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At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

A variant selection framework for genome graphs

Abstract Motivation Variation graph representations are projected to either replace or supplement conventional single genome references due to their ability to capture population genetic diversity and reduce reference bias. Vast catalogues of genetic variants for many species now exist, and it is natural to ask which among these are crucial to circumvent reference bias during read mapping. Results In this work, we propose a novel mathematical framework for variant selection, by casting it in terms of minimizing variation graph size subject to preserving paths of length α with at most δ differences. This framework leads to a rich set of problems based on the types of variants [e.g. single nucleotide polymorphisms (SNPs), indels or structural variants (SVs)], and whether the goal is to minimize the number of positions at which variants are listed or to minimize the total number of variants listed. We classify the computational complexity of these problems and provide efficient algorithms along with their software implementation when feasible. We empirically evaluate the magnitude of graph reduction achieved in human chromosome variation graphs using multiple α and δ parameter values corresponding to short and long-read resequencing characteristics. When our algorithm is run with parameter settings amenable to long-read mapping (α = 10 kbp, δ = 1000), 99.99% SNPs and 73% SVs can be safely excluded from human chromosome 1 variation graph. The graph size reduction can benefit downstream pan-genome analysis. Availability and implementation https://github.com/AT-CG/VF. Supplementary information Supplementary data are available at Bioinformatics online.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

CAPG: comprehensive allopolyploid genotyper

Genotyping by sequencing is a powerful tool for investigating genetic variation in plants, but many economically important plants are allopolyploids, where homoeologous similarity obscures the subgenomic origin of reads and confounds allelic and homoeologous SNPs. Recent polyploid genotyping methods use allelic frequencies, rate of heterozygosity, parental cross or other information to resolve read assignment, but good subgenomic references offer the most direct information. The typical strategy aligns reads to the joint reference, performs diploid genotyping within each subgenome, and filters the results, but persistent read misassignment results in an excess of false heterozygous calls. We introduce the Comprehensive Allopolyploid Genotyper (CAPG), which formulates an explicit likelihood to weight read alignments against both subgenomic references and genotype individual allopolyploids from whole-genome resequencing data. We demonstrate CAPG in allotetraploids, where it performs better than Genome Analysis Toolkit’s HaplotypeCaller applied to reads aligned to the combined subgenomic references.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Fitness factors impacting survival of a subsurface bacterium in contaminated groundwater

Many factors contribute to the ability of a microbial species to persist when encountering complexly contaminated environments, including time of exposure, the nature and concentration of contaminants, availability of nutritional resources, and possession of a combination of appropriate molecular mechanisms needed for survival. Herein we sought to identify genes that are most important for survival of Gram-negative Enterobacteriaceae in contaminated groundwater environments containing high concentrations of nitrate and metals using the metal-tolerant Oak Ridge Reservation isolate, Pantoea sp. MT58 (MT58). Survival fitness experiments in which a randomly barcoded transposon insertion (RB-TnSeq) library of MT58 was exposed directly to contaminated Oak Ridge Reservation groundwater samples from across a nitrate and mixed metal contamination plume were used to identify genes important for survival with increasing exposure times and concentrations of contaminants, and availability of a carbon source. Genes involved in controlling and using carbon, encoding transcriptional regulators, and related to Gram-negative outer membrane processes were among those found to be important for survival in contaminated Oak Ridge Reservation groundwater. A comparative genomics analysis of 75 Pantoea genus strains allowed us to further separate the survival determinants into core and non-core genes in the Pantoea pangenome, revealing insights into the survival of subsurface microorganisms during contaminant plume intrusion.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Emergence and disruption of cooperativity in a denitrifying microbial community

