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Combining RNA-SEQ Datasets from NASA GENELAB: An Evaluation of Correction Methods

Background: Conducting space biology experiments aboard the International Space Station, particularly those utilizing complex model organisms like mice, is expensive and difficult due to limited crew availability, hardware, and space. As a result, sample numbers from these studies are low, reducing the statistical power of any one experiment. Aggregating spaceflight datasets serves as a method to increase sample numbers, allowing for novel insights through bioinformatic analysis of ‘omics data from merged datasets. However, aggregating datasets can introduce unwanted variation including 1) differences in sample handling, processing, and sequencing platforms between datasets (technical variation) as well as 2) differences in experimental design between datasets. Methods: In the present study, NASA GeneLab-hosted RNAseq datasets from mouse liver tissues were used to evaluate several statistical methods to correct for this unwanted variation through two approaches, reference-based and standard. The following correction algorithms were applied with (reference-based) and/or without (standard) considering Universal Mouse RNA Reference samples: ComBat and ComBat_seq from the SVA package, the median polish, empirical Bayes, and ANOVA-based algorithms from the MBatch package, and negative binomial regression normalization in the DESeq2 package. For each approach, after the correction algorithm was applied, differential gene expression (DGE) analysis of flight and ground control samples was performed with the combined data. The robustness of each tool was evaluated using BatchQC to determine statistical differences between datasets before and after correction, Principal Component Analysis to evaluate global gene expression in samples before and after correction, and by comparing DGE analysis of individual datasets and combined datasets before and after correction. Results: The results showed that the reference-based approach introduced several additional (and likely artificial) differentially expressed genes when compared with the respective standard approach. Conclusions: Of the methods tested, standard ComBat_seq and DESeq2 were identified as the most robust correction methods for combining spaceflight mouse liver RNAseq datasets hosted on GeneLab.

Finsam Samson

INFLUENCE OF ACTN3 GENE ON MUSCLE HEALTH AND PHYSICAL FITNESS TO INFORM FUTURE INTERVENTIONS IN SPACEFLIGHT MISSIONS

INTRODUCTION: Exposure to reduced gravity environments leads to diminished muscle size, strength, and endurance. Preservation of physical fitness is critical for mission essential tasks such as extravehicular activities or adaptation to changes in gravity loads. Current countermeasures to maintain ISS astronauts’ muscle mass and fitness include dedicated time for a combination of cardiovascular exercise and resistance training. Countermeasure effectiveness is monitored through VO2 max and isometric mid-thigh pulls. It is important to understand both environmental and genetic contributors to astronaut physical fitness. Multiple genes, including ACTN3, are known to correlate with exercise phenotypes and have the potential to help personalize countermeasures based on an astronaut’s genotypic makeup. TOPIC: The ACTN3 gene encodes a protein expressed only in fast-twitch muscles and correlates with sprint and power phenotypes. A common polymorphism in ACTN3 gene is R577X (rs1815739), produced by a C−to−T base substitution resulting in a nonsense mutation from arginine (R) to a premature stop codon (X) present in approximately 18% of the population. This polymorphism causes an absence of α−actinin−3 in type II muscle fibers but does not lead to a disease phenotype. The RR genotype is associated with elite athletes, especially in sprint and power sports. The XX genotype is believed to be more common in endurance athletes. The ACTN3 gene also has potential associations with training adaptation, post-exercise recovery, and exercise-associated injuries. APPLICATION: Understanding how ACTN3 and other genetic determinates of fitness phenotypes affect astronaut physical performance can inform personalized exercise and recovery prescriptions. For example, individuals with the RR or RX genotype may respond better to high-load and low repetition exercise, while XX may benefit from high repetition with low weight exercise. Since the wild-type protein may confer more resistance to muscle damage, those individuals with the RR or RX genotype may benefit from high intensity interval training for improved VO2 max, whereas those with an XX genotype may benefit from low intensity, high volume endurance activity. Additionally, omics data related to health and performance could be used as biomarkers to monitor astronaut fitness and the effectiveness of training regimens during a mission. Learning objectives: • Learn about the phenotypic effects on muscle function and fitness secondary to R577X mutation in the ACTN3 gene • Learn how mutations in the ACTN3 gene may inform future countermeasures for future spaceflight missions

