@article{neves_taxonomic_2019, title = {Taxonomic and functional assessment using metatranscriptomics reveals the effect of {Angus} cattle on rumen microbial signatures}, volume = {1}, copyright = {All rights reserved}, issn = {1751-732X}, doi = {10.1017/S1751731119002453}, abstract = {A greater understanding of the rumen microbiota and its function may help find new strategies to improve feed efficiency in cattle. This study aimed to investigate whether the cattle breed affects specific ruminal taxonomic microbial groups and functions associated with feed conversion ratio (FCR), using two genetically related Angus breeds as a model. Total RNA was extracted from 24 rumen content samples collected from purebred Black and Red Angus bulls fed the same forage diet and then subjected to metatranscriptomic analysis. Multivariate discriminant analysis (sparse partial least square discriminant analysis (sPLS-DA)) and analysis of composition of microbiomes were conducted to identify microbial signatures characterizing Black and Red Angus cattle. Our analyses revealed relationships among bacterial signatures, host breeds and FCR. Although Black and Red Angus are genetically similar, sPLS-DA detected 25 bacterial species and 10 functions that differentiated the rumen microbial signatures between those two breeds. In Black Angus, we identified bacterial taxa Chitinophaga pinensis, Clostridium stercorarium and microbial functions with large and small subunits ribosomal proteins L16 and S7 exhibiting a higher abundance in the rumen microbiome. In Red Angus, nonetheless, we identified the poorly characterized bacterial taxon Oscillibacter valericigenes with a higher abundance and pathways related to carbohydrate metabolism. Analysis of composition of microbiomes revealed that C. pinensis and C. stercorarium exhibited a higher abundance in Black Angus compared to Red Angus associated with FCR, suggesting that these bacterial species may play a key role in the feed conversion efficiency of forage-fed bulls. This study highlights how the discovery of signatures of bacterial taxa and their functions can be used to harness the full potential of the rumen microbiome in Angus cattle.}, language = {eng}, number = {14}, journal = {Animal: An International Journal of Animal Bioscience}, author = {Neves, A. L. A. and Chen, Y. and Lê Cao, K.-A. and Mandal, S. and Sharpton, T. J. and McAllister, T. and Guan, L. L.}, month = oct, year = {2019}, pmid = {31662129}, keywords = {beef cattle, feed efficiency, microbiome, rumen bacteria, rumen microbial functions} } @article{kent_further_2019, title = {Further evaluation of the efficacy of emamectin benzoate for treating {Pseudocapillaria} tomentosa ({Dujardin} 1843) in zebrafish {Danio} rerio ({Hamilton} 1822)}, volume = {42}, copyright = {All rights reserved}, issn = {1365-2761}, doi = {10.1111/jfd.13057}, abstract = {Pseudocapillaria tomentosa is a pathogenic nematode parasite, causing emaciation and severe inflammatory lesions in the intestines in zebrafish Danio rerio (Hamilton 1822). Emamectin benzoate is commercially available analogue of ivermectin used for treating salmon for sea lice, under the brand name SLICE® , and we have used this for treating zebrafish with the P. tomentosa. Here, SLICE® , 0.2 per cent active emamectin benzoate, was used for oral treatments at 0.35 mg emamectin benzoate/kg fish/day for 14 days starting at 7 days post-exposure (dpe). Another experiment entailed initiating treatment during clinical disease (starting at 28 dpe). Early treatment was very effective, but delaying treatment was less so, presumably due to inappetence in clinically affected fish. We evaluated emamectin benzoate delivered in water, using Lice-Solve™ (mectinsol; 1.4\% active emamectin benzoate) in two experiments. Application of four 24-hr treatments, space over 7 days was initiated at 28 dpe at either 0.168 or 0.56 mg emamectin benzoate/L/bath, and both treatments completely eradicated infections. This was 3 or 10 times manufacture's recommended dose, but was not associated with clinical or histological side effects.}, language = {eng}, number = {10}, journal = {Journal of Fish Diseases}, author = {Kent, Michael L. and Watral, Virginia and Gaulke, Christopher A. and Sharpton, Thomas J.}, month = oct, year = {2019}, pmid = {31309582}, pmcid = {PMC6744302}, keywords = {emamectin benzoate, Pseudocapillaria tomentosa, zebrafish Danio rerio}, pages = {1351--1357} } @article{armour_metagenomic_2019, title = {A {Metagenomic} {Meta}-analysis {Reveals} {Functional} {Signatures} of {Health} and {Disease} in the {Human} {Gut} {Microbiome}}, volume = {4}, copyright = {All rights reserved}, issn = {2379-5077}, doi = {10.1128/mSystems.00332-18}, abstract = {While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific microbial functions that stratify healthy and diseased individuals. To improve our understanding of the relationship between the gut microbiome and health, we conducted the first integrative functional analysis of nearly 2,000 publicly available fecal metagenomic samples obtained from eight clinical studies. We identified characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Using regression modeling, we identified specific microbial functions that robustly stratify diseased individuals from healthy controls. Many of these functions overlapped multiple diseases, suggesting a general role in host health, while others were specific to a single disease and may indicate disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. IMPORTANCE The composition of the gut microbiome associates with a wide range of human diseases, but the mechanisms underpinning these associations are not well understood. To shift toward a mechanistic understanding, we integrated distinct metagenomic data sets to identify functions encoded in the gut microbiome that associate with multiple diseases, which may be important to human health. Additionally, we identified functions that associate with specific diseases, which may elucidate disease-specific etiologies. We demonstrated that the functions encoded in the microbiome can be used to classify disease status, but the inclusion of additional patient covariates may be necessary to obtain sufficient accuracy. Ultimately, this analysis advances our understanding of the gut microbiome functions that constitute a healthy microbiome and identifies potential targets for microbiome-based diagnostics and therapeutics.}, language = {eng}, number = {4}, journal = {mSystems}, author = {Armour, Courtney R. and Nayfach, Stephen and Pollard, Katherine S. and Sharpton, Thomas J.}, month = aug, year = {2019}, pmid = {31098399}, pmcid = {PMC6517693}, keywords = {arthritis, cancer, disease, humans, inflammatory bowel disease, liver cirrhosis, metagenomics, microbiome, obesity, type 2 diabetes}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\M9PKD5YM\\Armour et al. - 2019 - A Metagenomic Meta-analysis Reveals Functional Sig.pdf:application/pdf} } @article{raber_combined_2019, title = {Combined {Effects} of {Three} {High}-{Energy} {Charged} {Particle} {Beams} {Important} for {Space} {Flight} on {Brain}, {Behavioral} and {Cognitive} {Endpoints} in {B}6D2F1 {Female} and {Male} {Mice}}, volume = {10}, copyright = {All rights reserved}, issn = {1664-042X}, doi = {10.3389/fphys.2019.00179}, abstract = {The radiation environment in deep space includes the galactic cosmic radiation with different proportions of all naturally occurring ions from protons to uranium. Most experimental animal studies for assessing the biological effects of charged particles have involved acute dose delivery for single ions and/or fractionated exposure protocols. Here, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice 2 months following rapidly delivered, sequential irradiation with protons (1 GeV, 60\%), 16O (250 MeV/n, 20\%), and 28Si (263 MeV/n, 20\%) at 0, 25, 50, or 200 cGy at 4-6 months of age. Cortical BDNF, CD68, and MAP-2 levels were analyzed 3 months after irradiation or sham irradiation. During the dark period, male mice irradiated with 50 cGy showed higher activity levels in the home cage than sham-irradiated mice. Mice irradiated with 50 cGy also showed increased depressive behavior in the forced swim test. When cognitive performance was assessed, sham-irradiated mice of both sexes and mice irradiated with 25 cGy showed normal responses to object recognition and novel object exploration. However, object recognition was impaired in female and male mice irradiated with 50 or 200 cGy. For cortical levels of the neurotrophic factor BDNF and the marker of microglial activation CD68, there were sex × radiation interactions. In females, but not males, there were increased CD68 levels following irradiation. In males, but not females, there were reduced BDNF levels following irradiation. A significant positive correlation between BDNF and CD68 levels was observed, suggesting a role for activated microglia in the alterations in BDNF levels. Finally, sequential beam irradiation impacted the diversity and composition of the gut microbiome. These included dose-dependent impacts and alterations to the relative abundance of several gut genera, such as Butyricicoccus and Lachnospiraceae. Thus, exposure to rapidly delivered sequential proton, 16O ion, and 28Si ion irradiation significantly affects behavioral and cognitive performance, cortical levels of CD68 and BDNF in a sex-dependent fashion, and the gut microbiome.}, language = {eng}, number = {179}, journal = {Frontiers in Physiology}, author = {Raber, Jacob and Yamazaki, Joy and Torres, Eileen Ruth S. and Kirchoff, Nicole and Stagaman, Keaton and Sharpton, Thomas and Turker, Mitchell S. and Kronenberg, Amy}, month = mar, year = {2019}, pmid = {30914962}, pmcid = {PMC6422905}, keywords = {BDNF, CD68, charged particle radiation, depressive-like behavior, gut microbiome, home cage activity, object recognition, space flight}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\AK7NYGMJ\\Raber et al. - 2019 - Combined Effects of Three High-Energy Charged Part.pdf:application/pdf} } @article{li_combined_2019, title = {Combined {Genomic}, {Transcriptomic}, {Proteomic}, and {Physiological} {Characterization} of the {Growth} of {Pecoramyces} sp. {F}1 in {Monoculture} and {Co}-culture {With} a {Syntrophic} {Methanogen}}, volume = {10}, copyright = {All rights reserved}, issn = {1664-302X}, doi = {10.3389/fmicb.2019.00435}, abstract = {In this study, the effects of a syntrophic methanogen on the growth of Pecoramyces sp. F1 was investigated by characterizing fermentation profiles, as well as functional genomic, transcriptomic, and proteomic analysis. The estimated genome size, GC content, and protein coding regions of strain F1 are 106.83 Mb, 16.07\%, and 23.54\%, respectively. Comparison of the fungal monoculture with the methanogen co-culture demonstrated that during the fermentation of glucose, the co-culture initially expressed and then down-regulated a large number of genes encoding both enzymes involved in intermediate metabolism and plant cell wall degradation. However, the number of up-regulated proteins doubled at the late-growth stage in the co-culture. In addition, we provide a mechanistic understanding of the metabolism of this fungus in co-culture with a syntrophic methanogen. Further experiments are needed to explore this interaction during degradation of more complex plant cell wall substrates.}, language = {eng}, number = {435}, journal = {Frontiers in Microbiology}, author = {Li, Yuanfei and Li, Yuqi and Jin, Wei and Sharpton, Thomas J. and Mackie, Roderick I. and Cann, Isaac and Cheng, Yanfen and Zhu, Weiyun}, month = mar, year = {2019}, pmid = {30894845}, pmcid = {PMC6414434}, keywords = {anaerobic fungus, genome, iTRAQ, metabolism, methanogen, RNAseq}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\H3CPQM2J\\Li et al. - 2019 - Combined Genomic, Transcriptomic, Proteomic, and P.pdf:application/pdf} } @article{flannery_is_2019, title = {Is adolescence the missing developmental link in {Microbiome}-{Gut}-{Brain} axis communication?}, volume = {61}, copyright = {All rights reserved}, issn = {1098-2302}, doi = {10.1002/dev.21821}, abstract = {Gut microbial research has recently opened new frontiers in neuroscience and potentiated novel therapies for mental health problems (Mayer, et al., 2014). Much of our understanding of the gut microbiome's role in brain function and behavior, however, has been largely derived from research on nonhuman animals. Even less is known about how the development of the gut microbiome influences critical periods of neural and behavioral development, particularly adolescence. In this review, we first discuss why the gut microbiome has become increasingly relevant to developmental cognitive neuroscience and provide a synopsis of the known connections of the gut microbiome with social-affective brain function and behavior, specifically highlighting human developmental work when possible. We then focus on adolescence, a key period of neurobiological and social-affective development. Specifically, we review the links between the gut microbiome and six overarching domains of change during adolescence: (a) social processes, (b) motivation and behavior, (c) neural development, (d) cognition, (e) neuroendocrine function, and (f) physical health and wellness. Using a developmental science perspective, we summarize key changes across these six domains to underscore the promise for the gut microbiome to bidirectionally influence and transform adolescent development.