The genome of the intracellular bacterium of the coastal bivalve, Solemya velum: a blueprint for thriving in and out of symbiosis

Background: Symbioses between chemoautotrophic bacteria and marine invertebrates are rare examples of living systems that are virtually independent of photosynthetic primary production. These associations have evolved multiple times in marine habitats, such as deep-sea hydrothermal vents and reducing sediments, characterized by steep gradients of oxygen and reduced chemicals. Due to difficulties associated with maintaining these symbioses in the laboratory and culturing the symbiotic bacteria, studies of chemosynthetic symbioses rely heavily on culture independent methods. The symbiosis between the coastal bivalve, Solemya velum, and its intracellular symbiont is a model for chemosynthetic symbioses given its accessibility in intertidal environments and the ability to maintain it under laboratory conditions. To better understand this symbiosis, the genome of the S. velum endosymbiont was sequenced. Results: Relative to the genomes of obligate symbiotic bacteria, which commonly undergo erosion and reduction, the S. velum symbiont genome was large (2.7 Mb), GC-rich (51%), and contained a large number (78) of mobile genetic elements. Comparative genomics identified sets of genes specific to the chemosynthetic lifestyle and necessary to sustain the symbiosis. In addition, a number of inferred metabolic pathways and cellular processes, including heterotrophy, branched electron transport, and motility, suggested that besides the ability to function as an endosymbiont, the bacterium may have the capacity to live outside the host. Conclusions: The physiological dexterity indicated by the genome substantially improves our understanding of the genetic and metabolic capabilities of the S. velum symbiont and the breadth of niches the partners may inhabit during their lifecycle. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-924) contains supplementary material, which is available to authorized users

Finding the sources of missing heritability in a yeast cross

For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this "missing heritability" have been proposed. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to 50%. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits

Classification Accuracy of Neuroimaging Biomarkers in Attention-Deficit/Hyperactivity Disorder: Effects of Sample Size and Circular Analysis

BackgroundMotivated by an inconsistency between reports of high diagnosis-classification accuracies and known heterogeneity in attention-deficit/hyperactivity disorder (ADHD), this study assessed classification accuracy in studies of ADHD as a function of methodological factors that can bias results. We hypothesized that high classification results in ADHD diagnosis are inflated by methodological factors.MethodsWe reviewed 69 studies (of 95 studies identified) that used neuroimaging features to predict ADHD diagnosis. Based on reported methods, we assessed the prevalence of circular analysis, which inflates classification accuracy, and evaluated the relationship between sample size and accuracy to test if small-sample models tend to report higher classification accuracy, also an indicator of bias.ResultsCircular analysis was detected in 15.9% of ADHD classification studies, lack of independent test set was noted in 13%, and insufficient methodological detail to establish its presence was noted in another 11.6%. Accuracy of classification ranged from 60% to 80% in the 59.4% of reviewed studies that met criteria for independence of feature selection, model construction, and test datasets. Moreover, there was a negative relationship between accuracy and sample size, implying additional bias contributing to reported accuracies at lower sample sizes.ConclusionsHigh classification accuracies in neuroimaging studies of ADHD appear to be inflated by circular analysis and small sample size. Accuracies on independent datasets were consistent with known heterogeneity of the disorder. Steps to resolve these issues, and a shift toward accounting for sample heterogeneity and prediction of future outcomes, will be crucial in future classification studies in ADHD

Classification Accuracy of Neuroimaging Biomarkers in Attention-Deficit/Hyperactivity Disorder: Effects of Sample Size and Circular Analysis.

BackgroundMotivated by an inconsistency between reports of high diagnosis-classification accuracies and known heterogeneity in attention-deficit/hyperactivity disorder (ADHD), this study assessed classification accuracy in studies of ADHD as a function of methodological factors that can bias results. We hypothesized that high classification results in ADHD diagnosis are inflated by methodological factors.MethodsWe reviewed 69 studies (of 95 studies identified) that used neuroimaging features to predict ADHD diagnosis. Based on reported methods, we assessed the prevalence of circular analysis, which inflates classification accuracy, and evaluated the relationship between sample size and accuracy to test if small-sample models tend to report higher classification accuracy, also an indicator of bias.ResultsCircular analysis was detected in 15.9% of ADHD classification studies, lack of independent test set was noted in 13%, and insufficient methodological detail to establish its presence was noted in another 11.6%. Accuracy of classification ranged from 60% to 80% in the 59.4% of reviewed studies that met criteria for independence of feature selection, model construction, and test datasets. Moreover, there was a negative relationship between accuracy and sample size, implying additional bias contributing to reported accuracies at lower sample sizes.ConclusionsHigh classification accuracies in neuroimaging studies of ADHD appear to be inflated by circular analysis and small sample size. Accuracies on independent datasets were consistent with known heterogeneity of the disorder. Steps to resolve these issues, and a shift toward accounting for sample heterogeneity and prediction of future outcomes, will be crucial in future classification studies in ADHD

Finding the sources of missing heritability in a yeast cross.

For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this 'missing heritability' have been proposed. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits, and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to approximately 50 per cent. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits

Correction: Longitudinal microbiome profiling reveals impermanence of probiotic bacteria in domestic pigeons.

[This corrects the article DOI: 10.1371/journal.pone.0217804.]

Longitudinal microbiome profiling reveals impermanence of probiotic bacteria in domestic pigeons.

Probiotics are bacterial species or assemblages that are applied to animals and plants with the intention of altering the microbiome in a beneficial way. Probiotics have been linked to positive health effects such as faster disease recovery times in humans and increased weight gain in poultry. Pigeon fanciers often feed their show pigeons probiotics with the intention of increasing flight performance. The objective of our study was to determine the effect of two different probiotics, alone and in combination, on the fecal microbiome of Birmingham Roller pigeons. We sequenced fecal samples from 20 pigeons divided into three probiotic treatments, including prior to, during, and after treatment. Pre-treatment and control group samples were dominated by Actinobacteria, Firmicutes, Proteobacteria, and Cyanobacteria. Administration of a probiotic pellet containing Enterococcus faecium and Lactobacillus acidophilus resulted in increase in average relative abundance of Lactobacillus spp. from 4.7 ± 2.0% to 93.0 ± 5.3%. No significant effects of Enterococcus spp. were detected. Probiotic-induced shifts in the microbiome composition were temporary and disappeared within 2 days of probiotic cessation. Administration of a probiotic powder in drinking water that contained Enterococcus faecium and three Lactobacillus species had minimal effect on the microbiome. We conclude that supplementing Birmingham roller pigeons with the probiotic pellets, but not the probiotic powder, temporarily changed the microbiome composition. A next step is to experimentally test the effect of these changes in microbiome composition on host health and physical performance

Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation

Introduction A growing body of evidence suggests that specific, naturally occurring gut bacteria are under-represented in the intestinal tracts of subjects with type 2 diabetes (T2D) and that their functions, like gut barrier stability and butyrate production, are important to glucose and insulin homeostasis. The objective of this study was to test the hypothesis that enteral exposure to microbes with these proposed functions can safely improve clinical measures of glycemic control and thereby play a role in the overall dietary management of diabetes.Research design and methods We evaluated whether a probiotic comprised of these anaerobic bacteria would enhance dietary management by (1) manufacturing two novel probiotic formulations containing three (WBF-010) or five (WBF-011) distinct strains in a Current Good Manufacturing Practice (cGMP) facility, (2) establishing consistent live-cell concentrations, (3) confirming safety at target concentrations dispensed in both animal and human studies and (4) conducting a 12-week parallel, double-blind, placebo-controlled, proof-of-concept study in which subjects previously diagnosed with T2D (n=76) were randomly assigned to a two times a day regimen of placebo, WBF-010 or WBF-011.Results No safety or tolerability issues were observed. Compared with the placebo group, subjects administered WBF-011 (which contains inulin, Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis and Anaerobutyricum hallii) significantly improved in the primary outcome, glucose total area under the curve (AUC): −36.1 mg/dL/180 min, p=0.0500 and also improved in secondary outcomes, glycated hemoglobin (A1c): −0.6, glucose incremental-AUC: −28.6 mg/dL/180 min.Conclusions To our knowledge, this is the first randomized controlled trial to administer four of the five strains to human subjects with T2D. This proof-of-concept study (clinical trial number NCT03893422) shows that the intervention was safe and well tolerated and that supplementation with WBF-011 improves postprandial glucose control. The limited sample size and intersubject variability justifies future studies designed to confirm and expand on these observations