Anthropogenic perturbations to the nitrogen cycle, primarily through use of synthetic fertilizers, is driving an unprecedented increase in the emission of nitrous oxide (N 2 O), a potent greenhouse gas and an ozone depleting substance, causing urgency in identifying the sources and sinks of N 2 O. Microbial denitrification is a primary contributor to biotic production of N 2 O in anoxic regions of soil, marine systems, and wastewater treatment facilities. Here, through comprehensive genome analysis, we show that pathway partitioning is a ubiquitous mechanism of complete denitrification within microbial communities. We have investigated mechanisms and consequences of process partitioning of denitrification through detailed physiological characterization and kinetic modeling of a synthetic community of Rhodanobacter thiooxydans FW510-R12 and Acidovorax sp. GW101-3H11. We have discovered that these two bacterial isolates, from a heavily nitrate (NO 3 − ) contaminated superfund site, complete denitrification through the exchange of nitrite (NO 2 − ) and nitric oxide (NO). The process partitioning of denitrification and other processes, including amino acid metabolism, contribute to increased cooperativity within this denitrifying community. We demonstrate that certain contexts, such as high NO 3 − , cause unbalanced growth of community members, due to differences in their substrate utilization kinetics. The altered growth characteristics of community members drives accumulation of toxic NO 2 − , which disrupts denitrification causing N 2 O off gassing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Twenty-five years of Genomes OnLine Database (GOLD): data updates and new features in v.9

We report the Genomes OnLine Database (GOLD) (https://gold.jgi.doe.gov/) at the Department of Energy Joint Genome Institute (DOE-JGI) continues to maintain its role as one of the flagship genomic metadata repositories of the world. The ever-increasing number of projects and metadata are freely available to the user community world-wide. GOLD’s metadata is consumed by scientists and remains an important source for large-scale comparative genomics analysis initiatives. Encouraged by this active user engagement and growth, GOLD has continued to add new components and capabilities. The new features such as a public Application Programming Interface (API) and Ecosystem landing page as well as the growth of different entities in this current GOLD v.9 edition are described in detail in this manuscript.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

A Survey on the Expanding Scope and Interdisciplinary Opportunities for Processing-in-Memory Techniques

Processing-in-Memory (PIM) is emerging as a practical path to overcome the limitations of traditional von Neumann architectures. At its core, PIM systems implement computing primitives such as logic operations and multiply-accumulate acceleration through compute-in-memory, near-memory processing, or hybrid designs. The role of memory cells varies widely across technologies, acting as inputs, outputs, or analog accumulators through bit-lines and sense amplifiers. This diversity creates trade-offs in precision, bandwidth, latency, and programmability, making it difficult to build a unified understanding on the progress of the field. In this survey, we organize recent advances of PIM into three areas. First, we discuss the progress on the architectural optimizations of PIM and its integration with both DRAM and emerging non-volatile memories. Second, we examine how PIM is being used to accelerate key computing domains, including generative AI workloads and high-performance kernels, along with new approaches. Third, we highlight the growing adoption of PIM in computational sciences, where it is being applied to solve interdisciplinary problems such as genome analysis, mRNA quantification, mass spectrometry, quantum circuit simulation, wave modeling, and secure computation. Finally, we synthesize the major challenges that continue to slow PIM adoption, including manufacturing constraints, power delivery, thermal reliability, data consistency, runtime and memory-management coordination, and the difficulty of building portable software abstractions without sacrificing commercial viability. This work provides an updated, structured perspective on PIM’s potential across computing and computational sciences and the barriers that must be solved for it to reach its full impact.

Asifuzzaman, Kazi [Oak Ridge National Laboratory (↗
DOE OSTI2023

Identification of ancestral gnathostome Gli3 enhancers with activity in mammals

Abnormal expression of the transcriptional regulator and hedgehog (Hh) signaling pathway effector Gli3 is known to trigger congenital disease, most frequently affecting the central nervous system (CNS) and the limbs. Accurate delineation of the genomic cis-regulatory landscape controlling Gli3 transcription during embryonic development is critical for the interpretation of noncoding variants associated with congenital defects. Here, we employed a comparative genomic analysis on fish species with a slow rate of molecular evolution to identify seven previously unknown conserved noncoding elements (CNEs) in Gli3 intronic intervals (CNE15–21). Transgenic assays in zebrafish revealed that most of these elements drive activities in Gli3 expressing tissues, predominantly the fins, CNS, and the heart. Intersection of these CNEs with human disease associated SNPs identified CNE15 as a putative mammalian craniofacial enhancer, with conserved activity in vertebrates and potentially affected by mutation associated with human craniofacial morphology. Finally, comparative functional dissection of an appendage-specific CNE conserved in slowly evolving fish (elephant shark), but not in teleost (CNE14/hs1586) indicates co-option of limb specificity from other tissues prior to the divergence of amniotes and lobe-finned fish. In conclusion, these results uncover a novel subset of intronic Gli3 enhancers that arose in the common ancestor of gnathostomes and whose sequence components were likely gradually modified in other species during the process of evolutionary diversification.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Anaerobic benzene oxidation in Geotalea daltonii involves activation by methylation and is regulated by the transition state regulator AbrB