}, language = {eng}, number = {5}, journal = {Developmental Psychobiology}, author = {Flannery, Jessica and Callaghan, Bridget and Sharpton, Thomas and Fisher, Philip and Pfeifer, Jennifer}, month = jul, year = {2019}, pmid = {30690712}, pmcid = {PMC6776431}, keywords = {adolescence, development cognitive neuroscience, gut microbiome, gut-brain axis, social}, pages = {783--795} } @article{gaulke_longitudinal_2019, title = {A longitudinal assessment of host-microbe-parasite interactions resolves the zebrafish gut microbiome's link to {Pseudocapillaria} tomentosa infection and pathology}, volume = {7}, copyright = {All rights reserved}, issn = {2049-2618}, doi = {10.1186/s40168-019-0622-9}, abstract = {BACKGROUND: Helminth parasites represent a significant threat to the health of human and animal populations, and there is a growing need for tools to treat, diagnose, and prevent these infections. Recent work has turned to the gut microbiome as a utilitarian agent in this regard; components of the microbiome may interact with parasites to influence their success in the gut, meaning that the microbiome may encode new anthelmintic drugs. Moreover, parasite infections may restructure the microbiome's composition in consistent ways, implying that the microbiome may be useful for diagnosing infection. The innovation of these utilities requires foundational knowledge about how parasitic infection, as well as its ultimate success in the gut and impact on the host, relates to the gut microbiome. In particular, we currently possess limited insight into how the microbiome, host pathology, and parasite burden covary during infection. Identifying interactions between these parameters may uncover novel putative methods of disrupting parasite success. RESULTS: To identify interactions between parasite success and the microbiome, we quantified longitudinal associations between an intestinal helminth of zebrafish, Pseudocapillaria tomentosa, and the gut microbiome in 210 4-month-old 5D line zebrafish. Parasite burden and parasite-associated pathology varied in severity throughout the experiment in parasite-exposed fish, with intestinal pathologic changes becoming severe at late time points. Parasite exposure, burden, and intestinal lesions were correlated with gut microbial diversity. Robust generalized linear regression identified several individual taxa whose abundance predicted parasite burden, suggesting that gut microbiota may influence P. tomentosa success. Numerous associations between taxon abundance, burden, and gut pathologic changes were also observed, indicating that the magnitude of microbiome disruption during infection varies with infection severity. Finally, a random forest classifier accurately predicted a fish's exposure to the parasite based on the abundance of gut phylotypes, which underscores the potential for using the gut microbiome to diagnose intestinal parasite infection. CONCLUSIONS: These experiments demonstrate that P. tomentosa infection disrupts zebrafish gut microbiome composition and identifies potential interactions between the gut microbiota and parasite success. The microbiome may also provide a diagnostic that would enable non-destructive passive sampling for P. tomentosa and other intestinal pathogens in zebrafish facilities.}, language = {eng}, number = {1}, journal = {Microbiome}, author = {Gaulke, Christopher A. and Martins, Mauricio L. and Watral, Virginia G. and Humphreys, Ian R. and Spagnoli, Sean T. and Kent, Michael L. and Sharpton, Thomas J.}, month = jan, year = {2019}, pmid = {30678738}, pmcid = {PMC6346533}, keywords = {Animals, Bacteria, Dysbiosis, Female, Gastrointestinal Microbiome, Intestine, Male, Microbial Interactions, Microbiome, Nematoda, Nematode, Nematode Infections, Parasitism, Pseudocapillaria tomentosa, Zebrafish}, pages = {10}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\RU6NU29Y\\Gaulke et al. - 2019 - A longitudinal assessment of host-microbe-parasite.pdf:application/pdf} } @article{kirchoff_gut_2019, title = {The gut microbiome correlates with conspecific aggression in a small population of rescued dogs ({Canis} familiaris)}, volume = {7}, copyright = {All rights reserved}, issn = {2167-8359}, doi = {10.7717/peerj.6103}, abstract = {Aggression is a serious behavioral disorder in domestic dogs that endangers both dogs and humans. The underlying causes of canine aggression are poorly resolved and require illumination to ensure effective therapy. Recent research links the compositional diversity of the gut microbiome to behavioral and psychological regulation in other mammals, such as mice and humans. Given these observations, we hypothesized that the composition of the canine gut microbiome could associate with aggression. We analyzed fecal microbiome samples collected from a small population of pit bull type dogs seized from a dogfighting organization. This population included 21 dogs that displayed conspecific aggressive behaviors and 10 that did not. Beta-diversity analyses support an association between gut microbiome structure and dog aggression. Additionally, we used a phylogenetic approach to resolve specific clades of gut bacteria that stratify aggressive and non-aggressive dogs, including clades within Lactobacillus, Dorea, Blautia, Turicibacter, and Bacteroides. Several of these taxa have been implicated in modulating mammalian behavior as well as gastrointestinal disease states. Although sample size limits this study, our findings indicate that gut microorganisms are linked to dog aggression and point to an aggression-associated physiological state that interacts with the gut microbiome. These results also indicate that the gut microbiome may be useful for diagnosing aggressive behaviors prior to their manifestation and potentially discerning cryptic etiologies of aggression.}, language = {eng}, number = {e6103}, journal = {PeerJ}, author = {Kirchoff, Nicole S. and Udell, Monique A. R. and Sharpton, Thomas J.}, month = jan, year = {2019}, pmid = {30643689}, pmcid = {PMC6330041}, keywords = {Aggression, Dog, Fecal microbiota, Gut microbiome, Gut-brain axis}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\VSLGRIB7\\Kirchoff et al. - 2019 - The gut microbiome correlates with conspecific agg.pdf:application/pdf} } @article{gaulke_marginal_2018, title = {Marginal {Zinc} {Deficiency} and {Environmentally} {Relevant} {Concentrations} of {Arsenic} {Elicit} {Combined} {Effects} on the {Gut} {Microbiome}}, volume = {3}, copyright = {All rights reserved}, issn = {2379-5042}, doi = {10.1128/mSphere.00521-18}, abstract = {Extensive research shows that dietary variation and toxicant exposure impact the gut microbiome, yielding effects on host physiology. However, prior work has mostly considered such exposure-microbiome interactions through the lens of single-factor exposures. In practice, humans exposed to toxicants vary in their dietary nutritional status, and this variation may impact subsequent exposure of the gut microbiome. For example, chronic arsenic exposure affects 200 million people globally and is often comorbid with zinc deficiency. Zinc deficiency can enhance arsenic toxicity, but it remains unknown how zinc status impacts the gut microbiome's response to arsenic exposure and whether this response links to host toxicity. Using 16S amplicon sequencing, we examined the combinatorial effects of exposure to environmentally relevant concentrations of arsenic on the composition of the microbiome in C57BL/6 mice fed diets varying in zinc concentration. Arsenic exposure and marginal zinc deficiency independently altered microbiome diversity. When combined, their effects on microbiome community structure were amplified. Generalized linear models identified microbial taxa whose relative abundance in the gut was perturbed by zinc deficiency, arsenic, or their interaction. Further, we correlated taxonomic abundances with host DNA damage, adiponectin expression, and plasma zinc concentration to identify taxa that may mediate host physiological responses to arsenic exposure or zinc deficiency. Arsenic exposure and zinc restriction also result in increased DNA damage and decreased plasma zinc. These physiological changes are associated with the relative abundance of several gut taxa. These data indicate that marginal zinc deficiency sensitizes the microbiome to arsenic exposure and that the microbiome associates with some toxicological effects of arsenic.IMPORTANCE Xenobiotic compounds, such as arsenic, have the potential to alter the composition and functioning of the gut microbiome. The gut microbiome may also interact with these compounds to mediate their impact on the host. However, little is known about how dietary variation may reshape how the microbiome responds to xenobiotic exposures or how these modified responses may in turn impact host physiology. Here, we investigated the combinatorial effects of marginal zinc deficiency and physiologically relevant concentrations of arsenic on the microbiome. Both zinc deficiency and arsenic exposure were individually associated with altered microbial diversity and when combined elicited synergistic effects. Microbial abundance also covaried with host physiological changes, indicating that the microbiome may contribute to or be influenced by these pathologies. Collectively, this work demonstrates that dietary zinc intake influences the sensitivity of the microbiome to subsequent arsenic exposure.}, language = {eng}, number = {6}, journal = {mSphere}, author = {Gaulke, Christopher A. and Rolshoven, John and Wong, Carmen P. and Hudson, Laurie G. and Ho, Emily and Sharpton, Thomas J.}, month = dec, year = {2018}, pmid = {30518676}, pmcid = {PMC6282007}, keywords = {Animals, arsenic, Arsenic, Bacteria, DNA, Ribosomal, Gastrointestinal Microbiome, gut, Mice, Inbred C57BL, microbiome, RNA, Ribosomal, 16S, Sequence Analysis, DNA, zinc, Zinc}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\LGLTHTNG\\Gaulke et al. - 2018 - Marginal Zinc Deficiency and Environmentally Relev.pdf:application/pdf} } @article{kent_pseudocapillaria_2018, title = {Pseudocapillaria tomentosa in laboratory zebrafish {Danio} rerio: patterns of infection and dose response}, volume = {131}, copyright = {All rights reserved}, issn = {0177-5103}, shorttitle = {Pseudocapillaria tomentosa in laboratory zebrafish {Danio} rerio}, doi = {10.3354/dao03286}, abstract = {Parasites in wild populations almost always exhibit aggregation (overdispersion), in which relatively few hosts are infected with high numbers of the parasites. This pattern of infection has also been observed in laboratory studies, where many of the sources of natural variation are removed. Pseudocapillaria tomentosa (Nematoda) is common in zebrafish (Danio rerio) facilities. We describe here patterns of infections in zebrafish experimentally infected with larvated P. tomentosa eggs in various trials with defined numbers of eggs. One trial with eggs delivered in a gelatin diet is also included. Fish were exposed at 25, 75, and 200 eggs fish-1, and the minimal infectious dose was estimated to be 1.5 eggs fish-1. The ID50 (50\% infective dose) was calculated to be 17.5 eggs fish-1. We also included data from a trial and 2 previously published experiments with undefined doses in which zebrafish were exposed to infectious water and detritus from a tank that previously contained infected fish. All doses resulted in a high prevalence of infection ({\textgreater}70\%), except at the 25 eggs fish-1 dose, where the prevalence was 43-46\%. Mean abundance of worms corresponded to dose, from 0.57 worms fish-1 at 25 eggs fish-1 to 7 worms fish-1 at 200 eggs fish-1. Variance to mean ratios (V/M) and the k parameters showed aggregation across the 8 separate trials, including the gelatin diet. Aggregation increased with increased parasite abundance. Given the consistent observation of aggregation across our experiments, the zebrafish/P. tomentosa system provides a potentially robust, high-throughput model to investigate factors that influence differences in host susceptibility within defined populations.}, language = {eng}, number = {2}, journal = {Diseases of Aquatic Organisms}, author = {Kent, Michael L. and Gaulke, Christopher A. and Watral, Virginia and Sharpton, Thomas J.