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Search Results: 1 - 10 of 168128 matches for " Bas E. Dutilh "
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A global definition of expression context is conserved between orthologs, but does not correlate with sequence conservation
Bas E Dutilh, Martijn A Huynen, Berend Snel
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-10
Abstract: To compare gene expression between distant species on a global scale, we introduce the "expression context". The expression context of a gene is based on the co-expression with all other genes that have unambiguous counterparts in both genomes. Employing this new measure, we show 1) that the expression context is largely conserved between orthologs, and 2) that sequence identity shows little correlation with expression context conservation after gene duplication and speciation.This means that the degree of sequence identity has a limited predictive quality for differential expression context conservation between orthologs, and thus presumably also for other facets of gene function.The two main components of the function of a gene are its molecular function (what does it do, e.g. is it a hydrolase, is it DNA binding) and its functional context (with what other elements of the cell does it collaborate). Though both aspects can only be decisively determined in in vivo experiments, the incredible and increasing amount of experimental information assembled in databases enables more and more accurate predictions [1]. Because of the accuracy and speed with which algorithms can identify sequence similarity, the most commonly used tool for predicting gene function is doubtlessly sequence conservation. As the sequence is the blueprint for the three-dimensional structure, and therewith the enzymatic function of a gene, this method is particularly suitable for predicting the molecular function of an unknown gene, for example in a newly sequenced species.Predicting functional context, on the other hand, is a different story. This means inferring in silico in which process the gene plays a role. Whereas the molecular function is concrete, and can be described by the catalyzed chemical reaction, the functional context is more elusive and may best be described as a composition of the context (e.g. binding partners) of the encoded protein and the regulation of its expression in time
Asymmetric relationships between proteins shape genome evolution
Richard A Notebaart, Philip R Kensche, Martijn A Huynen, Bas E Dutilh
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-2-r19
Abstract: We show that the majority of relationships between enzymes in metabolic flux models of metabolism in Escherichia coli and Saccharomyces cerevisiae are asymmetric. We show furthermore that these asymmetric relationships are reflected in the expression of the genes encoding those enzymes, the effect of gene knockouts and the evolution of genomes. From the asymmetric relative dependency, one would expect that the gene that is relatively independent (B) can occur without the other dependent gene (A), but not the reverse. Indeed, when only one gene of an A->B pair is expressed, is essential, is present in a genome after an evolutionary gain or loss, it tends to be the independent gene (B). This bias is strongest for genes encoding proteins whose asymmetric relationship is evolutionarily conserved.The asymmetric relations between proteins that arise from the system properties of metabolic networks affect gene expression, the relative effect of gene knockouts and genome evolution in a predictable manner.Cellular processes can only be fully understood by considering how the functions of proteins depend upon each other. The relationship between two proteins can be symmetric - for example, when they mutually depend upon each other for their function within a protein complex. Proteins can also be asymmetrically related. This occurs when the function of one protein (A) depends on another protein (B), but the function of protein B does not depend on A: A→B. For example, in regulatory interactions, the function of the regulator depends on the presence of its target, but the target can often function without the regulator. Examples of asymmetrical relationships also exist in metabolism. For instance, multiple enzymes may produce the same substance (Figure 1), creating a situation in which the function of the proteins in the converging reaction fluxes (A) depends on the flux through B, but the function of B does not specifically depend on one of the converging fluxes. With the avai
FOCUS: an alignment-free model to identify organisms in metagenomes using non-negative least squares
Genivaldo Gueiros Z. Silva,Daniel A. Cuevas,Bas E. Dutilh,Robert A. Edwards
PeerJ , 2015, DOI: 10.7717/peerj.425
Abstract: One of the major goals in metagenomics is to identify the organisms present in a microbial community from unannotated shotgun sequencing reads. Taxonomic profiling has valuable applications in biological and medical research, including disease diagnostics. Most currently available approaches do not scale well with increasing data volumes, which is important because both the number and lengths of the reads provided by sequencing platforms keep increasing. Here we introduce FOCUS, an agile composition based approach using non-negative least squares (NNLS) to report the organisms present in metagenomic samples and profile their abundances. FOCUS was tested with simulated and real metagenomes, and the results show that our approach accurately predicts the organisms present in microbial communities. FOCUS was implemented in Python. The source code and web-sever are freely available at http://edwards.sdsu.edu/FOCUS.
Towards the Human Colorectal Cancer Microbiome
Julian R. Marchesi,Bas E. Dutilh,Neil Hall,Wilbert H. M. Peters,Rian Roelofs,Annemarie Boleij,Harold Tjalsma
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020447
Abstract: Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.
