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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.

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At least 739 records · Page 41
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Genome-wide functional screens enable the prediction of high activity CRISPR-Cas9 and -Cas12a guides in Yarrowia lipolytica

Abstract Genome-wide functional genetic screens have been successful in discovering genotype-phenotype relationships and in engineering new phenotypes. While broadly applied in mammalian cell lines and in E. coli , use in non-conventional microorganisms has been limited, in part, due to the inability to accurately design high activity CRISPR guides in such species. Here, we develop an experimental-computational approach to sgRNA design that is specific to an organism of choice, in this case the oleaginous yeast Yarrowia lipolytica . A negative selection screen in the absence of non-homologous end-joining, the dominant DNA repair mechanism, was used to generate single guide RNA (sgRNA) activity profiles for both SpCas9 and LbCas12a. This genome-wide data served as input to a deep learning algorithm, DeepGuide, that is able to accurately predict guide activity. DeepGuide uses unsupervised learning to obtain a compressed representation of the genome, followed by supervised learning to map sgRNA sequence, genomic context, and epigenetic features with guide activity. Experimental validation, both genome-wide and with a subset of selected genes, confirms DeepGuide’s ability to accurately predict high activity sgRNAs. DeepGuide provides an organism specific predictor of CRISPR guide activity that with retraining could be applied to other fungal species, prokaryotes, and other non-conventional organisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Major proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world’s most economically damaging agricultural diseases. Despite P. pachyrhizi’s impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Adaptive gene loss in the common bean pan-genome during range expansion and domestication

The common bean ( Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Seagrass genomes reveal ancient polyploidy and adaptations to the marine environment

Here, we present chromosome-level genome assemblies from representative species of three independently evolved seagrass lineages: Posidonia oceanica, Cymodocea nodosa, Thalassia testudinum and Zostera marina. We also include a draft genome of Potamogeton acutifolius, belonging to a freshwater sister lineage to Zosteraceae. All seagrass species share an ancient whole-genome triplication, while additional whole-genome duplications were uncovered for C. nodosa, Z. marina and P. acutifolius. Comparative analysis of selected gene families suggests that the transition from submerged-freshwater to submerged-marine environments mainly involved fine-tuning of multiple processes (such as osmoregulation, salinity, light capture, carbon acquisition and temperature) that all had to happen in parallel, probably explaining why adaptation to a marine lifestyle has been exceedingly rare. Major gene losses related to stomata, volatiles, defence and lignification are probably a consequence of the return to the sea rather than the cause of it. These new genomes will accelerate functional studies and solutions, as continuing losses of the savannahs of the sea are of major concern in times of climate change and loss of biodiversity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Leveraging single-cell genomics to expand the fungal tree of life

Environmental DNA surveys reveal that most fungal diversity represents uncultured species. We sequenced the genomes of eight uncultured species across the fungal tree of life using a new single-cell genomics pipeline. We show that, despite a large variation in genome and gene space recovery from each single amplified genome (SAG), ≥90% can be recovered by combining multiple SAGs. SAGs provide robust placement for early-diverging lineages and infer a diploid ancestor of fungi. Early-diverging fungi share metabolic deficiencies and show unique gene expansions correlated with parasitism and unculturability. Single-cell genomics holds great promise in exploring fungal diversity, life cycles and metabolic potential.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Genomic variation in 3,010 diverse accessions of Asian cultivated rice

Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence–absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

CheckV assesses the quality and completeness of metagenome-assembled viral genomes

Abstract Millions of new viral sequences have been identified from metagenomes, but the quality and completeness of these sequences vary considerably. Here we present CheckV, an automated pipeline for identifying closed viral genomes, estimating the completeness of genome fragments and removing flanking host regions from integrated proviruses. CheckV estimates completeness by comparing sequences with a large database of complete viral genomes, including 76,262 identified from a systematic search of publicly available metagenomes, metatranscriptomes and metaviromes. After validation on mock datasets and comparison to existing methods, we applied CheckV to large and diverse collections of metagenome-assembled viral sequences, including IMG/VR and the Global Ocean Virome. This revealed 44,652 high-quality viral genomes (that is, >90% complete), although the vast majority of sequences were small fragments, which highlights the challenge of assembling viral genomes from short-read metagenomes. Additionally, we found that removal of host contamination substantially improved the accurate identification of auxiliary metabolic genes and interpretation of viral-encoded functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A unified catalog of 204,938 reference genomes from the human gut microbiome