ABSTRACT Benzene is a widespread groundwater contaminant that persists under anoxic conditions. The aim of this study was to more accurately investigate anaerobic microbial degradation pathways to predict benzene fate and transport. Preliminary genomic analysis of Geotalea daltonii strain FRC-32, isolated from contaminated groundwater, revealed the presence of putative aromatic-degrading genes. G. daltonii was subsequently shown to conserve energy for growth on benzene as the sole electron donor and fumarate or nitrate as the electron acceptor. The hbs gene, encoding for 3-hydroxybenzylsuccinate synthase (Hbs), a homolog of the radical-forming, toluene-activating benzylsuccinate synthase (Bss), was upregulated during benzene oxidation in G. daltonii , while the bss gene was upregulated during toluene oxidation. Addition of benzene to the G. daltonii whole-cell lysate resulted in toluene formation, indicating that methylation of benzene was occurring. Complementation of σ 54 - (deficient) E. coli transformed with the bss operon restored its ability to grow in the presence of toluene, revealing bss to be regulated by σ 54 . Binding sites for σ 70 and the transition state regulator AbrB were identified in the promoter region of the σ 54 -encoding gene rpoN, and binding was confirmed. Induced expression of abrB during benzene and toluene degradation caused G. daltonii cultures to transition to the death phase. Our results suggested that G. daltonii can anaerobically oxidize benzene by methylation, which is regulated by σ 54 and AbrB. Our findings further indicated that the benzene, toluene, and benzoate degradation pathways converge into a single metabolic pathway, representing a uniquely efficient approach to anaerobic aromatic degradation in G. daltonii . IMPORTANCE The contamination of anaerobic subsurface environments including groundwater with toxic aromatic hydrocarbons, specifically benzene, toluene, ethylbenzene, and xylene, has become a global issue. Subsurface groundwater is largely anoxic, and further study is needed to understand the natural attenuation of these compounds. This study elucidated a metabolic pathway utilized by the bacterium Geotalea daltonii capable of anaerobically degrading the recalcitrant molecule benzene using a unique activation mechanism involving methylation. The identification of aromatic-degrading genes and AbrB as a regulator of the anaerobic benzene and toluene degradation pathways provides insights into the mechanisms employed by G. daltonii to modulate metabolic pathways as necessary to thrive in anoxic contaminated groundwater. Our findings contribute to the understanding of novel anaerobic benzene degradation pathways that could potentially be harnessed to develop improved strategies for bioremediation of groundwater contaminants.

Bullows, James E.↗
DOE OSTI2023

Characterization of a novel aromatic substrate-processing microcompartment in Actinobacteria

