scholarly journals The human gut virome database

2019 ◽  
Author(s):  
Ann C. Gregory ◽  
Olivier Zablocki ◽  
Allison Howell ◽  
Benjamin Bolduc ◽  
Matthew B. Sullivan
Keyword(s):  
Viral Particle ◽  
Human Microbiome ◽  
Species Level ◽  
Healthy Individuals ◽  
Human Gut ◽  
Detection Rates ◽  
Viral Genomes ◽  
Health And Disease ◽  
Meta Analyses ◽  
Viral Sequences

ABSTRACTThe gut microbiome profoundly impacts human health and disease, but viruses that infect these microbes are likely also important. Problematically, viral sequences are often missed due to insufficient reference viral genomes. Here we (i) built a human gut virome database, GVD, from 648 viral particle metagenomes or microbial metagenomes from 572 individuals previously searched for viruses, (ii) assessed its effectiveness, and (iii) conducted meta-analyses. GVD contains 13,203 unique viral populations (approximately species-level taxa) organized into 702 novel genera, which roughly doubles known phage genera and improves viral detection rates over NCBI viral RefSeq nearly 60-fold. Applying GVD, we assessed and rejected the idea of a ‘core’ gut virome in healthy individuals, and found through meta-analyses that technical artifacts are more impactful than any ‘treatment’ effect across the entire meta-study dataset. Together, this foundational resource and these findings will help human microbiome researchers better identify viral roles in health and disease.

scholarly journals Genome binning of viral entities from bulk metagenomics data

2021 ◽  
Author(s):  
Joachim Johansen ◽  
Damian R Plichta ◽  
Jakob Nybo Nissen ◽  
Marie Louise Jespersen ◽  
Shiraz A Shah ◽  
...  
Keyword(s):  
Deep Learning ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Gastrointestinal Diseases ◽  
Human Gut ◽  
Viral Genomes ◽  
Host Interactions ◽  
Metagenomics Data ◽  
Health And Disease ◽  
Viral Host Interactions

Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal are not well understood. In addition, a paucity of whole-virome datasets from subjects with gastrointestinal diseases is preventing a deeper understanding of the virome role in disease and in gastrointestinal ecology as a whole. By combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets we developed the Phages from Metagenomics Binning (PHAMB) approach for binning thousands of viral genomes directly from bulk metagenomics data. Simultaneously our methodology enables clustering of viral genomes into accurate taxonomic viral populations. We applied this methodology on the Human Microbiome Project 2 (HMP2) cohort and recovered 6,077 HQ genomes from 1,024 viral populations and explored viral-host interactions. We show that binning can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.

scholarly journals Rethinking antimicrobial stewardship paradigms in the context of the gut microbiome

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Farah Shahi ◽  
Kelly Redeker ◽  
James Chong
Keyword(s):  
Gut Microbiome ◽  
Human Microbiome ◽  
Health Impacts ◽  
Current Evidence ◽  
Gram Negative Bacteria ◽  
Human Gut ◽  
Routes Of Administration ◽  
Health And Disease ◽  
Diverse Community ◽  
Review Current

Abstract Ongoing concerns over the presence and persistence of antimicrobial resistance (AMR), particularly in Gram-negative bacteria, continue to have significant global health impacts. The gastrointestinal tract, or ‘gut’, environment amplifies AMR in the human gut microbiome, even in the absence of antibiotics. It constitutes a complex and diverse community of organisms, and patterns and alterations within it are increasingly being found to be associated with states of health and disease. Our understanding of the effects of routes of administration of antimicrobials on the gut microbiome is still lacking despite recent advances in metagenomics. In this article we review current evidence for antibiotic effects on gut microbiota and explore possible prescribing and stewardship approaches that would seek to minimize these effects. If we are to preserve existing and new antimicrobials, we need to consider their use in the context of their effect on gut ecology, and the human microbiome in general.

scholarly journals GutCyc: a Multi-Study Collection of Human Gut Microbiome Metabolic Models

2016 ◽  
Author(s):  
Aria S. Hahn ◽  
Tomer Altman ◽  
Kishori M. Konwar ◽  
Niels W. Hanson ◽  
Dongjae Kim ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Therapeutic Interventions ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Disease States ◽  
Health And Disease ◽  
Inflammatory Bowel

AbstractAdvances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GUTCYC, a compendium of environmental pathway genome databases constructed from 418 assembled human microbiome datasets using METAPATHWAYS, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the PATHWAY TOOLS software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GUTCYC provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GUTCYC data products are searchable online, or may be downloaded and explored locally using METAPATHWAYS and PATHWAY TOOLS.