Lynn K Stanwyck

Quantifying microbial roles in environmental iron oxidation via an integrated kinetics, `omics and metabolic modeling study (Final Report)

Iron oxyhydroxides are extremely reactive components of environmental systems, and therefore exert a strong influence on biogeochemical cycles. These oxyhydroxides strongly adsorb many biologically-relevant elements, including organic carbon and phosphate, as well as a wide range of metals including uranium and actinide species. Thus, the formation mechanism of iron oxyhydroxides are key to understanding both nutrient and contaminant cycling. Microorganisms can catalyze iron oxidation and promote the formation of Fe biominerals and thus are increasingly recognized as important players in biogeochemical cycling. However, it is completely unknown how much of environmental iron oxidation is biologically mediated versus abiotic, and various challenges in studying microbial iron oxidation have hindered accurate incorporation into hydrobiogeochemical models. The overarching goal of our work was to quantify and constrain microbial iron oxidation rates and use ‘omics to gain insight into the controls on this process, while developing tools to enable integration of biotic iron oxidation into hydrobiogeochemical models. Our work focused on the Savannah River Site (SRS) in South Carolina, where extensive microbial iron oxidation has been observed. At Tims Branch, part of the Argonne National Laboratory Wetland Hydrobiogeochemistry Science Focus Area (Argonne SFA), where groundwater discharges into a stream, iron-oxidizing microbial mats form and appear to be a major sink of uranium. In the wetlands that surround Tims Branch, there are wide swaths of iron microbial mats and flocs (mobilized mat). We measured biotic and abiotic iron oxidation rates using mats and water sampled from these sites and found that iron oxidation is primarily carried out by chemolithotrophic microorganisms. The resulting rate constants can be incorporated into models. These mats were characterized by metagenomics and metatranscriptomics, which showed that aerobic chemolithotrophs were the dominant iron-oxidizing bacteria (FeOB), and these included Gallionellaceae and Leptothrix, and possibly Rhodoferax, which is known as an Fe-reducer but may also oxidize Fe(II). This demonstrated that diverse FeOB can coexist and suggests that there are a range of niches and therefore drivers of chemolithotrophic iron oxidation. Analysis of reconstructed genomes strongly suggests that a major factor in diversity is carbon source, as genomes contained varied pathways for autotrophy and heterotrophy. We performed an in-depth analysis of Leptothrix ochracea genomes, since this sheath-former is one of the primary mat builders, yet its physiology remained unresolved. A combination of genomics, transcriptomics, and metabolic modeling suggest that L. ochracea grows mixotrophically using a combination of Fe(II) and organics for energy and both inorganic and organic carbon to create biomass. This contrasts with the largely autotrophic Gallionellaceae (Gallionella, Sideroxydans, and Ferriphaselus) also present in the mats and flocs. Remarkably, multiple FeOB, both Leptothrix and Gallionellaceae, showed activity in response to Fe(II) in live mat incubations. We tracked the gene expression of individual MAGs to Fe(II) and found that various autotrophic and heterotrophic FeOB responded to Fe(II), increasing expression of both carbon fixation and organic utilization genes. The results of the integrated field, kinetics, and omics studies give detailed insight into 1) the taxa that oxidize Fe, and 2) how they connect Fe, C, and N cycles. Towards the goal of connecting omics data to hydrobiogeochemical models, we worked with the KBase team to create a template metabolic model for chemolithotrophic iron oxidation. We initially modeled the well-characterized isolate Gallionellaceae Sideroxydans lithotrophicus, and also applied the model to the mixotroph L. ochracea. In all, we have characterized diverse FeOB in a representative wetland system and solved key problems that enable better incorporation of iron-oxidizing microbes into hydrobiogeochemical models.

