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Cell, Vol. 175, No. 1. (20 September 2018)
Abstract
Pathogen virulence exists on a continuum. The strategies that drive symptomatic or asymptomatic infections remain largely unknown. We took advantage of the concept of lethal dose 50 (LD50) to ask which component of individual non-genetic variation between hosts defines whether they survive or succumb to infection. Using the enteric pathogen Citrobacter, we found no difference in pathogen burdens between healthy and symptomatic populations. Iron metabolism-related genes were induced in asymptomatic hosts compared to symptomatic or naive mice. Dietary iron conferred complete protection ...
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Cell, Vol. 175, No. 1. (20 September 2018)
by James H. Sun, Linda Zhou, Daniel J. Emerson, et al.Sai A. Phyo, Katelyn R. Titus, Wanfeng Gong, Thomas G. Gilgenast, Jonathan A. Beagan, Beverly L. Davidson, Flora Tassone, Jennifer E. Phillips-Cremins
Abstract
More than 25 inherited human disorders are caused by the unstable expansion of repetitive DNA sequences termed short tandem repeats (STRs). A fundamental unresolved question is why some STRs are susceptible to pathologic expansion, whereas thousands of repeat tracts across the human genome are relatively stable. Here, we discover that nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. We identify a subset of boundaries with markedly higher CpG island density compared to the rest of the genome. daSTRs ...
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eLife, Vol. 7 (18 September 2018)
Abstract
Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize complex polysaccharides. Although vitamins and other nutrients are also essential for commensal fitness, much less is known about how commensal bacteria compete with each other or the host for these critical resources. Unlike in Escherichia coli, transport loci for vitamin B12 (cobalamin) and other corrinoids in human gut Bacteroides are replete with conserved genes encoding proteins whose functions are unknown. Here we report that one of these proteins, BtuG, is a ...
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eLife, Vol. 7 (18 September 2018)
by Inés Martínez, Maria X. Maldonado-Gomez, João Carlos C. Gomes-Neto, et al.Hatem Kittana, Hua Ding, Robert Schmaltz, Payal Joglekar, Roberto Jiménez J. Cardona, Nathan L. Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda E. Ramer-Tait, Jens Walter
Abstract
The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of ...
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by Stanislav S. Terekhov, Ivan V. Smirnov, Maja V. Malakhova, et al.Andrei E. Samoilov, Alexander I. Manolov, Anton S. Nazarov, Dmitry V. Danilov, Svetlana A. Dubiley, Ilya A. Osterman, Maria P. Rubtsova, Elena S. Kostryukova, Rustam H. Ziganshin, Maria A. Kornienko, Anna A. Vanyushkina, Olga N. Bukato, Elena N. Ilina, Valentin V. Vlasov, Konstantin V. Severinov, Alexander G. Gabibov, Sidney Altman
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Nature, Vol. 561, No. 7723. (05 September 2018), pp. 338-342
Abstract
Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to fifteen-fold differences in hotspot usage between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex-biased ...
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The ISME journal, Vol. 12, No. 10. (October 2018), pp. 2559-2574
by Jan F. Gogarten, T. Jonathan Davies, Jacquelynn Benjamino, et al.J. Peter Gogarten, Joerg Graf, Alexander Mielke, Roger Mundry, Michael C. Nelson, Roman M. Wittig, Fabian H. Leendertz, Sébastien Calvignac-Spencer
Abstract
Microbiomes impact a variety of processes including a host's ability to access nutrients and maintain health. While host species differences in microbiomes have been described across ecosystems, little is known about how microbiomes assemble, particularly in the ecological and social contexts in which they evolved. We examined gut microbiome composition in nine sympatric wild non-human primate (NHP) species. Despite sharing an environment and interspecific interactions, individuals harbored unique and persistent microbiomes influenced by host species, social group, and parentage, but surprisingly ...
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The ISME journal, Vol. 12, No. 10. (October 2018), pp. 2470-2478
Abstract
Marine microbes have tremendous diversity, but a fundamental question remains unanswered: why are there so many microbial species in the sea? The idea of functional redundancy for microbial communities has long been assumed, so that the high level of richness is often explained by the presence of different taxa that are able to conduct the exact same set of metabolic processes and that can readily replace each other. Here, we refute the hypothesis of functional redundancy for marine microbial communities by ...
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The ISME journal, Vol. 12, No. 10. (October 2018), pp. 2403-2416
Abstract
Endospore-formers in the human microbiota are well adapted for host-to-host transmission, and an emerging consensus points to their role in determining health and disease states in the gut. The human gut, more than any other environment, encourages the maintenance of endospore formation, with recent culture-based work suggesting that over 50% of genera in the microbiome carry genes attributed to this trait. However, there has been limited work on the ecological role of endospores and other stress-resistant cellular states in the human ...
