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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 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Linking crop traits to transcriptome differences in a progeny population of tetraploid potato

Background: Potato is the third most consumed crop in the world. Breeding for traits such as yield, product quality and pathogen resistance are main priorities. Identifying molecular signatures of these and other important traits is important in future breeding efforts. In this study, a progeny population from a cross between a breeding line, SW93–1015, and a cultivar, Désirée, was studied by trait analysis and RNA-seq in order to develop understanding of segregating traits at the molecular level and identify transcripts with expressional correlation to these traits. Transcript markers with predictive value for field performance applicable under controlled environments would be of great value for plant breeding.Results: A total of 34 progeny lines from SW93–1015 and Désirée were phenotyped for 17 different traits in a field in Nordic climate conditions and controlled climate settings. A master transcriptome was constructed with all 34 progeny lines and the parents through a de novo assembly of RNA-seq reads. Gene expression data obtained in a controlled environment from the 34 lines was correlated to traits by different similarity indices, including Pearson and Spearman, as well as DUO, which calculates the co-occurrence between high and low values for gene expression and trait. Our study linked transcripts to traits such as yield, growth rate, high laying tubers, late and tuber blight, tuber greening and early flowering. We found several transcripts associated to late blight resistance and transcripts encoding receptors were associated to Dickeya solani susceptibility. Transcript levels of a UBX-domain protein was negatively associated to yield and a GLABRA2 expression modulator was negatively associated to growth rate.Conclusion: In our study, we identify 100’s of transcripts, putatively linked based on expression with 17 traits of potato, representing both well-known and novel associations. This approach can be used to link the transcriptome to traits. We explore the possibility of associating the level of transcript expression from controlled, optimal environments to traits in a progeny population with different methods introducing the application of DUO for the first time on transcriptome data. We verify the expression pattern for five of the putative transcript markers in another progeny population.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma

Abstract Isocitrate dehydrogenase ( IDH ) wild‐type diffuse lower‐grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression‐based molecular classification of IDH wild‐type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild‐type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy‐three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild‐type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up‐regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A / CDKN2B , DMRTA1 , C9orf53 , and MTAP . Furthermore, we developed and validated a five‐gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild‐type diffuse LGGs and deepen our molecular understandi‐g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Wu, Fan↗
DOE OSTI2025

Ultra-high Information-content Chemical Imaging with Broadband Coherent Anti-Stokes Raman and Two-photon Fluorescence Lifetime Microscopy

Raman fingerprint spectroscopy and fluorescence lifetime imaging are emerging tools for studying metabolic profiles of biological specimens. While Raman fingerprint spectroscopy detects intrinsic molecular vibrations that reflect the molecular composition and chemical environment of a sample, fluorescence lifetime imaging measures changes in the excited-state lifetime of fluorophores that are sensitive to their microenvironments. Here, we present a multimodal imaging platform combining broadband coherent anti-Stokes Raman scattering (BCARS) and two-photon fluorescence lifetime imaging (2p-FLIM) microscopy that can acquire biologically relevant Raman fingerprint spectra and fluorescence lifetime signals in vivo and simultaneously. The tremendous chemical information obtained from spatially co-registered BCARS and 2p-FLIM images allows us to characterize the subtle differences between sub-cellular compartments and verify the potential false-positive results generated by fluorescence imaging alone. This is demonstrated by directly comparing the BCARS, 2p-FLIM, and two-photon excitation fluorescence(TPEF) signals simultaneously obtained from the same dye-stained organelle in the live, intact C. elegans expressing a green fluorescent protein (GFP) marker. In this work, we introduce the BCARS/2p-FLIM/TPEF setup scheme, the image acquisition steps, data processing, and representative results showing that the cross-modality imaging method enables rigorous characterization and in vivo detection at sub-cellular resolution. Furthermore, this protocol provides a framework for simultaneous chemical and fluorescence lifetime imaging to improve the accuracy of biological interpretation in complex living systems.

