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      Impact of antibiotic perturbation on fecal viral communities in mice


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          Viruses and bacteriophages have a strong impact on intestinal barrier function and the composition and functional properties of commensal bacterial communities. Shifts of the fecal virome might be involved in human diseases, including inflammatory bowel disease (IBD). Loss-of-function variants in the nucleotide-binding oligomerization domain-containing protein 2 ( NOD2) gene are associated with an increased risk of developing Crohn’s disease, a subtype of human chronic IBD, where specific changes in fecal viral communities have also been described. To improve our understanding of the dynamics of the enteric virome, we longitudinally characterized the virome in fecal samples from wild-type C57BL/6J and NOD2 knock-out mice in response to an antibiotic perturbation. Sequencing of virus-like particles demonstrated both a high diversity and high interindividual variation of the murine fecal virome composed of eukaryotic viruses and bacteriophages. Antibiotics had a significant impact on the fecal murine virome. Viral community composition only partially recovered in the observation period (10 weeks after cessation of antibiotics) irrespective of genotype. However, compositional shifts in the virome and bacteriome were highly correlated, suggesting that the loss of specific phages may contribute to prolonged dysregulation of the bacterial community composition. We suggest that therapeutic interference with the fecal virome may represent a novel approach in microbiota-targeted therapies.

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          Most cited references64

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              Fast gapped-read alignment with Bowtie 2.

              As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

                Author and article information

                Role: Editor
                G3 (Bethesda)
                G3: Genes|Genomes|Genetics
                Oxford University Press (US )
                January 2023
                22 November 2022
                22 November 2022
                : 13
                : 1
                : jkac293
                Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel , 24098 Kiel, Germany
                Zoological Institute, Christian-Albrechts University of Kiel , 24098 Kiel, Germany
                Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel , 24098 Kiel, Germany
                Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel , 24098 Kiel, Germany
                Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel , 24098 Kiel, Germany
                Author notes
                Present address for Jacqueline Moltzau Anderson: Department of Medicine, University of California San Francisco, 94117 San Francisco, CA, USA.
                Present address for Simone Lipinski: University Cancer Center Schleswig-Holstein, University Medical Center Campus Kiel, 24105 Kiel, Germany.
                Corresponding author: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU) Kiel, Rosalind-Franklin-Str. 12, Kiel 24105, Germany. Email: philip.rosenstiel@ 123456uksh.de

                Tim Lachnit contributed equally to this work. Authorship order was determined by the origin of the conceptualization and design of this work.

                Author information
                © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 27 June 2022
                : 27 October 2022
                : 26 November 2022
                Page count
                Pages: 12
                Funded by: Deutsche Forschungsgemeinschaft, DOI 10.13039/501100001659;

                virome,intestinal bacteriophages,antibiotic perturbation,nod2,resilience
                virome, intestinal bacteriophages, antibiotic perturbation, nod2, resilience


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