}, month = nov, year = {2018}, pmid = {30460918}, pmcid = {PMC6474349}, keywords = {Animals, Experimental infection, Female, Fish Diseases, Laboratory Animal Science, Male, Nematoda, Nematode Infections, Parasitism, Pseudocapillaria, Zebrafish}, pages = {121--131} } @article{gaulke_influence_2018, title = {The influence of ethnicity and geography on human gut microbiome composition}, volume = {24}, copyright = {All rights reserved}, issn = {1546-170X}, doi = {10.1038/s41591-018-0210-8}, abstract = {The taxonomic composition of the gut microbiome associates with patient ethnicity and geographic location. This association impacts the development of microbiome-based applications for personalized medicine.}, language = {eng}, number = {10}, journal = {Nature Medicine}, author = {Gaulke, Christopher A. and Sharpton, Thomas J.}, month = oct, year = {2018}, pmid = {30275567}, keywords = {Ethnic Groups, Gastrointestinal Microbiome, Gastrointestinal Tract, Geography, Humans, Microbiota}, pages = {1495--1496} } @article{gaulke_ecophylogenetics_2018, title = {Ecophylogenetics {Clarifies} the {Evolutionary} {Association} between {Mammals} and {Their} {Gut} {Microbiota}}, volume = {9}, copyright = {All rights reserved}, issn = {2150-7511}, doi = {10.1128/mBio.01348-18}, abstract = {Our knowledge of how the gut microbiome relates to mammalian evolution benefits from the identification of gut microbial taxa that are unexpectedly prevalent or unexpectedly conserved across mammals. Such taxa enable experimental determination of the traits needed for such microbes to succeed as gut generalists, as well as those traits that impact mammalian fitness. However, the punctuated resolution of microbial taxonomy may limit our ability to detect conserved gut microbes, especially in cases in which broadly related microbial lineages possess shared traits that drive their apparent ubiquity across mammals. To advance the discovery of conserved mammalian gut microbes, we developed a novel ecophylogenetic approach to taxonomy that groups microbes into taxonomic units based on their shared ancestry and their common distribution across mammals. Applying this approach to previously generated gut microbiome data uncovered monophyletic clades of gut bacteria that are conserved across mammals. It also resolved microbial clades exclusive to and conserved among particular mammalian lineages. Conserved clades often manifest phylogenetic patterns, such as cophylogeny with their host, that indicate that they are subject to selective processes, such as host filtering. Moreover, this analysis identified variation in the rate at which mammals acquire or lose conserved microbial clades and resolved a human-accelerated loss of conserved clades. Collectively, the data from this study reveal mammalian gut microbiota that possess traits linked to mammalian phylogeny, point to the existence of a core set of microbes that comprise the mammalian gut microbiome, and clarify potential evolutionary or ecologic mechanisms driving the gut microbiome's diversification throughout mammalian evolution.IMPORTANCE Our understanding of mammalian evolution has become microbiome-aware. While emerging research links mammalian biodiversity and the gut microbiome, we lack insight into which microbes potentially impact mammalian evolution. Microbes common to diverse mammalian species may be strong candidates, as their absence in the gut may affect how the microbiome functionally contributes to mammalian physiology to adversely affect fitness. Identifying such conserved gut microbes is thus important to ultimately assessing the microbiome's potential role in mammalian evolution. To advance their discovery, we developed an approach that identifies ancestrally related groups of microbes that distribute across mammals in a way that indicates their collective conservation. These conserved clades are presumed to have evolved a trait in their ancestor that matters to their distribution across mammals and which has been retained among clade members. We found not only that such clades do exist among mammals but also that they appear to be subject to natural selection and characterize human evolution.}, language = {eng}, number = {5}, journal = {mBio}, author = {Gaulke, Christopher A. and Arnold, Holly K. and Humphreys, Ian R. and Kembel, Steven W. and O'Dwyer, James P. and Sharpton, Thomas J.}, month = sep, year = {2018}, pmid = {30206171}, pmcid = {PMC6134092}, keywords = {Algorithms, Animals, Bacteria, Biodiversity, bioinformatics, Biological Evolution, Computational Biology, ecology, evolution, Gastrointestinal Microbiome, Gut microbiome, Host Microbial Interactions, Mammals, phylogeny, Phylogeny, RNA, Ribosomal, 16S, taxonomy}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\FIR9BHVH\\Gaulke et al. - 2018 - Ecophylogenetics Clarifies the Evolutionary Associ.pdf:application/pdf} } @article{torres_effects_2018, title = {Effects of {Sub}-{Chronic} {MPTP} {Exposure} on {Behavioral} and {Cognitive} {Performance} and the {Microbiome} of {Wild}-{Type} and {mGlu}8 {Knockout} {Female} and {Male} {Mice}}, volume = {12}, copyright = {All rights reserved}, issn = {1662-5153}, doi = {10.3389/fnbeh.2018.00140}, abstract = {Motor dysfunction is a hallmark of Parkinson's disease (PD); however, non-motor symptoms such as gastrointestinal dysfunction often arise prior to motor symptoms. Alterations in the gut microbiome have been proposed as the earliest event in PD pathogenesis. PD symptoms often demonstrate sex differences. Glutamatergic neurotransmission has long been linked to PD pathology. Metabotropic glutamate receptors (mGlu), a family of G protein-coupled receptors, are divided into three groups, with group III mGlu receptors mainly localized presynaptically where they can inhibit glutamate release in the CNS as well as in the gut. Additionally, the gut microbiome can communicate with the CNS via the gut-brain axis. Here, we assessed whether deficiency of metabotropic glutamate receptor 8 (mGlu8), group III mGlu, modulates the effects of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on behavioral and cognitive performance in female and male mice. We studied whether these effects are associated with changes in striatal tyrosine hydroxylase (TH) levels and the gut microbiome. Two-week sub-chronic MPTP increased activity of female and male wild-type (WT) and mGlu8 knockout (KO) mice in the open field. MPTP also showed genotype- and sex-dependent effects. MPTP increased the time WT, but not KO, females and males spent exploring objects. In WT mice, MPTP improved sensorimotor function in males but impaired it in females. Further, MPTP impaired cued fear memory in WT, but not KO, male mice. MPTP reduced striatal TH levels in WT and KO mice but these effects were only pronounced in males. MPTP treatment and genotype affected the diversity of the gut microbiome. In addition, there were significant associations between microbiome α-diversity and sensorimotor performance, as well as microbiome composition and fear learning. These results indicate that specific taxa may directly affect motor and fear learning or that the same physiological effects that enhance both forms of learning also alter diversity of the gut microbiome. MPTP's effect on motor and cognitive performance may then be, at least in part, be mediated by the gut microbiome. These data also support mGlu8 as a novel therapeutic target for PD and highlight the importance of including both sexes in preclinical studies.}, language = {eng}, number = {140}, journal = {Frontiers in Behavioral Neuroscience}, author = {Torres, Eileen Ruth S. and Akinyeke, Tunde and Stagaman, Keaton and Duvoisin, Robert M. and Meshul, Charles K. and Sharpton, Thomas J. and Raber, Jacob}, month = jul, year = {2018}, pmid = {30072879}, pmcid = {PMC6058038}, keywords = {behavioral performance, beta actin, gut microbiome, metabotropic glutamate receptor, Parkinson’s disease, tyrosine hydroxylase}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\23R2GNPX\\Torres et al. - 2018 - Effects of Sub-Chronic MPTP Exposure on Behavioral.pdf:application/pdf} } @article{sharpton_role_2018, title = {Role of the {Gut} {Microbiome} in {Vertebrate} {Evolution}}, volume = {3}, copyright = {All rights reserved}, issn = {2379-5077}, doi = {10.1128/mSystems.00174-17}, abstract = {Darwin referred to life as a struggle. Organisms compete for limited resources in nature, and their traits influence the outcome. Victory carries great weight as winners survive, reproduce, and progenate subsequent generations. Consequently, organismal traits that influence fitness drive adaptation and their discovery clarifies evolution. Recent research implicates the vertebrate gut microbiome as an agent of fitness, selection, and evolution. Going forward, we must define the functional effects of the gut microbiome to determine how it impacts evolution. Specifically, we must quantify how gut microbiome function diversifies in concert with vertebrate radiation and resolve specific functions that influence natural selection. In so doing, we can discover and potentially capitalize upon the mechanisms by which our gut microbiomes impact our physiology and fitness. Ultimately, we may come to find that while life involves struggle, it also depends upon cooperation.}, language = {eng}, number = {2}, journal = {mSystems}, author = {Sharpton, Thomas J.}, month = apr, year = {2018}, pmid = {29629413}, pmcid = {PMC5881020}, keywords = {coevolution, evolution, metabolome, metagenome, microbiome, vertebrates}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\F35S3FBU\\Sharpton - 2018 - Role of the Gut Microbiome in Vertebrate Evolution.pdf:application/pdf} } @article{allan_allelic_2018, title = {Allelic {Variation} in a {Single} {Genomic} {Region} {Alters} the {Microbiome} of the {Snail} {Biomphalaria} glabrata}, volume = {109}, copyright = {All rights reserved}, issn = {1465-7333}, doi = {10.1093/jhered/esy014}, abstract = {Freshwater snails are the intermediate hosts for numerous parasitic worms which can have negative consequences for human health and agriculture. Understanding the transmission of these diseases requires a more complete characterization of the immunobiology of snail hosts. This includes the characterization of its microbiome and genetic factors which may interact with this important commensal community. Allelic variation in the Guadeloupe resistance complex (GRC) genomic region of Guadeloupean Biomphalaria glabrata influences their susceptibility to schistosome infection and may have other roles in the snail immune response. In the present study, we examined whether a snail's GRC genotype has a role in shaping the bacterial diversity and composition present on or in whole snails. We show that the GRC haplotype, including the resistant genotype, has a significant effect on the diversity of bacterial species present in or on whole snails, including the relative abundances of Gemmatimonas aurantiaca and Micavibrio aeruginosavorus. These findings support the hypothesis that the GRC region is likely involved in pathways that can modify the microbial community of these snails and may have more immune roles in B. glabrata than originally believed. This is also one of few examples in which allelic variation at a particular locus has been shown to affect the microbiome in any species.}, language = {eng}, number = {5}, journal = {The Journal of Heredity}, author = {Allan, Euan R. O. and Tennessen, Jacob A. and Sharpton, Thomas J. and Blouin, Michael S.}, month = jun, year = {2018}, pmid = {29566237}, pmcid = {PMC6022664}, keywords = {Alleles, Animals, Biomphalaria, Genetic Variation, Genome, Haplotypes, Microbiota}, pages = {604--609}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\D5H5MRSU\\Allan et al. - 2018 - Allelic Variation in a Single Genomic Region Alter.pdf:application/pdf} } @article{cheng_progressive_2017, title = {Progressive {Colonization} of {Bacteria} and {Degradation} of {Rice} {Straw} in the {Rumen} by {Illumina} {Sequencing}}, volume = {8}, copyright = {All rights reserved}, issn = {1664-302X}, doi = {10.3389/fmicb.2017.02165}, abstract = {The aim of this study was to improve the utilization of rice straw as forage in ruminants by investigating the degradation pattern of rice straw in the dairy cow rumen. Ground up rice straw was incubated in situ in the rumens of three Holstein cows over a period of 72 h. The rumen fluid at 0 h and the rice straw at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 h were collected for analysis of the bacterial community and the degradation of the rice straw. The bacterial community and the carbohydrate-active enzymes in the rumen fluid were analyzed by metagenomics. The diversity of bacteria loosely and tightly attached to the rice straw was investigated by scanning electron microscopy and Miseq sequencing of 16S rRNA genes. The predominant genus in the rumen fluid was Prevotella, followed by Bacteroides, Butyrivibrio, unclassified Desulfobulbaceae, Desulfovibrio, and unclassified Sphingobacteriaceae. The main enzymes were members of the glycosyl hydrolase family, divided into four categories (cellulases, hemicellulases, debranching enzymes, and oligosaccharide-degrading enzymes), with oligosaccharide-degrading enzymes being the most abundant. No significant degradation of rice straw was observed between 0.5 and 6 h, whereas the rice straw was rapidly degraded between 6 and 24 h. The degradation then gradually slowed between 24 and 72 h. A high proportion of unclassified bacteria were attached to the rice straw and that Prevotella, Ruminococcus, and Butyrivibrio were the predominant classified genera in the loosely and tightly attached fractions. The composition of the loosely attached bacterial community remained consistent throughout the incubation, whereas a significant shift in composition was observed in the tightly attached bacterial community after 6 h of incubation. This shift resulted in a significant reduction in numbers of Bacteroidetes and a significant increase in numbers of Firmicutes. In conclusion, the degradation pattern of rice straw in the dairy cow rumen indicates a strong contribution by tightly attached bacteria, especially after 6 h incubation, but most of these bacteria were not taxonomically characterized. Thus, these bacteria should be further identified and subjected to functional analysis to improve the utilization of crop residues in ruminants.