Discovery of a hapE Mutation That Causes Azole Resistance in Aspergillus fumigatus through Whole Genome Sequencing and Sexual Crossing
Simone M. T. Camps, Bas E. Dutilh, Maiken C. Arendrup, Antonius J. M. M. Rijs, Eveline Snelders, Martijn A. Huynen, Paul E. Verweij, Willem J. G. Melchers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050034
Abstract: Azole compounds are the primary therapy for patients with diseases caused by Aspergillus fumigatus. However, prolonged treatment may cause resistance to develop, which is associated with treatment failure. The azole target cyp51A is a hotspot for mutations that confer phenotypic resistance, but in an increasing number of resistant isolates the underlying mechanism remains unknown. Here, we report the discovery of a novel resistance mechanism, caused by a mutation in the CCAAT-binding transcription factor complex subunit HapE. From one patient, four A. fumigatus isolates were serially collected. The last two isolates developed an azole resistant phenotype during prolonged azole therapy. Because the resistant isolates contained a wild type cyp51A gene and the isolates were isogenic, the complete genomes of the last susceptible isolate and the first resistant isolate (taken 17 weeks apart) were sequenced using Illumina technology to identify the resistance conferring mutation. By comparing the genome sequences to each other as well as to two A. fumigatus reference genomes, several potential non-synonymous mutations in protein-coding regions were identified, six of which could be confirmed by PCR and Sanger sequencing. Subsequent sexual crossing experiments showed that resistant progeny always contained a P88L substitution in HapE, while the presence of the other five mutations did not correlate with resistance in the progeny. Cloning the mutated hapE gene into the azole susceptible akuBKU80 strain showed that the HapE P88L mutation by itself could confer the resistant phenotype. This is the first time that whole genome sequencing and sexual crossing strategies have been used to find the genetic basis of a trait of interest in A. fumigatus. The discovery may help understand alternate pathways for azole resistance in A. fumigatus with implications for the molecular diagnosis of resistance and drug discovery.
Pyrosequencing of 16S rRNA gene amplicons to study the microbiota in the gastrointestinal tract of carp (Cyprinus carpio L.)
Maartje AHJ van Kessel, Bas E Dutilh, Kornelia Neveling, Michael P Kwint, Joris A Veltman, Gert Flik, Mike SM Jetten, Peter HM Klaren, Huub JM Op den Camp
AMB Express , 2011, DOI: 10.1186/2191-0855-1-41
Abstract: The intestine is a multifunctional organ system involved in the digestion and absorption of food, electrolyte balance, endocrine regulation of food metabolism and immunity against pathogens (Ringo et al. 2003). The gastrointestinal (GI) tract is inhabited by many different micro-organisms. As in mammals, this dynamic population of micro-organisms is of key importance for the health of the piscine host (Ringo et al. 2003; Rawls et al. 2004). The gut is also a potential route for pathogens to invade and infect their host. The micro-organisms in the GI tract are involved in the protection against these pathogens by the production of inhibitory compounds and competition for nutrients and space. As in mammals, the intestinal microbiota of fish can influence the expression of genes involved in epithelial proliferation, nutrient metabolism and innate immunity (Rawls et al. 2004). Due to their importance in animal health, the investigation of the intestinal microbiota of fish is highly relevant for aquaculture practice. We investigated the diversity of the microbiota in common carp (Cyprinus carpio), one of the most cultivated freshwater fish species worldwide (FAO, 2011).The morphology of the GI tract of fishes varies greatly among species. Common carp belong to the family of Cyprinidae, which are herbivorous, stomachless fish. These fish lack pyloric caeca, the finger-like blind sacs in the proximal intestine that increase the absorptive surface of the intestines in many fish (Ringo et al. 2003; Buddington and Diamond 1987). The composition of the gut microbiota of common carp has previously been investigated using culture-dependent methods (Sugita et al. 1990; Namba et al. 2007; Tsuchiya et al. 2008). Most bacterial species found in these studies were aerobes and facultative anaerobes. Two studies demonstrated a high abundance of Aeromonas species (Namba et al. 2007; Sugita et al. 1990). Other bacteria isolated were Enterobacteriaceae (Sugita et al. 1990; Namba et al. 20
Cell Wall Modifications during Conidial Maturation of the Human Pathogenic Fungus Pseudallescheria boydii
Sarah Ghamrawi, Gilles Rénier, Patrick Saulnier, Stéphane Cuenot, Agata Zykwinska, Bas E. Dutilh, Christopher Thornton, Sébastien Faure, Jean-Philippe Bouchara
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100290
