Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “DNA sequencing”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4

Beyond Nanopore Sequencing in Space: Identifying the Unknown

Astronaut Kate Rubins sequenced DNA on the International Space Station (ISS) for the first time in August 2016 (Figure 1A). A 2D sequencing library containing an equal mixture of lambda bacteriophage, Escherichia coli, and Mus musculus was prepared on the ground with a SQK_MAP006 kit and sent to the ISS frozen and loaded into R7.3 flow cells. After a total of 9 on-orbit sequencing runs over 6 months, it was determined that there was no decrease in sequencing performance on-orbit compared to ground controls (1). A total of ~280,000 and ~130,000 reads generated on-orbit and on the ground, respectively, identified 90% of reads that were attributed to 30% lambda bacteriophage, 30% Escherichia coli, and 30% M. musculus (Figure 1B). Extensive bioinformatics analysis determined comparable 2D and 1D read accuracies between flight and ground runs (Figure 1C), and data collected from the ISS were able to construct directed assemblies of E.coli and lambda genomes at 100% and M. musculus mitochondrial genome at 96.7%. These findings validate sequencing as a viable option for potential on-orbit applications such as environmental microbial monitoring and disease diagnosis. Current microbial monitoring of the ISS applies culture-based techniques that provide colony forming unit (CFU) data for air, water, and surface samples. The identity of the cultured microorganisms in unknown until sample return and ground-based analysis, a process that can take up to 60 days. For sequencing to benefit ISS applications, spaceflight-compatible sample preparation techniques are required. Subsequent to the testing of the MinION on-orbit, a sample-to-sequence method was developed using miniPCR™ and basic pipetting, which was only recently proven to be effective in microgravity. The work presented here details the in- flight sample preparation process and the first application of DNA sequencing on the ISS to identify unknown ISS-derived microorganisms.

Stahl, Sarah E.↗

Fine-scale evaluation of two standard 16S rRNA gene amplicon primer pairs for analysis of total prokaryotes and archaeal nitrifiers in differently managed soils

The advance of high-throughput molecular biology tools allows in-depth profiling of microbial communities in soils, which possess a high diversity of prokaryotic microorganisms. Amplicon-based sequencing of 16S rRNA genes is the most common approach to studying the richness and composition of soil prokaryotes. To reliably detect different taxonomic lineages of microorganisms in a single soil sample, an adequate pipeline including DNA isolation, primer selection, PCR amplification, library preparation, DNA sequencing, and bioinformatic post-processing is required. Besides DNA sequencing quality and depth, the selection of PCR primers and PCR amplification reactions arguably have the largest influence on the results. This study tested the performance and potential bias of two primer pairs, i.e., 515F (Parada)-806R (Apprill) and 515F (Parada)-926R (Quince) in the standard pipelines of 16S rRNA gene Illumina amplicon sequencing protocol developed by the Earth Microbiome Project (EMP), against shotgun metagenome-based 16S rRNA gene reads. The evaluation was conducted using five differently managed soils. We observed a higher richness of soil total prokaryotes by using reverse primer 806R compared to 926R, contradicting to in silico evaluation results. Both primer pairs revealed various degrees of taxon-specific bias compared to metagenome-derived 16S rRNA gene reads. Nonetheless, we found consistent patterns of microbial community variation associated with different land uses, irrespective of primers used. Total microbial communities, as well as ammonia oxidizing archaea (AOA), the predominant ammonia oxidizers in these soils, shifted along with increased soil pH due to agricultural management. In the unmanaged low pH plot abundance of AOA was dominated by the acid-tolerant NS-Gamma clade, whereas limed agricultural plots were dominated by neutral-alkaliphilic NS-Delta/NS-Alpha clades. This study stresses how primer selection influences community composition and highlights the importance of primer selection for comparative and integrative studies, and that conclusions must be drawn with caution if data from different sequencing pipelines are to be compared.

