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Article ; Online: Illuminating the Virosphere Through Global Metagenomics.

Call, Lee / Nayfach, Stephen / Kyrpides, Nikos C

Annual review of biomedical data science

2021 Volume 4, Page(s) 369–391

Abstract: Viruses are the most abundant biological entity on Earth, infect cellular organisms from all domains of life, and are central players in the global biosphere. Over the last century, the discovery and characterization of viruses have progressed steadily ... ...

Abstract	Viruses are the most abundant biological entity on Earth, infect cellular organisms from all domains of life, and are central players in the global biosphere. Over the last century, the discovery and characterization of viruses have progressed steadily alongside much of modern biology. In terms of outright numbers of novel viruses discovered, however, the last few years have been by far the most transformative for the field. Advances in methods for identifying viral sequences in genomic and metagenomic datasets, coupled to the exponential growth of environmental sequencing, have greatly expanded the catalog of known viruses and fueled the tremendous growth of viral sequence databases. Development and implementation of new standards, along with careful study of the newly discovered viruses, have transformed and will continue to transform our understanding of microbial evolution, ecology, and biogeochemical cycles, leading to new biotechnological innovations across many diverse fields, including environmental, agricultural, and biomedical sciences.
MeSH term(s)	Ecology ; Genome, Viral ; Metagenome ; Metagenomics ; Viruses/genetics
Language	English
Publishing date	2021-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2574-3414
ISSN (online)	2574-3414
DOI	10.1146/annurev-biodatasci-012221-095114
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Article ; Online: Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs.

Melendez Hebib, Valeria / Taft, Diana H / Stoll, Barbara / Liu, Jinxin / Call, Lee / Guthrie, Gregory / Jensen, Nick / Hair, Amy B / Mills, David A / Burrin, Douglas G

Nutrients

2023 Volume 15, Issue 11

Abstract: Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is ... ...

Abstract	Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic
MeSH term(s)	Animals ; Humans ; Bifidobacterium longum subspecies infantis ; Enterocolitis, Necrotizing/epidemiology ; Enterocolitis, Necrotizing/prevention & control ; Enterocolitis, Necrotizing/etiology ; Gastrointestinal Microbiome ; Incidence ; Milk, Human ; Probiotics ; Swine
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15112585
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Article ; Online: IMG/VR v4: an expanded database of uncultivated virus genomes within a framework of extensive functional, taxonomic, and ecological metadata.

Camargo, Antonio Pedro / Nayfach, Stephen / Chen, I-Min A / Palaniappan, Krishnaveni / Ratner, Anna / Chu, Ken / Ritter, Stephan J / Reddy, T B K / Mukherjee, Supratim / Schulz, Frederik / Call, Lee / Neches, Russell Y / Woyke, Tanja / Ivanova, Natalia N / Eloe-Fadrosh, Emiley A / Kyrpides, Nikos C / Roux, Simon

Nucleic acids research

2022 Volume 51, Issue D1, Page(s) D733–D743

Abstract: Viruses are widely recognized as critical members of all microbiomes. Metagenomics enables large-scale exploration of the global virosphere, progressively revealing the extensive genomic diversity of viruses on Earth and highlighting the myriad of ways ... ...

Abstract	Viruses are widely recognized as critical members of all microbiomes. Metagenomics enables large-scale exploration of the global virosphere, progressively revealing the extensive genomic diversity of viruses on Earth and highlighting the myriad of ways by which viruses impact biological processes. IMG/VR provides access to the largest collection of viral sequences obtained from (meta)genomes, along with functional annotation and rich metadata. A web interface enables users to efficiently browse and search viruses based on genome features and/or sequence similarity. Here, we present the fourth version of IMG/VR, composed of >15 million virus genomes and genome fragments, a ≈6-fold increase in size compared to the previous version. These clustered into 8.7 million viral operational taxonomic units, including 231 408 with at least one high-quality representative. Viral sequences in IMG/VR are now systematically identified from genomes, metagenomes, and metatranscriptomes using a new detection approach (geNomad), and IMG standard annotation are complemented with genome quality estimation using CheckV, taxonomic classification reflecting the latest taxonomic standards, and microbial host taxonomy prediction. IMG/VR v4 is available at https://img.jgi.doe.gov/vr, and the underlying data are available to download at https://genome.jgi.doe.gov/portal/IMG_VR.
MeSH term(s)	Databases, Genetic ; Genome, Viral ; Metadata ; Metagenomics ; Software
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac1037
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Article ; Online: Unraveling the functional dark matter through global metagenomics.

