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Open Science for Life in Space: Data Sharing and Tools for Knowledge Discovery

The fast-growing array of space biological data, which in the past was simply archived after minimal analysis, holds great potential if it can be reorganized and formatted for Open Science. Organizing the data for such analysis is a challenge because of its diverse nature (molecular, cellular, tissue, whole organism, behavior; tabular, imagery). Open Science is the concept that the more people have access to scientifically curated data, the more knowledge will be gained. This led NASA to start the development of GeneLab in 2015. GeneLab houses spaceflight and space-analog multi-omics datasets from plant, rodent, small animal, and microbial experiments. The success and knowledge gained from GeneLab led to a new alliance of NASA “Open Science Data Repositories” (OSDR), which include the Ames Life Sciences Data Archive (ALSDA) and the NASA Biological Institutional Scientific Collection (NBISC). Both are adopting the GeneLab data system, so data are more findable, accessible, interoperable, and reusable (FAIR). OSDR systems provide users the ability to upload, download, search, share, analyze, and visualize. Open Science also needs strong confidence in the data, which is gained through building science communities. With ~400 current members, GeneLab and ALSDA formed Analysis Working Groups (AWGs) to provide feedback on processing pipelines, metadata curation standards (for ‘omics and phenotypic-physiological-behavioral assays), and to collaborate in effectively reusing data. The AWG also led to the development of the Radiation Biology Ontology (RBO), ensuring radiation metadata are efficiently captured, connected, and interoperable. Feedback from the AWG provided design input toward the new single point-of-entry data submission portal for all investigators to submit, curate, and share their research data. Space biological data is now maximally open access, collected-curated with rich metadata, and formatted for interoperability to enable systems biology, meta-analysis, knowledge graphs, machine learning, modeling, and other reuse approaches. With potential for further federation of OSDR for data mining with traditional biological and medical databases (NIH, NCI, EBI, etc.), a new era for space biology has begun to support the knowledge discovery necessary for Lunar and Martian missions.

Ryan T Scott↗

Omics Research on the International Space Station

The International Space Station (ISS) is an orbiting laboratory whose goals include advancing science and technology research. Completion of ISS assembly ushered a new era focused on utilization, encompassing multiple disciplines such as Biology and Biotechnology, Physical Sciences, Technology Development and Demonstration, Human Research, Earth and Space Sciences, and Educational Activities. The research complement planned for upcoming ISS Expeditions 45&46 includes several investigations in the new field of omics, which aims to collectively characterize sets of biomolecules (e.g., genomic, epigenomic, transcriptomic, proteomic, and metabolomic products) that translate into organismic structure and function. For example, Multi‐Omics is a JAXA investigation that analyzes human microbial metabolic cross‐talk in the space ecosystem by evaluating data from immune dysregulation biomarkers, metabolic profiles, and microbiota composition. The NASA OsteoOmics investigation studies gravitational regulation of osteoblast genomics and metabolism. Tissue Regeneration uses pan‐omics approaches with cells cultured in bioreactors to characterize factors involved in mammalian bone tissue regeneration in microgravity. Rodent Research‐3 includes an experiment that implements pan‐omics to evaluate therapeutically significant molecular circuits, markers, and biomaterials associated with microgravity wound healing and tissue regeneration in bone defective rodents. The JAXA Mouse Epigenetics investigation examines molecular alterations in organ specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight. Lastly, Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), NASA's first foray into human omics research, applies integrated analyses to assess biomolecular responses to physical, physiological, and environmental stressors associated with spaceflight.