54 ENVIRONMENTAL SCIENCES

GeneLab for High Schools: Data Mining for the Next Generation

Modern biological sciences have become increasingly based on molecular biology and high-throughput molecular techniques, such as genomics, transcriptomics, and proteomics. NASA Scientists and the NASA Space Biology Program have aimed to examine the fundamental building blocks of life (RNA, DNA and protein) in order to understand the response of living organisms to space and aid in fundamental research discoveries on Earth. In an effort to enable NASA funded science to be available to everyone, NASA has collected the data from omics studies and curated them in a data system called GeneLab. Whilst most college-level interns, academics and other scientists have had some interaction with omics data sets and analysis tools, high school students often have not. Therefore, the Space Biology Program is implementing a new Summer Program for high-school students that aims to inspire the next generation of scientists to learn about and get involved in space research using GeneLabs Data System. The program consists of three main components core learning modules, focused on developing students knowledge on the Space Biology Program and Space Biology research, Genelab and the data system, and previous research conducted on model organisms in space; networking and team work, enabling students to interact with guest lecturers from local universities and their fellow peers, and also enabling them to visit local universities and genomics centers around the Bay area; and finally an independent learning project, whereby students will be required to form small groups, analyze a dataset on the Genelab platform, generate a hypothesis and develop a research plan to test their hypothesis. This program will not only help inspire high-school students to become involved in space-based research but will also help them develop key critical thinking and bioinformatics skills required for most college degrees and furthermore, will enable them to establish networks with their peers and connections with university Professors that may help them achieve their educational goals.

genelab

'Omics and Big Data in Harmful Algal Bloom Research

Phytoplankton, a group including eukaryotic microalgae and cyanobacteria, play a crucial climate role converting CO 2 into organic carbon through global primary production. They support a wide range of life, both freshwater and marine, from zooplankton to fish and mammals. While they are essential in nutrient cycles, certain phytoplankton species can proliferate excessively under favorable conditions, leading to harmful algal blooms (HABs) that pose significant threats to human and ecosystem health through the toxins they produce.

59 BASIC BIOLOGICAL SCIENCES

GeneLab: A Systems Biology Platform for Omics Analysis

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide the latest in terms of professional state-of-the-art bioinformatics platform for the space biology and radiation community to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare to existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all dataset. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era or on the International Space Station. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science

GeneLab: A Systems Biology Platform for Omics Analysis: Disseminate and Reuse Data, Tools, and Samples Post-Project

NASA's GeneLab includes an open-access repository of some 200 plus omics datasets generated by biological experiments relevant to spaceflight (including simulated cosmic radiation and microgravity). In order to maximize the intelligibility of these data, particularly for users with limited bioinformatics knowledge, GeneLab is now transforming the data in the repository into actual biological and physiological knowledge of the genetic and proteomic signatures found in these samples. This processed data is being derived by establishing standard data analysis workflows vetted by 114 scientists who are members of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). AWG members from institutes spanning the U.S. and four other countries participate on a voluntary basis. The AWGs meet monthly to discuss data mining, compare results and interpretations, and test forthcoming releases of the GeneLab Data Systems (GLDS). GLDS version 3.0 has been available to the general public since October 1st 2018, and has been providing a professional state-of-the-art bioinformatics platform for everyone in the space biology community to upload their data into a space biology omics data commons, to process their data with vetted standard workflows and to compare to existing analyses. The user interface for the platform is being designed to be accessible to a broad variety of users including those with limited bioinformatics experience, including high school and college students who can use it to learn about omics data analysis and space biology. As such, Genelab will constitute a powerful general public outreach capability of NASA and the Space Biology community at large. Data mining of the GeneLab database by the AWG has already started generating very interesting findings, including reports linking specific spaceflight conditions such as radiation, microgravity or carbon dioxide levels to molecular changes seen across various species. In this presentation, we will report on the current and future objectives for GeneLab, and review recent studies reported by the various AWGs relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.

