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NASA NTRSDate not supplied

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↗
NASA NTRSDate not supplied

Mitochondria Dysfunction Central in Driving Health Risks Associated with Spaceflight

Background: Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. Materials and Methods: One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA’s GeneLab platform (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation experiments, and simulated microgravity experiments. This presentation will provide an example of analysis and novel hypothesis generation that is being produced with GeneLab datasets. A comprehensive multi-omics approach was implemented correlating transcriptomics, proteomics, metabolomics, and methylation analysis. Results: We found that cells have stronger overall biological response than the tissues to spaceflight, with mitochondrial activity and innate immunity pathways being heavily impacted. NASA Twin Study results are consistent with a specific alteration in mitochondrial ATP production. Our results indicate that the space environment can directly induce mitochondrial damage, with mitochondrial dysfunctions being a cause for chronic inflammation and both being involved in the development of metabolic disorders that cause changes in lipid metabolism. We also found biological changes occurring during spaceflight with cell cycle, circadian rhythm and olfactory activity pathways can also influence and be influenced by alterations on mitochondrial activity

Afshin Beheshti↗
NASA NTRSDate not supplied

Enabling Biological Discovery Through Biospecimen Sharing: The Nasa Biological Institutional Scientific Collection

Understanding biological impacts from spaceflight hazards and the subsequent development of countermeasures are a high priority to enable humanity to venture back to the Moon, and then to Mars and beyond. Experiments have been conducted with model organisms flown to space and analogous investigations terrestrially, to identify biological mechanistic impacts from spaceflight hazards and to develop mitigation countermeasures, thus contributing towards basic and applied science goals. However, sending organisms into space is a costly endeavor. To maximize scientific return, all biospecimens not required by spaceflight-relevant Principal Investigators are harvested, preserved, and archived in the NASA Biological Institutional Scientific Collection (NBISC). Biospecimens are collected and preserved according to well-established standard operating procedures to maintain scientific quality and are available on-request by the international scientific community. NBISC currently stores over 32,000 biospecimens from Shuttle, International Space Station, and ground-based space analog investigations. Tissue sharing has resulted in at least 33 publications since 2011 and 51 requests since 2016. Many requests for NBISC biospecimens come from first-time investigators who subsequently submit grants as their point-of-entry into the field of spaceflight biology and health. The NBISC biorepository is part of the NASA ‘Open Science for Life in Space’ collaborative group of projects, which includes NASA Genelab, the Space Biology Program’s Biospecimen Sharing Program, Physical Sciences Informatics, and the Ames Life Sciences Data Archive. NBISC biospecimens have been awarded to NASA Genelab, who then generated various open access science ‘omics datasets through the GeneLab Sample Processing laboratory, with resulting data widely used for biological study. Other NBISC biospecimen awards have led to studies on fecal microbiome analysis, DNA damage analysis using single-cell DNA sequencing, enzymatic-pathway identification involved in spaceflight muscle atrophy, and characterization of ocular morphological changes. Of note, NBISC is expanded to include a new Space Microbial Culture Collection (SMCC) for the collection, identification, documentation, long-term preservation, and distribution of space-related microbial isolates.

Biospecimens↗
NASA NTRSDate not supplied

Biological Data for Deep Space Mission Support

Increased biomedical risks and challenges associated with deep space missions (cis-Lunar, Mars transit, Mars surface) require new knowledge discovery and development of novel ecosystem and biomedical support capabilities. This paradigm shift supporting distant and long-duration missions requires biological data to be findable, accessible, interoperable, reusable (FAIR), and maximally open-access (i.e., there is a data governance continuum from closed to mediated to embargoed to open). The NASA “Open Science Data Repositories” (OSDR) aims to meet scientific, technical, and operational spaceflight needs, and offers the ability to upload, download, search, share, analyze, and visualize data across physiological, behavioral, ‘omics, and environmental monitoring telemetry datasets. OSDR includes NASA GeneLab, NASA Ames Life Sciences Data Archive (ALSDA), and NASA Biological Institutional Scientific Collection (NBISC). In the past year, ALSDA has undergone a transformation in its data collection, curation, and architecture methods. Standardizing non-genomic (phenotypic) datasets was, and will continue to be, a challenge because of their diverse nature (e.g., molecular, cellular, tissue, whole organism behavior; micro-computed tomography, intraocular pressure, fluorescence microscopy, western blot, ultrasonography; tabular, images, video). This year ALSDA, alongside GeneLab, introduced the Biological Data Management Environment (BDME) with the purpose to accept submission of data from space relevant experiments including spaceflight, radiation, simulated gravity, gravitropism, isolation and confinement, hostile closed environments and/or distance from Earth. In addition to bringing together omics, phenotypic, physiological, bioimaging, and behavioral data into one repository. By integrating with GeneLab a multi-project submission portal aims to reduce the burden on PIs submitting data and enabling the discovery of both omics and phenotypic data. The purpose of ALSDA is to collect, curate, and make all non-human space-relevant biological data maximally findable, accessible, interoperable, and reusable (FAIR). These scope of ALSDA data collected and submitted by PIs include study design metadata, subject metadata, assay metadata (parameters), raw and processed assay data, assay imagery/video, and subject-experienced mission data telemetry (radiation, temperature, humidity, acoustics, vibrations, etc.). In 2021, a community of researchers rallied to form the ALSDA Analysis Working Group (AWG) and provided scientific consensus on dataset sample and assay metadata. The community and excitement around the ALSDA/OSDR system has already led to several data reuse studies, demonstrating value using machine learning (ML), knowledge graphs, and meta-analysis approaches.

space biology↗
NASA NTRSDate not supplied

Murine Host-gut Microbiota Interactions are Modulated During Spaceflight

The rodent habitat on the International Space Station has provided critical insight into the impact of spaceflight on mammalian physiology. These effects include dysfunction of carbohydrate, steroid and lipid metabolism, and immune response, as well as induction of symptoms characteristic of liver disease, insulin resistance, osteopenia and myopathy, which are anticipated to intensify over long-duration spaceflight. Although these physiological responses can involve the microbiome, the host-microorganism interactions during spaceflight are still largely unknown. NASA GeneLab curates a wide range of space research data and the current work harnesses GeneLab multi’omic data from recent Rodent Research studies to explore changes to gut microbiota during spaceflight and their associations with host physiology when compared to ground controls. Using a hybrid analysis of DNA barcoding and whole genome shotgun data, an array of bacteria, fungi and nematodes could be identified at species level, and significant differences in relative abundances associated with spaceflight. Functional prediction based on differential abundance of species and metagenome gene inventories as well as metatranscriptomic gene expression at the host-gut microbiome interface implicate microbiota interactions could contribute to spaceflight pathology. Harnessing carefully curated publicly available data, such as from Genelab, to generate multi‘omic space science discoveries can help decipher the complex host-microbiome interactions that influence both health on Earth and the feasibility of long-duration spaceflight.

Microbiome↗
NASA NTRSDate not supplied

Biological Data for Deep Space Mission Support

Increased biomedical risks and challenges associated with deep space missions (cis-Lunar, Mars transit, Mars surface) require new knowledge discovery and development of novel ecosystem and biomedical support capabilities. This paradigm shift supporting distant and long-duration missions requires biological data to be findable, accessible, interoperable, reusable (FAIR), and maximally open-access (i.e., there is a data governance continuum from closed to mediated to embargoed to open). The NASA “Open Science Data Repositories” (OSDR) aims to meet scientific, technical, and operational spaceflight needs, and offers the ability to upload, download, search, share, analyze, and visualize data across physiological, behavioral, ‘omics, and environmental monitoring telemetry datasets. OSDR includes NASA GeneLab, NASA Ames Life Sciences Data Archive (ALSDA), and NASA Biological Institutional Scientific Collection (NBISC). In the past year, ALSDA has undergone a transformation in its data collection, curation, and architecture methods. Standardizing non-genomic (phenotypic) datasets was, and will continue to be, a challenge because of their diverse nature (e.g., molecular, cellular, tissue, whole organism, behavior; micro-computed tomography, intraocular pressure, fluorescence microscopy, western blot, ultrasonography; tabular, images, video). This year ALSDA, alongside GeneLab, introduced the Biological Data Management Environment (BDME) with the purpose to accept submission of data from space relevant experiments including spaceflight, radiation, simulated gravity, gravitropism, isolation and confinement, hostile closed environments and/or distance from Earth. In addition to bringing together omics, phenotypic, physiological, bioimaging, and behavioral data into one repository. By integrating with GeneLab a multi-project submission portal aims to reduce the burden on PIs submitting data and enabling the discovery of both omics and phenotypic data. The purpose of ALSDA is to collect, curate, and make all non-human space-relevant biological data maximally findable, accessible, interoperable, and reusable (FAIR). These scope of ALSDA data collected and submitted by PIs include study design metadata, subject metadata, assay metadata (parameters), raw and processed assay data, assay imagery/video, and subject-experienced mission data telemetry (radiation, temperature, humidity, acoustics, vibrations, etc.). In 2021, a community of researchers rallied to form the ALSDA Analysis Working Group (AWG) and provided scientific consensus on dataset sample and assay metadata. The community and excitement around the ALSDA/OSDR system has already led to several data reuse studies, demonstrating value using machine learning (ML), knowledge graphs, and meta-analysis approaches.

space biology↗
NASA NTRSDate not supplied

Open Science for Plants in Space: Data Sharing, Standards, and Informatics for Reuse and Knowledge Discovery

Upcoming deep space missions rely on plants and crops for crew and ecosystem health. Access to space plant data enables scientists to gain a deeper understanding of biological responses to ionizing radiation, altered gravity, low atmospheric pressure, elevated CO2, and altered photoperiods. Open Science is the practice of making research available to all, while respecting diverse cultures, fostering collaborations with equity. 2023 is the ‘Year of Open Science’, and NASA has a 5-year Transform to Open Science (TOPS) mission designed to rapidly transform the agency toward an inclusive culture of open science. NASA’s Open Science Data Repository (OSDR) developed by NASA’s Biological and Physical Sciences Division provides access to data from space-relevant biological experiments. OSDR combines two databases, GeneLab and Ames Life Sciences Data Archive (ALSDA) to maximize access to standardized ‘omics (e.g., transcriptomics, proteomics) and phenotypic data (e.g., microscopy, biomass), respectively. OSDR started in 2014 with the creation of the first space-relevant FAIR (Findable, Accessible, Interoperable, Reusable) biological ‘omics repository (GeneLab), providing detailed metadata on investigation, sample, and assay levels. Today, GeneLab hosts 62 plant datasets which have led to 5 published peer-reviewed meta-analysis publications. Most of these publications were collaboration efforts under the OSDR Analysis Working Groups (AWGs). AWGs provide great opportunities for investigators to collaborate and set new standards for space-relevant data and metadata. The AWGs are welcoming any ASPB members interested in providing plant expertise for space biology. The addition of ALSDA to OSDR is also expanding analysis capability beyond ‘omics. Now is the time to get involved as a Subject Matter Expert as we establish the framework for modern plant data archiving through the AWGs. Investigators are invited to submit their space-relevant plant datasets to OSDR and visit the site to learn about the tools OSDR has to offer (osdr.nasa.gov/bio).

FAIR↗
NASA NTRSDate not supplied

Optimizing Single Nuclei Sequencing of Brain Samples From Space Flown Mice Across Age and Strain

The NASA GeneLab Sample Processing Laboratory offers high-throughput sequencing services to NASA-funded space biology researchers. Space biology studies have specific challenges such as low sample numbers, introducing susceptibility to batch effects from sample handling. These issues are compounded by complex protocols such as single-nuclei isolation and sequencing, which has recently become an attractive methodology for assessing the cellular diversity within spaceflight samples. High quality single-nuclei sequencing requires reproducible protocols to dissociate tissue and generate clean suspension of intact single nuclei. Producing single-nuclei suspension from brain tissue is particularly challenging due to cell type heterogeneity and the myelin sheath that carries over into the nuclei suspension as debris. Current procedures tend to be time consuming and sometimes include steps that can alter gene expression and create cell-type bias. Commercially available nuclei isolation kits, such as the 10X Genomics nuclei isolation kit, offers a streamlined way to process samples for nuclei isolation, thereby minimizing batch effects and enabling reproducibility. In this study, we report on the performance of the 10X Genomics nuclei isolation kit and Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit to generate sequencing libraries from space-flown mouse brain samples. Single nuclei sequencing was performed on frozen mouse brain tissue from two spaceflight missions, Rodent Research-10 (RR-10) and RR Reference Mission-2 (RRRM-2). RR-10 mice were female B6129SF2/J, euthanized at 18-19 weeks whereas RRRM-2 mice were female C57BL/6NTac, euthanized at 20 or 37 weeks. Sequencing data was processed using standard GeneLab data processing pipelines. We report evaluation of the performance of the 10X Genomics nuclei isolation kit for spaceflight samples from mouse brain, and evaluation of reproducibility across different mouse strains and age groups. We also report preliminary scientific results including cell type inference, cell clustering, and differentially expressed genes and pathways between spaceflight and ground control samples.

RR-10↗
NASA NTRS2025

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↗
NASA NTRS2016

Advances in Rodent Research Missions on the International Space Station

A research platform for rodent experiment on the ISS is a valuable tool for advancing biomedical research in space. Capabilities offered by the Rodent Research project developed at NASA Ames Research Center can support experiments of much longer duration on the ISS than previous experiments performed on the Space Shuttle. NASAs Rodent Research (RR)-1 mission was completed successfully and achieved a number of objectives, including validation of flight hardware, on-orbit operations, and science capabilities as well as support of a CASIS-sponsored experiment (Novartis) on muscle atrophy. Twenty C57BL6J adult female mice were launched on the Space-X (SpX) 4 Dragon vehicle, and thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all flight animals were healthy and displayed normal behavior, and higher levels of physical activity compared to ground controls. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized on-orbit and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. In general, the data obtained from the flight mice were comparable to those from the three groups of control mice (baseline, vivarium and ground controls, which were housed in flight hardware), showing that the ISS has adequate capability to support long-duration rodent experiments. The team recovered 35 tissues from 40 RR-1 frozen carcasses, yielding 3300 aliquots of tissues to distribute to the scientific community in the U.S., including NASAs GeneLab project and scientists via Space Biology's Biospecimen Sharing Program Ames Life Science Data Archive. Tissues also were distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were analyzed for transcriptomic, epigenomic and proteomic profiles; some of the data sets are now available to the scientific community through GeneLabs open science data website. A second long duration mission, Rodent Research-2 (RR-2) was completed on the ISS in 2015; 20 female C57BL6J mice were successfully maintained on the ISS for various durations, with the last group of 5 animals living on-orbit for 54 days. Furthermore, we continue to expand the ISSs capabilities by introducing new on-orbit technologies including blood collection and separation, bone densitometry scanning, muscle grip strength and anesthesia with recovery. In addition, series of ground-based verification testing to fly male mice and increase the total number of mice on-orbit from 20 to 40. Subsequent missions will provide the capability to return live mice from the ISS animals to evaluate recovery on Earth, further expanding operational and science capabilities of the RR project on the ISS.

Choi, S. Y.↗
NASA NTRS2016

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASA’s Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASA’s GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLab’s open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the program’s capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISS’s capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Council’s Decadal Survey released in 2011 and to maximize science return from each mission.

Choi, S.↗
NASA NTRS2021

Knowledge Network Embedding of Transcriptomic Data From Spaceflown Mice Uncovers Signs and Symptoms Associated With Terrestrial Diseases

There has long been an interest in understanding how the hazards from spaceflight may trigger or exacerbate human diseases. With the goal of advancing our knowledge on physiological changes during space travel, NASA GeneLab provides an open-source repository of multi-omics data from real and simulated spaceflight studies. Alone, this data enables identification of biological changes during spaceflight, but cannot infer how that may impact an astronaut at the phenotypic level. To bridge this gap, SPOKE, a heterogeneous knowledge graph connecting biological and clinical data from over 30 databases, was used in combination with GeneLab transcriptomic data from six studies. This integration identified critical symptoms and physiological changes incurred during spaceflight.

spaceflight↗
NASA NTRSDate not supplied

Expanding Biological Repository Data Available for Sharing and Knowledge Discovery

Biology has developed next-generation data science and alternative analytical approaches with methodologies which require principal investigator (PI) experimental assay data be re-used. This new approach involves mining multiple datasets at once from various hierarchical organizations of biological complexity, while concurrently evaluating how experimental factors affect endpoints of standard assays. The purpose of the NASA Ames Life Sciences Data Archive (ALSDA) is to collect, curate, and make findable, accessible, interoperable, and reusable (FAIR) all non-human space-relevant biological data. These data include mission metadata, subject metadata, assay metadata (parameters), raw and processed assay data, assay imagery, and subject-experienced telemetry (radiation, temperature, humidity, acoustics, vibrations). ALSDA has transformed to bring current biological repository data and all future collected data into this new scientific data mining reality. It has integrated into the ‘NASA Open Science’ group of projects to facilitate a suite of new tools and workflows to improve data accessibility and reusability by implementing data management plans, automating data submission agreements, and adopting the single-point-of-entry data submission portal, originally developed by NASA GeneLab. These systems required ALSDA to develop science assay configurations for the submission portal, capturing essential assay parameters according to established norms in each sub-field within biology. The submission portal expedites data collection by enhancing ease of PI data submission, providing a user interface and specificity for which data is to be submitted. ALSDA datasets are curated to maintain rich metadata, accuracy of datasets, data transparency, provenance, and additionally ensure data are machine-readable (e.g., R and Python languages). ALSDA integration with GeneLab and its analysis portals enable higher-order physiological-level datasets be mined in conjunction with -omics datasets. As ALSDA physiological-level datasets are published (micro-computed tomography, histology, intraocular pressure, hormonal assays, immunostaining, ultrasonography), the merging of hierarchical organizations of biological complexity from spaceflight will enable new knowledge discovery approaches.

Ryan T Scott↗
NASA NTRSDate not supplied

Enabling Space Biology Knowledge Discovery Through Biospecimen Sharing: The NASA Biological Institutional Scientific Collection and Space Microbial Culture Collection

NASA and international partners have conducted experiments in space to understand the biological impacts and address hazards to health. The resulting basic and applied science is imperative to enabling humanity to venture back to the Moon and then to Mars and beyond. Sending organisms into space is a costly endeavor. All biospecimens not required by spaceflight-relevant Principal Investigators are harvested, preserved, and archived in the NASA Biological Institutional Scientific Collection (NBISC) to maximize the scientific return. The NASA Biological and Physical Sciences (BPS) Division ‘Open Science’ endeavor includes NASA Genelab, the Space Biology Program’s Biospecimen Sharing Program, Physical Sciences Informatics, the Ames Life Sciences Data Archive, and NBISC to integrate extensive data and biospecimen resources from spaceflight and/or ground-based analog experiments. NBISC biospecimens are collected and preserved according to well-established standard operating procedures to maintain scientific quality and are available on-request by the international scientific community. NBISC currently stores over 32,000 biospecimens from Shuttle, International Space Station, and ground-based space analog investigations. Tissue sharing has resulted in at least 33 publications since 2011 and 48 requests since 2016. Many requests for NBISC biospecimen come from first-time investigators who subsequently submit grants as the port-of-entry into the field of space biology. Some NBISC biospecimens have been awarded to NASA Genelab, who then generate various ‘Open Science’ -omics data sets on their platform for bioinformatics. Other NBISC biospecimen awards have led to multiple studies such as fecal microbiome analysis, DNA damage analysis using single-cell DNA sequencing, enzymatic-pathway identification involved in spaceflight muscle atrophy, and characterization of ocular morphological changes. Of note, NBISC has expanded to include a new Space Microbial Culture Collection (SMCC) for the collection, identification, documentation, long-term preservation, and distribution of space-related microbial isolates.

biospecimens↗
NASA NTRSDate not supplied

NASA biological and physical sciences databases: who’s the FAIRest of them all?

Conceptual models are a key part of the foundation of scientific study. Scientific data discovery and retrieval are often inaccurate and incomplete because these models are not sufficiently well-incorporated into data retrieval systems. Systems often don’t provide the necessary tools to those producing scientific data to fully and unambiguously annotate them and the result is consumers of the data cannot find them efficiently. The capability of data archives to provide these tools to link data to underlying conceptual models is one of dimensions of the recently developed “FAIR” principles (https://www.go-fair.org/fair-principles/ ), and is key to many automated processes being able to operate on these data, particularly analytics involving artificial intelligence. We used an open-source web service to measure the FAIR compliance of the three data archives operated by NASA for the biological and physical sciences: the Life Sciences Data Archive, the Physical Sciences Informatics database, and GeneLab. The service ingests references to data sets in these archives, and then executes domain-non-specific examinations of these data and metadata that test compliance to the FAIR principles. Of the 22 metrics tested, GeneLab passed 11 (50%), and PSI and LSDA each passed 7 (32%). These data were gathered using only one representative data set from each archive and we anticipate variability in results as we continue to apply these metrics to other data. A preliminary study of the failure traces for each metric suggests there is a wide range of effort and complexity in the enhancements required for each system to elevate FAIR compliance, and this is the subject of continued investigation. This information has been and will likely continue to be important information in planning these enhancements, with the goal of increased readiness of the data for automated processes.

database↗
NASA NTRSDate not supplied

Biological Insights at the Interface of Multiple Arabidopsis Legacy Datasets

The NASA GeneLab database includes an open-access collection of datasets yielded by space biology experiments. Six Gene Lab Data Sets (GLDS’s) performed in Arabidopsis were selected for analysis (7/17/44/121/205/213), all of which included transcriptome data from spaceflight and ground control environments. Hardware, ecotype, environmental conditions, and other experimental conditions varied, allowing the observations of overarching gene expression impacts of microgravity on plant life without focusing on effects of specific experimental conditions. Using GeneLab pre-processed datasets as the basis for the study, RNA microarray data were analyzed to identify genes that showed altered expression in microgravity when compared to control samples for each individual GLDS. All differentially expressed genes were compared to locate differentially expressed genes common between spaceflight experiments. The most noteworthy result is that not one gene shared differential expression among the six GLDS’s. However, gene expression was not influenced randomly by the microgravity environment, as there were several gene ontology terms that were significantly enriched across all experiments. These included 20 significantly enriched biological processes, and although the genes which enriched each term varied, there were many cases of specific genes common to clusters of multiple GLDS’s. Gene expression such as NAC92 and ERF011 or membrane structural element FFP6 provide insight and direction toward understanding the plant response to spaceflight. Characterizing these common processes and the shared differentially expressed genes has demonstrated potential targets for further study to understand and modulate the biological response of plants in microgravity. Life on Earth has never been subjected to the absence of gravity as a selective pressure, so observing how life forms react to a microgravity environment could provide insight to our shared fundamental biological processes. It is also feasible that the genetic modification of specific genes linked to the microgravity response could improve health and yield of space crops.

Joseph Emhof↗
NASA NTRSDate not supplied

Enabling Space Biology Knowledge Discovery Through Biospecimen Sharing: The NASA Biological Institutional Scientific Collection

NASA and international partners have conducted experiments in space to understand the biological impacts and address hazards to health. The resulting basic and applied science is imperative to enabling humanity to venture back to the Moon and then to Mars and beyond. Sending organisms into space is a costly endeavor. All biospecimens not required by spaceflight-relevant Principal Investigators are harvested, preserved, and archived in the NASA Biological Institutional Scientific Collection (NBISC) to maximize the scientific return. The NASA Biological and Physical Sciences (BPS) Division has an ‘Open Science’ endeavor which includes NASA Genelab, the Space Biology Program’s Biospecimen Sharing Program, Physical Sciences Informatics, the Ames Life Sciences Data Archive, and NBISC. Its purpose is to integrate extensive data and biospecimen resources from spaceflight and/or ground-based analog experiments. NBISC biospecimens are collected and preserved according to well-established standard operating procedures to maintain scientific quality and are available on-request by the international scientific community. NBISC currently stores over 32,000 biospecimens from Shuttle, International Space Station, and ground-based space analog investigations. Tissue sharing has resulted in at least 33 publications since 2011 and 48 requests since 2016. Many requests for NBISC biospecimen come from first-time investigators who subsequently submit grants as the port-of-entry into the field of space biology. Some NBISC biospecimens have been awarded to NASA Genelab, who then generate various ‘Open Science’ -omics data sets on their platform for bioinformatics. Other NBISC biospecimen awards have led to multiple studies such as fecal microbiome analysis, DNA damage analysis using single-cell DNA sequencing, enzymatic-pathway identification involved in spaceflight muscle atrophy, and characterization of ocular morphological changes. Of note, NBISC has expanded to include a new Space Microbial Culture Collection (SMCC) for the collection, identification, documentation, long-term preservation, and distribution of space-related microbial isolates.

Ryan T. Scott↗
NASA NTRSDate not supplied

Multi-Omics Analysis of Mouse Retina Following Low Dose Radiation and/or Hindlimb Unloading

Rodent models have been used as analogs for studying the effects of spaceflight. NASA’s GeneLab provides access to omics datasets generated from spaceflight and ground-based experiments allowing for additional retrospective analysis. We used GeneLab’s GLDS-203, a dataset generated by researchers at Loma Linda University to study the impact of prolonged unloading and/or low-dose radiation on mouse retina. The purpose of this study was to understand the effect of gamma radiation and/or hindlimb unloading on mice retinas through a multi-omics analysis. In the experiment that generated the omics data, mice were irradiated with gamma-ray and/or subjected to hindlimb unloading for 21 days and multi-omics analysis was performed at 7 days, 1 month, or 4 months post exposure. In the current study, for each of the three timepoints, we compared epigenomic profiles for retinas from exposed mice against timepoint-matched controls. We identified a total of 5,271 differentially methylated loci (DML) and 321 differentially methylated regions (DMR; using a sliding window and step size of 500 bp) with methylation difference > 10% and q-value < 0.05 (sliding linear model corrected p-value) across the nine exposure groups. Highest correlation in methylation difference was seen for significant DMLs (q-value < 0.05) across different conditions at same post exposure timepoint (Figure 1).The location of DMLs and DMRs were characterized with respect to CpG islands and shores, putative promoters, gene body, and intergenic regions (Table 1). We analyzed RNA-seq counts and performed gene set enrichment analysis using differential expression results from comparing each exposure group to its timepoint-matched control group. Significant pathways (adjusted p-value <0.05) enriched in all three microgravity-only groups were related to morphogenesis of a branching epithelium, skeletal muscle cell differentiation, and response to fibroblast growth factor. Common processes across all timepoints in the radiation-only groups were retina homeostasis, synaptic vesicle exocytosis-endocytosis, and chemotaxis. In the combination groups, regulation of trans-synaptic signaling, and Rho protein signal transduction were enriched at all three timepoints. Processes related to purine nucleotide metabolism were enriched in all nine exposure groups, with activation at 1 month, and suppression at 7 days and 4 months. A total of 14 genes contained at least one DML and were differentially expressed at adjusted p-value < 0.05, including genes implicated in cataract development (Sipa1l3, Crybb3) and those involved in cytoskeletal organization (Plec, Flnb, Eef1a1). This analysis is part of a larger effort to understand the molecular mechanisms following spaceflight exposures that can help translate effects observed in animal models to human impacts.

Prachi Kothiyal↗