}, language = {eng}, number = {2165}, journal = {Frontiers in Microbiology}, author = {Cheng, Yanfen and Wang, Ying and Li, Yuanfei and Zhang, Yipeng and Liu, Tianyi and Wang, Yu and Sharpton, Thomas J. and Zhu, Weiyun}, month = nov, year = {2017}, pmid = {29163444}, pmcid = {PMC5681530}, keywords = {carbohydrate-active enzymes, fiber degradation, metagenome, rice straw, ruminal bacteria}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\LHYR9UKW\\Cheng et al. - 2017 - Progressive Colonization of Bacteria and Degradati.pdf:application/pdf} } @article{burns_transmission_2018, title = {Transmission of a common intestinal neoplasm in zebrafish by cohabitation}, volume = {41}, copyright = {All rights reserved}, issn = {1365-2761}, doi = {10.1111/jfd.12743}, abstract = {Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water. Intestinal lesions were observed in recipient fish in all exposure groups, including transmissions from previous recipient fish, and moribund fish exhibited a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed recipients compared to unexposed control fish. We further tracked the presence of the Mycoplasma sp. using a targeted PCR test on individual dissected intestines or faeces or tank faeces. Original donor and exposed fish populations were positive for Mycoplasma, while corresponding unexposed control fish were negative. This study indicates an infectious aetiology for these transmissible tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma species.}, language = {eng}, number = {4}, journal = {Journal of Fish Diseases}, author = {Burns, A. R. and Watral, V. and Sichel, S. and Spagnoli, S. and Banse, A. V. and Mittge, E. and Sharpton, T. J. and Guillemin, K. and Kent, M. L.}, month = apr, year = {2018}, pmid = {29023774}, pmcid = {PMC5844789}, keywords = {Adenocarcinoma, Animals, Carcinoma, Small Cell, Fish Diseases, intestinal, Intestinal Neoplasms, Mycoplasma, Mycoplasma Infections, Mycoplasma penetrans, neoplasia, RNA, Bacterial, RNA, Ribosomal, 16S, transmission, zebrafish, Zebrafish}, pages = {569--579}, file = {Accepted Version:C\:\\Users\\sharptot\\Zotero\\storage\\XJVSRPV4\\Burns et al. - 2018 - Transmission of a common intestinal neoplasm in ze.pdf:application/pdf} } @article{wilson_draft_2017, title = {Draft {Genome} {Sequence} of {Pseudomonas} sp. {Strain} {DrBHI}1 ({Phylum} {Proteobacteria})}, volume = {5}, copyright = {All rights reserved}, issn = {2169-8287}, doi = {10.1128/genomeA.01090-17}, abstract = {Here, we report the draft genome sequence of Pseudomonas sp. strain DrBHI1. The total assembly length is 5,649,751 bp in 146 contigs. This strain was isolated from zebrafish (Danio rerio) feces.}, language = {eng}, number = {39}, journal = {Genome Announcements}, author = {Wilson, Alexandria K. and Watral, Virginia G. and Kent, Michael L. and Sharpton, Thomas J. and Gaulke, Christopher A.}, month = sep, year = {2017}, pmid = {28963227}, pmcid = {PMC5624773}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\TRHDMFIN\\Wilson et al. - 2017 - Draft Genome Sequence of Pseudomonas sp. Strain Dr.pdf:application/pdf} } @article{sharpton_development_2017, title = {Development of {Inflammatory} {Bowel} {Disease} {Is} {Linked} to a {Longitudinal} {Restructuring} of the {Gut} {Metagenome} in {Mice}}, volume = {2}, copyright = {All rights reserved}, issn = {2379-5077}, doi = {10.1128/mSystems.00036-17}, abstract = {The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate microbiome-mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where damped transforming growth factor β (TGF-β) signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including damped acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, levels of lipooligosaccharide transporter abundance diverge prior to immune activation, indicating that it could be a predisease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundances of particular taxa, including several species of Bacteroides, correlate with immune activation. These discoveries were enabled by our use of generalized linear mixed-effects models to test for differences in longitudinal profiles between healthy and diseased mice while accounting for the distributions of taxon and gene counts in metagenomic data. These findings demonstrate that longitudinal metagenomics is useful for discovering the potential mechanisms through which the gut microbiome becomes altered in IBD. IMPORTANCE IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading to disease onset. By performing weekly metagenomic sequencing and mixed-effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study was novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development.}, language = {eng}, number = {5}, journal = {mSystems}, author = {Sharpton, Thomas and Lyalina, Svetlana and Luong, Julie and Pham, Joey and Deal, Emily M. and Armour, Courtney and Gaulke, Christopher and Sanjabi, Shomyseh and Pollard, Katherine S.}, month = oct, year = {2017}, pmid = {28904997}, pmcid = {PMC5585689}, keywords = {inflammatory bowel disease, lipooligosaccharide transporter, longitudinal, metagenomics, protein function, statistics}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\F5Z2M6J8\\Sharpton et al. - 2017 - Development of Inflammatory Bowel Disease Is Linke.pdf:application/pdf} } @article{foster_metacoder:_2017, title = {Metacoder: {An} {R} package for visualization and manipulation of community taxonomic diversity data}, volume = {13}, copyright = {All rights reserved}, issn = {1553-7358}, shorttitle = {Metacoder}, doi = {10.1371/journal.pcbi.1005404}, abstract = {Community-level data, the type generated by an increasing number of metabarcoding studies, is often graphed as stacked bar charts or pie graphs that use color to represent taxa. These graph types do not convey the hierarchical structure of taxonomic classifications and are limited by the use of color for categories. As an alternative, we developed metacoder, an R package for easily parsing, manipulating, and graphing publication-ready plots of hierarchical data. Metacoder includes a dynamic and flexible function that can parse most text-based formats that contain taxonomic classifications, taxon names, taxon identifiers, or sequence identifiers. Metacoder can then subset, sample, and order this parsed data using a set of intuitive functions that take into account the hierarchical nature of the data. Finally, an extremely flexible plotting function enables quantitative representation of up to 4 arbitrary statistics simultaneously in a tree format by mapping statistics to the color and size of tree nodes and edges. Metacoder also allows exploration of barcode primer bias by integrating functions to run digital PCR. Although it has been designed for data from metabarcoding research, metacoder can easily be applied to any data that has a hierarchical component such as gene ontology or geographic location data. Our package complements currently available tools for community analysis and is provided open source with an extensive online user manual.}, language = {eng}, number = {2}, journal = {PLoS computational biology}, author = {Foster, Zachary S. L. and Sharpton, Thomas J. and Grünwald, Niklaus J.}, month = feb, year = {2017}, pmid = {28222096}, pmcid = {PMC5340466}, keywords = {Algorithms, Computer Graphics, DNA, DNA Barcoding, Taxonomic, Genetic Variation, High-Throughput Nucleotide Sequencing, Programming Languages, User-Computer Interface}, pages = {e1005404}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\NWYPWFKX\\Foster et al. - 2017 - Metacoder An R package for visualization and mani.pdf:application/pdf} } @article{conley_increasing_2017, title = {Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats}, volume = {61}, copyright = {All rights reserved}, issn = {1613-4133}, doi = {10.1002/mnfr.201600372}, abstract = {SCOPE: Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age-related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. METHODS AND RESULTS: Six-month-old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham-operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low-dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high-dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose-dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. CONCLUSION: These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX.}, language = {eng}, number = {5}, journal = {Molecular Nutrition \& Food Research}, author = {Conley, Melissa N. and Roberts, Cooper and Sharpton, Thomas J. and Iwaniec, Urszula T. and Hord, Norman G.}, month = may, year = {2017}, pmid = {28087899}, pmcid = {PMC5434898}, keywords = {Absorptiometry, Photon, Alcaligenaceae, Animals, Bacteroidaceae, Biomarkers, Bone Density, Bone Resorption, Cancellous Bone, Dietary nitrate, Disease Models, Animal, DNA, Bacterial, Dose-Response Relationship, Drug, Feces, Female, Firmicutes, Gastrointestinal Microbiome, Nitrates, Nitric oxide, Nitric Oxide, Osteocalcin, Osteoporosis, Ovariectomy, Postmenopause, Rats, Rats, Sprague-Dawley, Sequence Analysis, DNA, Vegetables}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\BNC54GEB\\Conley et al. - 2017 - Increasing dietary nitrate has no effect on cancel.pdf:application/pdf} } @article{gaulke_triclosan_2016, title = {Triclosan {Exposure} {Is} {Associated} with {Rapid} {Restructuring} of the {Microbiome} in {Adult} {Zebrafish}}, volume = {11}, copyright = {All rights reserved}, issn = {1932-6203}, doi = {10.1371/journal.pone.0154632}, abstract = {Growing evidence indicates that disrupting the microbial community that comprises the intestinal tract, known as the gut microbiome, can contribute to the development or severity of disease. As a result, it is important to discern the agents responsible for microbiome disruption. While animals are frequently exposed to a diverse array of environmental chemicals, little is known about their effects on gut microbiome stability and structure. Here, we demonstrate how zebrafish can be used to glean insight into the effects of environmental chemical exposure on the structure and ecological dynamics of the gut microbiome. Specifically, we exposed forty-five adult zebrafish to triclosan-laden food for four or seven days or a control diet, and analyzed their microbial communities using 16S rRNA amplicon sequencing. Triclosan exposure was associated with rapid shifts in microbiome structure and diversity. We find evidence that several operational taxonomic units (OTUs) associated with the family Enterobacteriaceae appear to be susceptible to triclosan exposure, while OTUs associated with the genus Pseudomonas appeared to be more resilient and resistant to exposure. We also found that triclosan exposure is associated with topological alterations to microbial interaction networks and results in an overall increase in the number of negative interactions per microbe in these networks. Together these data indicate that triclosan exposure results in altered composition and ecological dynamics of microbial communities in the gut. Our work demonstrates that because zebrafish afford rapid and inexpensive interrogation of a large number of individuals, it is a useful experimental system for the discovery of the gut microbiome's interaction with environmental chemicals.}, language = {eng}, number = {5}, journal = {PloS One}, author = {Gaulke, Christopher A. and Barton, Carrie L. and Proffitt, Sarah and Tanguay, Robert L. and Sharpton, Thomas J.