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At least 109 records · Page 6

Creating Benchmark Data for Artificial Intelligence and Machine Learning Space Biology Research

To identify an appropriate AI/ML approach for a specific problem, the best practice is to measure algorithm performance through the benchmarking process. A scientific benchmark consists of an AI-ready dataset and a reference implementation on a specific scientific question. The NASA Science Mission Directorate (SMD) has started the “Benchmark Initiative for AI/ML to create scientific benchmark datasets in three applications: 1) scientific benchmarking, which finds the best algorithm for a specific problem; 2) application benchmarking, which measures algorithm performance against a set of parameters; and 3) system benchmarking, which evaluates performance of hardware and software architecture. Currently, there are no standardized datasets available to benchmark AI/ML algorithms in the domain of space biology. In this work, we constructed two AI/ML-ready biological datasets from experiments in space-flown mice: cellular imaging and RNA-seq. First, radiation-exposed immune cells harbor DNA damage foci that can be fluorescently marked to visualize the amount of damage following exposure to ionizing radiation. However, such large datasets are difficult to analyze visually, due to imaging inconsistencies and human bias, and classical image processing approaches can fail on imaging artifacts. AI/ML are therefore exciting alternative, providing the speed of machines and the accuracy of humans. We have made this dataset available at https://registry.opendata.aws/bps_microscopy/. Second, high-throughput nucleic acid sequencing (DNA-seq, RNA-seq) has become widespread in biomedical research due to the growing availability and affordability of these assays. However, most sequencing datasets suffer from high dimensionality and low sample count. In this work, we used a generative adversarial network to synthesize a standardized, AI-ready, publicly available benchmark dataset for space biology RNA-seq data with sufficient space-flown and ground control mouse liver samples from NASA GeneLab. This dataset is available at https://registry.opendata.aws/bps_rnaseq/. These datasets are now fully open the Space Biology community to test their favorite AI/ML approaches.

James Casaletto↗

Experiment requirements: Vitamin D metabolites and bone demineralization, Spacelab 2, experiment no. 1

As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned.

Schnoes, H. K.↗

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

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

Amanda M Saravia-Butler↗

Instrument detects bacterial life forms

Instrument assays enzymatic bioluminescent reaction that occurs when adenosine triphosphate /ATP/ combines with lucifrase and luciferin. Module assembly minimizes need for hardware associated with reaction fluid and waste transfer. System is applicable in marine biology and aerospace and medical fields.

Plakas, C.↗

Open Science for Plants in Space: Improvements in NASA's Open Science Data Repository

Upcoming deep space missions will rely on plants for crew and ecosystem health. Open access space biology data enables scientists to examine the biological responses of plants to ionizing radiation, altered gravity, elevated CO2, and many other abiotic stressors. NASA has declared 2023 as the ‘Year of Open Science’ and created a 5-year Transform to Open Science (TOPS) initiative designed to rapidly transform the agency toward an inclusive culture of open science. NASA’s Open Science Data Repository (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. Current OSDR standards include the ISA (Investigation-Study-Assay) experiment model, assay metadata configurations, and standardized terminology and ontologies. In 2024 OSDR will include a new suite of features for improved FAIR compliance including downloadable plant metadata templates, data submission tools and overall improved AI-readiness of plant datasets. AI/ML methods can be helpful tools to overcome the inherent challenges of space biology research (small sample size, sparse and heterogeneous data etc.). However these methods are built on an assumption of normalized and well-curated data. OSDR’s new curation tools will improve users ability to leverage ML and AI methods to model space biology data and better understand the complex effects of spaceflight on living systems across hierarchical biological levels. We look forward to sharing our advances with the spaceflight community.