16S rRNA gene amplicon Illumina sequencing↗

Epigenetic Control of Drought Response in Sorghum (EPICON)

Genetic manipulation of crops to increase the presence of desirable traits has been critical to increasing agricultural productivity. These changes have primarily involved modification of the plant’s DNA sequence. However, there is increasing evidence that environmental responses are also mediated by epigenetics, which involves heritable changes without changes in DNA sequence. Epigenetic changes have been shown to play a major role in regulating plant responses to drought, an increasing problem worldwide due to climate change. In general, exposure of plants to water limitation triggers epigenetic changes, which include remodeling of chromatin, the network of DNA, RNA and various proteins making up chromosomes, and related changes in regulatory mechanisms. EPICON’s efforts focus on unraveling the role epigenetic signals play in acclimation to and recovery from drought through effects on individual transcription factors or transcriptional networks that direct entire metabolic pathways. To achieve this goal we will follow responses to water deprivation in sorghum, a widely cultivated cereal with recognized drought tolerance. In EPICON’s field trials, sorghum will be grown under controlled irrigation conditions. Leaf and root samples will be taken to perform molecular phenotyping to track changes in epigenetic, transcriptomic, metabolomic and proteomic footprints. Analysis of this data will provide a better understanding of the epigenetic processes related to drought tolerance, leading to our ultimate goal of identifying transcriptional regulators and pathways controlling drought resistance. The identified genetic targets and their regulatory pathways will be used in future efforts to improve growth of sorghum and other crops in the field and in marginal lands under water-limiting conditions.

59 BASIC BIOLOGICAL SCIENCES↗

Genomad v1.0

Genomad aims to identify mobile genetic elements (namely, viruses and plasmids) from DNA sequence data. It uses a combination of marker gene identification and machine learning models to find likely virus/plasmid candidates in environmental DNA sequencing data. It has an improved classification performance over similar tools.

Camargo, Antonio↗

Biological Information Signal Processor

Biological Information Signal Processor (BISP) is computing system analyzing data on deoxyribonucleic acid (DNA) sequences for molecular genetic analysis. Includes coprocessors, specialized microprocessors complementing present and future computers by performing rapidly most-time-consuming DNA-sequence-analyzing functions, establishing relationships (alignments) between both global sequences and defining patterns in multiple sequences. Also includes state-of-art software and data-base systems on both conventional and parallel computer systems to augment analytical abilities of developmental coprocessors.

Chow, Edward T.↗

Sequencing to Station in 12 Months (Targeting Orbital 5 Launch, March 30th)

The Biomolecule Sequencer is a Commercial Off-The-Shelf device developed by Oxford Nanopore Technologies and implements a method of DNA sequencing unlike any other current sequencers. The device measures changes in electrical current through a nanopore depending on the sequence of the DNA strand that is passing through it. Since the technology is built on nanometer-scale ion pores, the hardware itself is exceptionally small (3 x 1 x 58 inches), lightweight (less than 120 grams with USB cable), and powered only by a USB connection. The sequencing device is permanent, while the flow cells, to which the samples are added, are periodically replaced. The goal of our upcoming technology demonstration on ISS is to provide evidence that DNA sequencing in space is possible, which holds the exciting potential to enable the identification of microorganisms, monitor changes in microbes and humans in response to spaceflight, and possibly aid in the detection of DNA-based life elsewhere in the universe.

microorganisms↗

ISS External Microorganisms: Collecting Planetary Protection Samples During Extravehicular Activity

Introduction: We have designed1, built, and tested a sampling kit (Fig. 1) to aseptically collect microbiological samples from exterior surfaces on the ISS (International Space Station). The kit was flown to ISS as part of the NG-19 commercial cargo mission in August of 2023. Astronauts will use the kit to collect samples from six exterior surfaces on ISS. These samples will be frozen at -80°C after collection and returned to the ground for next generation DNA sequencing. The results of this experiment will help inform planetary protection requirements for crewed missions. We hypothesize that there are detectable microbial communities outside ISS and that these communities originate from inside ISS. Current life support systems do not include any components for reducing microbial leakage. Gases are vented from inside ISS without filtration and there are currently no protocols in place to minimize bioburden on space suit exteriors prior to use. It is important to quantify the bioburden on current vehicles so that achievable limits can be set for crewed missions to astrobiologically relevant locations like Mars. Figure 1: The sampling kit contains eight swab canisters in total (six on the top and two on the bottom). A resuable end effector (1) is used to remove and reinstall the swabs. The kit also contains a handrail (2), tether loop (3), and, bayonet probes(4) to allow easy manipulation during EVA. Methods: We have designed a kit to carry 8 commercially available foam swabs into and out of vacuum without compromising the swabs’ sterility. The specially designed swab canisters contain a 0.2 µm Teflon filter that allows the canister to accommodate pressure changes without introducing unwanted contaminants. The kit meets existing EVA (Extravehicular Activity) safety requirements and has been used by human test subjects in the neutral buoyance lab and at vacuum in test chambers at the Johnson Space Center. In the early part of 2024, astronauts will use this sampling kit to swab six surfaces on the exterior of ISS. We will collect samples from: the airlock vestibule, the interior surface of the airlock thermal cover, an exterior handrail, a vent connected to the CO2 removal system, and a vent connected to the payload vacuum system inside ISS. Approximately 300 cm2 will be swabbed at each location. A seventh swab will be exposed to the vacuum of space without touching any surfaces as a blank. The eighth swab will remain sealed as a process control. After the EVA the swab kit will be frozen at -80°C and returned to earth at the earliest possible opportunity. The samples will remain frozen until they are thawed for next generation DNA sequencing on earth. We will use amplicon sequencing to identify any bacteria, archaea or fungi present in the samples. If there is enough DNA present, we will use shotgun metagenomic sequencing to further characterize the microbial ecology outside ISS. Preliminary Results: Results from ground-based testing demonstrate that the swab kit is capable of cycling in and out of vacuum without contaminating the swabs. Test subjects, wearing flight-like EVA gloves could remove swabs from the canister and sample discrete locations without inadvertently touching any other surfaces. Several types of bacteria and fungi were collected during these ground tests and survived up to 6 hours at vacuum. This includes non-spore forming bacterial like Staphyloccus capitis that are not traditionally considered extremophiles. Shotgun metagenomic sequencing of the ground-test samples revealed bacteria associated with human skin and airways on the exterior of space suits used during these tests 2 In addition to these results we will present preliminary results from our space-flight samples. We will also present lessons learned from attempting to collect microbiological samples during an EVA and describe how our results will affect planetary protection requirements for future crewed missions.