Xu, Haoyu [Georgia Institute of Technology, Atlant↗
DOE OSTI2022

Preparing for the next pandemic via transfer learning from existing diseases with hierarchical multi-modal BERT: a study on COVID-19 outcome prediction

Abstract Developing prediction models for emerging infectious diseases from relatively small numbers of cases is a critical need for improving pandemic preparedness. Using COVID-19 as an exemplar, we propose a transfer learning methodology for developing predictive models from multi-modal electronic healthcare records by leveraging information from more prevalent diseases with shared clinical characteristics. Our novel hierarchical, multi-modal model ( $${\textsc {TransMED}}$$ T R A N S MED ) integrates baseline risk factors from the natural language processing of clinical notes at admission, time-series measurements of biomarkers obtained from laboratory tests, and discrete diagnostic, procedure and drug codes. We demonstrate the alignment of $${\textsc {TransMED}}$$ T R A N S MED ’s predictions with well-established clinical knowledge about COVID-19 through univariate and multivariate risk factor driven sub-cohort analysis. $${\textsc {TransMED}}$$ T R A N S MED ’s superior performance over state-of-the-art methods shows that leveraging patient data across modalities and transferring prior knowledge from similar disorders is critical for accurate prediction of patient outcomes, and this approach may serve as an important tool in the early response to future pandemics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

RNAi-Mediated Manipulation of Cuticle Coloration Genes in Lygus hesperus Knight (Hemiptera: Miridae)

Cuticle coloration in insects is a consequence of the accumulation of pigments in a species-specific pattern. Numerous genes are involved in regulating the underlying processes of melanization and sclerotization, and their manipulation can be used to create externally visible markers of successful gene editing. To clarify the roles for many of these genes and examine their suitability as phenotypic markers in Lygus hesperus Knight (western tarnished plant bug), transcriptomic data were screened for sequences exhibiting homology with the Drosophila melanogaster proteins. Complete open reading frames encoding putative homologs for six genes (aaNAT, black, ebony, pale, tan, and yellow) were identified, with two variants for black. Sequence and phylogenetic analyses supported preliminary annotations as cuticle pigmentation genes. In accord with observable difference in color patterning, expression varied for each gene by developmental stage, adult age, body part, and sex. Knockdown by injection of dsRNA for each gene produced varied effects in adults, ranging from the non-detectable (black 1, yellow), to moderate decreases (pale, tan) and increases (black 2, ebony) in darkness, to extreme melanization (aaNAT). Based solely on its expression profile and highly visible phenotype, aaNAT appears to be the best marker for tracking transgenic L. hesperus.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Refinement of the “ Candidatus Accumulibacter” genus based on metagenomic analysis of biological nutrient removal (BNR) pilot-scale plants operated with reduced aeration

Members of the “Candidatus Accumulibacter” genus are widely studied as key polyphosphate-accumulating organisms (PAOs) in biological nutrient removal (BNR) facilities performing enhanced biological phosphorus removal (EBPR). This diverse lineage includes 18 “Ca. Accumulibacter” species, which have been proposed based on the phylogenetic divergence of the polyphosphate kinase 1 (ppk1) gene and genome-scale comparisons of metagenome-assembled genomes (MAGs). Phylogenetic classification based on the 16S rRNA genetic marker has been difficult to attain because most “Ca. Accumulibacter” MAGs are incomplete and often do not include the rRNA operon. Here, we investigate the “Ca. Accumulibacter” diversity in pilot-scale treatment trains performing BNR under low dissolved oxygen (DO) conditions using genome-resolved metagenomics. Using long-read sequencing, we recovered medium- and high-quality MAGs for 5 of the 18 “Ca. Accumulibacter” species, all with rRNA operons assembled, which allowed a reassessment of the 16S rRNA-based phylogeny of this genus and an analysis of phylogeny based on the 23S rRNA gene.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling

Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which are essential regulators of stem cell biology, yet the structural basis of Wnt signaling through Fzd remains poorly understood. Here we report the structure of an unliganded human Fzd5 determined by single-particle cryo-EM at 3.7 Å resolution, with the aid of an antibody chaperone acting as a fiducial marker. We also analyzed the topology of low-resolution XWnt8/Fzd5 complex particles, which revealed extreme flexibility between the Wnt/Fzd-CRD and the Fzd-TM regions. Analysis of Wnt/β-catenin signaling in response to Wnt3a versus a ‘surrogate agonist’ that cross-links Fzd to LRP6, revealed identical structure-activity relationships. Thus, canonical Wnt/β-catenin signaling appears to be principally reliant on ligand-induced Fzd/LRP6 heterodimerization, versus the allosteric mechanisms seen in structurally analogous class A G protein-coupled receptors, and Smoothened. These findings deepen our mechanistic understanding of Wnt signal transduction, and have implications for harnessing Wnt agonism in regenerative medicine.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Lanthanide-dependent alcohol dehydrogenases require an essential aspartate residue for metal coordination and enzymatic function

The lanthanide elements (Ln 3+ ), those with atomic numbers 57–63 (excluding promethium, Pm 3+ ), form a cofactor complex with pyrroloquinoline quinone (PQQ) in bacterial XoxF methanol dehydrogenases (MDHs) and ExaF ethanol dehydrogenases (EDHs), expanding the range of biological elements and opening novel areas of metabolism and ecology. Other MDHs, known as MxaFIs, are related in sequence and structure to these proteins, yet they instead possess a Ca 2+ -PQQ cofactor. An important missing piece of the Ln 3+ puzzle is defining what features distinguish enzymes that use Ln 3+ -PQQ cofactors from those that do not. In this work, using XoxF1 MDH from the model methylotrophic bacterium Methylorubrum extorquens AM1, we investigated the functional importance of a proposed lanthanide-coordinating aspartate residue. We report two crystal structures of XoxF1, one with and another without PQQ, both with La 3+ bound in the active-site region and coordinated by Asp 320 . Using constructs to produce either recombinant XoxF1 or its D320A variant, we show that Asp 320 is needed for in vivo catalytic function, in vitro activity, and La 3+ coordination. XoxF1 and XoxF1 D320A, when produced in the absence of La 3+ , coordinated Ca 2+ but exhibited little or no catalytic activity. We also generated the parallel substitution in ExaF to produce ExaF D319S and found that this variant loses the capacity for efficient ethanol oxidation with La 3+ . These results provide evidence that a Ln 3+ -coordinating aspartate is essential for the enzymatic functions of XoxF MDHs and ExaF EDHs, supporting the notion that sequences of these enzymes, and the genes that encode them, are markers for Ln 3+ metabolism.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Complete sequences of conjugal helper plasmids pRK2013 and pEVS104

We present the complete sequences of two commonly used conjugal helper plasmids: pRK2013 and pEVS104. These sequences will enable engineering of custom helper plasmids, for example, with different antibiotic markers or origins of replication. We provide both sequence information and plasmid maps to aid future engineering efforts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting

Single-cell multiomics provides comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. Here, we introduce nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), an integrated platform that enables global profiling of the transcriptome and proteome from same single cells via RNA sequencing and mass spectrometry-based proteomics, respectively. Benchmarking of nanoSPLITS demonstrates high measurement precision with deep proteomic and transcriptomic profiling of single-cells. We apply nanoSPLITS to cyclin-dependent kinase 1 inhibited cells and found phospho-signaling events could be quantified alongside global protein and mRNA measurements, providing insights into cell cycle regulation. We extend nanoSPLITS to primary cells isolated from human pancreatic islets, introducing an efficient approach for facile identification of unknown cell types and their protein markers by mapping transcriptomic data to existing large-scale single-cell RNA sequencing reference databases. Accordingly, we establish nanoSPLITS as a multiomic technology incorporating global proteomics and anticipate the approach will be critical to furthering our understanding of biological systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Proteomic and phosphoproteomic measurements enhance ability to predict ex vivo drug response in AML

