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Coeli R.,Genomics and Computational Biology Group | Oliveira G.,Genomics and Computational Biology Group | Oliveira G.,National Institute of Science and Technology in Tropical Diseases
PLoS Neglected Tropical Diseases | Year: 2013

Background:Schistosomiasis has a considerable impact on public health in many tropical and subtropical areas. In the new world, schistosomiasis is caused by the digenetic trematode Schistosoma mansoni. Chemotherapy is the main measure for controlling schistosomiasis, and the current drug of choice for treatment is praziquantel (PZQ). Although PZQ is efficient and safe, its repetitive large-scale use in endemic areas may lead to the selection of resistant strains. Isolates less susceptible to PZQ have been found in the field and selected for in the laboratory. The impact of selecting strains with a decreased susceptibility phenotype on disease dynamics and parasite population genetics is not fully understood. This study addresses the impact of PZQ pressure on the genetics of a laboratory population by analyzing frequency variations of polymorphic genetic markers.Methodology:Infected mice were treated with increasing PZQ doses until the highest dose of 3×300 mg/Kg was reached. The effect of PZQ treatment on the parasite population was assessed using five polymorphic microsatellite markers. Parasitological and genetic data were compared with those of the untreated control. After six parasite generations submitted to treatment, it was possible to obtain a S. mansoni population with decreased susceptibility to PZQ. In our experiments we also observed that female worms were more susceptible to PZQ than male worms.Conclusions:The selective pressure exerted by PZQ led to decreased genetic variability in S. mansoni and increased endogamy. The understanding of how S. mansoni populations respond to successive drug pressure has important implications on the appearance and maintenance of a PZQ resistance phenotype in endemic regions. © 2013 Coeli et al.


PubMed | Genomics and Computational Biology Group, Federal University of Pampa, Rothamsted Research and Federal University of Viçosa
Type: | Journal: Journal of microbiological methods | Year: 2016

Controversy surrounding bacterial phylogenies has become one of the most important challenges for microbial ecology. Comparative analyses with nucleotide databases and phylogenetic reconstruction of the amplified 16S rRNA genes from DGGE (Denaturing Gradient Gel Electrophoresis) excised bands have been used by several researchers for the identification of organisms in complex samples. Here, we individually analyzed DGGE-excised 16S rRNA gene bands from 10 certified bacterial strains of different species, and demonstrated that this kind of approach can deliver erroneous outcomes to researchers, besides causing/emphasizing errors in public databases.


PubMed | Genomics and Computational Biology Group, University of Groningen and Academy of Sciences of the Czech Republic
Type: Journal Article | Journal: The ISME journal | Year: 2016

Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in -diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal -diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem.


Almeida G.T.,University of Sao Paulo | Lage R.C.G.,Genomics and Computational Biology Group | Anderson L.,University of Sao Paulo | Venancio T.M.,University of Sao Paulo | And 8 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis. Methodology: We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay. Principal Findings: We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect. Conclusions: Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone. © 2015 Almeida et al.


Coimbra R.S.,Center for Excellence in Bioinformatics | Coimbra R.S.,Genomics and Computational Biology Group | Artiguenave F.,University of Évry Val d'Essonne | Jacques L.S.R.Z.,Center for Excellence in Bioinformatics | And 2 more authors.
Journal of Clinical Microbiology | Year: 2010

Escherichia coli and Shigella O antigens can be inferred using the rfb-restriction fragment length polymorphism (RFLP) molecular test. We present herein a dynamic programming algorithm-based software to compare the rfb-RFLP patterns of clinical isolates with those in a database containing the 171 previously published patterns corresponding to all known E. coli/Shigella O antigens. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Coimbra R.S.,Center for Excellence in Bioinformatics | Coimbra R.S.,Genomics and Computational Biology Group | Vanderwall D.E.,Glaxosmithkline | Oliveira G.C.,Center for Excellence in Bioinformatics | Oliveira G.C.,Genomics and Computational Biology Group
BMC Genomics | Year: 2010

Background: Retrieving pertinent information from biological scientific literature requires cutting-edge text mining methods which may be able to recognize the meaning of the very ambiguous names of biological entities. Aliases of a gene share a common vocabulary in their respective collections of PubMed abstracts. This may be true even when these aliases are not associated with the same subset of documents. This gene-specific vocabulary defines a unique fingerprint that can be used to disclose ambiguous aliases. The present work describes an original method for automatically assessing the ambiguity levels of gene aliases in large gene terminologies based exclusively in the content of their associated literature. The method can deal with the two major problems restricting the usage of current text mining tools: 1) different names associated with the same gene; and 2) one name associated with multiple genes, or even with non-gene entities. Important, this method does not require training examples.Results: Aliases were considered " ambiguous" when their Jaccard distance to the respective official gene symbol was equal or greater than the smallest distance between the official gene symbol and one of the three internal controls (randomly picked unrelated official gene symbols). Otherwise, they were assigned the status of " synonyms" . We evaluated the coherence of the results by comparing the frequencies of the official gene symbols in the text corpora retrieved with their respective " synonyms" or " ambiguous" aliases. Official gene symbols were mentioned in the abstract collections of 42 % (70/165) of their respective synonyms. No official gene symbol occurred in the abstract collections of any of their respective ambiguous aliases. In overall, querying PubMed with official gene symbols and " synonym" aliases allowed a 3.6-fold increase in the number of unique documents retrieved.Conclusions: These results confirm that this method is able to distinguish between synonyms and ambiguous gene aliases based exclusively on their vocabulary fingerprint. The approach we describe could be used to enhance the retrieval of relevant literature related to a gene. © 2010 Coimbra et al; licensee BioMed Central Ltd.


