrates the capacity of GL4U for training young scientists and encouraging data re-use.

Jonathan Matthew Galazka

NASA GeneLab Multi-study Visualization Portal

NASA GeneLab has helped advance the field of Space Biology by providing a public repository where researchers can store, share, analyze and visualize the results of space flight related omics experiments. The GeneLab data visualization portal allows any user, regardless of bioinformatics knowledge or access to computational resources, to interact with the experimental data, draw their own conclusions, and gain insights about the effects of space on living systems. These tools help democratize scientific research and foster the NASA Open Science initiative. The new multi-study feature of the GeneLab visualization platform allows users to mine study metadata from RNA sequencing (RNA-seq) experiments to identify samples of interest by filtering datasets based on organism, tissue, assay technology type, and/or factor. Once samples are selected from multiple datasets, users can combine and normalize the sample data, then utilize the visualization displays, including Principal Component Analysis (PCA) plots, to assess sample distributions. Finally, users can perform differential gene expression analysis on the combined data and visualize the results through PCA plots, Volcano plots, Pair plots, Heatmap, Ideogram and Gene Set Enrichment Analysis. All user-generated results and visualizations will be available for download. Here, we present a biological study using samples from multiple GeneLab RNA-seq datasets and analyzed using the multi-study visualization platform to demonstrate inter- and intra-study variability, as well as commonly differentially expressed genes between spaceflight and ground control conditions across datasets. This new feature opens a wide range of possibilities and opportunities for further development including combining other assay technology types and integration with batch effect correction techniques and machine learning applications. Overall, this tool allows users to increase the statistical power of individual experiments, validate hypothesis, identify patterns, and opens the door to new and exciting research.

space biology

Spaceflight Biospecimen Sharing in Support of Science Discovery and Exploration

For decades, NASA and international partners have flown non-human biological experiments in space to understand the effects of spaceflight and address potential biological hazards. Sending organisms into space is a costly endeavor which makes space-flown biological specimens a valuable resource. To enable maximum scientific return, samples not required by the Principal Investigators are harvested and collected mostly by NASA’s Space Biology Biospecimen Sharing Program. These specimens are collected according to well-established SOPs that maintain quality and integrity. The specimens are then preserved, archived, and made available to the international scientific community through NASA’s Institutional Scientific Collection (ISC) at Ames Research Center (ARC). The ISC-ARC biospecimens and descriptive metadata are findable and accessible for request through the Life Sciences Data Archive (LSDA). The NASA ISC-ARC currently stores over 32,000 specimens from Shuttle, International Space Station, and ground-based investigations (spaceflight analog experiments involving either hindlimb unloading, centrifugation, or partial weight-bearing study designs). Tissues are predominantly from mice and rats, though samples are also available from bacteria and quail. The specimens include tissues from many physiological systems including musculoskeletal, neurosensory, reproductive, respiratory, circulatory, and digestive. Tissues are stored at -80°C, -20°C, +4°C, or ambient and preserved in various fixatives. Descriptive metadata is available for all samples. Historically, these tissues have been used for a wide range of analyses, including histology, genomics, and transcriptomics. Plans are underway to expand the ISC-ARC beyond the mostly-rodent contents, to include a space-relevant microbial culture collection including bacteria, fungi, and yeast. This expansion of the ISC-ARC will now involve identifying and standardizing best practices for microbial curations. To ensure safe long-term storage of microbial isolates, a microbiology laboratory will be dedicated for identification, cell culture, and lyophilization. Awarding of tissue to public science investigators has resulted in 33 publications since 2011, with 48 requests being submitted since 2016. Of note, NASA GeneLab has been awarded ISC-ARC biospecimens in the past few years. GeneLab processes the biospecimens to generate various levels of ‘omics’ data, which are published on GeneLab’s open access online platform for bioinformatics analysis and visualization. This has helped a systems biology community grow around the processed-biospecimens’ datasets, resulting in many new publications and insights. Websites: https://www.nasa.gov/ames/research/space-biosciences/isc-bsp ; https://lsda.jsc.nasa.gov/Biospecimen

Ryan T. Scott

Enabling Space Biological Knowledge Discovery Through Image and Video Data Sharing

