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      Viruses in the fecal microbiota of monozygotic twins and their mothers

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          Abstract

          Viral diversity and lifecycles are poorly understood in the human gut and other body habitats. Therefore, we sequenced the viromes (metagenomes) of virus-like particles isolated from fecal samples collected from adult female monozygotic twins and their mothers at three time points over a one-year period. These datasets were compared to datasets of sequenced bacterial 16S rRNA genes and total fecal community DNA. Co-twins and their mothers share a significantly greater degree of similarity in their fecal bacterial communities than do unrelated individuals. In contrast, viromes are unique to individuals regardless of their degree of genetic relatedness. Despite remarkable interpersonal variations in viromes and their encoded functions, intrapersonal diversity is very low, with >95% of virotypes retained over the period surveyed, and with viromes dominated by a few temperate phage that exhibit remarkable genetic stability. These results indicate that a predatory viral-microbial dynamic, manifest in a number of other characterized environmental ecosystems, is notably absent in the very distal intestine.

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          Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

          The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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            Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex.

            We constructed error-correcting DNA barcodes that allow one run of a massively parallel pyrosequencer to process up to 1,544 samples simultaneously. Using these barcodes we processed bacterial 16S rRNA gene sequences representing microbial communities in 286 environmental samples, corrected 92% of sample assignment errors, and thus characterized nearly as many 16S rRNA genes as have been sequenced to date by Sanger sequencing.
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              The TIGRFAMs database of protein families.

              TIGRFAMs is a collection of manually curated protein families consisting of hidden Markov models (HMMs), multiple sequence alignments, commentary, Gene Ontology (GO) assignments, literature references and pointers to related TIGRFAMs, Pfam and InterPro models. These models are designed to support both automated and manually curated annotation of genomes. TIGRFAMs contains models of full-length proteins and shorter regions at the levels of superfamilies, subfamilies and equivalogs, where equivalogs are sets of homologous proteins conserved with respect to function since their last common ancestor. The scope of each model is set by raising or lowering cutoff scores and choosing members of the seed alignment to group proteins sharing specific function (equivalog) or more general properties. The overall goal is to provide information with maximum utility for the annotation process. TIGRFAMs is thus complementary to Pfam, whose models typically achieve broad coverage across distant homologs but end at the boundaries of conserved structural domains. The database currently contains over 1600 protein families. TIGRFAMs is available for searching or downloading at www.tigr.org/TIGRFAMs.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                0028-0836
                1476-4687
                2 June 2010
                15 July 2010
                1 January 2011
                : 466
                : 7304
                : 334-338
                Affiliations
                [1 ]Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108
                [2 ]Department of Biology, San Diego State University, San Diego, CA 92182
                [3 ]Advanced Water Management Centre, The University of Queensland, QLD, Australia
                [4 ]Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108
                Author notes

                Author contributions A.R. and J.I.G designed the experiments, A.H. recruited the patients, A.R, M.H, and N.H. generated the data, A.R., F.A., F.R, and J.I.G. interpreted the results, A.R., F.R., and J.I.G. wrote the paper.

                Author information Virome datasets are accessible in the NCBI Short Read Archive under accession number SRA012183. 16S rRNA and fecal microbiome datasets are available in GenBank under genome project ID 32089 and SRA002775. RNA-Seq data are deposited in Gene Expression Omnibus (GSE21906; see Methods for further details).

                Correspondence to: jgordon@ 123456wustl.edu
                Article
                nihpa208953
                10.1038/nature09199
                2919852
                20631792
                85779fec-f0e9-478b-a51c-856ae09e75e4

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                History
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P01 DK078669-03S1 ||DK
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