}, month = may, year = {2016}, pmid = {27191725}, pmcid = {PMC4871530}, keywords = {Animals, Anti-Infective Agents, Local, Drug Resistance, Gastrointestinal Microbiome, Metagenome, Metagenomics, Microbiota, RNA, Ribosomal, 16S, Triclosan, Zebrafish}, pages = {e0154632}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\J8D854KW\\Gaulke et al. - 2016 - Triclosan Exposure Is Associated with Rapid Restru.pdf:application/pdf} } @article{conley_aging_2016, title = {Aging and serum {MCP}-1 are associated with gut microbiome composition in a murine model}, volume = {4}, copyright = {All rights reserved}, issn = {2167-8359}, doi = {10.7717/peerj.1854}, abstract = {Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.}, language = {eng}, number = {e1854}, journal = {PeerJ}, author = {Conley, Melissa N. and Wong, Carmen P. and Duyck, Kyle M. and Hord, Norman and Ho, Emily and Sharpton, Thomas J.}, month = mar, year = {2016}, pmid = {27069796}, pmcid = {PMC4824877}, keywords = {Aging, Immunity, Immunosenescence, Inflammaging, Inflammation, Mice, Microbiome}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\GHHRKPBW\\Conley et al. - 2016 - Aging and serum MCP-1 are associated with gut micr.pdf:application/pdf} } @article{kent_effects_2016, title = {Effects of {Subclinical} {Mycobacterium} chelonae {Infections} on {Fecundity} and {Embryo} {Survival} in {Zebrafish}}, volume = {13}, copyright = {All rights reserved}, issn = {1557-8542}, doi = {10.1089/zeb.2015.1204}, abstract = {Mycobacteriosis is the second most common infectious disease in zebrafish research colonies, and most often this is caused by Mycobacterium chelonae. The infection is characterized by multiple granulomas in the kidney, coelomic cavity, particularly the ovary. However, most fish still appear clinically normal. Developmental genetics remain a primary area of research with the zebrafish model, and hence, an important use of adult zebrafish is as brood fish to produce embryos. We investigated the effects of experimentally induced M. chelonae infections on fecundity. A total of 480 5D wild-type zebrafish were divided into four groups: controls, males infected, females infected, and both sexes. Exposed fish developed high prevalence of infection, including many females with ovarian infections. Fish were then first subjected to four separate group spawns with four replicate tanks/group. Then, a third of the fish were subjected to pairwise spawns, representing 20 pairs/group, and then the pairs were evaluated by histopathology. Overall, the group and pairwise spawns resulted numerous eggs and viable embryos. However, we found no statistical correlations between infection status and number of eggs or viability. In contrast to Egg Associated Inflammation and Fibroplasia, lesions in infected ovaries were more localized, with large regions of the ovary appearing normal.}, language = {eng}, number = {Suppl 1}, journal = {Zebrafish}, author = {Kent, Michael L. and Watral, Virginia G. and Kirchoff, Nicole S. and Spagnoli, Sean T. and Sharpton, Thomas J.}, month = jul, year = {2016}, pmid = {27031171}, pmcid = {PMC4931727}, keywords = {Animals, Asymptomatic Infections, Embryo, Nonmammalian, Fertility, Fish Diseases, Incidence, Mycobacterium chelonae, Mycobacterium Infections, Nontuberculous, Prevalence, Survival Analysis, Zebrafish}, pages = {S88--95}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\9DG736AX\\Kent et al. - 2016 - Effects of Subclinical Mycobacterium chelonae Infe.pdf:application/pdf} } @article{nayfach_automated_2015, title = {Automated and {Accurate} {Estimation} of {Gene} {Family} {Abundance} from {Shotgun} {Metagenomes}}, volume = {11}, copyright = {All rights reserved}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1004573}, abstract = {Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn's disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease.}, language = {eng}, number = {11}, journal = {PLoS computational biology}, author = {Nayfach, Stephen and Bradley, Patrick H. and Wyman, Stacia K. and Laurent, Timothy J. and Williams, Alex and Eisen, Jonathan A. and Pollard, Katherine S. and Sharpton, Thomas J.}, month = nov, year = {2015}, pmid = {26565399}, pmcid = {PMC4643905}, keywords = {Chromosome Mapping, Computer Simulation, Crohn Disease, Genetic Markers, Humans, Metagenome, Metagenomics, Microbiota, Models, Genetic}, pages = {e1004573}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\CN8AA9ZX\\Nayfach et al. - 2015 - Automated and Accurate Estimation of Gene Family A.pdf:application/pdf} } @article{sharpton_modeling_2015, title = {Modeling the {Context}-{Dependent} {Associations} between the {Gut} {Microbiome}, {Its} {Environment}, and {Host} {Health}}, volume = {6}, copyright = {All rights reserved}, issn = {2150-7511}, doi = {10.1128/mBio.01367-15}, abstract = {Changes in the gut microbiome are often associated with disease. One of the major goals in microbiome research is determining which components of this complex system are responsible for the observed differences in health state. Most studies apply a reductionist approach, wherein individual organisms are evaluated independently of the surrounding context of the microbiome. While such methods have yielded valuable insights into the microbiome, they fail to identify patterns that may be obscured by contextual variation. A recent report by Schubert et al. [A. M. Schubert, H. Sinani, and P. D. Schloss, mBio 6(4):e00974-15, 2015, doi: 10.1128/mBio.00974-15] communicates an alternative approach to the study of the microbiome's association with host health. By coupling a multifactored experimental design with regression modeling, the authors are able to profile context-dependent changes in the microbiome and predict health status. This work underscores the value of incorporating model-based procedures into the investigation of the microbiome and illustrates the potential clinical transformations that may arise through their use.}, language = {eng}, number = {5}, journal = {mBio}, author = {Sharpton, Thomas J. and Gaulke, Christopher A.}, month = sep, year = {2015}, pmid = {26350971}, pmcid = {PMC4600117}, keywords = {Animals, Anti-Bacterial Agents, Clostridium difficile, Feces, Gastrointestinal Microbiome}, pages = {e01367--01315}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\SJ2A6Q2R\\Sharpton and Gaulke - 2015 - Modeling the Context-Dependent Associations betwee.pdf:application/pdf} } @article{odwyer_backbones_2015, title = {Backbones of evolutionary history test biodiversity theory for microbes}, volume = {112}, copyright = {All rights reserved}, issn = {1091-6490}, doi = {10.1073/pnas.1419341112}, abstract = {Identifying the ecological and evolutionary mechanisms that determine biological diversity is a central question in ecology. In microbial ecology, phylogenetic diversity is an increasingly common and relevant means of quantifying community diversity, particularly given the challenges in defining unambiguous species units from environmental sequence data. We explore patterns of phylogenetic diversity across multiple bacterial communities drawn from different habitats and compare these data to evolutionary trees generated using theoretical models of biodiversity. We have two central findings. First, although on finer scales the empirical trees are highly idiosyncratic, on coarse scales the backbone of these trees is simple and robust, consistent across habitats, and displays bursts of diversification dotted throughout. Second, we find that these data demonstrate a clear departure from the predictions of standard neutral theories of biodiversity and that an alternative family of generalized models provides a qualitatively better description. Together, these results lay the groundwork for a theoretical framework to connect ecological mechanisms to observed phylogenetic patterns in microbial communities.}, language = {eng}, number = {27}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, author = {O'Dwyer, James P. and Kembel, Steven W. and Sharpton, Thomas J.}, month = jul, year = {2015}, pmid = {26106159}, pmcid = {PMC4500224}, keywords = {Algorithms, Bacteria, Biodiversity, Biological Evolution, coalescent theory, Ecology, Ecosystem, macroecology, microbial biodiversity, Models, Biological, phylogeny, Phylogeny, Species Specificity}, pages = {8356--8361}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\SK9BSYLA\\O'Dwyer et al. - 2015 - Backbones of evolutionary history test biodiversit.pdf:application/pdf} } @article{quandt_metagenome_2015, title = {Metagenome sequence of {Elaphomyces} granulatus from sporocarp tissue reveals {Ascomycota} ectomycorrhizal fingerprints of genome expansion and a {Proteobacteria}-rich microbiome}, volume = {17}, copyright = {All rights reserved}, issn = {1462-2920}, doi = {10.1111/1462-2920.12840}, abstract = {Many obligate symbiotic fungi are difficult to maintain in culture, and there is a growing need for alternative approaches to obtaining tissue and subsequent genomic assemblies from such species. In this study, the genome of Elaphomyces granulatus was sequenced from sporocarp tissue. The genome assembly remains on many contigs, but gene space is estimated to be mostly complete. Phylogenetic analyses revealed that the Elaphomyces lineage is most closely related to Talaromyces and Trichocomaceae s.s. The genome of E. granulatus is reduced in carbohydrate-active enzymes, despite a large expansion in genome size, both of which are consistent with what is seen in Tuber melanosporum, the other sequenced ectomycorrhizal ascomycete. A large number of transposable elements are predicted in the E. granulatus genome, especially Gypsy-like long terminal repeats, and there has also been an expansion in helicases. The metagenome is a complex community dominated by bacteria in Bradyrhizobiaceae, and there is evidence to suggest that the community may be reduced in functional capacity as estimated by KEGG pathways. Through the sequencing of sporocarp tissue, this study has provided insights into Elaphomyces phylogenetics, genomics, metagenomics and the evolution of the ectomycorrhizal association.}, language = {eng}, number = {8}, journal = {Environmental Microbiology}, author = {Quandt, C. Alisha and Kohler, Annegret and Hesse, Cedar N. and Sharpton, Thomas J. and Martin, Francis and Spatafora, Joseph W.}, month = aug, year = {2015}, pmid = {25753751}, keywords = {Base Sequence, Bradyrhizobiaceae, DNA Transposable Elements, DNA, Fungal, Eurotiales, Fruiting Bodies, Fungal, Genome, Fungal, Metagenome, Metagenomics, Microbiota, Mycorrhizae, Phylogeny, Sequence Analysis, DNA, Talaromyces}, pages = {2952--2968} } @article{skewes-cox_profile_2014, title = {Profile hidden {Markov} models for the detection of viruses within metagenomic sequence data}, volume = {9}, copyright = {All rights reserved}, issn = {1932-6203}, doi = {10.1371/journal.pone.0105067}, abstract = {Rapid, sensitive, and specific virus detection is an important component of clinical diagnostics. Massively parallel sequencing enables new diagnostic opportunities that complement traditional serological and PCR based techniques. While massively parallel sequencing promises the benefits of being more comprehensive and less biased than traditional approaches, it presents new analytical challenges, especially with respect to detection of pathogen sequences in metagenomic contexts. To a first approximation, the initial detection of viruses can be achieved simply through alignment of sequence reads or assembled contigs to a reference database of pathogen genomes with tools such as BLAST. However, recognition of highly divergent viral sequences is problematic, and may be further complicated by the inherently high mutation rates of some viral types, especially RNA viruses. In these cases, increased sensitivity may be achieved by leveraging position-specific information during the alignment process. Here, we constructed HMMER3-compatible profile hidden Markov models (profile HMMs) from all the virally annotated proteins in RefSeq in an automated fashion using a custom-built bioinformatic pipeline. We then tested the ability of these viral profile HMMs ("vFams") to accurately classify sequences as viral or non-viral. Cross-validation experiments with full-length gene sequences showed that the vFams were able to recall 91\% of left-out viral test sequences without erroneously classifying any non-viral sequences into viral protein clusters. Thorough reanalysis of previously published metagenomic datasets with a set of the best-performing vFams showed that they were more sensitive than BLAST for detecting sequences originating from more distant relatives of known viruses. To facilitate the use of the vFams for rapid detection of remote viral homologs in metagenomic data, we provide two sets of vFams, comprising more than 4,000 vFams each, in the HMMER3 format. We also provide the software necessary to build custom profile HMMs or update the vFams as more viruses are discovered (http://derisilab.ucsf.edu/software/vFam).