Aaron B. Regberg↗

ISS External Microorganisms: Collecting Planetary Protection Samples During Extravehicular Activity

Introduction: We have designed1, built, and tested a sampling kit (Fig. 1) to aseptically collect microbiological samples from exterior surfaces on the ISS (International Space Station). The kit was flown to ISS as part of the NG-19 commercial cargo mission in August of 2023. Astronauts will use the kit to collect samples from six exterior surfaces on ISS. These samples will be frozen at -80°C after collection and returned to the ground for next generation DNA sequencing. The results of this experiment will help inform planetary protection requirements for crewed missions. We hypothesize that there are detectable microbial communities outside ISS and that these communities originate from inside ISS. Current life support systems do not include any components for reducing microbial leakage. Gases are vented from inside ISS without filtration and there are currently no protocols in place to minimize bioburden on space suit exteriors prior to use. It is important to quantify the bioburden on current vehicles so that achievable limits can be set for crewed missions to astrobiologically relevant locations like Mars. Figure 1: The sampling kit contains eight swab canisters in total (six on the top and two on the bottom). A resuable end effector (1) is used to remove and reinstall the swabs. The kit also contains a handrail (2), tether loop (3), and, bayonet probes(4) to allow easy manipulation during EVA. Methods: We have designed a kit to carry 8 commercially available foam swabs into and out of vacuum without compromising the swabs’ sterility. The specially designed swab canisters contain a 0.2 µm Teflon filter that allows the canister to accommodate pressure changes without introducing unwanted contaminants. The kit meets existing EVA (Extravehicular Activity) safety requirements and has been used by human test subjects in the neutral buoyance lab and at vacuum in test chambers at the Johnson Space Center. In the early part of 2024, astronauts will use this sampling kit to swab six surfaces on the exterior of ISS. We will collect samples from: the airlock vestibule, the interior surface of the airlock thermal cover, an exterior handrail, a vent connected to the CO2 removal system, and a vent connected to the payload vacuum system inside ISS. Approximately 300 cm2 will be swabbed at each location. A seventh swab will be exposed to the vacuum of space without touching any surfaces as a blank. The eighth swab will remain sealed as a process control. After the EVA the swab kit will be frozen at -80°C and returned to earth at the earliest possible opportunity. The samples will remain frozen until they are thawed for next generation DNA sequencing on earth. We will use amplicon sequencing to identify any bacteria, archaea or fungi present in the samples. If there is enough DNA present, we will use shotgun metagenomic sequencing to further characterize the microbial ecology outside ISS. Preliminary Results: Results from ground-based testing demonstrate that the swab kit is capable of cycling in and out of vacuum without contaminating the swabs. Test subjects, wearing flight-like EVA gloves could remove swabs from the canister and sample discrete locations without inadvertently touching any other surfaces. Several types of bacteria and fungi were collected during these ground tests and survived up to 6 hours at vacuum. This includes non-spore forming bacterial like Staphyloccus capitis that are not traditionally considered extremophiles. Shotgun metagenomic sequencing of the ground-test samples revealed bacteria associated with human skin and airways on the exterior of space suits used during these tests 2 In addition to these results we will present preliminary results from our space-flight samples. We will also present lessons learned from attempting to collect microbiological samples during an EVA and describe how our results will affect planetary protection requirements for future crewed missions.