ABSTRACT We have discovered a new cluster of genes that is found exclusively in the Actinobacteria phylum. This locus includes genes for the 2-aminophenol meta -cleavage pathway and the shell proteins of a bacterial microcompartment (BMC) and has been named aromatics (ARO) for its putative role in the breakdown of aromatic compounds. In this study, we provide details about the distribution and composition of the ARO BMC locus and conduct phylogenetic, structural, and functional analyses of the first two enzymes in the catabolic pathway: a unique 2-aminophenol dioxygenase, which is exclusively found alongside BMC shell genes in Actinobacteria, and a semialdehyde dehydrogenase, which works downstream of the dioxygenase. Genomic analysis reveals variations in the complexity of the ARO loci across different orders. Some loci are simple, containing shell proteins and enzymes for the initial steps of the catabolic pathway, while others are extensive, encompassing all the necessary genes for the complete breakdown of 2-aminophenol into pyruvate and acetyl-CoA. Furthermore, our analysis uncovers two subtypes of ARO BMC that likely degrade either 2-aminophenol or catechol, depending on the presence of a pathway-specific gene within the ARO locus. The precise precursor of 2-aminophenol, which serves as the initial substrate and/or inducer for the ARO pathway, remains unknown, as our model organism Micromonospora rosaria cannot utilize 2-aminophenol as its sole energy source. However, using enzymatic assays, we demonstrate the dioxygenase’s ability to cleave both 2-aminophenol and catechol in vitro , in collaboration with the aldehyde dehydrogenase, to facilitate the rapid conversion of these unstable and toxic intermediates. IMPORTANCE Bacterial microcompartments (BMCs) are proteinaceous organelles that are widespread among bacteria and provide a competitive advantage in specific environmental niches. Studies have shown that the genetic information necessary to form functional BMCs is encoded in loci that contain genes encoding shell proteins and the enzymatic core. This allows the bioinformatic discovery of BMCs with novel functions and expands our understanding of the metabolic diversity of BMCs. ARO loci, found only in Actinobacteria, contain genes encoding for phylogenetically remote shell proteins and homologs of the meta -cleavage degradation pathway enzymes that were shown to convert central aromatic intermediates into pyruvate and acetyl-CoA in gamma Proteobacteria. By analyzing the gene composition of ARO BMC loci and characterizing two core enzymes phylogenetically, structurally, and functionally, we provide an initial functional characterization of the ARO BMC, the most unusual BMC identified to date, distinctive among the repertoire of studied BMCs.

2-AP 1,6-dioxygenase↗
DOE OSTI2020

Distributed Berkeley Efficient Long-Read to Long-Read Aligner and Overlapper (DiBELLA) v1.0.0

We present a parallel algorithm and scalable implementation for genome analysis, specifically the problem of finding overlaps and alignments for data from "third generation" long read sequencers. While long sequences of DNA offer enormous advantages for biological analysis and insight, current long read sequencing instruments have high error rates and therefore require different approaches to analysis than their short read counterparts. Our work focuses on an efficient distributed-memory parallelization of an accurate single-node algorithm for overlapping and aligning long reads. We achieve scalability of this irregular algorithm by addressing the competing issues of increasing parallelism, minimizing communication, constraining the memory footprint, and ensuring good load balance. The resulting application, DiBELLA, is the first distributed memory overlapper and aligner specifically designed for long reads and parallel scalability.

Ellis, Marquita↗
DOE OSTI2024

Multicellular magnetotactic bacteria are genetically heterogeneous consortia with metabolically differentiated cells

Consortia of multicellular magnetotactic bacteria (MMB) are currently the only known example of bacteria without a unicellular stage in their life cycle. Because of their recalcitrance to cultivation, most previous studies of MMB have been limited to microscopic observations. To study the biology of these unique organisms in more detail, we use multiple culture-independent approaches to analyze the genomics and physiology of MMB consortia at single-cell resolution. We separately sequenced the metagenomes of 22 individual MMB consortia, representing 8 new species, and quantified the genetic diversity within each MMB consortium. This revealed that, counter to conventional views, cells within MMB consortia are not clonal. Single consortia metagenomes were then used to reconstruct the species-specific metabolic potential and infer the physiological capabilities of MMB. To validate genomic predictions, we performed stable isotope probing (SIP) experiments and interrogated MMB consortia using fluorescence in situ hybridization (FISH) combined with nanoscale secondary ion mass spectrometry (NanoSIMS). By coupling FISH with bioorthogonal noncanonical amino acid tagging (BONCAT), we explored their in situ activity as well as variation of protein synthesis within cells. We demonstrate that MMB consortia are mixotrophic sulfate reducers and that they exhibit metabolic differentiation between individual cells, suggesting that MMB consortia are more complex than previously thought. These findings expand our understanding of MMB diversity, ecology, genomics, and physiology, as well as offer insights into the mechanisms underpinning the multicellular nature of their unique lifestyle.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Crystal structure of the kinase domain of a receptor tyrosine kinase from a choanoflagellate, Monosiga brevicollis

Genomic analysis of the unicellular choanoflagellate, Monosiga brevicollis (MB), revealed the remarkable presence of cell signaling and adhesion protein domains that are characteristically associated with metazoans. Strikingly, receptor tyrosine kinases, one of the most critical elements of signal transduction and communication in metazoans, are present in choanoflagellates. We determined the crystal structure at 1.95 Å resolution of the kinase domain of the M . brevicollis receptor tyrosine kinase C8 (RTKC8, a member of the choanoflagellate receptor tyrosine kinase C family) bound to the kinase inhibitor staurospaurine. The chonanoflagellate kinase domain is closely related in sequence to mammalian tyrosine kinases (~ 40% sequence identity to the human Ephrin kinase domain EphA3) and, as expected, has the canonical protein kinase fold. The kinase is structurally most similar to human Ephrin (EphA5), even though the extracellular sensor domain is completely different from that of Ephrin. The RTKC8 kinase domain is in an active conformation, with two staurosporine molecules bound to the kinase, one at the active site and another at the peptide-substrate binding site. To our knowledge this is the first example of staurospaurine binding in the Aurora A activation segment (AAS). We also show that the RTKC8 kinase domain can phosphorylate tyrosine residues in peptides from its C-terminal tail segment which is presumably the mechanism by which it transmits the extracellular stimuli to alter cellular function.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Novel Extracellular Electron Transfer Channels in a Gram-Positive Thermophilic Bacterium

Biogenic transformation of Fe minerals, associated with extracellular electron transfer (EET), allows microorganisms to exploit high-potential refractory electron acceptors for energy generation. EET-capable thermophiles are dominated by hyperthermophilic archaea and Gram-positive bacteria. Information on their EET pathways is sparse. Here, we describe EET channels in the thermophilic Gram-positive bacterium Carboxydothermus ferrireducens that drive exoelectrogenesis and rapid conversion of amorphous mineral ferrihydrite to large magnetite crystals. Microscopic studies indicated biocontrolled formation of unusual formicary-like ultrastructure of the magnetite crystals and revealed active colonization of anodes in bioelectrochemical systems (BESs) by C. ferrireducens . The internal structure of micron-scale biogenic magnetite crystals is reported for the first time. Genome analysis and expression profiling revealed three constitutive c -type multiheme cytochromes involved in electron exchange with ferrihydrite or an anode, sharing insignificant homology with previously described EET-related cytochromes thus representing novel determinants of EET. Our studies identify these cytochromes as extracellular and reveal potentially novel mechanisms of cell-to-mineral interactions in thermal environments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Molecular evolution of human coronavirus-NL63, -229E, -HKU1 and -OC43 in hospitalized children in China

Human coronaviruses (HCoVs) HCoV-NL63, HCoV-229E, HCoV-HKU1 and HCoV-OC43 have been circulated in the human population worldwide, and they are associated with a broad range of respiratory diseases with varying severity. However, there are neither effective therapeutic drugs nor licensed vaccines available for the treatment and prevention of infections by the four HCoVs. In this study, we collected nasopharyngeal aspirates of children hospitalized for respiratory tract infection in China during 2014–2018 and conducted next-generation sequencing. Sequences of four HCoVs were then selected for an in-depth analysis. Genome sequences of 2 HCoV-NL63, 8 HCoV-229E, 2 HCoV-HKU1, and 6 HCoV-OC43 were obtained. Based on the full-length S gene, a strong temporal signal was found in HCoV-229E and the molecular evolutionary rate was 6 × 10 −4 substitutions/site/year. Based on the maximum-likelihood (ML) phylogenetic tree of complete S gene, we designated H78 as a new sub-genotype C2 of HCoV-HKU1, and the obtained P43 sequence was grouped into the reported novel genotype K of HCoV-OC43 circulating in Guangzhou, China. Based on the complete genome, potential recombination events were found to occur as two phenomena, namely intraspecies and interspecies. Moreover, we observed two amino acid substitutions in the S1 subunit of obtained HCoV-NL63 (G534V) and HCoV-HKU1 (H512R), while residues 534 and 512 are important for the binding of angiotensin-converting enzyme 2 and neutralizing antibodies, respectively. Our findings might provide a clue for the molecular evolution of the four HCoVs and help in the early diagnosis, treatment and prevention of broad-spectrum HCoV infection.