Computational Approaches for Unraveling the Effects of Variation in the Human Genome and Microbiome

2020 ◽  
Vol 3 (1) ◽  
pp. 411-432
Author(s):  
Chengsheng Zhu ◽  
Maximilian Miller ◽  
Zishuo Zeng ◽  
Yanran Wang ◽  
Yannick Mahlich ◽  
...  
Keyword(s):  
Human Genome ◽  
Critical Role ◽  
Human Microbiome ◽  
Healthy Individuals ◽  
Computational Tools ◽  
The Past ◽  
Disease States ◽  
Health And Disease ◽  
Taxonomic Groups ◽  
Genome Variants

The past two decades of analytical efforts have highlighted how much more remains to be learned about the human genome and, particularly, its complex involvement in promoting disease development and progression. While numerous computational tools exist for the assessment of the functional and pathogenic effects of genome variants, their precision is far from satisfactory, particularly for clinical use. Accumulating evidence also suggests that the human microbiome's interaction with the human genome plays a critical role in determining health and disease states. While numerous microbial taxonomic groups and molecular functions of the human microbiome have been associated with disease, the reproducibility of these findings is lacking. The human microbiome–genome interaction in healthy individuals is even less well understood. This review summarizes the available computational methods built to analyze the effect of variation in the human genome and microbiome. We address the applicability and precision of these methods across their possible uses. We also briefly discuss the exciting, necessary, and now possible integration of the two types of data to improve the understanding of pathogenicity mechanisms.

scholarly journals Microbiome in Eosinophilic Esophagitis—Metagenomic, Metatranscriptomic, and Metabolomic Changes: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan D. Busing ◽  
Matthew Buendia ◽  
Yash Choksi ◽  
Girish Hiremath ◽  
Suman R. Das
Keyword(s):  
Systematic Review ◽  
Eosinophilic Esophagitis ◽  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Gastrointestinal Diseases ◽  
Published Data ◽  
Human Gut ◽  
Esophageal Biopsy ◽  
Biochemical Alterations ◽  
Meta Analyses

Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE).Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed.Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included.Results: A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy (n = 3), esophageal string test (n = 1), salivary sampling (n = 1), or stool specimen (n = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy (n = 2) and blood plasma (n = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls.Conclusions: While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.

scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish C Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z Li
Keyword(s):  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Geographic Region ◽  
Antibody Treatment ◽  
Viral Genomes ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Abstract Background Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

Integration of viral DNA sequences in cells transformed by adenovirus 2 or SV40

1980 ◽  
Vol 210 (1180) ◽  
pp. 423-435 ◽  
Keyword(s):  
Cell Lines ◽  
Dna Sequences ◽  
Viral Genome ◽  
Viral Dna ◽  
Viral Genomes ◽  
Viral Dnas ◽  
Cellular Dna ◽  
Viral Insertion ◽  
Viral Sequences ◽  
Heteroduplex Formation

We have cloned and propagated in prokaryotic vectors the viral DNA sequences that are integrated in a variety of cells transformed by adenovirus 2 or SV40. Analysis of the clones reveals that the viral DNA sequences sometimes are arranged in a simple fashion, collinear with the viral genome; in other cell lines there are complex arrangements of viral sequences in which tracts of the viral genome are inverted with respect to each other. In several cases the nucleotide sequences at the joints between cell and viral sequences have been determined: usually there is a sharp transition between cellular and viral DNAs. The viral sequences are integrated at different locations within the genomes of different cell lines; likewise there is no specific site on the viral genomes at which integration occurs. Sometimes the viral sequences are integrated within repetitive cellular DNA, and sometimes within unique sequences. In some cases there is evidence that the viral sequences along with the flanking cell DNA have been amplified after integration. The sequences that flank the viral insertion in the line of SV40-transformed rat cells known as 14B have been used as probes to isolate, from untransformed rat cells, clones that carry the region of the chromosome in which integration occurred. Analysis of the structure of these clones by restriction endonuclease digestion and heteroduplex formation shows that a rearrangement of cellular sequences has occurred, presumably as a consequence of integration.

scholarly journals The Glycine Lipids ofBacteroides thetaiotaomicronAre Important for Fitness during GrowthIn VivoandIn Vitro

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acid ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cellular Membrane ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Health And Disease ◽  
And Function

ABSTRACTAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by theN-acylation of the amino acid, and this is followed by subsequentO-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes anN-acyltransferase activity responsible for the production of a monoacylated glycine calledN-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes sequenced so far, theglsBgene is located immediately downstream from a gene, namedglsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicron, and we confirm thatglsBis required for the production of GL inB. thetaiotaomicron. Moreover, we show thatglsBis important for the ability ofB. thetaiotaomicronto adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacteriumB. thetaiotaomicron.IMPORTANCEThe gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from theBacteroidales, an order that includesBacteroidesandPrevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced byBacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation ofB. thetaiotaomicronto a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut byB. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant inB. thetaiotaomicronand therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

scholarly journals Nora virus, a persistent virus in Drosophila, defines a new picorna-like virus family

2006 ◽  
Vol 87 (10) ◽  
pp. 3045-3051 ◽  
Author(s):  
Mazen S. Habayeb ◽  
Sophia K. Ekengren ◽  
Dan Hultmark
Keyword(s):  
Persistent Infection ◽  
Open Reading Frames ◽  
Close Relative ◽  
Virus Family ◽  
Viral Genomes ◽  
Persistent Infections ◽  
New Family ◽  
Nora Virus ◽  
Persistent Virus ◽  
Viral Sequences

Several viruses, including picornaviruses, are known to establish persistent infections, but the mechanisms involved are poorly understood. Here, a novel picorna-like virus, Nora virus, which causes a persistent infection in Drosophila melanogaster, is described. It has a single-stranded, positive-sense genomic RNA of 11879 nt, followed by a poly(A) tail. Unlike other picorna-like viruses, the genome has four open reading frames (ORFs). One ORF encodes a picornavirus-like cassette of proteins for virus replication, including an iflavirus-like RNA-dependent RNA polymerase and a helicase that is related to those of mammalian picornaviruses. The three other ORFs are not closely related to any previously described viral sequences. The unusual sequence and genome organization in Nora virus suggest that it belongs to a new family of picorna-like viruses. Surprisingly, Nora virus could be detected in all tested D. melanogaster laboratory stocks, as well as in wild-caught material. The viral titres varied enormously, between 104 and 1010 viral genomes per fly in different stocks, without causing obvious pathological effects. The virus was also found in Drosophila simulans, a close relative of D. melanogaster, but not in more distantly related Drosophila species. It will now be possible to use Drosophila genetics to study the factors that control this persistent infection.

scholarly journals Characteristics of preceding Ia activity on postactivation depression in health and disease

2015 ◽  
Vol 113 (10) ◽  
pp. 3751-3758 ◽  
Author(s):  
Behdad Tahayori ◽  
Bahman Tahayori ◽  
David Koceja
Keyword(s):  
Patient Group ◽  
H Reflex ◽  
Separate Experiment ◽  
Healthy Individuals ◽  
Fisher Discriminant Analysis ◽  
Fisher Discriminant ◽  
Exponential Decrease ◽  
Health And Disease ◽  
Abnormal Pattern ◽  
Postactivation Depression

Previous activation of the soleus Ia afferents causes a depression in the amplitude of the H-reflex. This mechanism is referred to as postactivation depression (PAD) and is suggested to be presynaptically mediated. With the use of a paired reflex depression paradigm (eliciting two H-reflexes with conditioning-test intervals from 80 ms to 300 ms), PAD was examined in a group of healthy individuals and a group of hemiplegic patients. Healthy individuals showed substantial depression of the test H-reflex at all intervals. Although the patient group showed substantially less depression at all intervals, increasing the interval between the two reflexes sharply reduced the depression. In a separate experiment, we varied the size of the conditioning H-reflex against a constant test H-reflex. In healthy individuals, by increasing the size of the conditioning H-reflex, the amplitude of the test H-reflex exponentially decreased. In the patient group, however, this pattern was dependent on the conditioning-test interval; increasing the size of the conditioning H-reflex caused an exponential decrease in the size of the test reflex at intervals shorter than 150 ms. This pattern was similar to that of healthy individuals. However, conducting the same protocol at a longer interval (300 ms) in these patients resulted in an abnormal pattern (instead of an exponential decrease in the size of the test reflex, exaggerated responses were observed). Fisher discriminant analysis suggested that these two patterns (which differed only in the timing between the two stimuli) were substantially different from each other. Therefore, it is suggested that the abnormal pattern of PAD in hemiplegic stroke patients could be a contributing factor for the pathophysiology of spasticity.

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