}, language = {eng}, number = {8}, journal = {PloS One}, author = {Skewes-Cox, Peter and Sharpton, Thomas J. and Pollard, Katherine S. and DeRisi, Joseph L.}, month = aug, year = {2014}, pmid = {25140992}, pmcid = {PMC4139300}, keywords = {Computational Biology, Humans, Markov Chains, Metagenomics, Sequence Alignment, Software, Viruses}, pages = {e105067}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\DN6JQQZR\\Skewes-Cox et al. - 2014 - Profile hidden Markov models for the detection of .pdf:application/pdf} } @article{sharpton_introduction_2014, title = {An introduction to the analysis of shotgun metagenomic data}, volume = {5}, copyright = {All rights reserved}, issn = {1664-462X}, doi = {10.3389/fpls.2014.00209}, abstract = {Environmental DNA sequencing has revealed the expansive biodiversity of microorganisms and clarified the relationship between host-associated microbial communities and host phenotype. Shotgun metagenomic DNA sequencing is a relatively new and powerful environmental sequencing approach that provides insight into community biodiversity and function. But, the analysis of metagenomic sequences is complicated due to the complex structure of the data. Fortunately, new tools and data resources have been developed to circumvent these complexities and allow researchers to determine which microbes are present in the community and what they might be doing. This review describes the analytical strategies and specific tools that can be applied to metagenomic data and the considerations and caveats associated with their use. Specifically, it documents how metagenomes can be analyzed to quantify community structure and diversity, assemble novel genomes, identify new taxa and genes, and determine which metabolic pathways are encoded in the community. It also discusses several methods that can be used compare metagenomes to identify taxa and functions that differentiate communities.}, language = {eng}, number = {209}, journal = {Frontiers in Plant Science}, author = {Sharpton, Thomas J.}, month = jun, year = {2014}, pmid = {24982662}, pmcid = {PMC4059276}, keywords = {bioinformatics, host–microbe interactions, metagenome, microbial diversity, microbiome, microbiota, review}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\TXT9NDCB\\Sharpton - 2014 - An introduction to the analysis of shotgun metagen.pdf:application/pdf} } @article{kent_post-mortem_2014, title = {Post-mortem sporulation of {Ceratomyxa} shasta ({Myxozoa}) after death in adult {Chinook} salmon}, volume = {100}, copyright = {All rights reserved}, issn = {1937-2345}, doi = {10.1645/13-490.1}, abstract = {Ceratomyxa shasta (Myxozoa) is a common gastrointestinal pathogen of salmonid fishes in the Pacific Northwest of the United States. We have been investigating this parasite in adult Chinook salmon ( Oncorhynchus tshawytscha ) in the Willamette River, Oregon. In prior work, we observed differences in the pattern of development of C. shasta in adult salmon compared to juvenile salmon. Adult salmon consistently had large numbers of prespore stages in many of the fish that survived to spawn in the fall. However, myxospores were rarely observed, even though they were exposed and presumably infected for months before spawning. We evaluated the ability of C. shasta to sporulate following fish death because it is reported that myxosores are common in carcasses of Chinook salmon. We collected the intestine from 30 adult salmon immediately after artificial spawning and death (T0). A total of 23 fish were infected with C. shasta based on histology, but only a few myxospores were observed in 1 fish by histology. Intestines of these fish were examined at T0 and T7 (latter held at 17 C for 7 days) using quantified wet mount preparations. An increase in myxospore concentrations was seen in 39\% of these fish, ranging between a 1.5- to a 14.5-fold increase. The most heavily infected fish exhibited a 4.6-fold increase from 27,841 to 129,352 myxospores/cm. This indicates, supported by various statistical analyses, that under certain conditions presporogonic forms are viable and continue to sporulate after death in adult salmon. Considering the life cycle of C. shasta and anadromous salmon, the parasite may have evolved 2, non-mutually exclusive developmental strategies. In young fish (parr and smolts), the parasite sporulates shortly after infection and is released into freshwater from either live or dead fish before their migration to seawater, where the alternate host is absent. The second strategy occurs in adult salmon, particularly spring Chinook salmon, which become infected upon their return to freshwater in the spring or early summer. For several months throughout the summer, only prespore stages are observed in most fish, even at the time of spawning. But once the fish dies, environmental conditions experienced by C. shasta change and viable presporogonic stages are induced to sporulate. As the post-spawned fish occur in the upper reaches of rivers, the myxospores would be released in a freshwater environment that would provide a reasonable opportunity for them to encounter their freshwater polychaete hosts, which reside downstream.}, language = {eng}, number = {5}, journal = {The Journal of Parasitology}, author = {Kent, M. L. and Soderlund, K. and Thomann, Estela and Schreck, C. B. and Sharpton, T. J.}, month = oct, year = {2014}, pmid = {24725089}, keywords = {Animals, Fish Diseases, Fresh Water, Gastrointestinal Diseases, Intestines, Liver, Myxozoa, Oregon, Parasitic Diseases, Animal, Salmon, Spores}, pages = {679--683} } @article{kidd_exome_2014, title = {Exome capture from saliva produces high quality genomic and metagenomic data}, volume = {15}, copyright = {All rights reserved}, issn = {1471-2164}, doi = {10.1186/1471-2164-15-262}, abstract = {BACKGROUND: Targeted capture of genomic regions reduces sequencing cost while generating higher coverage by allowing biomedical researchers to focus on specific loci of interest, such as exons. Targeted capture also has the potential to facilitate the generation of genomic data from DNA collected via saliva or buccal cells. DNA samples derived from these cell types tend to have a lower human DNA yield, may be degraded from age and/or have contamination from bacteria or other ambient oral microbiota. However, thousands of samples have been previously collected from these cell types, and saliva collection has the advantage that it is a non-invasive and appropriate for a wide variety of research. RESULTS: We demonstrate successful enrichment and sequencing of 15 South African KhoeSan exomes and 2 full genomes with samples initially derived from saliva. The expanded exome dataset enables us to characterize genetic diversity free from ascertainment bias for multiple KhoeSan populations, including new exome data from six HGDP Namibian San, revealing substantial population structure across the Kalahari Desert region. Additionally, we discover and independently verify thirty-one previously unknown KIR alleles using methods we developed to accurately map and call the highly polymorphic HLA and KIR loci from exome capture data. Finally, we show that exome capture of saliva-derived DNA yields sufficient non-human sequences to characterize oral microbial communities, including detection of bacteria linked to oral disease (e.g. Prevotella melaninogenica). For comparison, two samples were sequenced using standard full genome library preparation without exome capture and we found no systematic bias of metagenomic information between exome-captured and non-captured data. CONCLUSIONS: DNA from human saliva samples, collected and extracted using standard procedures, can be used to successfully sequence high quality human exomes, and metagenomic data can be derived from non-human reads. We find that individuals from the Kalahari carry a higher oral pathogenic microbial load than samples surveyed in the Human Microbiome Project. Additionally, rare variants present in the exomes suggest strong population structure across different KhoeSan populations.}, language = {eng}, number = {262}, journal = {BMC genomics}, author = {Kidd, Jeffrey M. and Sharpton, Thomas J. and Bobo, Dean and Norman, Paul J. and Martin, Alicia R. and Carpenter, Meredith L. and Sikora, Martin and Gignoux, Christopher R. and Nemat-Gorgani, Neda and Adams, Alexandra and Guadalupe, Moraima and Guo, Xiaosen and Feng, Qiang and Li, Yingrui and Liu, Xiao and Parham, Peter and Hoal, Eileen G. and Feldman, Marcus W. and Pollard, Katherine S. and Wall, Jeffrey D. and Bustamante, Carlos D. and Henn, Brenna M.}, month = apr, year = {2014}, pmid = {24708091}, pmcid = {PMC4051168}, keywords = {Exome, Genome, Human, Genomics, Genotype, High-Throughput Nucleotide Sequencing, HLA Antigens, Humans, Metagenomics, Microbiota, Molecular Sequence Data, Mouth, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptors, KIR, Saliva}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\KP72A3VZ\\Kidd et al. - 2014 - Exome capture from saliva produces high quality ge.pdf:application/pdf} } @article{finucane_taxonomic_2014, title = {A taxonomic signature of obesity in the microbiome? {Getting} to the guts of the matter}, volume = {9}, copyright = {All rights reserved}, issn = {1932-6203}, shorttitle = {A taxonomic signature of obesity in the microbiome?}, doi = {10.1371/journal.pone.0084689}, abstract = {Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.}, language = {eng}, number = {1}, journal = {PloS One}, author = {Finucane, Mariel M. and Sharpton, Thomas J. and Laurent, Timothy J. and Pollard, Katherine S.}, month = jan, year = {2014}, pmid = {24416266}, pmcid = {PMC3885756}, keywords = {Adult, Bacteria, Body Mass Index, Case-Control Studies, Classification, Gastrointestinal Tract, Humans, Microbiota, Obesity}, pages = {e84689}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\SNZI7DTX\\Finucane et al. - 2014 - A taxonomic signature of obesity in the microbiome.pdf:application/pdf} } @article{ladau_global_2013, title = {Global marine bacterial diversity peaks at high latitudes in winter}, volume = {7}, copyright = {All rights reserved}, issn = {1751-7370}, doi = {10.1038/ismej.2013.37}, abstract = {Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms.}, language = {eng}, number = {9}, journal = {The ISME journal}, author = {Ladau, Joshua and Sharpton, Thomas J. and Finucane, Mariel M. and Jospin, Guillaume and Kembel, Steven W. and O'Dwyer, James and Koeppel, Alexander F. and Green, Jessica L. and Pollard, Katherine S.}, month = sep, year = {2013}, pmid = {23514781}, pmcid = {PMC3749493}, keywords = {Bacteria, Bacterial Physiological Phenomena, Biodiversity, DNA, Ribosomal, Environment, Humans, Models, Biological, Oceans and Seas, Seasons, Seawater, Water Microbiology}, pages = {1669--1677}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\SKCT28TS\\Ladau et al. - 2013 - Global marine bacterial diversity peaks at high la.pdf:application/pdf} } @article{sharpton_sifting_2012, title = {Sifting through genomes with iterative-sequence clustering produces a large, phylogenetically diverse protein-family resource}, volume = {13}, copyright = {All rights reserved}, issn = {1471-2105}, doi = {10.1186/1471-2105-13-264}, abstract = {BACKGROUND: New computational resources are needed to manage the increasing volume of biological data from genome sequencing projects. One fundamental challenge is the ability to maintain a complete and current catalog of protein diversity. We developed a new approach for the identification of protein families that focuses on the rapid discovery of homologous protein sequences. RESULTS: We implemented fully automated and high-throughput procedures to de novo cluster proteins into families based upon global alignment similarity. Our approach employs an iterative clustering strategy in which homologs of known families are sifted out of the search for new families. The resulting reduction in computational complexity enables us to rapidly identify novel protein families found in new genomes and to perform efficient, automated updates that keep pace with genome sequencing. We refer to protein families identified through this approach as "Sifting Families," or SFams. Our analysis of {\textasciitilde}10.5 million protein sequences from 2,928 genomes identified 436,360 SFams, many of which are not represented in other protein family databases. We validated the quality of SFam clustering through statistical as well as network topology-based analyses. CONCLUSIONS: We describe the rapid identification of SFams and demonstrate how they can be used to annotate genomes and metagenomes. The SFam database catalogs protein-family quality metrics, multiple sequence alignments, hidden Markov models, and phylogenetic trees. Our source code and database are publicly available and will be subject to frequent updates (http://edhar.genomecenter.ucdavis.edu/sifting\_families/).