Love, John↗

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↗

Identification of Health Events in Astronaut Missions Using Longitudinal Molecular Signature Detection

Individualized health monitoring can now incorporate a precision medicine approach, profiling multiple molecular and physiological measures of health (generalized omics) longitudinally to enable the timely diagnosis and treatment of disease. Such measurements can include blood chemistries, gene expression data, metabolite measurements, and digital device data. We will present our work on extending such an approach to monitoring individual astronaut health for deep space missions. We have developed and implemented novel algorithms to monitor and detect physiolgical state departures from individualized healthy astronaut baselines , utilizing and biologically annotating generalized omics. Our new methods can detect baseline deviations across omics corresponding to potentially adverse medical events. Events pointing to changes in individual health are then compared across individuals to identify common responses and detect changes affecting multiple crewmembers. We show the utility of our methods in detecting temporal health changes across subjects using retrospective Earth and astronaut mission data (metabolite and immune marker data across multiple missions), in order for this technique t o be applicable for future missions.

G I Mias↗

Spaceflight Biospecimen and Data Sharing in Support of Science Discovery and Exploration

For decades, NASA and international partners have conducted biological experiments in space to understand effects of spaceflight and address potential hazards. To enable spaceflight back to the Moon, and then to Mars and beyond, it is imperative to further understand basic science and health risks associated with spaceflight, along with developing countermeasures. The sending of experiments and organisms into space is a costly endeavor. To maximize scientific return, sharing with the scientific community both space-flown biospecimens and data from completed experiments is essential. New fundamental, applied, and bioinformatic science insights can be gained from specimen and data sharing efforts. Data reuse enables spaceflight health risk modeling, analyzing adverse outcomes across spaceflight hazards, and deep space autonomous support for the flight medical officer. Space-flown biospecimens not required by mission Principal Investigators are regularly archived and made available for scientific request. The largest biorepository of these samples are found within NASA’s Institutional Scientific Collection at Ames Research Center (ISC-ARC), which stores over 32,000 specimens mostly from Shuttle and International Space Station (ISS) missions, but also some ground-based analog samples. The Ames Life Sciences Data Archive manages the ISC-ARC. Tissues are predominantly from mice and rats, though samples are also available from bacteria and quail. Only a handful of other similar collections exist worldwide. Rodent biospecimens exposed to simulated space radiation at Brookhaven National Laboratory are archived under the purview of NASA HRP Space Radiation Element. Microbial collection and analyses from 20 years of routine environmental monitoring of air, surfaces, and water systems of the ISS were performed to ensure a safe environment for astronauts. Samples from the ISC-ARC, space radiation and microbial collections are searchable and requestable through the NASA Life Sciences Data Archive (LSDA). Decades of planetary protection microbial isolates derived from spacecraft bioburden are archived in JPL’s microbial collection. Rodent biospecimens from spaceflight investigations conducted by the Japan Aerospace Exploration Agency (JAXA) are archived and available at the JAXA Biorepository at Tsukuba Space Center. The Russian Institute of Biomedical Problems also has a collection of animal, microbial, cellular, and fungi available for research from ground analog experiments. Several data repositories exist for scientists to utilize. The LSDA is the primary NASA source of life sciences research data and information. It contains decades of spaceflight and ground-analog research involving human, microbial, cellular, plant, and animal subjects. Data is collected from NASA-funded investigations through the Human Research Program and the Space Biology Program. The NASA Lifetime Surveillance of Astronaut Health collects and grants access to clinical and occupational health monitoring data from astronauts, with a list and description of data collected available for request through the LSDA. NASA GeneLab at ARC collects genomic, transcriptomic, proteomic, and metabolomic data from any species. It is a repository and platform for collaborative open-science bioinformatic approaches. JAXA is establishing an ‘omics-based repository in collaboration with the Tohoku Medical Megabank (ToMMo), called the JAXA-ToMMo Integrated Biobank for Space Life Science. Overall, the sharing of these biospecimen and data resources can assist researchers worldwide in understanding spaceflight effects on biology, along with enabling next generation data science applications for space exploration platforms. Websites: https://lsda.jsc.nasa.gov/ ; https://www.nasa.gov/ames/research/space-biosciences/isc-bsp ; https://www.nasa.gov/ames/research/space-biosciences/alsda

Ryan T. Scott↗

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗

Open Science for Life in Space: Data Sharing and Tools for Knowledge Discovery

The next era in human space exploration is rapidly approaching. The use of health countermeasures and biomonitoring systems for space missions are required to counteract space health hazards and to support life to thrive in deep space (e.g., humans, animals, plants, crops; entire ecosystems within spacecrafts/habitats/spacesuits). The development of these mission components will be highly dependent on our understanding of basic biological and health responses to myriad space hazards (ionizing radiation, altered gravitational fields, altered day-night cycles, confined isolation, hostile-closed environments, distance-duration from Earth, planetary dust-regolith, and extreme temperatures/atmospheres). The fast-growing array of space biological and mission telemetry data, which in the past was simply archived after minimal analysis, holds great potential once applied to these mission challenges if it can be reorganized and formatted for Open Science. Organizing the data for such analysis is a challenge because of its multi-hierarchical, multi-modal, and heterogenous nature (molecular, cellular, tissue, organ, whole organism, behavior, ecosystem, microbiome; tabular, omics, imaging, video, biospecimen, environmental physical-chemical telemetry). This session focuses on current approaches in this domain such as: making space biological data FAIR (findable, accessible, interoperable, reusable), effective data ingestion/dissemination, observational versus experimental data, Open Science collaborations, data analysis techniques, AI/ML/knowledge graph/modeling methods, and data integration/discovery tools.

open science↗

Conclusions of a Mini Technical Interchange Meeting on New Cross Risk Integration Projects Managed by the NASA Space Radiation Element

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease, and central nervous system decrements. Recently, the SRE was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross-Risk Integration Projects (CRIP). CRIP serves 3 broad purposes: - Services: Generate samples and data and manage the receipt, inventory, archive, and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities—includes NASA Omics Archive project and various human and animal sample repositories. - Method Development: Identify and evaluate new-to-NASA research or analysis methods or techniques that could fundamentally improve existing or planned research efforts—includes the Translational Radiation Research and Countermeasures Project. - Enabling Capabilities: Demonstrate real-world application by adapting, adopting, and/or developing capabilities to benefit crew health and performance and improve risk mitigation—includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion of results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here, a summary of the studies presented at the SRE-sponsored mini-TIM at the HRP IWS along with the goals and objectives of the CRIP projects is communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work, some of which are funded under CRIP by the Space Radiation Element.

Janapriya Saha↗

The Radiation Biology Ontology: A New Tool Supporting FAIR Principles Across Radiation Biology Facilitating Data Discovery and Integration

Development of the Radiation Biology Ontology (RBO) was motivated by the need for a comprehensive, well-structured ontology for encoding radiation biology metadata. The primary use-cases were archiving data in the STORE database (https://www.storedb.org/), the repository for the RadoNorm Project, and in GeneLab (https://genelab.nasa.gov), NASA’s ‘omics database. The scope of radiobiology research ranges from physics to radiation oncology to socio-legal studies; no existing ontology has the necessary breadth or depth. In addition, a formal ontology has the advantage of being usable for machine learning and, importantly, for tasks like data integration, knowledge extraction from the scientific literature and for query extension and data classification. Standardisation of metadata is one of the primary objectives of the FAIR principles for open data; RBO is an important landmark for FAIR radiation biology data.

ontology↗

GeneLab: NASA's Open Access, Collaborative Platform for Systems Biology and Space Medicine

NASA is investing in GeneLab1 (http:genelab.nasa.gov), a multi-year effort to maximize utilization of the limited resources to conduct biological and medical research in space, principally aboard the International Space Station (ISS). High-throughput genomic, transcriptomic, proteomic or other omics analyses from experiments conducted on the ISS will be stored in the GeneLab Data Systems (GLDS), an open-science information system that will also include a biocomputation platform with collaborative science capabilities, to enable the discovery and validation of molecular networks.

Berrios, Daniel C.↗

GeneLab: NASA's Open Access, Collaborative Platform for Systems Biology and Space Medicine

NASA is investing in GeneLab1 (http:genelab.nasa.gov), a multi-year effort to maximize utilization of the limited resources to conduct biological and medical research in space, principally aboard the International Space Station (ISS). High-throughput genomic, transcriptomic, proteomic or other omics analyses from experiments conducted on the ISS will be stored in the GeneLab Data Systems (GLDS), an open-science information system that will also include a biocomputation platform with collaborative science capabilities, to enable the discovery and validation of molecular networks.