Nature

2023 Volume 622, Issue 7983, Page(s) 594–602

Abstract: Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and ... ...

Abstract	Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and activities
MeSH term(s)	Cluster Analysis ; Metagenome/genetics ; Metagenomics/methods ; Proteins/chemistry ; Proteins/classification ; Proteins/genetics ; Databases, Protein ; Protein Conformation ; Microbiology
Chemical Substances	Proteins
Language	English
Publishing date	2023-10-11
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-06583-7
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Article ; Online: Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome.

Nayfach, Stephen / Páez-Espino, David / Call, Lee / Low, Soo Jen / Sberro, Hila / Ivanova, Natalia N / Proal, Amy D / Fischbach, Michael A / Bhatt, Ami S / Hugenholtz, Philip / Kyrpides, Nikos C

Nature microbiology

2021 Volume 6, Issue 7, Page(s) 960–970

Abstract: Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 ... ...

Abstract	Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts.
MeSH term(s)	Archaea/virology ; Bacteria/virology ; Bacteriophages/genetics ; Catalogs as Topic ; DNA Viruses/classification ; DNA Viruses/genetics ; DNA, Viral/genetics ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Genetic Variation ; Genome, Viral/genetics ; Humans ; Metagenomics ; Phylogeny ; Viral Proteins/genetics
Chemical Substances	DNA, Viral ; Viral Proteins
Language	English
Publishing date	2021-06-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-021-00928-6
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Article ; Online: Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC

Call, Lee / Stoll, Barbara / Oosterloo, Berthe / Ajami, Nadim / Sheikh, Fariha / Wittke, Anja / Waworuntu, Rosaline / Berg, Brian / Petrosino, Joseph / Olutoye, Oluyinka / Burrin, Douglas

Microbiome. 2018 Dec., v. 6, no. 1

2018

Abstract: Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids ...

Abstract	Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored. Our objective was to characterize the effects of lactose- and corn syrup solid-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC. Preterm piglets (103 days gestation) were given total parenteral nutrition (2 days) followed by gradual (5 days) advancement of enteral feeding of formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS), or 1:1 mix (MIX). Gut contents and mucosal samples were collected and analyzed for microbial profiles by sequencing the V4 region of the 16S rRNA gene. Metabolomic profiles of cecal contents and plasma were analyzed by LC/GC mass spectrometry. NEC incidence was 14, 50, and 44% in the LAC, MIX, and CSS groups, respectively. The dominant classes of bacteria were Bacilli, Clostridia, and Gammaproteobacteria. The number of observed OTUs was lowest in colon contents of CSS-fed pigs. CSS-based formula was associated with higher Bacilli and lower Clostridium from clusters XIVa and XI in the colon. NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum. Plasma from NEC piglets was enriched with metabolites of purine metabolism, aromatic amino acid metabolism, and bile acids. Markers of glycolysis, e.g., lactate, were increased in the cecal contents of CSS-fed pigs and in plasma of pigs which developed NEC. Feeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence. We conclude that feeding preterm piglets a corn syrup solid vs. lactose-based formula increases the incidence of NEC and produces distinct metabolomic signatures despite modest changes in microbiome profiles.
Keywords	Bacilli ; Clostridium ; amino acids ; animal disease models ; bacteria ; bile acids ; blood plasma ; bottle feeding ; cecum ; colon ; corn syrup ; disease incidence ; disease severity ; enteral feeding ; enterocolitis ; gamma-Proteobacteria ; glycolysis ; ileum ; infant formulas ; intestinal microorganisms ; intestinal mucosa ; lactic acid ; lactose ; metabolites ; metabolomics ; microbiome ; nutrient content ; piglet feeding ; piglets ; premature birth ; purines ; risk factors ; species richness ; stomach ; total parenteral nutrition
Language	English
Dates of publication	2018-12
Document type	Article ; Online
Note	Resource is Open Access ; Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
ZDB-ID	2697425-3
ISSN	2049-2618
ISSN	2049-2618
DOI	10.1186/s40168-018-0498-0
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Article ; Online: IMG/PR: a database of plasmids from genomes and metagenomes with rich annotations and metadata.