Increased biomedical risks associated with deep space crewed missions (cis-Lunar, Mars transit/surface) require development of health countermeasures, novel ecosystem support, risk modeling, and fundamental space biological knowledge discovery. Molecular-omics, physiological-phenotypic-behavioral, and environmental-radiation telemetry data from space biological and health studies are needed for reuse by scientists to address these tasks. The data as well as space-relevant biospecimens are being made more findable, accessible, interoperable, and reusable through NASA’s Open Science Data Repository (OSDR). This new OSDR umbrella grouping includes NASA GeneLab, the NASA Ames Life Sciences Data Archive (ALSDA), and the NASA Biological Institutional Scientific Collection. The OSDR system design appropriately handles metadata and processed-tabular results from ALSDA studies collected from space experiments. But raw and processed ALSDA bioimage and video datasets require an expansion of OSDR’s data architecture to handle ingestion, curation, and egress. The academic-industry bioimaging field saw a scientific renaissance in the past several years through leveraging open-source software, international collaborations, machine learning, and other open science/programming approaches. As crewed missions and more biological experiments are on the deep space horizon, OSDR is embracing data stewardship through listening to feedback from subject matter experts and designing an expanded architecture which is appropriate for NASA’s goals to enable analysis and reuse of bioimaging and video data for the public science community.Discovery Through Image and Video Data Sharing

space biology

Systemic Alterations with Spaceflight Associated Health Risks Originating from Both Circulating miRNAs and Mitochondrial Biology

The many known health risks currently associated with space travel include increased risk of cardiovascular disease, cancer, central nervous system related diseases, muscle degeneration, and changes with host-gut microbiome interactions that can have profound impact with these and other health risks. The majority of the risk from space travel stem of the two components of the space environment which are microgravity and radiation. Two specific systemic effects have been uncovered by us to impact the body as a whole due to the space environment. One factor is related from our earlier work (Beheshti et al, PLOS One, 2018), we predicted that there is a systemic component of the host that causes general increased health risks due to spaceflight driven by a circulating microRNA (miRNA) signature consisting of 13 miRNAs that directly regulates both p53 and TGF1. MiRNAs are small non-coding RNA molecules with a negative and post-transcriptional regulation on gene expression) are increasingly recognized as major systemic regulators of responses to stressors, including microgravity, oxidative stress, and DNA damage. In addition, due to the size and stability of miRNAs, it is known that miRNAs can circulate throughout the body and have been found in the majority of the bodily fluids including blood, urine, saliva, and tears. Here, we start to dissect the actual impact of this miRNA signature on both the radiation and microgravity components and prove that this miRNA signature actually exists in the circulation of a host. The other systemic factor we uncovered was the impact the mitochondria on the whole body due to spaceflight. We hypothesize that spaceflight may promote a physiologic response driven by systemic mitochondria pathways leading to metabolic disorder stemming from the liver and directly impacting other organs and tissues. A systems biology method was implemented utilizing GeneLab datasets that involved in vitro experiments performed at the low Earth orbit, in vivo experiments involving mice flown to space, and finally human physiological data from astronauts. A comprehensive multi-omics approach was implemented which involved correlating transcriptomic analysis with proteomics, metabolomics, and methylation analysis. This approach led us to confirm our hypothesis that a systemic mitochondrial driven response is responsible for increasing potential health risk and is conserved from the in vitro studies, to the in vivo studies, and finally confirmed in astronauts.

Radiation

Open Science for Life in Space

Understanding how biology changes in response spaceflight and how these changes affect crew and craft is important to the design of safe, robust and effective space missions. Advances in analytical technologies allow large volumes of new data to be generated from space biological experiments, and a growing library of legacy data can be re-analyzed in the context of a greater understanding of biological systems. This enables powerful insights into how biology changes during spaceflight. However, for this to be fully realized additional tools, programs, and communities must be developed. Now a developing suite of interconnected open science resources (GeneLab, the Ames Life Sciences Data Archive, the NASA Biological Institutional Science Collection, the Biospecimen Sharing Program) can be leveraged by dedicated Analysis Working Groups to accelerate the pace of discovery in the space biological sciences.

Open Science

Overview of the Translational Radiation Research and Countermeasures (TRRaC) Project in Space Radiation

The Translational Radiation Research and Countermeasures (TRRaC) Project was initiated by the Space Radiation (SR) Element within NASA’s Human Research Program (HRP) to support the SR mission to understand and characterize the space radiation environment, understand and quantify radiation-associated risks, and mitigate the impacts of radiation-induced adverse health outcomes to enable human space exploration. TRRaC’s mission is to translate radiation research results from experimental studies and epidemiological data to humans and astronauts using bioinformatics and computational modeling. TRRaC will leverage existing datasets such as those available from NASA’s GeneLab repository and human medical radiation exposure registries, along with relevant data generated from ground-based research at molecular, cellular, tissue, and system levels, to: (1) refine the radiation dose rate effectiveness factor, (2) characterize radiation quality effects to improve estimates of the risk of exposure-induced death (REID) from space-relevant radiation exposures, and (3) identify pathways and biomarkers for cancer, cardiovascular disease, and central nervous system changes that are impacted by space radiation exposure.