FAIR↗

Monoclonal antibodies directed against surface molecules of multicell spheroids

The objective of this project is to generate a library of monoclonal antibodies (MAb's) to surface molecules involved in the cell-cell interactions of mammalian cells grown as multicell spheroids (MCS). MCS are highly organized 3-dimensional multicellular structures which exhibit many characteristics in vivo tissues not found in conventional monolayer or suspension culture. They also provide a functional assay for surface adhesion molecules. In brief, MCS combine the relevance of organized tissues with the accuracy of in vitro methodology. Further, one can manipulate these MCS experimentally to discern important information about their biology.

Martinez, Andrew O.↗

An assay for intermolecular exchange of alpha crystallin

An affinity column of alpha crystallin linked to cyanogen bromide-activated Sepharose was developed to study the exchange of alpha subunits. Alpha crystallin bound to the Sepharose-alpha complex was dissociated with 8 mol/l urea, followed by quantitation using high-performance reverse-phase liquid chromatography. The time course of binding at 37 degrees C showed a hyperbolic binding pattern reaching equilibrium between 6-18 hr. Under these conditions, binding of beta and gamma crystallins to the same matrix was less than 10% of the alpha values, as was binding of alpha to glycine-coupled Sepharose. This assay was used to demonstrate changes in the subunit exchange of alpha crystallins present in high molecular weight versus lower molecular weight aggregates of the human lens. These results show that this binding procedure was a specific reproducible assay that might be used to study intermolecular interactions of the alpha crystallins.

NASA Discipline Cell Biology↗

Bayesian Framework For Bioburden Density Calculations To Perform Planetary Protection Probabilistic Risk Assessment

The planetary protection discipline aims to minimize the microbial contamination on spacecraft to prevent the inadvertent contamination of other planetary bodies, known as forward planetary protection (PP). Planetary protection probabilistic risk assessment (PRA) relies on two core methodologies-the contamination probability event tree analysis and statistical parameter estimation. Planetary protection engineers combine several techniques to estimate the bioburden present on spacecraft components. A direct assay to enumerate CFU (colony forming units) is the preferred methodology, but given a similar processing environment the bioburden present on certain components is inferred using: (1) a NASA defined bioburden estimate based upon the biological cleanliness of the manufacturing/assembly environment or (2) sampled data from a similar spacecraft component. The paper presents an empirical Bayesian framework to systematically treat bioburden estimation and its uncertainties on different levels starting with measurement procedures to combining different components to subsystems and whole spacecraft. It is shown that the Bayesian approach can effectively handle estimations and their uncertainties at different levels and produce a reliable estimate for bioburden to be used to evaluate the probability of contamination.

Seuylemezian, Arman↗

NASA GeneLab Multi-study Visualization Portal

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

space biology↗

Radiation-induced bystander effect and adaptive response in mammalian cells

Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Discipline Radiation Health↗

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

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

GeneLab↗

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

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

Microgravity↗

Automated life-detection experiments for the Viking mission to Mars

As part of the Viking mission to Mars in 1975, an automated set of instruments is being built to test for the presence of metabolizing organisms on that planet. Three separate modules are combined in this instrument so that samples of the Martian surface can be subjected to a broad array of experimental conditions so as to measure biological activity. The first, the Pyrolytic Release Module, will expose surface samples to a mixture of C-14O and C-14O2 in the presence of Martian atmosphere and a light source that simulates the Martian visible spectrum. The assay system is designed to determine the extent of assimilation of CO or CO2 into organic compounds. The Gas Exchange Module will incubate surface samples in a humidified CO2 atmosphere. At specified times, portions of the incubation atmosphere will be analyzed by gas chromatography to detect the release or uptake of CO2 and several additional gases. The Label Release Module will incubate surface samples with a dilute aqueous solution of simple radioactive organic substrates in Martian atmosphere, and the gas phase will be monitored continuously for the release of labeled CO2.