Abstract: Progress in extending the life expectancy of cystic fibrosis (CF) patients remains jeopardized by the increasing incidence of fungal respiratory infections. Pseudallescheria boydii (P. boydii), an emerging pathogen of humans, is a filamentous fungus frequently isolated from the respiratory secretions of CF patients. It is commonly believed that infection by this fungus occurs through inhalation of airborne conidia, but the mechanisms allowing the adherence of Pseudallescheria to the host epithelial cells and its escape from the host immune defenses remain largely unknown. Given that the cell wall orchestrates all these processes, we were interested in studying its dynamic changes in conidia as function of the age of cultures. We found that the surface hydrophobicity and electronegative charge of conidia increased with the age of culture. Melanin that can influence the cell surface properties, was extracted from conidia and estimated using UV-visible spectrophotometry. Cells were also directly examined and compared using electron paramagnetic resonance (EPR) that determines the production of free radicals. Consistent with the increased amount of melanin, the EPR signal intensity decreased suggesting polymerization of melanin. These results were confirmed by flow cytometry after studying the effect of melanin polymerization on the surface accessibility of mannose-containing glycoconjugates to fluorescent concanavalin A. In the absence of melanin, conidia showed a marked increase in fluorescence intensity as the age of culture increased. Using atomic force microscopy, we were unable to find rodlet-forming hydrophobins, molecules that can also affect conidial surface properties. In conclusion, the changes in surface properties and biochemical composition of the conidial wall with the age of culture highlight the process of conidial maturation. Mannose-containing glycoconjugates that are involved in immune recognition, are progressively masked by polymerization of melanin, an antioxidant that is commonly thought to allow fungal escape from the host immune defenses.
Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis
Daniela Bezemer?,Anne Cori?,Oliver Ratmann?,Ard van Sighem?,Hillegonda S. Hermanides?,Bas E. Dutilh,Luuk Gras?,Nuno Rodrigues Faria?,Rob van den Hengel?,Ashley J. Duits
PLOS Medicine , 2015, DOI: 10.1371/journal.pmed.1001898
Abstract: Background The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions The resurgent HIV epidemic amongst MSM in the Netherlands is
Taxonomic and Functional Microbial Signatures of the Endemic Marine Sponge Arenosclera brasiliensis
Amaro E. Trindade-Silva, Cintia Rua, Genivaldo G. Z. Silva, Bas E. Dutilh, Ana Paula B. Moreira, Robert A. Edwards, Eduardo Hajdu, Gisele Lobo-Hajdu, Ana Tereza Vasconcelos, Roberto G. S. Berlinck, Fabiano L. Thompson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039905
Abstract: The endemic marine sponge Arenosclera brasiliensis (Porifera, Demospongiae, Haplosclerida) is a known source of secondary metabolites such as arenosclerins A-C. In the present study, we established the composition of the A. brasiliensis microbiome and the metabolic pathways associated with this community. We used 454 shotgun pyrosequencing to generate approximately 640,000 high-quality sponge-derived sequences (~150 Mb). Clustering analysis including sponge, seawater and twenty-three other metagenomes derived from marine animal microbiomes shows that A. brasiliensis contains a specific microbiome. Fourteen bacterial phyla (including Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Cloroflexi) were consistently found in the A. brasiliensis metagenomes. The A. brasiliensis microbiome is enriched for Betaproteobacteria (e.g., Burkholderia) and Gammaproteobacteria (e.g., Pseudomonas and Alteromonas) compared with the surrounding planktonic microbial communities. Functional analysis based on Rapid Annotation using Subsystem Technology (RAST) indicated that the A. brasiliensis microbiome is enriched for sequences associated with membrane transport and one-carbon metabolism. In addition, there was an overrepresentation of sequences associated with aerobic and anaerobic metabolism as well as the synthesis and degradation of secondary metabolites. This study represents the first analysis of sponge-associated microbial communities via shotgun pyrosequencing, a strategy commonly applied in similar analyses in other marine invertebrate hosts, such as corals and algae. We demonstrate that A. brasiliensis has a unique microbiome that is distinct from that of the surrounding planktonic microbes and from other marine organisms, indicating a species-specific microbiome.
Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate
Nicole A Datson, Maarten C Morsink, Srebrena Atanasova, Victor W Armstrong, Hans Zischler, Christina Schlumbohm, Bas E Dutilh, Martijn A Huynen, Brigitte Waegele, Andreas Ruepp, E Ronald de Kloet, Eberhard Fuchs
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-190
Abstract: Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846].We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model.The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. Not only their close genetic, physiological and metabolic similarity to humans but also several unique physiological differences between Old World and New World primates, underlie its widespread use as an animal model in studies involving aspects of infectious disease, stem cell research, neural and cognitive sciences, toxicology and drug development and reproductive biology. More
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