Berrios, Daniel C.↗

Temporal RNA Integrity Analysis of Archived Spaceflight Biological Samples from ALSDA from 1991 to 2016

The purpose of this study is to assess the quality of spaceflight tissues stored in Ames Life Science Data Archive (ALSDA) freezers. Garnering information for downstream functional analysis such as generation of omics datasets from tissues is, in part, dependent on the state of sample preservation. To assess the viability of a select group of tissues, RNA integrity number (RIN) values were calculated for RNA extracted from rodent livers. Rat livers from Spacelab Life Sciences 1 (SLS-1) and mouse livers from Commercial Biomedical Test Module 3 (CBTM-3), Rodent Research 1 (RR1), and Rodent Research 3 (RR3) were tested. It was found that mean RIN values from CBTM3, RR1, and RR3 were suitable for downstream functional analysis (RIN greater than 5) while the mean RIN value for SLS-1 was not (RIN equal to 2.5 plus or minus 0.1). Information from this study could lay the foundation for future efforts in determining the types of assays that are most appropriate for different tissues in ALSDA freezers, which would maximize the scientific return on rare spaceflight samples.

ALSDA↗

MULTI-OMICS STUDY OF THE EFFECT OF REDOX-ACTIVE METALLOPORPHYRIN ON MURINE RETINA DURING SPACEFLIGHT

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗

Multi-Omics Study of the Effect of Redox-Active Metalloporphyrin on Murine Retina During Spaceflight

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗

Expanding Repository Data Available For Sharing and Knowledge Discovery

Some of the hardest space biology and space health challenges require data-intensive, bioinformatic, meta-analytical, and computer-assisted research approaches. These challenges include examining interdisciplinary space life science research across experiments and across interacting spaceflight hazards (radiation, altered gravity, confinement, hostile-closed environments, distance-duration from Earth). The approaches to confront these challenges involve mining multiple datasets simultaneously from various hierarchical organizations of biological complexity, all while concurrently evaluating how experimental design factors affect endpoints of standard assays. To enable this field, it is essential that principal investigators (PIs) submit data in a structure so it can be maximally re-used. The purpose of the NASA Ames Life Sciences Data Archive (ALSDA) is to collect, curate, and make publicly available all non-human space-relevant biological data. ALSDA must also ensure data are open-access, and maximally findable, accessible, interoperable, and reusable (FAIR). The scope of ALSDA data collected and submitted by PIs include subject and study design metadata, assay metadata parameters, raw and processed assay data, assay imagery/video, and subject-experienced mission data telemetry (radiation, temperature, humidity, acoustics, vibrations, etc.). ALSDA recently integrated into a collaborative group of Open Science projects to facilitate a suite of new tools and workflows that will improve data submission, accessibility, and reusability by implementing digital data submission agreements, and adopting the data management system originally developed by NASA GeneLab. ALSDA intends to bring current biological repository data and all future collected data into this new scientific data reuse reality. This new suite of tools will enable ALSDA to deploy a science curation system using scientific assay configurations for the data submission portal. It will capture essential assay parameters according to established standards 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. Data submissions can be brought into cutting-edge informatic analysis portals to enable mining of physiological, behavioral, biochemical, and imaging datasets in conjunction with ‘omics-level datasets. As ALSDA datasets are submitted, curated, and published (e.g., micro-computed tomography, histology, pulse oximetry, serum metabolites, magnetic resonance imaging, intraocular pressure, novel object recognition, etc.), the merging together of spaceflight data along this multi-hierarchical complexity of biology will enable informatics and data-intensive approaches resulting in knowledge discoveries across missions, space hazards, and biological disciplines.