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eLife, Vol. 7 (10 September 2018)
posted to evolution fly interaction tf tfbs
by djkt
on 2018-09-17 21:16:30
Abstract
Convergent evolutionary events in independent lineages provide an opportunity to understand why evolution favors certain outcomes over others. We studied such a case where a large set of genes-those coding for the ribosomal proteins-gained cis-regulatory sequences for a particular transcription regulator (Mcm1) in independent fungal lineages. We present evidence that these gains occurred because Mcm1 shares a mechanism of transcriptional activation with an ancestral regulator of the ribosomal protein genes, Rap1. Specifically, we show that Mcm1 and Rap1 have the inherent ...
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by Eilis Hannon, Olivia Knox, Karen Sugden, et al.Joe Burrage, Chloe C. Y. Wong, Daniel W. Belsky, David L. Corcoran, Louise Arseneault, Terrie E. Moffitt, Avshalom Caspi, Jonathan Mill
posted to methylation qtl twin
by djkt
on 2018-09-17 21:11:14
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Abstract
The mechanisms by which different microbes colonize the healthy human gut versus other body sites, the gut in disease states, or other environments remain largely unknown. Identifying microbial genes influencing fitness in the gut could lead to new ways to engineer probiotics or disrupt pathogenesis. We approach this problem by measuring the statistical association between a species having a gene and the probability that the species is present in the gut microbiome. The challenge is that closely related species tend to ...
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Genome biology, Vol. 19, No. 1. (24 August 2018)
by Peter Kerpedjiev, Nezar Abdennur, Fritz Lekschas, et al.Chuck McCallum, Kasper Dinkla, Hendrik Strobelt, Jacob M. Luber, Scott B. Ouellette, Alaleh Azhir, Nikhil Kumar, Jeewon Hwang, Soohyun Lee, Burak H. Alver, Hanspeter Pfister, Leonid A. Mirny, Peter J. Park, Nils Gehlenborg
Abstract
We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io ...
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Gut (31 August 2018)
by Raul Y. Tito, Samuel Chaffron, Clara Caenepeel, et al.Gipsi Lima-Mendez, Jun Wang, Sara Vieira-Silva, Gwen Falony, Falk Hildebrand, Youssef Darzi, Leen Rymenans, Chloë Verspecht, Peer Bork, Severine Vermeire, Marie Joossens, Jeroen Raes
Abstract
Human gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as Blastocystis, an enteric stramenopiles with worldwide distribution. Here, we surveyed the prevalence and subtype variation of Blastocystis in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between Blastocystis subtypes and identified microbiota-host covariates and quantified microbiota differentiation relative to subtype abundances. We profiled stool samples from 616 healthy individuals from the FGFP ...
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BMC biology, Vol. 16, No. 1. (07 August 2018)
Abstract
The human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary ...
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Genome biology and evolution, Vol. 10, No. 8. (01 August 2018), pp. 1858-1874
by Louis S. Ates, Anzaan Dippenaar, Fadel Sayes, et al.Alexandre Pawlik, Christiane Bouchier, Laurence Ma, Robin M. Warren, Wladimir Sougakoff, Laleh Majlessi, Jeroen W. J. van Heijst, Florence Brossier, Roland Brosch
Abstract
Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed ...
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Genome biology and evolution, Vol. 10, No. 8. (01 August 2018), pp. 2023-2036
Abstract
The human prefrontal cortex (PFC) differs from that of other primates with respect to size, histology, and functional abilities. Here, we analyzed genome-wide expression data of humans, chimpanzees, and rhesus macaques to discover evolutionary changes in transcription factor (TF) networks that may underlie these phenotypic differences. We determined the co-expression networks of all TFs with species-specific expression including their potential target genes and interaction partners in the PFC of all three species. Integrating these networks allowed us inferring an ancestral network ...
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Abstract
Three-dimensional genome structures play a key role in gene regulation and cell functions. Characterization of genome structures necessitates single-cell measurements. This has been achieved for haploid cells but has remained a challenge for diploid cells. We developed a single-cell chromatin conformation capture method, termed Dip-C, that combines a transposon-based whole-genome amplification method to detect many chromatin contacts, called META (multiplex end-tagging amplification), and an algorithm to impute the two chromosome haplotypes linked by each contact. We reconstructed the genome structures of ...