Klein, H. P.↗

A quantitative assay for intercellular aggregation

In an earlier communication (Munn et al., J Immunol. Methods 166: 11-25, 1993), we presented the initial development of a quantitative assay for monitoring the rates of cellular aggregation based on digital image processing and video microscopy. This study describes some important enhancements and modifications to the procedure. A new index is introduced to characterize the three-dimensional morphology of the aggregates. This index is based on temporal changes in the projected area of the cells and cell aggregates during the course of the experiment. By drawing an analogy with the kinetic theory of gases, we have also introduced a procedure to normalize for variations in cell seeding density among different experiments. In addition, the image analysis technique has been improved by introducing a background subtraction algorithm to remove illumination defects and an adaptive segmentation procedure. These improvements allowed us to completely automate the image analysis procedure, thus minimizing user intervention and improving the reproducibility of the measurements. The enhanced visual assay is evaluated using some recent results from our studies on homotypic lymphocyte aggregation.

Non-NASA Center↗

Field Analysis of Microbial Contamination Using Three Molecular Methods in Parallel

Advanced technologies with the capability of detecting microbial contamination remain an integral tool for the next stage of space agency proposed exploration missions. To maintain a clean, operational spacecraft environment with minimal potential for forward contamination, such technology is a necessity, particularly, the ability to analyze samples near the point of collection and in real-time both for conducting biological scientific experiments and for performing routine monitoring operations. Multiple molecular methods for detecting microbial contamination are available, but many are either too large or not validated for use on spacecraft. Two methods, the adenosine- triphosphate (ATP) and Limulus Amebocyte Lysate (LAL) assays have been approved by the NASA Planetary Protection Office for the assessment of microbial contamination on spacecraft surfaces. We present the first parallel field analysis of microbial contamination pre- and post-cleaning using these two methods as well as universal primer-based polymerase chain reaction (PCR).

Morris, H.↗

Investigating Biological Responses to Deep Space Radiation for Missions Beyond Low Earth Orbit (LEO) using Yeast

To enable long-term spaceflight missions and establish habitation on the Moon and Mars, we require a comprehensive understanding of the effects of chronic deep space radiation exposure on humans. BioSentinel is NASA’s first biological CubeSat to venture beyond Low Earth Orbit (LEO). It utilizes Saccharomyces cerevisiae (budding yeast) as a model organism to study biological responses to deep space radiation. Yeast share significant genetic homology with humans, including basic cellular metabolism and DNA repair mechanisms. In addition, unlike human cell cultures, yeast can survive the duration and constraints of a deep space mission. BioSentinel measures biological responses using an optical system and alamarBlue oxidation-reduction (redox) dye. Two strains of yeast are studied - a wild-type and a rad51 mutant strain that is deficient in DNA repair. Changes in metabolism and growth are monitored throughout the nominal 6-month mission. Preliminary tests indicate a significant change in the alamarBlue response to low-dose ionizing radiation (IR). Additionally, rad51 cells have shown an IR dose-dependent decrease in glucose uptake and accumulation of oxidized NADH (NAD+). These biomolecules are involved in reactions responsible for basic cell processes, including growth and development, signaling, and respiration. The current study expanded upon previous data by exposing yeast to deep space-relevant radiation. Glucose and NADH/NAD+ assays were conducted on yeast subjected to varying dosages of high-energy Fe-56 and simulated galactic cosmic rays (GCRs). The resulting data was analyzed using Excel and GraphPad Prism. A particular focus was to identify biomolecules resulting from aerobic respiration, which requires the presence of oxygen, or anaerobic processes. As long-term spaceflight missions draw near, it is increasingly important to characterize biological processes affected by the conditions of deep space. Studying biomolecular damage caused by deep space radiation may enable the development of engineering controls or biomedical therapeutics that mitigate health complications for future astronauts.