}, language = {eng}, number = {264}, journal = {BMC bioinformatics}, author = {Sharpton, Thomas J. and Jospin, Guillaume and Wu, Dongying and Langille, Morgan G. I. and Pollard, Katherine S. and Eisen, Jonathan A.}, month = oct, year = {2012}, pmid = {23061897}, pmcid = {PMC3481395}, keywords = {Cluster Analysis, Databases, Protein, Genomics, Molecular Sequence Annotation, Phylogeny, Proteins, Sequence Alignment, Sequence Analysis, Protein, Sequence Homology, Amino Acid}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\XW5YC64Q\\Sharpton et al. - 2012 - Sifting through genomes with iterative-sequence cl.pdf:application/pdf} } @article{whiston_comparative_2012, title = {Comparative transcriptomics of the saprobic and parasitic growth phases in {Coccidioides} spp}, volume = {7}, copyright = {All rights reserved}, issn = {1932-6203}, doi = {10.1371/journal.pone.0041034}, abstract = {Coccidioides immitis and C. posadasii, the causative agents of coccidioidomycosis, are dimorphic fungal pathogens, which grow as hyphae in the saprobic phase in the environment and as spherules in the parasitic phase in the mammalian host. In this study, we use comparative transcriptomics to identify gene expression differences between the saprobic and parasitic growth phases. We prepared Illumina mRNA sequencing libraries for saprobic-phase hyphae and parasitic-phase spherules in vitro for C. immitis isolate RS and C. posadasii isolate C735 in biological triplicate. Of 9,910 total predicted genes in Coccidioides, we observed 1,298 genes up-regulated in the saprobic phase of both C. immitis and C. posadasii and 1,880 genes up-regulated in the parasitic phase of both species. Comparing the saprobic and parasitic growth phases, we observed considerable differential expression of cell surface-associated genes, particularly chitin-related genes. We also observed differential expression of several virulence factors previously identified in Coccidioides and other dimorphic fungal pathogens. These included alpha (1,3) glucan synthase, SOWgp, and several genes in the urease pathway. Furthermore, we observed differential expression in many genes predicted to be under positive selection in two recent Coccidioides comparative genomics studies. These results highlight a number of genes that may be crucial to dimorphic phase-switching and virulence in Coccidioides. These observations will impact priorities for future genetics-based studies in Coccidioides and provide context for studies in other fungal pathogens.}, language = {eng}, number = {7}, journal = {PloS One}, author = {Whiston, Emily and Zhang Wise, Hua and Sharpton, Thomas J. and Jui, Ginger and Cole, Garry T. and Taylor, John W.}, month = jul, year = {2012}, pmid = {22911737}, pmcid = {PMC3401177}, keywords = {Coccidioides, Gene Expression Profiling, Gene Expression Regulation, Fungal, Transcriptome, Virulence Factors}, pages = {e41034}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\3A2BHPDW\\Whiston et al. - 2012 - Comparative transcriptomics of the saprobic and pa.pdf:application/pdf} } @article{wylie_novel_2012, title = {Novel bacterial taxa in the human microbiome}, volume = {7}, copyright = {All rights reserved}, issn = {1932-6203}, doi = {10.1371/journal.pone.0035294}, abstract = {The human gut harbors thousands of bacterial taxa. A profusion of metagenomic sequence data has been generated from human stool samples in the last few years, raising the question of whether more taxa remain to be identified. We assessed metagenomic data generated by the Human Microbiome Project Consortium to determine if novel taxa remain to be discovered in stool samples from healthy individuals. To do this, we established a rigorous bioinformatics pipeline that uses sequence data from multiple platforms (Illumina GAIIX and Roche 454 FLX Titanium) and approaches (whole-genome shotgun and 16S rDNA amplicons) to validate novel taxa. We applied this approach to stool samples from 11 healthy subjects collected as part of the Human Microbiome Project. We discovered several low-abundance, novel bacterial taxa, which span three major phyla in the bacterial tree of life. We determined that these taxa are present in a larger set of Human Microbiome Project subjects and are found in two sampling sites (Houston and St. Louis). We show that the number of false-positive novel sequences (primarily chimeric sequences) would have been two orders of magnitude higher than the true number of novel taxa without validation using multiple datasets, highlighting the importance of establishing rigorous standards for the identification of novel taxa in metagenomic data. The majority of novel sequences are related to the recently discovered genus Barnesiella, further encouraging efforts to characterize the members of this genus and to study their roles in the microbial communities of the gut. A better understanding of the effects of less-abundant bacteria is important as we seek to understand the complex gut microbiome in healthy individuals and link changes in the microbiome to disease.}, language = {eng}, number = {6}, journal = {PloS One}, author = {Wylie, Kristine M. and Truty, Rebecca M. and Sharpton, Thomas J. and Mihindukulasuriya, Kathie A. and Zhou, Yanjiao and Gao, Hongyu and Sodergren, Erica and Weinstock, George M. and Pollard, Katherine S.}, month = jun, year = {2012}, pmid = {22719826}, pmcid = {PMC3374617}, keywords = {DNA, Ribosomal, Humans, Metagenome, Metagenomics}, pages = {e35294}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\86YCS7P2\\Wylie et al. - 2012 - Novel bacterial taxa in the human microbiome.pdf:application/pdf} } @article{human_microbiome_project_consortium_framework_2012, title = {A framework for human microbiome research}, volume = {486}, copyright = {All rights reserved}, issn = {1476-4687}, doi = {10.1038/nature11209}, abstract = {A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.}, language = {eng}, number = {7402}, journal = {Nature}, author = {{Human Microbiome Project Consortium}}, month = jun, year = {2012}, pmid = {22699610}, pmcid = {PMC3377744}, keywords = {Adolescent, Adult, Bacteria, Female, Humans, Male, Metagenome, Metagenomics, Reference Standards, RNA, Ribosomal, 16S, Statistics as Topic, Young Adult}, pages = {215--221}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\YBV3K2F9\\Human Microbiome Project Consortium - 2012 - A framework for human microbiome research.pdf:application/pdf} } @article{human_microbiome_project_consortium_structure_2012, title = {Structure, function and diversity of the healthy human microbiome}, volume = {486}, copyright = {All rights reserved}, issn = {1476-4687}, doi = {10.1038/nature11234}, abstract = {Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99\% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.}, language = {eng}, number = {7402}, journal = {Nature}, author = {{Human Microbiome Project Consortium}}, month = jun, year = {2012}, pmid = {22699609}, pmcid = {PMC3564958}, keywords = {Adolescent, Adult, Bacteria, Biodiversity, Ecosystem, Female, Health, Humans, Male, Metabolic Networks and Pathways, Metagenome, Metagenomics, Phenotype, RNA, Ribosomal, 16S, Young Adult}, pages = {207--214}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\YASHD62W\\Human Microbiome Project Consortium - 2012 - Structure, function and diversity of the healthy h.pdf:application/pdf} } @article{sharpton_phylotu:_2011, title = {{PhylOTU}: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data}, volume = {7}, copyright = {All rights reserved}, issn = {1553-7358}, shorttitle = {{PhylOTU}}, doi = {10.1371/journal.pcbi.1001061}, abstract = {Microbial diversity is typically characterized by clustering ribosomal RNA (SSU-rRNA) sequences into operational taxonomic units (OTUs). Targeted sequencing of environmental SSU-rRNA markers via PCR may fail to detect OTUs due to biases in priming and amplification. Analysis of shotgun sequenced environmental DNA, known as metagenomics, avoids amplification bias but generates fragmentary, non-overlapping sequence reads that cannot be clustered by existing OTU-finding methods. To circumvent these limitations, we developed PhylOTU, a computational workflow that identifies OTUs from metagenomic SSU-rRNA sequence data through the use of phylogenetic principles and probabilistic sequence profiles. Using simulated metagenomic data, we quantified the accuracy with which PhylOTU clusters reads into OTUs. Comparisons of PCR and shotgun sequenced SSU-rRNA markers derived from the global open ocean revealed that while PCR libraries identify more OTUs per sequenced residue, metagenomic libraries recover a greater taxonomic diversity of OTUs. In addition, we discover novel species, genera and families in the metagenomic libraries, including OTUs from phyla missed by analysis of PCR sequences. Taken together, these results suggest that PhylOTU enables characterization of part of the biosphere currently hidden from PCR-based surveys of diversity?}, language = {eng}, number = {1}, journal = {PLoS computational biology}, author = {Sharpton, Thomas J. and Riesenfeld, Samantha J. and Kembel, Steven W. and Ladau, Joshua and O'Dwyer, James P. and Green, Jessica L. and Eisen, Jonathan A. and Pollard, Katherine S.}, month = jan, year = {2011}, pmid = {21283775}, pmcid = {PMC3024254}, keywords = {Cluster Analysis, Genomics, Phylogeny, Polymerase Chain Reaction, RNA, Ribosomal}, pages = {e1001061}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\9IGPSKV5\\Sharpton et al. - 2011 - PhylOTU a high-throughput procedure quantifies mi.pdf:application/pdf} } @article{neafsey_population_2010, title = {Population genomic sequencing of {Coccidioides} fungi reveals recent hybridization and transposon control}, volume = {20}, copyright = {All rights reserved}, issn = {1549-5469}, doi = {10.1101/gr.103911.109}, abstract = {We have sequenced the genomes of 18 isolates of the closely related human pathogenic fungi Coccidioides immitis and Coccidioides posadasii to more clearly elucidate population genomic structure, bringing the total number of sequenced genomes for each species to 10. Our data confirm earlier microsatellite-based findings that these species are genetically differentiated, but our population genomics approach reveals that hybridization and genetic introgression have recently occurred between the two species. The directionality of introgression is primarily from C. posadasii to C. immitis, and we find more than 800 genes exhibiting strong evidence of introgression in one or more sequenced isolates. We performed PCR-based sequencing of one region exhibiting introgression in 40 C. immitis isolates to confirm and better define the extent of gene flow between the species. We find more coding sequence than expected by chance in the introgressed regions, suggesting that natural selection may play a role in the observed genetic exchange. We find notable heterogeneity in repetitive sequence composition among the sequenced genomes and present the first detailed genome-wide profile of a repeat-induced point mutation (RIP) process distinctly different from what has been observed in Neurospora. We identify promiscuous HLA-I and HLA-II epitopes in both proteomes and discuss the possible implications of introgression and population genomic data for public health and vaccine candidate prioritization. This study highlights the importance of population genomic data for detecting subtle but potentially important phenomena such as introgression.}, language = {eng}, number = {7}, journal = {Genome Research}, author = {Neafsey, Daniel E. and Barker, Bridget M. and Sharpton, Thomas J. and Stajich, Jason E. and Park, Daniel J. and Whiston, Emily and Hung, Chiung-Yu and McMahan, Cody and White, Jared and Sykes, Sean and Heiman, David and Young, Sarah and Zeng, Qiandong and Abouelleil, Amr and Aftuck, Lynne and Bessette, Daniel and Brown, Adam and FitzGerald, Michael and Lui, Annie and Macdonald, J. Pendexter and Priest, Margaret and Orbach, Marc J. and Galgiani, John N. and Kirkland, Theo N. and Cole, Garry T. and Birren, Bruce W. and Henn, Matthew R. and Taylor, John W. and Rounsley, Steven D.}, month = jul, year = {2010}, pmid = {20516208}, pmcid = {PMC2892095}, keywords = {Base Sequence, California, Coccidioides, DNA Transposable Elements, Evolution, Molecular, Gene Expression Regulation, Fungal, Genetic Variation, Genome, Fungal, Hybridization, Genetic, Metagenomics, Molecular Sequence Data, Mutagenesis, Insertional, Polymorphism, Single Nucleotide, Repetitive Sequences, Nucleic Acid, Sequence Analysis, DNA}, pages = {938--946}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\AKLBU5K9\\Neafsey et al. - 2010 - Population genomic sequencing of Coccidioides fung.pdf:application/pdf} } @article{sharpton_comparative_2009, title = {Comparative genomic analyses of the human fungal pathogens {Coccidioides} and their relatives}, volume = {19}, copyright = {All rights reserved}, issn = {1549-5469}, doi = {10.1101/gr.087551.108}, abstract = {While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.