Aaron B. Regberg↗

Remote sensing of cytotype and its consequences for canopy damage in quaking aspen

Abstract Mapping geographic mosaics of genetic variation and their consequences via genotype x environment interactions at large extents and high resolution has been limited by the scalability of DNA sequencing. Here, we address this challenge for cytotype (chromosome copy number) variation in quaking aspen, a drought‐impacted foundation tree species. We integrate airborne imaging spectroscopy data with ground‐based DNA sequencing data and canopy damage data in 391 km 2 of southwestern Colorado. We show that (1) aspen cover and cytotype can be remotely sensed at 1 m spatial resolution, (2) the geographic mosaic of cytotypes is heterogeneous and interdigitated, (3) triploids have higher leaf nitrogen, canopy water content, and carbon isotope shifts (δ 13 C) than diploids, and (4) canopy damage varies among cytotypes and depends on interactions with topography, canopy height, and trait variables. Triploids are at higher risk in hotter and drier conditions.

Blonder, Benjamin↗

Performance of methods for SARS-CoV-2 variant detection and abundance estimation within mixed population samples

The accurate identification of SARS-CoV-2 (SC2) variants and estimation of their abundance in mixed population samples (e.g., air or wastewater) is imperative for successful surveillance of community level trends. Assessing the performance of SC2 variant composition estimators (VCEs) should improve our confidence in public health decision making. Here, we introduce a linear regression based VCE and compare its performance to four other VCEs: two re-purposed DNA sequence read classifiers (Kallisto and Kraken2), a maximum-likelihood based method (Lineage deComposition for Sars-Cov-2 pooled samples (LCS)), and a regression based method (Freyja). We simulated DNA sequence datasets of known variant composition from both Illumina and Oxford Nanopore Technologies (ONT) platforms and assessed the performance of each VCE. We also evaluated VCEs performance using publicly available empirical wastewater samples collected for SC2 surveillance efforts. Bioinformatic analyses were performed with a custom NextFlow workflow (C-WAP, CFSAN Wastewater Analysis Pipeline). Relative root mean squared error (RRMSE) was used as a measure of performance with respect to the known abundance and concordance correlation coefficient (CCC) was used to measure agreement between pairs of estimators. Based on our results from simulated data, Kallisto was the most accurate estimator as it had the lowest RRMSE, followed by Freyja. Kallisto and Freyja had the most similar predictions, reflected by the highest CCC metrics. We also found that accuracy was platform and amplicon panel dependent. For example, the accuracy of Freyja was significantly higher with Illumina data compared to ONT data; performance of Kallisto was best with ARTICv4. However, when analyzing empirical data there was poor agreement among methods and variations in the number of variants detected (e.g., Freyja ARTICv4 had a mean of 2.2 variants while Kallisto ARTICv4 had a mean of 10.1 variants). This work provides an understanding of the differences in performance of a number of VCEs and how accurate they are in capturing the relative abundance of SC2 variants within a mixed sample (e.g., wastewater). Such information should help officials gauge the confidence they can have in such data for informing public health decisions.

60 APPLIED LIFE SCIENCES↗

Shedding Light on Microbial Dark Matter with A Universal Language of Life

The majority of microbial genomes have yet to be cultured, and most proteins predicted from microbial genomes or sequenced from the environment cannot be functionally annotated. As a result, current computational approaches to describe microbial systems rely on incomplete reference databases that cannot adequately capture the full functional diversity of the microbial tree of life, limiting our ability to model high-level features of biological sequences. The scientific community needs a means to capture the functionally and evolutionarily relevant features underlying biology, independent of our incomplete reference databases. Such a model can form the basis for transfer learning tasks, enabling downstream applications in environmental microbiology, medicine, and bioengineering. Here we present LookingGlass, a deep learning model capturing a “universal language of life”. LookingGlass encodes contextually-aware, functionally and evolutionarily relevant representations of short DNA reads, distinguishing reads of disparate function, homology, and environmental origin. We demonstrate the ability of LookingGlass to be fine-tuned to perform a range of diverse tasks: to identify novel oxidoreductases, to predict enzyme optimal temperature, and to recognize the reading frames of DNA sequence fragments. LookingGlass is the first contextually-aware, general purpose pre-trained “biological language” representation model for short-read DNA sequences. LookingGlass enables functionally relevant representations of otherwise unknown and unannotated sequences, shedding light on the microbial dark matter that dominates life on Earth.