Acute Myeloid Leukemia (AML) affects 20,000 patients in the US annually with a five-year survival rate of approximately 25%. One reason for the low survival rate is the high prevalence of clonal evolution that gives rise to heterogeneous sub-populations of leukemic cells with diverse mutation spectra, which eventually leads to disease relapse. This genetic heterogeneity drives the activation of complex signaling pathways that is reflected at the protein level. This diversity makes it difficult to treat AML with targeted therapy, requiring custom patient treatment protocols tailored to each individual’s leukemia. Toward this end, the Beat AML research program prospectively collected genomic and transcriptomic data from over 1000 AML patients and carried out ex vivo drug sensitivity assays to identify genomic signatures that could predict patient-specific drug responses. However, there are inherent weaknesses in using only genetic and transcriptomic measurements as surrogates of drug response, particularly the absence of direct information about phosphorylation-mediated signal transduction. As a member of the Clinical Proteomic Tumor Analysis Consortium, we have extended the molecular characterization of this cohort by collecting proteomic and phosphoproteomic measurements from a subset of these patient samples (38 in total) to evaluate the hypothesis that proteomic signatures can improve the ability to predict response to 26 drugs in AML ex vivo samples. In this work we describe our systematic, multi-omic approach to evaluate proteomic signatures of drug response and compare protein levels to other markers of drug response such as mutational patterns. We explore the nuances of this approach using two drugs that target key pathways activated in AML: quizartinib (FLT3) and trametinib (Ras/MEK), and show how patient-derived signatures can be interpreted biologically and validated in cell lines. In conclusion, this pilot study demonstrates strong promise for proteomics-based patient stratification to assess drug sensitivity in AML.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Longitudinal analysis of host protein serum signatures of treatment and recovery in pulmonary tuberculosis

A better understanding of treatment progression and recovery in pulmonary tuberculosis (TB) infectious disease is crucial. This study analyzed longitudinal serum samples from pulmonary TB patients undergoing interventional treatment to identify surrogate markers for TB-related outcomes. Serum that was collected at baseline and 8, 17, 26, and 52 weeks from 30 TB patients experiencing durable cure were evaluated and compared using a sensitive LC-MS/MS proteomic platform for the detection and quantification of differential host protein signatures relative to timepoint. The global proteome signature was analyzed for statistical differences across the time course and between disease severity and treatment groups. A total of 676 proteins showed differential expression in the serum over these timepoints relative to baseline. Comparisons to understand serum protein dynamics at 8 weeks, treatment endpoints at 17 and 26 weeks, and post-treatment at 52 weeks were performed. The largest protein abundance changes were observed at 8 weeks as the initial effects of antibiotic treatment strongly impacted inflammatory and immune modulated responses. However, the largest number of proteome changes was observed at the end of treatment time points 17 and 26 weeks respectively. Post-treatment 52-week results showed an abatement of differential proteome signatures from end of treatment, though interestingly those proteins uniquely significant at post-treatment were almost exclusively downregulated. Patients were additionally stratified based upon disease severity and compared across all timepoints, identifying 461 discriminating proteome signatures. These proteome signatures collapsed into discrete expression profiles with distinct pathways across immune activation and signaling, hemostasis, and metabolism annotations. Insulin-like growth factor (IGF) and Integrin signaling maintained a severity signature through 52 weeks, implying an intrinsic disease severity signature well into the post-treatment timeframe. Previous proteome studies have primarily focused on the 8-week timepoint in relation to culture conversion status. While this study confirms previous observations, it also highlights some differences. The inclusion of additional end of treatment and post-treatment time points offers a more comprehensive assessment of treatment progression within the serum proteome. Examining the expression dynamics at these later time periods will help in the investigation of relapse patients and has provided indicative markers of response and recovery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement

Time-lapse images of cells and tissues contain rich information about dynamic cell behaviours, which reflect the underlying processes of proliferation, differentiation and morphogenesis. However, we lack computational tools for effective inference. Here we exploit deep reinforcement learning (DRL) to infer cell–cell interactions and collective cell behaviours in tissue morphogenesis from three-dimensional (3D) time-lapse images. We use hierarchical DRL (HDRL), known for multiscale learning and data efficiency, to examine cell migrations based on images with a ubiquitous nuclear label and simple rules formulated from empirical statistics of the images. When applied to Caenorhabditis elegans embryogenesis, HDRL reveals a multiphase, modular organization of cell movement. Imaging with additional cellular markers confirms the modular organization as a novel migration mechanism, which we term sequential rosettes. Furthermore, HDRL forms a transferable model that successfully differentiates sequential rosettes-based migration from others. Our study demonstrates a powerful approach to infer the underlying biology from time-lapse imaging without prior knowledge.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Pathogenic SIV infection is associated with acceleration of epigenetic age in rhesus macaques

HIV infection accelerates biological aging, but the contribution of the host’s age to this process is unknown. We investigated the influence of SIV infection in macaques (SIVmac) on the risk of comorbidities and aging in young and old rhesus macaques (RMs) by assessing pathogenesis markers, DNA methylation–based epigenetic age (EA), and EA acceleration (EAA) in blood and tissues. Initially, upon SIV infection, the young RMs showed greater resilience to CD4 + T cell depletion, better control of T cell activation, hypercoagulation, and excessive inflammation, yet this resilience was progressively lost in the advanced stages of infection. During the late stages of infection, the young RMs, but not the aged ones, showed an increase in EA in PBMCs; also, EAA in the cerebellum and heart of young RMs was higher compared with old RMs. SIV infection was more pathogenic in aged animals in early stages, leading to a more rapid disease progression; however, accelerated aging mostly affected young animals, so that the levels of multiple key pathogenesis markers in the young RMs converged toward those specific to aged ones in the late stages of infection. We conclude that SIV infection–driven age acceleration is tissue specific, and that host age influences the susceptibility of different tissues to enhanced aging.

Research & Experimental Medicine↗
NASA NTRS2003

Dual reporter transgene driven by 2.3Col1a1 promoter is active in differentiated osteoblasts

AIM: As quantitative and spatial analyses of promoter reporter constructs are not easily performed in intact bone, we designed a reporter gene specific to bone, which could be analyzed both visually and quantitatively by using chloramphenicol acetyltransferase (CAT) and a cyan version of green fluorescent protein (GFPcyan), driven by a 2.3-kb fragment of the rat collagen promoter (Col2.3). METHODS: The construct Col2.3CATiresGFPcyan was used for generating transgenic mice. Quantitative measurement of promoter activity was performed by CAT analysis of different tissues derived from transgenic animals; localization was performed by visualized GFP in frozen bone sections. To assess transgene expression during in vitro differentiation, marrow stromal cell and neonatal calvarial osteoblast cultures were analyzed for CAT and GFP activity. RESULTS: In mice, CAT activity was detected in the calvaria, long bone, teeth, and tendon, whereas histology showed that GFP expression was limited to osteoblasts and osteocytes. In cell culture, increased activity of CAT correlated with increased differentiation, and GFP activity was restricted to mineralized nodules. CONCLUSION: The concept of a dual reporter allows a simultaneous visual and quantitative analysis of transgene activity in bone.

Non-NASA Center↗
DOE OSTI2021

NMIIA promotes tumorigenesis and prevents chemosensitivity in colorectal cancer by activating AMPK/mTOR pathway