Kyra Keenan↗

Organic Biomarker-Based Assays to Evaluate Total Bioburden and Organic Compounds on Space Flight Hardware

Meeting planetary protection (PP) requirements for space flight hardware may involve bioburden reduction by dry heat microbial reduction (DHMR). The NASA standard assay to demonstrate the reduction of organisms involves the swabbing of surfaces, heat shock of the extracted samples, plating of the samples on Trypticase Soy Agar (TSA), and counting colony forming units after an incubation period. The standard assay uses enumeration of heat tolerant spore-formers as a proxy for total bioburden and is generally expected to provide a lower limit. We suggest that a better estimate of the total bioburden could be obtained through sampling and analysis of organic biomarkers. As biological organisms are fundamentally organic in chemistry (i.e. carbon containing materials) it is important to characterize the biomarker compounds that are released from organisms that 1) exist on flight hardware before microbial reduction and 2) left behind from the killed organisms following microbial reduction.

Locke, Darren R.↗

A Comprehensive Assessment of Biologicals Contained Within Commercial Airliner Cabin Air

Both culture-based and culture-independent, biomarker-targeted microbial enumeration and identification technologies were employed to estimate total microbial and viral burden and diversity within the cabin air of commercial airliners. Samples from each of twenty flights spanning three commercial carriers were collected via air-impingement. When the total viable microbial population was estimated by assaying relative concentrations of the universal energy carrier ATP, values ranged from below detection limits (BDL) to 4.1 x 106 cells/cubic m of air. The total viable microbial population was extremely low in both of Airline A (approximately 10% samples) and C (approximately 18% samples) compared to the samples collected aboard flights on Airline A and B (approximately 70% samples). When samples were collected as a function of time over the course of flights, a gradual accumulation of microbes was observed from the time of passenger boarding through mid-flight, followed by a sharp decline in microbial abundance and viability from the initiation of descent through landing. It is concluded in this study that only 10% of the viable microbes of the cabin air were cultivable and suggested a need to employ state-of-the art molecular assay that measures both cultivable and viable-but-non-cultivable microbes. Among the cultivable bacteria, colonies of Acinetobacter sp. were by far the most profuse in Phase I, and Gram-positive bacteria of the genera Staphylococcus and Bacillus were the most abundant during Phase II. The isolation of the human pathogens Acinetobacter johnsonii, A. calcoaceticus, Janibacter melonis, Microbacterium trichotecenolyticum, Massilia timonae, Staphylococcus saprophyticus, Corynebacterium lipophiloflavum is concerning, as these bacteria can cause meningitis, septicemia, and a handful of sometimes fatal diseases and infections. Molecular microbial community analyses exhibited presence of the alpha-, beta-, gamma-, and delta- proteobacteria, as well as Gram-positive bacteria, Fusobacteria, Cyanobacteria, Deinococci, Bacterioidetes, Spirochetes, and Planctomyces in varying abundance. Neisseria meningitidis rDNA sequences were retrieved in great abundance from Airline A followed by Streptococcus oralis/mitis sequences. Pseudomonas synxantha sequences dominated Airline B clone libraries, followed by those of N. meningitidis and S. oralis/mitis. In Phase II, Airline C, sequences representative of more than 113 species, enveloping 12 classes of bacteria, were retrieved. Proteobacterial sequences were retrieved in greatest frequency (58% of all clone sequences), followed in short order by those stemming from Gram-positives bacteria (31% of all clone sequences). As for overall phylogenetic breadth, Gram-positive and alpha-proteobacteria seem to have a higher affinity for international flights, whereas beta-and gamma-proteobacteria are far more common about domestic cabin air parcels in Airline C samples. Ultimately, the majority of microbial species circulating throughout the cabin airs of commercial airliners are commensal, infrequently pathogenic normal flora of the human nasopharynx and respiratory system. Many of these microbes likely originate from the oral and nasal cavities, and lungs of passengers and flight crew and are disseminated unknowingly via routine conversation, coughing, sneezing, and stochastic passing of fomites. The data documented in this study will be useful to generate a baseline microbial population database and can be utilized to develop biosensor instrumentation for monitoring microbial quality of cabin or urban air.

microbial diversity↗