Torrieri R.,Center for Excellence in Bioinformatics | Oliveira F.S.,Center for Excellence in Bioinformatics | Oliveira G.,Center for Excellence in Bioinformatics | Oliveira G.,Genomics and Computational Biology Group | And 2 more authors.
PLoS ONE | Year: 2012

In the last years, there was an exponential increase in the number of publicly available genomes. Once finished, most genome projects lack financial support to review annotations. A few of these gene annotations are based on a combination of bioinformatics evidence, however, in most cases, annotations are based solely on sequence similarity to a previously known gene, which was most probably annotated in the same way. As a result, a large number of predicted genes remain unassigned to any functional category despite the fact that there is enough evidence in the literature to predict their function. We developed a classifier trained with term-frequency vectors automatically disclosed from text corpora of an ensemble of genes representative of each functional category of the J. Craig Venter Institute Comprehensive Microbial Resource (JCVI-CMR) ontology. The classifier achieved up to 84% precision with 68% recall (for confidence≥0.4), F-measure 0.76 (recall and precision equally weighted) in an independent set of 2,220 genes, from 13 bacterial species, previously classified by JCVI-CMR into unambiguous categories of its ontology. Finally, the classifier assigned (confidence≥0.7) to functional categories a total of 5,235 out of the ~24 thousand genes previously in categories "Unknown function" or "Unclassified" for which there is literature in MEDLINE. Two biologists reviewed the literature of 100 of these genes, randomly picket, and assigned them to the same functional categories predicted by the automatic classifier. Our results confirmed the hypothesis that it is possible to confidently assign genes of a real world repository to functional categories, based exclusively on the automatic profiling of its associated literature. The LitProf - Gene Classifier web server is accessible at: www.cebio.org/litprofGC. © 2012 Torrieri et al.


PubMed | Genomics and Computational Biology Group, Federal University of Minas Gerais and Center for Genomic Regulation
Type: | Journal: BMC genomics | Year: 2015

Leishmaniasis is a neglected parasitic disease with diverse clinical manifestations and a complex epidemiology. It has been shown that its parasite-related traits vary between species and that they modulate infectivity, pathogenicity, and virulence. However, understanding of the species-specific adaptations responsible for these features and their evolutionary background is limited. To improve our knowledge regarding the parasite biology and adaptation mechanisms of different Leishmania species, we conducted a proteome-wide phylogenomic analysis to gain insights into Leishmania evolution.The analysis of the reconstructed phylomes (totaling 45,918 phylogenies) allowed us to detect genes that are shared in pathogenic Leishmania species, such as calpain-like cysteine peptidases and 3a2rel-related proteins, or genes that could be associated with visceral or cutaneous development. This analysis also established the phylogenetic relationship of several hypothetical proteins whose roles remain to be characterized. Our findings demonstrated that gene duplication constitutes an important evolutionary force in Leishmania, acting on protein families that mediate host-parasite interactions, such as amastins, GP63 metallopeptidases, cathepsin L-like proteases, and our methods permitted a deeper analysis of their phylogenetic relationships.Our results highlight the importance of proteome wide phylogenetic analyses to detect adaptation and evolutionary processes in different organisms and underscore the need to characterize the role of expanded and species-specific proteins in the context of Leishmania evolution by providing a framework for the phylogenetic relationships of Leishmania proteins. Phylogenomic data are publicly available for use through PhylomeDB (http://www.phylomedb.org).


PubMed | Genomics and Computational Biology Group, Federal University of São Paulo, Biosystems Informatics Group and University of Sao Paulo
Type: Journal Article | Journal: PloS one | Year: 2015

In order to establish new infections HIV-1 particles need to attach to receptors expressed on the cellular surface. HIV-1 particles interact with a cell membrane receptor known as CD4 and subsequently with another cell membrane molecule known as a co-receptor. Two major different co-receptors have been identified: C-C chemokine Receptor type 5 (CCR5) and C-X-C chemokine Receptor type 4 (CXCR4) Previous reports have demonstrated cellular modifications upon HIV-1 binding to its co-receptors including gene expression modulations. Here we investigated the effect of viral binding to either CCR5 or CXCR4 co-receptors on viral diversity after a single round of reverse transcription. CCR5 and CXCR4 pseudotyped viruses were used to infect non-stimulated and stimulated PBMCs and purified CD4 positive cells. We adopted the SOLiD methodology to sequence virtually the entire proviral DNA from all experimental infections. Infections with CCR5 and CXCR4 pseudotyped virus resulted in different patterns of genetic diversification. CCR5 virus infections produced extensive proviral diversity while in CXCR4 infections a more localized substitution process was observed. In addition, we present pioneering results of a recently developed method for the analysis of SOLiD generated sequencing data applicable to the study of viral quasi-species. Our findings demonstrate the feasibility of viral quasi-species evaluation by NGS methodologies. We presented for the first time strong evidence for a host cell driving mechanism acting on the HIV-1 genetic variability under the control of co-receptor stimulation. Additional investigations are needed to further clarify this question, which is relevant to viral diversification process and consequent disease progression.


PubMed | Genomics and Computational Biology Group, Vale Technology Institute and University of Sao Paulo
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2015

Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect.Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.

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