Comprehensive, high-quality reference genomes are required for functional characterization and taxonomic assignment of the human gut microbiota. We present the Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the number of gut proteins in comparison to those present in the Integrated Gene Catalog. More than 70% of the UHGG species lack cultured representatives, and 40% of the UHGP lack functional annotations. Intraspecies genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which are specific to individual human populations. The UHGG and UHGP collections will enable studies linking genotypes to phenotypes in the human gut microbiome.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Genomic features of bacterial adaptation to plants

Plants intimately associate with diverse bacteria. Plant-associated bacteria have ostensibly evolved genes that enable them to adapt to plant environments. However, the identities of such genes are mostly unknown, and their functions are poorly characterized. In this study, we sequenced 484 genomes of bacterial isolates from roots of Brassicaceae, poplar, and maize. We then compared 3,837 bacterial genomes to identify thousands of plant-associated gene clusters. Genomes of plant-associated bacteria encode more carbohydrate metabolism functions and fewer mobile elements than related non-plant-associated genomes do. We experimentally validated candidates from two sets of plant-associated genes: one involved in plant colonization, and the other serving in microbe–microbe competition between plant-associated bacteria. We also identified 64 plant-associated protein domains that potentially mimic plant domains; some are shared with plant-associated fungi and oomycetes. In conclusion, this work expands the genome-based understanding of plant–microbe interactions and provides potential leads for efficient and sustainable agriculture through microbiome engineering.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Genome-based classification of micromonosporae with a focus on their biotechnological and ecological potential

There is a need to clarify relationships within the actinobacterial genus Micromonospora, the type genus of the family Micromonosporaceae, given its biotechnological and ecological importance. Here, draft genomes of 40 Micromonospora type strains and two non-type strains are made available through the Genomic Encyclopedia of Bacteria and Archaea project and used to generate a phylogenomic tree which showed they could be assigned to well supported phyletic lines that were not evident in corresponding trees based on single and concatenated sequences of conserved genes. DNA G+C ratios derived from genome sequences showed that corresponding data from species descriptions were imprecise. Emended descriptions include precise base composition data and approximate genome sizes of the type strains. antiSMASH analyses of the draft genomes show that micromonosporae have a previously unrealised potential to synthesize novel specialized metabolites. Close to one thousand biosynthetic gene clusters were detected, including NRPS, PKS, terpenes and siderophores clusters that were discontinuously distributed thereby opening up the prospect of prioritising gifted strains for natural product discovery. The distribution of key stress related genes provide an insight into how micromonosporae adapt to key environmental variables. Genes associated with plant interactions highlight the potential use of micromonosporae in agriculture and biotechnology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Metabotyping as a Stopover in Genome-to-Phenome Mapping

Predicting phenotypic expression from genomic and environmental information is arguably the greatest challenge in today’s biology. Being able to survey genomic content, e.g., as singlenucleotide polymorphism data, within a diverse population and predict the phenotypes of external traits, represents the holy grail across genome-informed disciplines, from personal medicine and nutrition to plant breeding. In the present study, we propose a two-step procedure in bridging the genome to phenome gap where external phenotypes are viewed as emergent properties of internal phenotypes, such as molecular profiles, in interaction with the enviorment. Using biomass accumulation and shoot-root allometry as external traits in diverse genotypes of the model grass Brachypodium distachyon , we established correlative models between genotypes and metabolite profiles (metabotypes) as internal phenotypes, and between metabotypes and external phenotypes under two contrasting watering regimes. Our results demonstrate the potential for employing metabotypes as an integrator in predicting external phenotypes from genomic information.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Whole-genome demography of COVID-19 virus during its pandemic period and on “panvalent” vaccine design