}, language = {eng}, number = {10}, journal = {Genome Research}, author = {Sharpton, Thomas J. and Stajich, Jason E. and Rounsley, Steven D. and Gardner, Malcolm J. and Wortman, Jennifer R. and Jordar, Vinita S. and Maiti, Rama and Kodira, Chinnappa D. and Neafsey, Daniel E. and Zeng, Qiandong and Hung, Chiung-Yu and McMahan, Cody and Muszewska, Anna and Grynberg, Marcin and Mandel, M. Alejandra and Kellner, Ellen M. and Barker, Bridget M. and Galgiani, John N. and Orbach, Marc J. and Kirkland, Theo N. and Cole, Garry T. and Henn, Matthew R. and Birren, Bruce W. and Taylor, John W.}, month = oct, year = {2009}, pmid = {19717792}, pmcid = {PMC2765278}, keywords = {Animals, Coccidioides, Genetic Speciation, Genome, Fungal, Genomics, Histoplasma, Humans, Mitosporic Fungi, Molecular Sequence Data, Onygenales, Phylogeny, Selection, Genetic, Sequence Analysis, DNA, Synteny}, pages = {1722--1731}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\PLHY4M6X\\Sharpton et al. - 2009 - Comparative genomic analyses of the human fungal p.pdf:application/pdf} } @article{sharpton_mechanisms_2008, title = {Mechanisms of intron gain and loss in {Cryptococcus}}, volume = {9}, copyright = {All rights reserved}, issn = {1474-760X}, doi = {10.1186/gb-2008-9-1-r24}, abstract = {BACKGROUND: Genome comparisons across deep phylogenetic divergences have revealed that spliceosomal intron gain and loss are common evolutionary events. However, because of the deep divergences involved in these comparisons, little is understood about how these changes occur, particularly in the case of intron gain. To ascertain mechanisms of intron gain and loss, we compared five relatively closely related genomes from the yeast Cryptococcus. RESULTS: We observe a predominance of intron loss over gain and identify a relatively slow intron loss rate in Cryptococcus. Some genes preferentially lose introns and a large proportion of intron losses occur in the middle of genes (so called internal intron loss). Finally, we identify a gene that displays a differential number of introns in a repetitive DNA region. CONCLUSION: Based the observed patterns of intron loss and gain, population resequencing and population genetic analysis, it appears that recombination causes the widely observed but poorly understood phenomenon of internal intron loss and that DNA repeat expansion can create new introns in a population.}, language = {eng}, number = {1}, journal = {Genome Biology}, author = {Sharpton, Thomas J. and Neafsey, Daniel E. and Galagan, James E. and Taylor, John W.}, month = jan, year = {2008}, pmid = {18234113}, pmcid = {PMC2395259}, keywords = {Base Sequence, Cryptococcus, DNA Repeat Expansion, Evolution, Molecular, Introns, Molecular Sequence Data, Phylogeny, Recombination, Genetic, Sequence Alignment}, pages = {R24}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\QPWXE8LM\\Sharpton et al. - 2008 - Mechanisms of intron gain and loss in Cryptococcus.pdf:application/pdf} } @article{sharpton_leveraging_2006, title = {Leveraging the knowledge of our peers: online communities hold the promise to enhance scientific research}, volume = {4}, copyright = {All rights reserved}, issn = {1545-7885}, shorttitle = {Leveraging the knowledge of our peers}, doi = {10.1371/journal.pbio.0040199}, language = {eng}, number = {6}, journal = {PLoS biology}, author = {Sharpton, Thomas J. and Jhaveri, Arpan A.}, month = jun, year = {2006}, pmid = {16752946}, pmcid = {PMC1475690}, keywords = {Access to Information, Information Dissemination, Internet, Peer Group, Research, Software}, pages = {e199}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\2FVEEQB4\\Sharpton and Jhaveri - 2006 - Leveraging the knowledge of our peers online comm.pdf:application/pdf} } @article{jiang_microbiome_2019, title = {Microbiome {Multi}-{Omics} {Network} {Analysis}: {Statistical} {Considerations}, {Limitations}, and {Opportunities}}, volume = {10}, copyright = {All rights reserved}, shorttitle = {Microbiome {Multi}-{Omics} {Network} {Analysis}}, url = {https://www.frontiersin.org/articles/10.3389/fgene.2019.00995/full}, doi = {10.3389/fgene.2019.00995}, abstract = {The advent of large-scale microbiome studies affords newfound analytical opportunities to understand how these communities of microbes operate and relate to their environment. However, the analytical methodology needed to model microbiome data and integrate them with other data constructs remains nascent. This emergent analytical toolset frequently ports over techniques developed in other multi-omics investigations, especially the growing array of statistical and computational techniques for integrating and representing data through networks. While network analysis has emerged as a powerful approach to modeling microbiome data, oftentimes by integrating these data with other types of omics data to discern their functional linkages, it is not always evident if the statistical details of the approach being applied are consistent with the assumptions of microbiome data or how they impact data interpretation. In this review, we overview some of the most important network methods for integrative analysis, with an emphasis on methods that have been applied or have great potential to be applied to the analysis of multi-omics integration of microbiome data. We compare advantages and disadvantages of various statistical tools, assess their applicability to microbiome data, and discuss their biological interpretability. We also highlight on-going statistical challenges and opportunities for integrative network analysis of microbiome data.}, number = {995}, urldate = {2019-11-11}, journal = {Frontiers in Genetics}, author = {Jiang, Duo and Armour, Courtney R. and Hu, Chenxiao and Mei, Meng and Tian, Chuan and Sharpton, Thomas J. and Jiang, Yuan}, month = nov, year = {2019}, file = {Frontiers | Microbiome Multi-Omics Network Analysis\: Statistical Considerations, Limitations, and Opportunities | Genetics:C\:\\Users\\sharptot\\Zotero\\storage\\5JLQS8ZX\\full.html:text/html} } @article{morelan_microbiome_2019, title = {Microbiome {Variation} in an {Intertidal} {Sea} {Anemone} {Across} {Latitudes} and {Symbiotic} {States}}, volume = {6}, copyright = {All rights reserved}, issn = {2296-7745}, url = {https://www.frontiersin.org/articles/10.3389/fmars.2019.00007/full}, doi = {10.3389/fmars.2019.00007}, abstract = {Many cnidarians form symbiotic relationships with brown dinoflagellate algae in the genus Symbiodinium. Bacteria are important to this symbiosis, with diverse functions such as providing nutrients to the symbiont and pathogen protection to the cnidarian. Disrupted bacterial communities are associated with thermally stressed cnidarians, which have a higher likelihood of expelling their symbionts, an event called bleaching. To better understand the association between thermal tolerance and bacterial community structure, we studied communities associated with an exceptionally thermal tolerant cnidarian, Anthopleura elegantissima. This intertidal symbiotic sea anemone is distributed from the subtropical waters of Baja California to subarctic Alaska, and experiences daily temperature fluctuations of up to 20ºC. It is also flexible in its symbioses, predominantly hosting Symbiodinium, but occasionally hosting the green algae Elliptochloris marina or existing without symbionts in an aposymbiotic state. We used 16S rRNA gene amplicon sequencing to characterize the natural variation of microbial communities associated with Anthopleura elegantissima in these three symbiotic states and across a latitudinal gradient. In this study, we identified a core microbiome, made up predominantly of taxa typically found in coastal seawater. We found that the communities associated with A. elegantissima were weakly linked to latitude. Diversity analyses revealed significantly higher species richness values for microbial communities associated with anemones hosting E. marina. Lastly the microbiome communities associated with different symbiotic states were compositionally distinct. Taken together, our results suggest that the structure of microbial communities associated with these temperate cnidarians is tightly linked to symbiotic state and weakly linked to other biogeographic phenomena.}, language = {English}, number = {7}, urldate = {2019-11-11}, journal = {Frontiers in Marine Science}, author = {Morelan, Ian A. and Gaulke, Christopher A. and Sharpton, Thomas J. and Vega Thurber, Rebecca and Denver, Dee R.}, month = jan, year = {2019}, keywords = {16S, Cnidaria, Microbiome analysis, Rocky interdial zone, Symbiodinium, Symbiosis}, file = {Full Text PDF:C\:\\Users\\sharptot\\Zotero\\storage\\Y2K44R6J\\Morelan et al. - 2019 - Microbiome Variation in an Intertidal Sea Anemone .pdf:application/pdf} } @article{wang_corals_2018, title = {Corals and {Their} {Microbiomes} {Are} {Differentially} {Affected} by {Exposure} to {Elevated} {Nutrients} and a {Natural} {Thermal} {Anomaly}}, volume = {5}, copyright = {All rights reserved}, issn = {2296-7745}, url = {https://www.frontiersin.org/articles/10.3389/fmars.2018.00101/full}, doi = {10.3389/fmars.2018.00101}, abstract = {Nutrient pollution can increase the prevalence and severity of coral disease and bleaching in ambient temperature conditions or during experimental thermal challenge. However, there have been few opportunities to study the effects of nutrient pollution during natural thermal anomalies. Here we present results from an experiment conducted during the 2014 bleaching event in the Florida Keys, USA, that exposed Agaricia sp. (Undaria) and Siderastrea siderea corals to 3 types of elevated nutrients: nitrogen alone, phosphorous alone, and the combination of nitrogen and phosphorus. Overall, bleaching prevalence and severity was high regardless of treatment, but nitrogen enrichment alone both prolonged bleaching and increased coral mortality in Agaricia corals. At the same time, the elevated temperatures increased the prevalence of Dark Spot Syndrome (DSS), a disease typically associated with cold temperatures in Siderastrea siderea corals. However, nutrient exposure alone did not increase the prevalence or severity of disease, suggesting that thermal stress overwhelms the effects of nutrient pollution on this disease during such an extreme thermal event. Analysis of 85 Siderastrea siderea microbial metagenomes also showed that the thermal event was correlated with significant shifts in the composition and function of the associated microbiomes, and corals with DSS had microbiomes distinct from apparently healthy corals. In particular, we identified shifts in viral, archaeal, and fungal families. These shifts were likely driven by the extreme temperatures or other environmental co-variates occurring during the 2014 bleaching event. However, no microbial taxa were correlated with signs of DSS. Furthermore, although nutrient exposure did not affect microbial alpha diversity, it did significantly affect microbiome beta-diversity, an effect that was independent of time. These results suggest that strong thermal anomalies and local nutrient pollution both interact and act independently to alter coral health in a variety of ways, that ultimately contribute to disease, bleaching, and mortality of reefs in the Florida Keys.}, language = {English}, number = {7}, urldate = {2019-11-11}, journal = {Frontiers in Marine Science}, author = {Wang, Lu and Shantz, Andrew A. and Payet, Jérôme P. and Sharpton, Thomas J. and Foster, Amelia and Burkepile, Deron E. and Vega Thurber, Rebecca}, month = mar, year = {2018}, keywords = {Bacteria, Bleaching, corals, Dark Spot Syndrome, Disease, Fungi, reefs, Viruses}, file = {Full Text PDF:C\:\\Users\\sharptot\\Zotero\\storage\\22UMLIG8\\Wang et al. - 2018 - Corals and Their Microbiomes Are Differentially Af.pdf:application/pdf} } @article{huttenhower_advancing_2014, title = {Advancing the microbiome research community}, volume = {159}, copyright = {All rights reserved}, issn = {1097-4172}, doi = {10.1016/j.cell.2014.09.022}, abstract = {The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology.}, language = {eng}, number = {2}, journal = {Cell}, author = {Huttenhower, Curtis and Knight, Rob and Brown, C. Titus and Caporaso, J. Gregory and Clemente, Jose C. and Gevers, Dirk and Franzosa, Eric A. and Kelley, Scott T. and Knights, Dan and Ley, Ruth E. and Mahurkar, Anup and Ravel, Jacques and {Scientists for Advancement of Microbiome Research} and White, Owen}, month = oct, year = {2014}, pmid = {25303518}, pmcid = {PMC4221798}, keywords = {Animals, Biomedical Research, Guidelines as Topic, Humans, Microbiological Techniques, Microbiota, National Institutes of Health (U.S.), United States}, pages = {227--230}, file = {Full Text:C\:\\Users\\sharptot\\Zotero\\storage\\SH7LHRU6\\Huttenhower et al. - 2014 - Advancing the microbiome research community.pdf:application/pdf} }