Parastou Eslami

GeneLab: Multi-Omics Investigation of Rodent Research-1 Bio-Banked Tissues

NASAs Rodent Research (RR) project is playing a critical role in advancing biomedical research on the physiological effects of space environments. Due to the limited resources for conducting biological experiments aboard the International Space Station (ISS), it is imperative to use crew time efficiently while maximizing high-quality science return. NASAs GeneLab project has as its primary objectives to 1) further increase the value of these experiments using a multi-omics, systems biology-based approach, and 2) disseminate these data without restrictions to the scientific community. The current investigation assessed viability of RNA, DNA, and protein extracted from archived RR-1 tissue samples for epigenomic, transcriptomic, and proteomic assays. During the first RR spaceflight experiment, a variety of tissue types were harvested from subjects, snap-frozen or RNAlater-preserved, and then stored at least a year at -80OC after return to Earth. They were then prioritized for this investigation based on likelihood of significant scientific value for spaceflight research. All tissues were made available to GeneLab through the bio-specimen sharing program managed by the Ames Life Science Data Archive and included mouse adrenal glands, quadriceps, gastrocnemius, tibialis anterior, extensor digitorum longus, soleus, eye, and kidney. We report here protocols for and results of these tissue extractions, and thus, the feasibility and value of these kinds of omics analyses. In addition to providing additional opportunities for investigation of spaceflight effects on the mouse transcriptome and proteome in new kinds of tissues, our results may also be of value to program managers for the prioritization of ISS crew time for rodent research activities. Support from the NASA Space Life and Physical Sciences Division and the International Space Station Program is gratefully acknowledged.

GeneLab

NASA Open Science Data Repository: Open Science for Life in Space

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.

OSDR

New Developments in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.

Shirazi, Yasaman

GeneLab

GeneLab collects and enables analysis of spaceflight and ground-based spaceflight simulation genomic data, RNA and protein expression, and metabolic profiles. It interfaces with other existing databases containing spaceflight omic data. The 2011 National Research Council (NRC) Decadal Survey on NASA Life and Physical Sciences called for increased opportunities for multi-investigator spaceflight opportunities and greater use of genomic approaches to meet the needs of NASA researchers. To address these recommendations of the NRC Decadal Survey, the Space Life and Physical Sciences Research and Applications Division of NASA's Human Exploration and Operations Mission Directorate has initiated a transition to an Open Science architecture to increase research opportunities, and has developed the GeneLab Platform based on highly leveraged and integrated bioinformatics analytics. GeneLab is an interactive, open-access resource where scientists can upload, download, store, search, share, transfer, and analyze omics data from spaceflight and corresponding analogue experiments. Users can explore GeneLab datasets in the Data Repository, analyze data using the Analysis Platform, visualize high-order data and create collaborative projects using the Collaborative Workspace. Our primary goal is to maximize the utilization of the valuable biological research conducted aboard the International Space Station (ISS) by collecting genomic, transcriptomic, proteomic, and metabolomics data known as “omics”. By providing a portal linking processed data to flight parameters, GeneLab enables exploration of the molecular network responses of terrestrial biology to the space environment. This allows researchers to understand the complex responses of biological systems to the space environment. This technology development activity was transferred from the Human Exploration and Operations Mission Directorate to the Science Mission Directorate Division of Biological and Physical Sciences (BPS) in October 2020.

GeneLab

GeneLab Analysis Working Group Kick-Off Meeting

Goals to achieve for GeneLab AWG - GL vision - Review of GeneLab AWG charter Timeline and milestones for 2018 Logistics - Monthly Meeting - Workshop - Internship - ASGSR Introduction of team leads and goals of each group Introduction of all members Q/A Three-tier Client Strategy to Democratize Data Physiological changes, pathway enrichment, differential expression, normalization, processing metadata, reproducibility, Data federation/integration with heterogeneous bioinformatics external databases The GLDS currently serves over 100 omics investigations to the biomedical community via open access. In order to expand the scope of metadata record searches via the GLDS, we designed a metadata warehouse that collects and updates metadata records from external systems housing similar data. To demonstrate the capabilities of federated search and retrieval of these data, we imported metadata records from three open-access data systems into the GLDS metadata warehouse: NCBI's Gene Expression Omnibus (GEO), EBI's PRoteomics IDEntifications (PRIDE) repository, and the Metagenomics Analysis server (MG-RAST). Each of these systems defines metadata for omics data sets differently. One solution to bridge such differences is to employ a common object model (COM) to which each systems' representation of metadata can be mapped. Warehoused metadata records are then transformed at ETL to this single, common representation. Queries generated via the GLDS are then executed against the warehouse, and matching records are shown in the COM representation (Fig. 1). While this approach is relatively straightforward to implement, the volume of the data in the omics domain presents challenges in dealing with latency and currency of records. Furthermore, the lack of a coordinated has been federated data search for and retrieval of these kinds of data across other open-access systems, so that users are able to conduct biological meta-investigations using data from a variety of sources. Such meta-investigations are key to corroborating findings from many kinds of assays and translating them into systems biology knowledge and, eventually, therapeutics.