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Cell, Vol. 174, No. 6. (06 September 2018)
by Sven Heinz, Lorane Texari, Michael G. B. Hayes, et al.Matthew Urbanowski, Max W. Chang, Ninvita Givarkes, Alexander Rialdi, Kris M. White, Randy A. Albrecht, Lars Pache, Ivan Marazzi, Adolfo García-Sastre, Megan L. Shaw, Christopher Benner
posted to chromatin elongation expression structure
by djkt ✚
on 2018-09-11 19:36:03
Abstract
How transcription affects genome 3D organization is not well understood. We found that during influenza A (IAV) infection, rampant transcription rapidly reorganizes host cell chromatin interactions. These changes occur at the ends of highly transcribed genes, where global inhibition of transcription termination by IAV NS1 protein causes readthrough transcription for hundreds of kilobases. In these readthrough regions, elongating RNA polymerase II disrupts chromatin interactions by inducing cohesin displacement from CTCF sites, leading to locus decompaction. Readthrough transcription into heterochromatin regions switches ...
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Cell, Vol. 174, No. 6. (06 September 2018)
by Jotham Suez, Niv Zmora, Gili Zilberman-Schapira, et al.Uria Mor, Mally Dori-Bachash, Stavros Bashiardes, Maya Zur, Dana Regev-Lehavi, Rotem Ben-Zeev Brik, Sara Federici, Max Horn, Yotam Cohen, Andreas E. Moor, David Zeevi, Tal Korem, Eran Kotler, Alon Harmelin, Shalev Itzkovitz, Nitsan Maharshak, Oren Shibolet, Meirav Pevsner-Fischer, Hagit Shapiro, Itai Sharon, Zamir Halpern, Eran Segal, Eran Elinav
Abstract
Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed ...
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Cell, Vol. 174, No. 6. (06 September 2018)
by Niv Zmora, Gili Zilberman-Schapira, Jotham Suez, et al.Uria Mor, Mally Dori-Bachash, Stavros Bashiardes, Eran Kotler, Maya Zur, Dana Regev-Lehavi, Rotem Ben-Zeev B. Brik, Sara Federici, Yotam Cohen, Raquel Linevsky, Daphna Rothschild, Andreas E. Moor, Shani Ben-Moshe, Alon Harmelin, Shalev Itzkovitz, Nitsan Maharshak, Oren Shibolet, Hagit Shapiro, Meirav Pevsner-Fischer, Itai Sharon, Zamir Halpern, Eran Segal, Eran Elinav
Abstract
Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered ...
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Microbiome, Vol. 6, No. 1. (06 August 2018)
Abstract
Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to ...
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mSphere, Vol. 3, No. 2. (r 2018)
Abstract
A wide diversity of fungi have been detected in the human gastrointestinal (GI) tract with the potential to provide or influence important functions. However, many of the fungi most commonly detected in stool samples are also present in food or the oral cavity. Therefore, to recognize which gut fungi are likely to have a sustained influence on human health, there is a need to separate transient members of the GI tract from true colonizers. To identify colonizing fungi, the eukaryotic rRNA ...
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Nature biotechnology, Vol. 36, No. 8. (06 August 2018), pp. 686-691
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Nature biotechnology, Vol. 36, No. 8. (06 August 2018), pp. 682-686
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Nature (22 August 2018)
by Viviane Slon, Fabrizio Mafessoni, Benjamin Vernot, et al.Cesare de Filippo, Steffi Grote, Bence Viola, Mateja Hajdinjak, Stéphane Peyrégne, Sarah Nagel, Samantha Brown, Katerina Douka, Tom Higham, Maxim B. Kozlikin, Michael V. Shunkov, Anatoly P. Derevianko, Janet Kelso, Matthias Meyer, Kay Prüfer, Svante Pääbo
Abstract
Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago1,2. Here we present the genome of 'Denisova 11', a bone fragment from Denisova Cave (Russia)3 and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave4-6. The mother came from a population more closely related ...
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eLife, Vol. 7 (20 August 2018)
Abstract
Disentangling the effect on genomic diversity of natural selection from that of demography is notoriously difficult, but necessary to properly reconstruct the history of species. Here, we use high-quality human genomic data to show that purifying selection at linked sites (i.e. background selection, BGS) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. We find that the magnitude and relative importance of BGS and gBGC are largely determined by variation in recombination rate ...