Biology↗

Expanding Repository Data Available For Sharing And Knowledge Discovery

Some of the hardest space biology and space health challenges require data-intensive, bioinformatic, meta-analytical, and computer-assisted research approaches. These challenges include examining interdisciplinary space life science research across experiments and across interacting spaceflight hazards (radiation, altered gravity, confinement, hostile-closed environments, distance-duration from Earth). The approaches to confront these challenges involve mining multiple datasets simultaneously from various hierarchical organizations of biological complexity, all while concurrently evaluating how experimental design factors affect endpoints of standard assays. To enable this field, it is essential that principal investigators (PIs) submit data in a structure so it can be maximally re-used. The purpose of the NASA Ames Life Sciences Data Archive (ALSDA) is to collect, curate, and make publicly available all non-human space-relevant biological data. ALSDA must also ensure data are open-access, and maximally findable, accessible, interoperable, and reusable (FAIR). The scope of ALSDA data collected and submitted by PIs include subject and study design metadata, assay metadata parameters, raw and processed assay data, assay imagery/video, and subject-experienced mission data telemetry (radiation, temperature, humidity, acoustics, vibrations, etc.). ALSDA recently integrated into a collaborative group of Open Science projects to facilitate a suite of new tools and workflows that will improve data submission, accessibility, and reusability by implementing digital data submission agreements, and adopting the data management system originally developed by NASA GeneLab. ALSDA intends to bring current biological repository data and all future collected data into this new scientific data reuse reality. This new suite of tools will enable ALSDA to deploy a science curation system using scientific assay configurations for the data submission portal. It will capture essential assay parameters according to established standards 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. Data submissions can be brought into cutting-edge informatic analysis portals to enable mining of physiological, behavioral, biochemical, and imaging datasets in conjunction with ‘omics-level datasets. As ALSDA datasets are submitted, curated, and published (e.g., micro-computed tomography, histology, pulse oximetry, serum metabolites, magnetic resonance imaging, intraocular pressure, novel object recognition, etc.), the merging together of spaceflight data along this multi-hierarchical complexity of biology will enable informatics and data-intensive approaches resulting in knowledge discoveries across missions, space hazards, and biological disciplines.

life science↗

Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy capability will allow for optical sectioning of biological tissues to determine microanatomical localization of biomarkers. Furthermore, NASA's geneLAB effort addresses integration of genomic, epigenomic, transcriptomic, proteomic and metabolomic datasets, by applying an innovative open source science platform for multi-investigator high throughput utilization of the ISS. In sum, the expanding ISS capability for analysis of biomolecules is enabling innovative research in a broad spectrum of areas such as cellular and molecular biology, biotechnology, tissue engineering, biomedicine, and Omics, providing manifold benefits for humanity.

Guinart-Ramirez, Y.↗

Evaluating the Efficacy of Conditional Variational Autoencoders in Generating Synthetic Single Nuclei RNA-Seq Data for Space Biology Research

Astronauts are subject to unique stressors during spaceflight, leading to changes in their cellular function. However, neither astronauts nor model organisms respond the same to spaceflight, and research implicates a contribution of omics components in differential responses. Understanding how gene expression affects astronaut health is critical for the success of long-term space missions, prompting interest in developing personalized predictive models leveraging artificial intelligence (AI) and machine learning (ML) techniques. Developing such models requires extensive data, which is challenging to obtain and share. This study explores the use of conditional variational autoencoders (CVAEs) to synthetically generate single-nuclei RNA-seq (snRNA-seq) data. CVAEs build on standard variational autoencoders (VAEs) by conditioning data generation on covariates like sample identity and mission parameters, enhancing the relevance of generated data for specific contexts. For our work, we built two CVAEs with varying degrees of sparsity to optimize both interpretability and generative power. We train and validate models on existing snRNA-seq data collected from the brain tissue of mice subjected to spaceflight conditions and their ground control counterparts. We evaluate model performance using statistical tests and visualizations to compare synthetic data to real data. We aim to demonstrate that these prototype CVAE architectures could be used in future space biology work and that this is a method worth further exploring.

Sarah Golts↗