Omics

NASA GeneLab Space Omics Database: Expanding from Space to Ionizing Radiation Data on the Ground

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or ground experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide a state-of-the-art bioinformatics platform for the space biology and radiation communities to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare with existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all datasets. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era on the International Space Station and on other orbiting platforms. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science

The NASA Open Science Data Repository: Biomedical Fair Data, Analysis Tools, User Communities, Publications, and Discoveries for Deep Space Missions

Increased biomedical risks and challenges associated with deep space missions require new knowledge discovery, new health countermeasures, and development of novel ecosystems, life support, crop production, and biomedical support capabilities. To meet NASA’s Moon to Mars strategic program goals for Human and Biological Sciences, findable, accessible, interoperable, reusable (FAIR), and maximally open-access data is going to be required to enable humanity to thrive in deep space. Indeed, this cornerstone perspective on FAIR and maximally open access data was also recommended in the recent 2023-2032 Decadal Survey from the National Academies of Sciences, Engineering, and Medicine. The NASA Open Science Data Repository (OSDR) is a maximally open access and FAIR database, and meets various scientific, technical, and operational spaceflight needs. It offers public users and submitters the ability to upload, download, search, share, analyze, and visualize data across ‘omics, physiological, phenotypic, behavioral, bioimaging, video, and environmental monitoring telemetry datasets. OSDR includes NASA GeneLab, NASA Ames Life Sciences Data Archive, and the NASA Biological Institutional Scientific Collection. OSDR has >455 studies with datasets from model organisms and non-NASA human astronauts. There are ~12 datasets from the Inspiration 4 (I4) mission, spanning metagenomics, comprehensive metabolic panels, clonal hematopoiesis, spatial transcriptomics, proteomics, and cytokine panels. In the interest of data privacy, two I4 datasets have raw FASTQ and FASTA files relating to the epitranscriptome, and a new request feature is live in OSDR (with a backend review process established) which was developed based on industry norms. OSDR also recently began a collaboration with the European Space Agency (ESA) to scientifically curate and make available >200 terabytes of human and model organism space-relevant data. The OSDR submission portal is designed to ingest and curate ~25 ‘omics assay data types, and ~50 physiological-phenotypic-imaging assay data types, spanning ultrasonography, micro-computed tomography, histology, morphometric photography, rebound tonometry, gait analysis, optical coherence tomography, novel object recognition, flow cytometry, and immunohistochemistry. A suite of analysis tools are available for OSDR users including: 1) an Environmental Data Application to compare radiation, CO2, relative humidity, temperature, and other telemetry across missions and subjects, 2) the RadLab database, a collaboration between NASA, ESA, the German and Italian Space Agencies, and the Bulgarian Academy of Sciences, which compiles radiation measurements relevant to human spaceflight and provides tools for accessing and manipulating the data, and 3) a Multi-study visualization tool which enables users to look across and combine GeneLab’s omics datasets across different experiments and missions. There are ~600 volunteer OSDR Analysis Working Group (AWG) members who: 1) provide feedback on scientific standards for reuse (subject and assay metadata; processing pipelines; dataset formats and uniformed structures for machine-readability), and 2) collaborate to mine-reuse OSDR data conducting scientific analysis. OSDR has enabled 60 publications as of September 2023, many directly from AWG collaborations most notably the Cell Press package in 2020. Lastly, there are at least 15 articles which mine OSDR data part of a package of ~50 articles across Nature Portfolio with research stemming from I4, the Japan Aerospace Exploration Agency, NASA Space Biology, and the NASA Human Research Program.

space biology

NASA Open Science Data Repository: Biomedical FAIR Data, Analysis Tools, User Communities, and Discoveries for Deep Space Missions