Camargo, Antonio Pedro / Call, Lee / Roux, Simon / Nayfach, Stephen / Huntemann, Marcel / Palaniappan, Krishnaveni / Ratner, Anna / Chu, Ken / Mukherjeep, Supratim / Reddy, T B K / Chen, I-Min A / Ivanova, Natalia N / Eloe-Fadrosh, Emiley A / Woyke, Tanja / Baltrus, David A / Castañeda-Barba, Salvador / de la Cruz, Fernando / Funnell, Barbara E / Hall, James P J /

Mukhopadhyay, Aindrila / Rocha, Eduardo P C / Stalder, Thibault / Top, Eva / Kyrpides, Nikos C

Nucleic acids research

2023 Volume 52, Issue D1, Page(s) D164–D173

Abstract: Plasmids are mobile genetic elements found in many clades of Archaea and Bacteria. They drive horizontal gene transfer, impacting ecological and evolutionary processes within microbial communities, and hold substantial importance in human health and ... ...

Abstract	Plasmids are mobile genetic elements found in many clades of Archaea and Bacteria. They drive horizontal gene transfer, impacting ecological and evolutionary processes within microbial communities, and hold substantial importance in human health and biotechnology. To support plasmid research and provide scientists with data of an unprecedented diversity of plasmid sequences, we introduce the IMG/PR database, a new resource encompassing 699 973 plasmid sequences derived from genomes, metagenomes and metatranscriptomes. IMG/PR is the first database to provide data of plasmid that were systematically identified from diverse microbiome samples. IMG/PR plasmids are associated with rich metadata that includes geographical and ecosystem information, host taxonomy, similarity to other plasmids, functional annotation, presence of genes involved in conjugation and antibiotic resistance. The database offers diverse methods for exploring its extensive plasmid collection, enabling users to navigate plasmids through metadata-centric queries, plasmid comparisons and BLAST searches. The web interface for IMG/PR is accessible at https://img.jgi.doe.gov/pr. Plasmid metadata and sequences can be downloaded from https://genome.jgi.doe.gov/portal/IMG_PR.
MeSH term(s)	Humans ; Metagenome ; Metadata ; Software ; Databases, Genetic ; Plasmids/genetics ; Microbiota
Language	English
Publishing date	2023-11-06
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad964
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Article ; Online: IMG/VR v3: an integrated ecological and evolutionary framework for interrogating genomes of uncultivated viruses.

Roux, Simon / Páez-Espino, David / Chen, I-Min A / Palaniappan, Krishna / Ratner, Anna / Chu, Ken / Reddy, T B K / Nayfach, Stephen / Schulz, Frederik / Call, Lee / Neches, Russell Y / Woyke, Tanja / Ivanova, Natalia N / Eloe-Fadrosh, Emiley A / Kyrpides, Nikos C

Nucleic acids research

2020 Volume 49, Issue D1, Page(s) D764–D775

Abstract: Viruses are integral components of all ecosystems and microbiomes on Earth. Through pervasive infections of their cellular hosts, viruses can reshape microbial community structure and drive global nutrient cycling. Over the past decade, viral sequences ... ...

Abstract	Viruses are integral components of all ecosystems and microbiomes on Earth. Through pervasive infections of their cellular hosts, viruses can reshape microbial community structure and drive global nutrient cycling. Over the past decade, viral sequences identified from genomes and metagenomes have provided an unprecedented view of viral genome diversity in nature. Since 2016, the IMG/VR database has provided access to the largest collection of viral sequences obtained from (meta)genomes. Here, we present the third version of IMG/VR, composed of 18 373 cultivated and 2 314 329 uncultivated viral genomes (UViGs), nearly tripling the total number of sequences compared to the previous version. These clustered into 935 362 viral Operational Taxonomic Units (vOTUs), including 188 930 with two or more members. UViGs in IMG/VR are now reported as single viral contigs, integrated proviruses or genome bins, and are annotated with a new standardized pipeline including genome quality estimation using CheckV, taxonomic classification reflecting the latest ICTV update, and expanded host taxonomy prediction. The new IMG/VR interface enables users to efficiently browse, search, and select UViGs based on genome features and/or sequence similarity. IMG/VR v3 is available at https://img.jgi.doe.gov/vr, and the underlying data are available to download at https://genome.jgi.doe.gov/portal/IMG_VR.
MeSH term(s)	Base Sequence ; Cluster Analysis ; Databases, Genetic ; Ecosystem ; Evolution, Molecular ; Genome, Viral ; Geography ; Molecular Sequence Annotation ; Sequence Homology, Nucleic Acid ; User-Computer Interface ; Viruses/genetics
Language	English
Publishing date	2020-10-29
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkaa946
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Article: Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs

Journal of Lipid Research. 2020 July, v. 61, no. 7

2020

Abstract: Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil ...

Abstract	Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, and γ-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. The colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid-sensitive gram-positive bacteria.
Keywords	Clostridium ; Enterobacteriaceae ; Gram-positive bacteria ; anaerobes ; bacterial communities ; bile acids ; bilirubin ; biomarkers ; blood plasma ; cholestasis ; colon ; dietary fat ; emulsions ; fatty acid composition ; gamma-glutamyltransferase ; intestinal microorganisms ; liver ; liver function ; metabolomics ; parenteral feeding ; piglets ; premature birth ; soybean oil
Language	English
Dates of publication	2020-07
Size	p. 1038-1051.
Publishing place	Elsevier BV
Document type	Article
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1194/jlr.ra120000652
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Article ; Online: Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC.

Call, Lee / Stoll, Barbara / Oosterloo, Berthe / Ajami, Nadim / Sheikh, Fariha / Wittke, Anja / Waworuntu, Rosaline / Berg, Brian / Petrosino, Joseph / Olutoye, Oluyinka / Burrin, Douglas

Microbiome

2018 Volume 6, Issue 1, Page(s) 111

Abstract: Background: Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn ...

Abstract	Background: Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored. Objective: Our objective was to characterize the effects of lactose- and corn syrup solid-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC. Design/methods: Preterm piglets (103 days gestation) were given total parenteral nutrition (2 days) followed by gradual (5 days) advancement of enteral feeding of formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS), or 1:1 mix (MIX). Gut contents and mucosal samples were collected and analyzed for microbial profiles by sequencing the V4 region of the 16S rRNA gene. Metabolomic profiles of cecal contents and plasma were analyzed by LC/GC mass spectrometry. Results: NEC incidence was 14, 50, and 44% in the LAC, MIX, and CSS groups, respectively. The dominant classes of bacteria were Bacilli, Clostridia, and Gammaproteobacteria. The number of observed OTUs was lowest in colon contents of CSS-fed pigs. CSS-based formula was associated with higher Bacilli and lower Clostridium from clusters XIVa and XI in the colon. NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum. Plasma from NEC piglets was enriched with metabolites of purine metabolism, aromatic amino acid metabolism, and bile acids. Markers of glycolysis, e.g., lactate, were increased in the cecal contents of CSS-fed pigs and in plasma of pigs which developed NEC. Conclusions: Feeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence. We conclude that feeding preterm piglets a corn syrup solid vs. lactose-based formula increases the incidence of NEC and produces distinct metabolomic signatures despite modest changes in microbiome profiles.
MeSH term(s)	Animal Feed/analysis ; Animals ; Bacillus/classification ; Bacillus/genetics ; Bacillus/isolation & purification ; Clostridium/classification ; Clostridium/genetics ; Clostridium/isolation & purification ; Dietary Carbohydrates ; Enteral Nutrition ; Enterocolitis, Necrotizing/etiology ; Enterocolitis, Necrotizing/microbiology ; Female ; Gammaproteobacteria/classification ; Gammaproteobacteria/genetics ; Gammaproteobacteria/isolation & purification ; Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract/microbiology ; High Fructose Corn Syrup/administration & dosage ; Lactose/administration & dosage ; Pregnancy ; Premature Birth ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Swine
Chemical Substances	Dietary Carbohydrates ; High Fructose Corn Syrup ; RNA, Ribosomal, 16S ; Lactose (J2B2A4N98G)
Language	English
Publishing date	2018-06-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2697425-3
ISSN	2049-2618 ; 2049-2618
ISSN (online)	2049-2618
ISSN	2049-2618
DOI	10.1186/s40168-018-0498-0
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