With over 16 million submitted genomic sequences, the SARS-CoV-2 (SC2) virus, the cause of the most recent worldwide COVID-19 pandemic, has become the most sequenced genome of all known viruses, revealing, for example, a vast number of expanding viral lineages. Since the pandemic phase appears to be over, we performed a retrospective re-examination of the demographic grouping pattern and their genomic characteristics during the entire pandemic period up to the peak of the last pandemic wave. For our study, we extracted from the NCBI only unique viral sequences and converted each sequence data to a relational vector, indicating the presence/absence of each variational event compared to a “reference” sequence. Our study revealed several genomic features that are unexpected or different from those of previous studies. For example, approximately 44,000 variants with unique sequences emerged during the pandemic period; they group into only four major viral-genomic groups and each has a set of mostly unique highly-conserved variant-genotypes (HCVGs); and a small set from the first (“ancestral”) group was inherited by the three (“descendant”) groups, suggesting that HCVGs in the next group may be predictable from the current group(s). Such a concept may be potentially important in designing “panvalent” vaccines against the current and future waves of viral infections.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Wireworm (Coleoptera: Elateridae) genomic analysis reveals putative cryptic species, population structure, and adaptation to pest control

The larvae of click beetles (Coleoptera: Elateridae), known as “wireworms,” are agricultural pests that pose a substantial economic threat worldwide. We produced one of the first wireworm genome assemblies (Limonius californicus), and investigated population structure and phylogenetic relationships of three species (L. californicus, L. infuscatus, L. canus) across the northwest US and southwest Canada using genome-wide markers (RADseq) and genome skimming. We found two species (L. californicus and L. infuscatus) are comprised of multiple genetically distinct groups that diverged in the Pleistocene but have no known distinguishing morphological characters, and therefore could be considered cryptic species complexes. We also found within-species population structure across relatively short geographic distances. Genome scans for selection provided preliminary evidence for signatures of adaptation associated with different pesticide treatments in an agricultural field trial for L. canus. We demonstrate that genomic tools can be a strong asset in developing effective wireworm control strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Topologically associating domain boundaries are required for normal genome function

Topologically associating domain (TAD) boundaries partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotypes1,2,3, but the overall extent to which this occurs remains unknown. Here we demonstrate that targeted deletions of TAD boundaries cause a range of disruptions to normal in vivo genome function and organismal development. We used CRISPR genome editing in mice to individually delete eight TAD boundaries (11–80 kb in size) from the genome. All deletions examined resulted in detectable molecular or organismal phenotypes, which included altered chromatin interactions or gene expression, reduced viability, and anatomical phenotypes. We observed changes in local 3D chromatin architecture in 7 of 8 (88%) cases, including the merging of TADs and altered contact frequencies within TADs adjacent to the deleted boundary. For 5 of 8 (63%) loci examined, boundary deletions were associated with increased embryonic lethality or other developmental phenotypes. For example, a TAD boundary deletion near Smad3/Smad6 caused complete embryonic lethality, while a deletion near Tbx5/Lhx5 resulted in a severe lung malformation. Our findings demonstrate the importance of TAD boundary sequences for in vivo genome function and reinforce the critical need to carefully consider the potential pathogenicity of noncoding deletions affecting TAD boundaries in clinical genetics screening.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Comparative genomics of Mollicutes-related endobacteria supports a late invasion into Mucoromycota fungi

Abstract Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria (MRE). It has been hypothesized that MRE were acquired by a common ancestor and transmitted vertically. Alternatively, MRE endosymbionts could have invaded after the divergence of Mucoromycota lineages and subsequently spread to new hosts horizontally. To better understand the evolutionary history of MRE symbionts, we generated and analyzed four complete MRE genomes from two Mortierellaceae genera: Linnemannia (MRE-L) and Benniella (MRE-B). These genomes include the smallest known of fungal endosymbionts and showed signals of a tight relationship with hosts including a reduced functional capacity and genes transferred from fungal hosts to MRE. Phylogenetic reconstruction including nine MRE from mycorrhizal fungi revealed that MRE-B genomes are more closely related to MRE from Glomeromycotina than MRE-L from the same host family. We posit that reductions in genome size, GC content, pseudogene content, and repeat content in MRE-L may reflect a longer-term relationship with their fungal hosts. These data indicate Linnemannia and Benniella MRE were likely acquired independently after their fungal hosts diverged from a common ancestor. This work expands upon foundational knowledge on minimal genomes and provides insights into the evolution of bacterial endosymbionts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

(Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans

Despite having serious clinical manifestations, Cellulosimicrobium cellulans remain under-reported with only three genome sequences available at the time of writing. Genome sequences of C. cellulans LMG16121, C. cellulans J36 and Cellulosimicrobium sp. strain MM were used to determine distribution of pathogenicity islands (PAIs) across C. cellulans , which revealed 49 potential marker genes with known association to human infections, e.g. Fic and VbhA toxin-antitoxin system. Oligonucleotide composition-based analysis of orthologous proteins (n = 791) across three genomes revealed significant negative correlation (P < 0.05) between frequency of optimal codons ( F opt ) and gene G+C content, highlighting the G+C-biased gene conversion (gBGC) effect across Cellulosimicrobium strains. Bayesian molecular-clock analysis performed on three virulent PAI proteins (Fic; D-alanyl-D-alanine-carboxypeptidase; transposase) dated the divergence event at 300 million years ago from the most common recent ancestor. Synteny-based annotation of hypothetical proteins highlighted gene transfers from non-pathogenic bacteria as a key factor in the evolution of PAIs. Additonally, deciphering the metagenomic islands using strain MM's genome with environmental data from the site of isolation (hot-spring biofilm) revealed (an)aerobic respiration as population segregation factor across the in situ cohorts. Furthermore, using reference genomes and metagenomic data, our results highlight the emergence and evolution of PAIs in the genus Cellulosimicrobium .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Transcriptional burst frequency and burst size are equally modulated across the human genome

Gene expression occurs either as an episodic process, characterized by pulsatile bursts or as a constitutive, Poisson-like accumulation of gene products. It is not clear which mode of gene expression (constitutive versus bursty) predominates across a genome or how transcriptional dynamics are influenced by genomic position and promoter sequence. Here, we use time-lapse fluorescence microscopy, building off of theoretical studies that exploit the time-resolved structure of stochastic fluctuations in gene expression, to develop a three-dimensional method for mapping underlying gene-regulatory mechanisms. Over 8,000 individual human genomic loci were analyzed, and at virtually all loci, episodic bursting as opposed to constitutive expression was found to be the predominant mode of expression. Quantitative analysis of the expression dynamics at these 8,000 loci indicates that both frequency and size of transcriptional bursts vary equally across the human genome independent of promoter sequence. Strikingly, weaker expression loci modulate burst frequency to increase activity, while stronger expression loci modulate burst size to increase activity. Transcriptional activators, such as TNF, generate similar patterns of change in burst frequency and burst size. In summary, transcriptional bursting dominates across the human genome, both burst frequency and burst size vary by chromosomal location, and transcriptional activators alter burst frequency and burst size, depending on the expression level of the locus.

noise biology↗
DOE OSTI2013

Genomic responses in mouse models poorly mimic human inflammatory diseases

Murine models have been extensively used in recent decades to identify and test drug candidates for subsequent human trials (1–3). However, few of these human trials have shown success (4–7). The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed (8–11). Despite commentaries that question the merit of an overreliance of animal systems to model human immunology (3, 12, 13), in the absence of systematic evidence, investigators and public regulators assume that results from animal research reflect human disease. To date, there have been no studies to systematically evaluate, on a molecular basis, how well the murine clinical models mimic human inflammatory diseases in patients. The Inflammation and Host Response to Injury, Large Scale Collaborative Research Program has completed multiple studies on the genomic responses to systemic inflammation in patients and human volunteers as well as murine models (14–18). These datasets include genome-wide expression analysis on white blood cells obtained from serial blood draws in 167 patients up to 28 d after severe blunt trauma (15), 244 patients up to 1 y after burn injury, and 4 healthy humans for 24 h after administration of low-dose bacterial endotoxin (14) and expression analysis on analogous samples from well-established mouse models of trauma, burns, and endotoxemia (16 treated and 16 controls per model) (16–18). In humans, severe inflammatory stress produces a genomic storm affecting all major cellular functions and pathways (15) and therefore, provided sufficient perturbations to allow comparisons between the genes in the human conditions and their orthologs in the murine models. In this article, we report on a systematic comparison of the genomic response between human inflammatory diseases andmurine models. First, we compared the correlations of gene expression changes with trauma, burns, and endotoxemia between human subjects and corresponding mouse models. Second, we characterized and compared the temporal gene response patterns seen in these human conditions and models. Third, we also identified the major signaling pathways significantly regulated in the inflammatory response to human injuries and compared them with the human in vivo endotoxemia model and three murine models. Fourth, we sought and evaluated representative patient and murine studies of several additional acute inflammatory diseases. These results show that the genomic responses to different acute inflammatory stresses are highly similar in humans, but these responses are not reproduced in the current mouse models. New approaches need be explored to improve the ways that human diseases are studied.

Seok, Junhee↗