Increased biomedical risks and challenges associated with deep space missions require new knowledge discovery, new health countermeasures, and development of novel ecosystems, life support, crop production, and biomedical support capabilities. To meet NASA’s Moon to Mars strategic program goals for Human and Biological Sciences, findable, accessible, interoperable, reusable (FAIR), and maximally open-access data is going to be required to enable humanity to thrive in deep space. Indeed, this cornerstone perspective on FAIR and maximally open access data was also recommended in the recent 2023-2032 Decadal Survey from the National Academies of Sciences, Engineering, and Medicine. The NASA Open Science Data Repository (OSDR) is a maximally open access and FAIR database, and meets various scientific, technical, and operational spaceflight needs. It offers public users and submitters the ability to upload, download, search, share, analyze, and visualize data across ‘omics, physiological, phenotypic, behavioral, bioimaging, video, and environmental monitoring telemetry datasets. OSDR includes NASA GeneLab, NASA Ames Life Sciences Data Archive, and the NASA Biological Institutional Scientific Collection. OSDR has >455 studies with datasets from model organisms and non-NASA human astronauts. There are ~12 datasets from the Inspiration 4 (I4) mission, spanning metagenomics, comprehensive metabolic panels, clonal hematopoiesis, spatial transcriptomics, proteomics, and cytokine panels. In the interest of data privacy, two I4 datasets have raw FASTQ and FASTA files relating to the epitranscriptome, and a new request feature is live in OSDR (with a backend review process established) which was developed based on industry norms. OSDR also recently began a collaboration with the European Space Agency (ESA) to scientifically curate and make available >200 terabytes of human and model organism space-relevant data. The OSDR submission portal is designed to ingest and curate ~25 ‘omics assay data types, and ~50 physiological-phenotypic-imaging assay data types, spanning ultrasonography, micro-computed tomography, histology, morphometric photography, rebound tonometry, gait analysis, optical coherence tomography, novel object recognition, flow cytometry, and immunohistochemistry. A suite of analysis tools are available for OSDR users including: 1) an Environmental Data Application to compare radiation, CO2, relative humidity, temperature, and other telemetry across missions and subjects, 2) the RadLab database, a collaboration between NASA, ESA, the German and Italian Space Agencies, and the Bulgarian Academy of Sciences, which compiles radiation measurements relevant to human spaceflight and provides tools for accessing and manipulating the data, and 3) a Multi-study visualization tool which enables users to look across and combine GeneLab’s omics datasets across different experiments and missions. There are ~600 volunteer OSDR Analysis Working Group (AWG) members who: 1) provide feedback on scientific standards for reuse (subject and assay metadata; processing pipelines; dataset formats and uniformed structures for machine-readability), and 2) collaborate to mine-reuse OSDR data conducting scientific analysis. OSDR has enabled 60 publications as of September 2023, many directly from AWG collaborations most notably the Cell Press package in 2020. Lastly, there are at least 15 articles which mine OSDR data part of a package of ~50 articles across Nature Portfolio with research stemming from I4, the Japan Aerospace Exploration Agency, NASA Space Biology, and the NASA Human Research Program.

open access

Evaluation of normalization strategies for mass spectrometry-based multi-omics datasets

Introduction Data normalization is crucial for multi-omics integration, reducing systematic errors and maximizing the likelihood of discovering true biological variation. Most studies assess normalization for a single omics type or use datasets from separate experiments. Few address time-course data, where normalization might bias temporal differentiation. In this study, we compared common normalization methods and a machine learning approach, Systematical Error Removal using Random Forest (SERRF), using multi-omics datasets generated from the same experiment—even from the same cell lysate. Objectives To develop a straightforward process to assess normalization effects and identify the most robust methods across multi-omics datasets. Methods We analyzed metabolomics, lipidomics, and proteomics datasets from primary human cardiomyocytes and motor neurons exposed to acetylcholine-active compounds over time. Normalization effectiveness was evaluated based on improvement in QC features consistency and observing the change in treatment and time-related variance. Results Probabilistic Quotient Normalization (PQN) and Locally Estimated Scatterplot Smoothing (LOESS) QC were identified as optimal for metabolomics and lipidomics, while PQN, Median, and LOESS normalization excelled for proteomics. These methods consistently enhanced QC feature consistency in metabolomics and lipidomics, and preserved time-related variance or treatment-related variance in proteomics, demonstrating their effectiveness and robustness. SERRF normalization, applied only to metabolomics in this study, outperformed other methods in some datasets but inadvertently masked treatment-related variance in others. Conclusion Our evaluation identified PQN and LoessQC as the top methods for metabolomics and lipidomics, and PQN, Median, and Loess normalization for proteomics, in multi-omics integration in a temporal study.

