Phage-inclusive profiling of human gut microbiomes with Phanta

Pinto, Yishay; Chakraborty, Meenakshi; Jain, Navami; Bhatt, Ami S.

doi:10.1038/s41587-023-01799-4

Cited by 15 publications

(16 citation statements)

References 74 publications

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“…As the attention of microbiome scientists turns towards phages, we believe it will be important to establish the rules of engagement of these viruses and their host bacteria. Phage-aware or trans-kingdom approaches, such as Marker-MAGu or recently developed Phanta 33 , will need to be adopted to this end. For example, can we identify promising phages for use in phage therapy based on how their appearance or disappearance in individuals’ guts effects potentially pathogenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

Phage-bacteria dynamics during the first years of life revealed by trans-kingdom marker gene analysis

Tisza,

Lloyd,

Hoffman

et al. 2023

Preprint

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Humans are colonized with commensal bacteria soon after birth, and, while this colonization is affected by lifestyle and other factors, bacterial colonization proceeds through well-studied phases. However, less is known about phage communities in early human development due to small study sizes, inability to leverage large databases, and lack of appropriate bioinformatics tools. In this study, whole genome shotgun sequencing data from the TEDDY study, composed of 12,262 longitudinal samples from 887 children in 4 countries, is reanalyzed to assess phage and bacterial dynamics simultaneously. Reads from these samples were mapped to marker genes from both bacteria and a new database of tens of thousands of phage taxa from human microbiomes. We uncover that each child is colonized by hundreds of different phages during the early years, and phages are more transitory than bacteria. Participants’ samples continually harbor new phage species over time whereas the diversification of bacterial species begins to saturate. Phage data improves the ability for machine learning models to discriminate samples by country. Finally, while phage populations were individual-specific, striking patterns arose from the larger dataset, showing clear trends of ecological succession amongst phages, which correlated well with putative host bacteria. Improved understanding of phage-bacterial relationships may reveal new means by which to shape and modulate the microbiome and its constituents to improve health and reduce disease, particularly in vulnerable populations where antibiotic use and/or other more drastic measures may not be advised.

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Section: Discussionmentioning

confidence: 99%

Phage-bacteria dynamics during the first years of life revealed by trans-kingdom marker gene analysis

Tisza,

Lloyd,

Hoffman

et al. 2023

Preprint

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“…for Oblin-1, -lower 40 for Oblin-2) 60 and a final pHMM was computed. msaconverter 83 was used throughout.…”

Section: Protein Homology Bioinformaticsmentioning

confidence: 99%

“…Initially, RDVA Obelisk sequences were searched against the IMG/M spacer database using blastn (default settings), only keeping perfect matches with no gaps or mismatches (k-mers) -the longest k-mer match between a given spacer/Obelisk pairing was kept. Next, all kept spacers containing any 12-mer match to common Illumina sequencing adaptors were omitted using KmerCatcher (default settings) 60 . For each remaining spacer, the information content was estimated 99 by comparing how efficiently the compression algorithm zip (-9) 100 could "deflate" a given spacer -a larger length normalised deflation indicates a less complex spacer sequence that is less likely to be unambiguously mapped to a specific (Obelisk) sequence.…”

Section: Obelisk Spacer Analysismentioning

confidence: 99%

Viroid-like colonists of human microbiomes

Zheludev,

Edgar,

Lopez-Galiano

et al. 2024

Preprint

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Here, we describe the 'Obelisks,' a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. 'Obelisks' share several properties: (i) apparently circular RNA ~1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the 'Oblins'. We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ~7% of analysed stool metatranscriptomes (29/440) and in ~50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species (Streptococcus sanguinis) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.

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“…Phages, viruses that infect prokaryotes, are among the most abundant genetic entities on earth, yet until the advent of affordable metagenomic sequencing, only a small number of human microbiome-related phages were known. Now, DNA viruses are estimated to outnumber bacteria in the human gut 2:1 1 and certain phages, such as the prototypical crAssphage (Carjivirus communis), are thought to be among the most prevalent and abundant genetic entities associated with humans 2 . Despite these advances, human associated phages remain under-characterized and under-cultured despite their importance in shaping both microbial communities and human health [3][4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Analysis and culturing of the prototypic crAssphage reveals a phage-plasmid lifestyle

Schmidtke,

Hickey,

Liachko

et al. 2024

Preprint

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The prototypic crAssphage (Carjivirus communis) is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For the last decade, crAssphage has escaped plaque-dependent culturing efforts, leading us to investigate alternative lifestyles that might explain its widespread success. Through genomic analyses and culturing, we find that crAssphage uses a phage-plasmid lifestyle to persist extrachromosomally. Plasmid-related genes are more highly expressed than those implicated in phage maintenance. Leveraging this finding, we use a plaque-free culturing approach to measure crAssphage replication in culture with Phocaeicola vulgatus, Phocaeicola dorei, and Bacteroides stercoris, revealing a broad host range. We demonstrate that crAssphage persists with its hosts in culture without causing major cell lysis events or integrating into host chromosomes. The ability to switch between phage and plasmid lifestyles within a wide range of hosts contributes to the prolific nature of crAssphage in the human gut microbiome.

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Phage-inclusive profiling of human gut microbiomes with Phanta

Cited by 15 publications

References 74 publications

Phage-bacteria dynamics during the first years of life revealed by trans-kingdom marker gene analysis

Phage-bacteria dynamics during the first years of life revealed by trans-kingdom marker gene analysis

Viroid-like colonists of human microbiomes

Analysis and culturing of the prototypic crAssphage reveals a phage-plasmid lifestyle

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