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Cell, Vol. 174, No. 5. (23 August 2018)
by Darren A. Cusanovich, Andrew J. Hill, Delasa Aghamirzaie, et al.Riza M. Daza, Hannah A. Pliner, Joel B. Berletch, Galina N. Filippova, Xingfan Huang, Lena Christiansen, William S. DeWitt, Choli Lee, Samuel G. Regalado, David F. Read, Frank J. Steemers, Christine M. Disteche, Cole Trapnell, Jay Shendure
posted to atac-seq rodent single_cell
by djkt ✚
on 2018-08-27 19:45:39
Abstract
We applied a combinatorial indexing assay, sci-ATAC-seq, to profile genome-wide chromatin accessibility in ∼100,000 single cells from 13 adult mouse tissues. We identify 85 distinct patterns of chromatin accessibility, most of which can be assigned to cell types, and ∼400,000 differentially accessible elements. We use these data to link regulatory elements to their target genes, to define the transcription factor grammar specifying each cell type, and to discover in vivo correlates of heterogeneity in accessibility within cell types. We develop a technique ...
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Molecular biology and evolution (19 June 2018)
Abstract
The relative evolutionary rates at individual sites in proteins are informative measures of conservation or adaptation. Often used as evolutionarily-aware conservation scores, relative rates reveal key functional or strongly-selected residues. Estimating rates in a phylogenetic context requires specifying a protein substitution model, which is typically a phenomenological model trained on a large empirical dataset. A strong emphasis has traditionally been placed on selecting the "best-fit" model, with the implicit understanding that suboptimal or otherwise ill-fitting models might bias inferences. However, the ...
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eLife, Vol. 7 (14 August 2018)
Abstract
We present a multispecies coalescent model for quantitative traits that allows for evolutionary inferences at micro- and macroevolutionary scales. A major advantage of this model is its ability to incorporate genealogical discordance underlying a quantitative trait. We show that discordance causes a decrease in the expected trait covariance between more closely related species relative to more distantly related species. If unaccounted for, this outcome can lead to an overestimation of a trait's evolutionary rate, to a decrease in its phylogenetic signal, ...
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Genome biology, Vol. 19, No. 1. (25 July 2018)
Abstract
Enhancers play an important role in morphological evolution and speciation by controlling the spatiotemporal expression of genes. Previous efforts to understand the evolution of enhancers in primates have typically studied many enhancers at low resolution, or single enhancers at high resolution. Although comparative genomic studies reveal large-scale turnover of enhancers, a specific understanding of the molecular steps by which mammalian or primate enhancers evolve remains elusive. We identified candidate hominoid-specific liver enhancers from H3K27ac ChIP-seq data. After locating orthologs in 11 ...
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Genome biology, Vol. 19, No. 1. (30 July 2018)
Abstract
Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates ...
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Trends in genetics : TIG, Vol. 34, No. 9. (September 2018), pp. 653-665
Abstract
Cells in a multicellular organism fulfill specific functions by enacting cell-type-specific programs of gene regulation. Single-cell RNA sequencing technologies have provided a transformative view of cell-type-specific gene expression, the output of cell-type-specific gene regulatory programs. This review discusses new single-cell genomic technologies that complement single-cell RNA sequencing by providing additional readouts of cellular state beyond the transcriptome. We highlight regression models as a simple yet powerful approach to relate gene expression to other aspects of cellular state, and in doing so, ...
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Trends in genetics : TIG, Vol. 34, No. 9. (September 2018), pp. 693-703
Abstract
Evolutionary dynamics in laboratory microbial evolution experiments can be surprisingly complex. In the past two decades, observations of these dynamics have challenged simple models of adaptation and have shown that clonal interference, hitchhiking, ecological diversification, and contingency are widespread. In recent years, advances in high-throughput strain maintenance and phenotypic assays, the dramatically reduced cost of genome sequencing, and emerging methods for lineage barcoding have made it possible to observe evolutionary dynamics at unprecedented resolution. These new methods can now begin to ...
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Nature, Vol. 560, No. 7718. (August 2018), pp. 325-330
by Uri Ben-David, Benjamin Siranosian, Gavin Ha, et al.Helen Tang, Yaara Oren, Kunihiko Hinohara, Craig A. Strathdee, Joshua Dempster, Nicholas J. Lyons, Robert Burns, Anwesha Nag, Guillaume Kugener, Beth Cimini, Peter Tsvetkov, Yosef E. Maruvka, Ryan O'Rourke, Anthony Garrity, Andrew A. Tubelli, Pratiti Bandopadhayay, Aviad Tsherniak, Francisca Vazquez, Bang Wong, Chet Birger, Mahmoud Ghandi, Aaron R. Thorner, Joshua A. Bittker, Matthew Meyerson, Gad Getz, Rameen Beroukhim, Todd R. Golub
Abstract
Human cancer cell lines are the workhorse of cancer research. Although cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here we use genomic analyses of 106 human cell lines grown in two laboratories to show extensive clonal diversity. Further comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 ...