60 APPLIED LIFE SCIENCES

GeneLab for High Schools – Bioinformatic Training For Students And Educators

Modern biological sciences are increasingly based on high-throughput molecular techniques, including genomics, transcriptomics, and proteomics. NASA’s GeneLab program has collected extensive data from ‘omics’ studies, curated them into an accessible platform and provided data analysis/visualization tools to facilitate the generation of new hypotheses and research directions. GeneLab for High Schools (GL4HS), launched in 2017, has endeavored to utilize this database and provide tools for students to understand and analyze omics datasets whilst also learning about spaceflight research. The GL4HS program ran in person at Ames from 2017-2019 and has run virtually since 2020. Each year fifteen high school students are trained to analyze and interpret GeneLab transcriptomic data. Additionally, in the last several years we have expanded our “teacher training program” to include 10 teachers total in an effort to enable this program to be utilized in classrooms across the USA. Teachers also join the NASA GeneLab Education Working Group (EWG) enabling support as they implement custom GL4HS modules into their classrooms. The GL4HS program consists of three main components – (1) core learning modules, (2) networking and teamwork, and (3) an independent learning project. Students are also taught critical networking and science communication skills facilitating their ability to ‘sell their science’ in innovative and creative ways. This program has enabled students to learn about biology in space and to have a glimpse into the world of research for the first time. Many of the students in this program shared that the course was transformative to their perception about biological sciences and how it linked to other areas of STEM. The ultimate and long-term goal of GL4HS is to expand the program to multiple locations thereby facilitating the reach of NASA Space Biology beyond NASA-centric regions.

GeneLab

NASA GeneLab Platform Utilized for Space Radiation Dosimetry Biological Response Compared to Radiation Ground Studies

Ionizing radiation from Galactic Cosmic Rays (GCR) is one of the major risk factors factor that will impact health of astronauts on extended missions outside the protective effects of the Earth's magnetic field. Currently there are gaps in our knowledge of the health risks associated with chronic low dose, low dose rate ionizing radiation, specifically ions associated with high (H) atomic number (Z) and energy (E). The NASA GeneLab project (genelab.nasa.gov) aims to provide a detailed library of Omics datasets associated with biological samples exposed to HZE. The GeneLab Data System (GLDS) includes datasets from both spaceflight and ground-based studies, a majority of which involved exposure to ionizing radiation. Recently GeneLab has also assessed radiation dosimetry data with omics datasets associated with samples flown to the International Space Station (ISS). The combination of the detailed information on radiation exposure for ground-based studies and curated dosimetry information for spaceflight experiments allows GeneLab to be the first comprehensive Omics database for space related research from which an investigator can generate hypotheses to direct future experiments utilizing both ground and space biological radiation data. We demonstrate the usefulness of these datasets by analyzing multiple GeneLab datasets associated with both radiation ground-based studies and spaceflight studies. The radiation ground based studies we analyzed includes both in vivo and in vitro work with a range ions from protons to iron particles with doses from 0.1Gy to 2Gy. These datasets were compared to both in vivo and in vitro datasets from samples flown to the ISS and on shorter shuttle missions with total doses of 0.1 mGy to 30 mGys. From this analysis we were able to associate distinct biological signatures associating specific ions to specific biological response to radiation exposure in space. For example, we discovered radiation biological response related to cardiovascular effects from proton ground studies are the dominating response for samples related to cardiovascular effects on the ISS. With this work we will provide a summary of how different ions will impact different biological response in space and how this can be used in future studies to assess optimal ground experiments to simulate space radiation.