Non-muscle myosin IIA (NMIIA) has been reported to be involved in the carcinogenesis and malignant progression of various human tumors. However, the role and potential mechanism of NMIIA in the biological functions and apoptosis in colorectal cancer (CRC) remain elusive. In this study, we found that NMIIA was overexpressed in CRC tissues and significantly associated with poor survival in CRC patients. In addition, NMIIA promoted CRC cell proliferation and invasion via activating the AMPK/mTOR pathway in vitro, and NMIIA knockdown inhibited CRC growth in vivo. Meanwhile, NMIIA knockdown downregulated the CSCs markers (CD44 and CD133) expression in CRC cells. Furthermore, AMPK/mTOR pathway activation effectively reversed the NMIIA knockdown-induced inhibition of proliferation, invasion and stemness in CRC cells. Finally, NMIIA protects CRC cells from 5-FU-induced apoptosis and proliferation inhibition through the AMPK/mTOR pathway. Taken together, these results indicate that NMIIA plays a pivotal role in CRC growth and progression by regulating AMPK/mTOR pathway activation, and it may act as a novel therapeutic target prognostic factor in CRC.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2000

Aqueous two-phase partition applied to the isolation of plasma membranes and Golgi apparatus from cultured mammalian cells

Partitioning in dextran-poly(ethylene)glycol (PEG) aqueous-aqueous phase systems represents a mature technology with many applications to separations of cells and to the preparation of membranes from mammalian cells. Most applications to membrane isolation and purification have focused on plasma membranes, plasma membrane domains and separation of right side-out and inside-out plasma membrane vesicles. The method exploits a combination of membrane properties, including charge and hydrophobicity. Purification is based upon differential distributions of the constituents in a sample between the two principal compartments of the two phases (upper and lower) and at the interface. The order of affinity of animal cell membranes for the upper phase is: endoplasmic reticulum <mitochondria<Golgi apparatus<lysosomes and endosomes< plasma membranes. Salt concentrations and temperature affect partitioning behavior and must be precisely standardized. In some cases, it is more fortuitous to combine aqueous two-phase partition with other procedures to obtain a more highly purified preparation. A procedure is described for preparation of Golgi apparatus from transformed mammalian cells that combines aqueous two-phase partition and centrifugation. Also described is a periodic NADH oxidase, a new enzyme marker for right side-out plasma membrane vesicles not requiring detergent disruptions for measurement of activity.

Non-NASA Center↗
DOE OSTI2020

FeGenie: a comprehensive tool for the identification of iron genes and iron gene neighborhoods in genomes and metagenome assemblies

Iron is a micronutrient for nearly all life on Earth. It can be used as an electron donor and electron acceptor by iron-oxidizing and iron-reducing microorganisms and is used in a variety of biological processes, including photosynthesis and respiration. While it is the fourth most abundant metal in the Earth’s crust, iron is often limiting for growth in oxic environments because it is readily oxidized and precipitated. Much of our understanding of how microorganisms compete for and utilize iron is based on laboratory experiments. However, the advent of next-generation sequencing and surge in publicly available sequence data has made it possible to probe the structure and function of microbial communities in the environment. To bridge the gap between our understanding of iron acquisition, iron redox cycling, iron storage, and magnetosome formation in model microorganisms and the plethora of sequence data available from environmental studies, we have created a comprehensive database of hidden Markov models (HMMs) based on genes related to iron acquisition, storage, and reduction/oxidation in Bacteria and Archaea. Along with this database, we present FeGenie, a bioinformatics tool that accepts genome and metagenome assemblies as input and uses our comprehensive HMM database to annotate provided datasets with respect to iron-related genes and gene neighborhood. An important contribution of this tool is the efficient identification of genes involved in iron oxidation and dissimilatory iron reduction, which have been largely overlooked by standard annotation pipelines. We validated FeGenie against a selected set of 28 isolate genomes and showcase its utility in exploring iron genes present in 27 metagenomes, 4 isolate genomes from human oral biofilms, and 17 genomes from candidate organisms, including members of the candidate phyla radiation. We show that FeGenie accurately identifies iron genes in isolates. Furthermore, analysis of metagenomes using FeGenie demonstrates that the iron gene repertoire and abundance of each environment is correlated with iron richness. While this tool will not replace the reliability of culture-dependent analyses of microbial physiology, it provides reliable predictions derived from the most up-to-date genetic markers. FeGenie’s database will be maintained and continually updated as new genes are discovered.

59 BASIC BIOLOGICAL SCIENCES↗