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The ISME journal (13 June 2018)
Abstract
Information on how the oral microbiome develops during early childhood and how external factors influence this ecological process is scarce. We used high-throughput sequencing to characterize bacterial composition in saliva samples collected at 3, 6, 12, 24 months and 7 years of age in 90 longitudinally followed children, for whom clinical, dietary and health data were collected. Bacterial composition patterns changed through time, starting with "early colonizers", including Streptococcus and Veillonella; other bacterial genera such as Neisseria settled after 1 or ...
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The ISME journal (13 June 2018)
Abstract
The second messenger cyclic diguanylate (c-di-GMP) is ubiquitously used by bacteria to modulate and shift between different phenotypes including motility, biofilm formation and virulence. Here we show that c-di-GMP-associated genes are widespread on plasmids and that enzymes that synthesize or degrade c-di-GMP are preferentially encoded on transmissible plasmids. Additionally, expression of enzymes that synthesize c-di-GMP was found to increase both biofilm formation and, interestingly, conjugative plasmid transfer rates. ...
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Nature biotechnology, Vol. 35, No. 1. (January 2017), pp. 81-89
by Stefanía Magnúsdóttir, Almut Heinken, Laura Kutt, et al.Dmitry A. Ravcheev, Eugen Bauer, Alberto Noronha, Kacy Greenhalgh, Christian Jäger, Joanna Baginska, Paul Wilmes, Ronan M. Fleming, Ines Thiele
Abstract
Genome-scale metabolic models derived from human gut metagenomic data can be used as a framework to elucidate how microbial communities modulate human metabolism and health. We present AGORA (assembly of gut organisms through reconstruction and analysis), a resource of genome-scale metabolic reconstructions semi-automatically generated for 773 human gut bacteria. Using this resource, we identified a defined growth medium for Bacteroides caccae ATCC 34185. We also showed that interactions among modeled species depend on both the metabolic potential of each species and ...
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Abstract
In microbiome studies, an important goal is to detect differential abundance of microbes across clinical conditions and treatment options. However, the microbiome compositional data (quantified by relative abundance) are highly skewed, bounded in [0, 1), and often have many zeros. A two-part model is commonly used to separate zeros and positive values explicitly by two submodels: a logistic model for the probability of a specie being present in Part I, and a Beta regression model for the relative abundance conditional on ...
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posted to community_assembly crispr immunity
by djkt
on 2018-08-13 18:07:37
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Cell, Vol. 174, No. 4. (09 August 2018)
posted to crispr phage
by djkt
on 2018-08-13 18:05:12
Abstract
Bacteria utilize CRISPR-Cas adaptive immune systems for protection from bacteriophages (phages), and some phages produce anti-CRISPR (Acr) proteins that inhibit immune function. Despite thorough mechanistic and structural information for some Acr proteins, how they are deployed and utilized by a phage during infection is unknown. Here, we show that Acr production does not guarantee phage replication when faced with CRISPR-Cas immunity, but instead, infections fail when phage population numbers fall below a critical threshold. Infections succeed only if a sufficient Acr ...
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Cell, Vol. 174, No. 4. (09 August 2018)
posted to crispr phage
by djkt
on 2018-08-13 18:03:02
Abstract
Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here, we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate. ...
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Nature (08 August 2018)
by Gioele La Manno, Ruslan Soldatov, Amit Zeisel, et al.Emelie Braun, Hannah Hochgerner, Viktor Petukhov, Katja Lidschreiber, Maria E. Kastriti, Peter Lönnerberg, Alessandro Furlan, Jean Fan, Lars E. Borm, Zehua Liu, David van Bruggen, Jimin Guo, Xiaoling He, Roger Barker, Erik Sundström, Gonçalo Castelo-Branco, Patrick Cramer, Igor Adameyko, Sten Linnarsson, Peter V. Kharchenko
Abstract
RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here we show that RNA velocity-the time derivative of the gene expression state-can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA ...
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Cell, Vol. 174, No. 4. (09 August 2018)
by Arpiar Saunders, Evan Z. Macosko, Alec Wysoker, et al.Melissa Goldman, Fenna M. Krienen, Heather de Rivera, Elizabeth Bien, Matthew Baum, Laura Bortolin, Shuyu Wang, Aleksandrina Goeva, James Nemesh, Nolan Kamitaki, Sara Brumbaugh, David Kulp, Steven A. McCarroll
posted to cns rna-seq rodent single_cell
by djkt
on 2018-08-13 17:55:36
Abstract
The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in ...
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