GeneLab

Transcriptomics and Proteomics Discussion

This presentation will cover the the basic pipelines for transcriptomics and proteomics that the GeneLab Analysis Working Groups (AWGs) have so far determined to be optimal. Basic transcriptomic pipelines will first be presented from primary analysis to higher-order systems analysis. Examples of how the data has been analyzed will be presented. Proteomics pipelines will also be presented compiled from various AWG members. Discussion will be generated from the AWG members to reach a consensus for each omic type.

Transcriptomics

Enabling Model Organism and Commercial Astronaut Data Access Through the NASA Open Science Data Repository

NASA’s Open Science Data Repository (OSDR) brings together omics data from NASA’s GeneLab project and non-omics data, including physiological, phenotypic, imaging, and behavioral data from NASA’s Ames Life Sciences Data Archive (ALSDA) collected from decades of space biology research, providing open and FAIR (findable, accessible, interoperable, and reusable) access of these precious data to scientists world-wide. This rich source of meticulously curated metadata and data from spaceflight and analog studies has been mined by the scientific community resulting in dozens of high impact scientific publications that reveals a complex network of molecular and physiological effects of spaceflight across living systems, from microbes to plants, to mammals. Understanding how these effects translate to the human condition is critical as we move deeper into the era of commercial space travel. However, the integration of data, specifically omics data, from astronauts is particularly challenging due to their sensitive nature. OSDR has risen to this challenge by developing a mechanism to control access to identifiable levels of omics data, such as raw sequence data, while enabling public access to processed, unidentifiable, data and associated metadata that will allow the scientific community to interrogate human astronaut data alongside data from model organisms to begin answering these critical questions. The 2021 SpaceX Inspiration4 (I4) mission collected a comprehensive atlas of biological measurements from four civilian astronauts, providing a wealth of data to characterize the effects of spaceflight on the human body. These data include both non-omics and omics assays such as direct RNA sequencing (RNA-seq), single nuclei ATAC-seq and RNA-seq, metagenomics, proteomics, and comprehensive metabolic and cytokine panels, all of which have been integrated into the OSDR system across no less than 9 studies. Each study has been carefully curated using community-backed OSDR standards for sample and assay level metadata ensuring these data are findable and accessible. In addition to hosting both raw and processed data from the principal investigator team for each assay type, the GeneLab team plans to re-process the I4 omics data using GeneLab’s standard processing pipelines. The GeneLab processed data outputs will allow for comparisons across studies on OSDR and enable visualization of these data through the OSDR data visualization platform thereby enabling data reusability and interoperability. Here we describe the robust privacy and security protocols implemented by OSDR to safeguard sensitive health data from astronauts while facilitating metadata and processed data sharing for research purposes. We further provide a road map for navigating the vast amount of data provided for each I4 study on the OSDR, including experimental design, associated experiments, payloads, and missions, data generation and analysis protocols, and associated scientific articles. Additionally, we illustrate how to interrogate the standardized metadata provided in the sample and assay tables as well as various means to download and access the data including programmatically through the GeneLab Open API (GLOpenAPI). The open access of datasets in NASA’s OSDR provides a unique opportunity for the scientific community, as well as citizen scientists and students, to continue using OSDR resources to further unlock profound insights into the consequences of space travel on the human body. Through implementation of security measures to protect sensitive human data, the OSDR seeks to strengthen the science exchange between the Biological and Physical Sciences Program and the Human Research Program, per recommendation 4-1 of the 2023-2032 Decadal Survey, and encourage further sharing and dissemination of astronaut data to provide the scientific community with the resources needed to lay the groundwork for developing targeted mitigation strategies to help withstand the rigors of long-duration spaceflight.

Amanda Marie Saravia-butler