Beheshti, Afshin

The NASA Open Science Data Repository: Biomedical Data, Analysis Tools, and Informatic Collaborations

Increased biomedical risks and challenges associated with deep space missions require knowledge discovery, health countermeasures, and biomedical support capabilities. Maximally open-access and reusable data is needed by developers, scientists, and engineers to develop these systems. The NASA Open Science Data Repository (OSDR) is a maximally open access and FAIR database (ie., findable, accessible, interoperable, and reusable), and meets various scientific, technical, and operational needs. It offers users and submitters the ability to upload, download, search, share, analyze, cite, and visualize data across ‘omics, physiological, phenotypic, payload, hardware, behavioral, bioimaging, video, and environmental monitoring telemetry datasets. OSDR is an expanded database, based upon the successes of NASA GeneLab. OSDR has >460 studies with datasets covering model organisms to non-NASA human astronauts. There are ~12 datasets from the Inspiration 4 (I4) mission, spanning metagenomics, comprehensive metabolic panels, clonal hematopoiesis, spatial transcriptomics, proteomics, and cytokine panels. In the interest of data privacy, two I4 datasets with raw files relating to the epitranscriptome, and a new request feature is live in OSDR (with a backend review process established) developed from industry norms. OSDR is collecting and curating biomedical human data from a new sub-orbital research flight and is open to more space life science/biomedical submissions from the international and commercial sectors. OSDR also recently began a collaboration with the European Space Agency (ESA) to collect and curate >200 terabytes of human and model organism data. The OSDR submission portal is designed to ingest and curate ~25 ‘omics and ~50 physiological-phenotypic-imaging assay data types. Tools available for OSDR users include: 1) an Environmental Data Application to compare radiation, CO2, relative humidity, temperature, and other telemetry across missions and subjects, 2) the RadLab database, a collaboration between NASA, ESA, the German and Italian Space Agencies, and the Bulgarian Academy of Sciences, and 3) a Multi-study visualization tool which enables users to look across and combine ‘omics datasets. There are ~600 volunteer OSDR Analysis Working Group (AWG) members providing feedback on scientific data/metadata standards and collaborating to mine-reuse OSDR in research. OSDR/GeneLab has enabled ~60 publications reusing data as of October 2023.

space biology

Biological Research and Space Health Enabled by Machine Learning to Support Deep Space Missions

A key science goal of the NASA “Moon to Mars” campaign is to understand how biology responds to the Lunar, Martian, and deep space environments in order to advance fundamental knowledge and support human space missions. Through artificial intelligence (AI) and machine learning (ML), a paradigm shift has begun in space biosciences and engineered astronaut health systems, to enable Earth-independence and mission operations autonomy. We describe current AI/ML methods to support 1) fundamental biology, 2) in situ analytics, 3) high performance computing, 4) automated science, 5) self-driving labs, 6) remote data management, 7) integrated mission biomonitoring, and 8) a Precision Space Health system. AI/ML approaches that can be integrated to support these domains include active learning, explainable AI, adaptive learning, causal inference, knowledge graphs, federated learning, transfer learning, and large language models. Finally, we present results from several current ML projects that are underway in the space biology field to address key challenges of small sample n, high feature count, heterogeneity, and sparse data. These include 1) connecting omics to phenotypic data using an ensemble model to infer causality of rodent liver health disruption, 2) usage of explainable ML to interrogate muscular underpinnings of muscle atrophy, 3) ML models analyzing and determining directed acyclic graphs of human health risk leveraging rodent bone datasets, 4) usage of large pre-trained models connecting biomedical knowledgebases with small spaceflight datasets to understand gene-to-gene interactions, and 5) a suite of benchmarked open science datasets enabling programmers to identify best algorithms to answer space biology questions.

space biology

FAIR Assessments

Presentation on Findable Accessible Interoperable and Reusable (FAIR) Assessment approaches for data.

FAIR