A Hoarfrost↗

Nanopore Activity Assays for Detection of Biomarker Protease Activity: Design and Testing of Substrates for Both Nanopore Sequencing and PCR-Based Detection Methods

The work performed in this project has demonstrated the ability to construct proteolytic enzyme substrates that are PCR and sequencing-readable reporter molecules. Specifically, the goal was to detect those reporter molecules via PCR and Oxford Nanopore Technologies MinION sequencing methods following exposure to the biomarker protease thrombin. The assay development focused on binding the constructed peptide-oligonucleotide chimera to immobilized streptavidin. The action of thrombin on the peptide portion of the molecule released the oligonucleotide for detection. Detection of protease activity was demonstrated in a concentration-dependent manner using MALDI-MS, RT-PCR and DNA sequencing. Additional steps to remove background release of reporter molecules during the assay was used to improve the difference in detected oligonucleotide reporter following protease activity. Additional steps in assay development will be to (1) test the assay in an appropriate matrix, (2) investigate detection using additional DNA sequencing platforms and (3) demonstrate multiplexed detection of multiple protease markers in a single reaction.

59 BASIC BIOLOGICAL SCIENCES↗

cWINNOWER Algorithm for Finding Fuzzy DNA Motifs

The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if multiple mutated copies of the motif (i.e., the signals) are present in the DNA sequence in sufficient abundance. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum number of detectable motifs qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc, by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12000 for (l,d) = (15,4).

Liang, Shoudan↗

Molecular evidence for a terrestrial origin of snakes

Biologists have debated the origin of snakes since the nineteenth century. One hypothesis suggests that snakes are most closely related to terrestrial lizards, and reduced their limbs on land. An alternative hypothesis proposes that snakes are most closely related to Cretaceous marine lizards, such as mosasaurs, and reduced their limbs in water. A presumed close relationship between living monitor lizards, believed to be close relatives of the extinct mosasaurs, and snakes has bolstered the marine origin hypothesis. Here, we show that DNA sequence evidence does not support a close relationship between snakes and monitor lizards, and thus supports a terrestrial origin of snakes.

Environment↗

cWINNOWER algorithm for finding fuzzy dna motifs

The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if a clique consisting of a sufficiently large number of mutated copies of the motif (i.e., the signals) is present in the DNA sequence. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum detectable clique size qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12,000 for (l, d) = (15, 4). Copyright Imperial College Press.

Evaluation Studies↗

Fractals in biology and medicine

Our purpose is to describe some recent progress in applying fractal concepts to systems of relevance to biology and medicine. We review several biological systems characterized by fractal geometry, with a particular focus on the long-range power-law correlations found recently in DNA sequences containing noncoding material. Furthermore, we discuss the finding that the exponent alpha quantifying these long-range correlations ("fractal complexity") is smaller for coding than for noncoding sequences. We also discuss the application of fractal scaling analysis to the dynamics of heartbeat regulation, and report the recent finding that the normal heart is characterized by long-range "anticorrelations" which are absent in the diseased heart.

Review↗

Microbial monitoring of spacecraft and associated environments

Rapid microbial monitoring technologies are invaluable in assessing contamination of spacecraft and associated environments. Universal and widespread elements of microbial structure and chemistry are logical targets for assessing microbial burden. Several biomarkers such as ATP, LPS, and DNA (ribosomal or spore-specific), were targeted to quantify either total bioburden or specific types of microbial contamination. The findings of these assays were compared with conventional, culture-dependent methods. This review evaluates the applicability and efficacy of some of these methods in monitoring the microbial burden of spacecraft and associated environments. Samples were collected from the surfaces of spacecraft, from surfaces of assembly facilities, and from drinking water reservoirs aboard the International Space Station (ISS). Culture-dependent techniques found species of Bacillus to be dominant on these surfaces. In contrast, rapid, culture-independent techniques revealed the presence of many Gram-positive and Gram-negative microorganisms, as well as actinomycetes and fungi. These included both cultivable and noncultivable microbes, findings further confirmed by DNA-based microbial detection techniques. Although the ISS drinking water was devoid of cultivable microbes, molecular-based techniques retrieved DNA sequences of numerous opportunistic pathogens. Each of the methods tested in this study has its advantages, and by coupling two or more of these techniques even more reliable information as to microbial burden is rapidly obtained. Copyright 2004 Springer-Verlag.

Environmental Monitoring/methods↗