Shao, Nan↗
DOE OSTI2026

Growth-associated polyhydroxybutyrate accumulation in Azospira suillum PS during aerobic and perchlorate respiration

Polyhydroxyalkanoates (PHAs) are widespread microbial storage polymers increasingly recognized for roles beyond carbon and energy storage, including redox homeostasis and stress physiology. While PHA accumulation is classically associated with stationary-phase metabolism under severe nutrient imbalance, comparatively little is known about growth-associated PHA synthesis in facultative anaerobes with unusual respiratory strategies. Here, we investigated polyhydroxybutyrate (PHB) metabolism in Azospira suillum PS, a genetically tractable perchlorate-reducing bacterium capable of both aerobic and anaerobic respiration. Using physiological growth experiments, targeted gene deletions, PHB extractions, and intracellular redox measurements, we examined PHB accumulation under varying respiratory and nutrient conditions. We demonstrate that PHB accumulates during exponential growth under moderately nitrogen-limited conditions, both aerobically and during perchlorate respiration, representing a rare example of growth-associated PHB synthesis under anaerobic conditions. Genomic analysis revealed four phaC homologs, one of which could not be deleted under the experimental conditions tested and co-localized with phaB and phaR. Redox profiling further revealed a strong positive correlation between PHB accumulation and intracellular NADPH/NADP+ ratios. Together, these findings expand the physiological contexts in which PHB synthesis is known to occur and highlight perchlorate-respiring bacteria as underexplored model systems for studying growth-integrated carbon and redox storage strategies.

Meier, David A O↗
DOE OSTI2022

Alicyclobacillus mali FL18 as a Novel Source of Glycosyl Hydrolases: Characterization of a New Thermophilic β-Xylosidase Tolerant to Monosaccharides

A thermo-acidophilic bacterium, Alicyclobacillus mali FL18, was isolated from a hot spring of Pisciarelli, near Naples, Italy; following genome analysis, a novel putative β-xylosidase, AmβXyl, belonging to the glycosyl hydrolase (GH) family 3 was identified. A synthetic gene was produced, cloned in pET-30a(+), and expressed in Escherichia coli BL21 (DE3) RIL. The purified recombinant protein, which showed a dimeric structure, had optimal catalytic activity at 80 °C and pH 5.6, exhibiting 60% of its activity after 2 h at 50 °C and displaying high stability (more than 80%) at pH 5.0–8.0 after 16 h. AmβXyl is mainly active on both para-nitrophenyl-β-D-xylopyranoside (K M 0.52 mM, k cat 1606 s -1 , and k cat /K M 3088.46 mM -1 ·s -1 ) and para-nitrophenyl-α-L-arabinofuranoside (K M 10.56 mM, k cat 2395.8 s -1 , and k cat /K M 226.87 mM -1 ·s -1 ). Thin-layer chromatography showed its ability to convert xylooligomers (xylobiose and xylotriose) into xylose, confirming that AmβXyl is a true β-xylosidase. Furthermore, no inhibitory effect on enzymatic activity by metal ions, detergents, or EDTA was observed except for 5 mM Cu 2+ . AmβXyl showed an excellent tolerance to organic solvents; in particular, the enzyme increased its activity at high concentrations (30%) of organic solvents such as ethanol, methanol, and DMSO. Lastly, the enzyme showed not only a good tolerance to inhibition by xylose, arabinose, and glucose, but was activated by 0.75 M xylose and up to 1.5 M by both arabinose and glucose. The high tolerance to organic solvents and monosaccharides together with other characteristics reported above suggests that AmβXyl may have several applications in many industrial fields.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents

The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact.

59 BASIC BIOLOGICAL SCIENCES↗