eQED: an efficient method for interpreting eQTL associations using protein networks

Analysis of expression quantitative trait loci (eQTLs) is an emerging technique in which individuals are genotyped across a panel of genetic markers and, simultaneously, phenotyped using DNA microarrays. Because of the spacing of markers and linkage disequilibrium, each marker may be near many genes making it difficult to finely map which of these genes are the causal factors responsible for the observed changes in the downstream expression. To address this challenge, we present an efficient method for prioritizing candidate genes at a locus. This approach, called ‘eQTL electrical diagrams' (eQED), integrates eQTLs with protein interaction networks by modeling the two data sets as a wiring diagram of current sources and resistors. eQED achieved a 79% accuracy in recovering a reference set of regulator–target pairs in yeast, which is significantly higher than the performance of three competing methods. eQED also annotates 368 protein–protein interactions with their directionality of information flow with an accuracy of approximately 75%

Comparative modeling of DNA and RNA polymerases from Moniliophthora perniciosa mitochondrial plasmid

<p>Abstract</p> <p>Background</p> <p>The filamentous fungus <it>Moniliophthora perniciosa </it>(Stahel) Aime & Phillips-Mora is a hemibiotrophic Basidiomycota that causes witches' broom disease of cocoa (<it>Theobroma cacao </it>L.). This disease has resulted in a severe decrease in Brazilian cocoa production, which changed the position of Brazil in the market from the second largest cocoa exporter to a cocoa importer. Fungal mitochondrial plasmids are usually invertrons encoding DNA and RNA polymerases. Plasmid insertions into host mitochondrial genomes are probably associated with modifications in host generation time, which can be involved in fungal aging. This association suggests activity of polymerases, and these can be used as new targets for drugs against mitochondrial activity of fungi, more specifically against witches' broom disease. Sequencing and modeling: DNA and RNA polymerases of <it>M. perniciosa </it>mitochondrial plasmid were completely sequenced and their models were carried out by Comparative Homology approach. The sequences of DNA and RNA polymerase showed 25% of identity to 1XHX and 1ARO (pdb code) using BLASTp, which were used as templates. The models were constructed using Swiss PDB-Viewer and refined with a set of Molecular Mechanics (MM) and Molecular Dynamics (MD) in water carried out with AMBER 8.0, both working under the ff99 force fields, respectively. Ramachandran plots were generated by Procheck 3.0 and exhibited models with 97% and 98% for DNA and RNA polymerases, respectively. MD simulations in water showed models with thermodynamic stability after 2000 ps and 300 K of simulation.</p> <p>Conclusion</p> <p>This work contributes to the development of new alternatives for controlling the fungal agent of witches' broom disease.</p

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise

Background: Inbred individuals reared in controlled environments display considerable variance in many complex traits but the underlying cause of this intangible variation has been an enigma. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process.Results: Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28) show greater coefficients of variance in body weight than their wild-type littermates. Trim28 mutants additionally develop metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide gene expression analyses identified 284 significantly dysregulated genes in Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes a G-protein coupled receptor implicated in lipid metabolism, showing the greatest average change in expression (7.8-fold higher in mutants). This gene also showed highly variable expression between mutant individuals.Conclusions: These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans

A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

BACKGROUND: Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. RESULTS: We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. CONCLUSION: We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension

Do Queens of Bumblebee Species Differ In Their Choice Of Flower Colour Morphs Of Corydalis Cava (Fumariaceae)?

International audienceAbstractBumblebee queens require a continuous supply of flowering food plants from early spring for the successful development of annual colonies. Early in spring, Corydalis cava provides essential nectar and pollen resources and a choice of flower colour. In this paper, we examine flower colour choice (purple or white) in C. cava and verify the hypothesis that bumblebee queens differ in their choice of flower colour. A total of 10,615 observations of flower visits were made in spring 2011 and spring 2014 near Poznań, western Poland. Our results suggest that Bombus lucorum/cryptarum used purple flowers less, while Bombus terrestris used purple flowers more and Bombus hortorum showed no preference. Therefore, the colour morphs of C. cava are probably co-evolutionary adaptations to the development of another part of the insect community which has different colour preferences

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi