Isomorphic semantic mapping of variant call format (VCF2RDF).

Summary: The move of computational genomics workflows to Cloud Computing platforms is associated with a new level of integration and interoperability that challenges existing data representation formats. The Variant Calling Format (VCF) is in a particularly sensitive position in that regard, with both clinical and consumer-facing analysis tools relying on this self-contained description of genomic variation in Next Generation Sequencing (NGS) results. In this report we identify an isomorphic map between VCF and the reference Resource Description Framework. RDF is advanced by the World Wide Web Consortium (W3C) to enable representations of linked data that are both distributed and discoverable. The resulting ability to decompose VCF reports of genomic variation without loss of context addresses the need to modularize and govern NGS pipelines for Precision Medicine. Specifically, it provides the flexibility (i.e. the indexing) needed to support the wide variety of clinical scenarios and patient-facing governance where only part of the VCF data is fitting. Availability and Implementation: Software libraries with a claim to be both domain-facing and consumer-facing have to pass the test of portability across the variety of devices that those consumers in fact adopt. That is, ideally the implementation should itself take place within the space defined by web technologies. Consequently, the isomorphic mapping function was implemented in JavaScript, and was tested in a variety of environments and devices, client and server side alike. These range from web browsers in mobile phones to the most popular micro service platform, NodeJS. The code is publicly available at https://github.com/ibl/VCFr , with a live deployment at: http://ibl.github.io/VCFr/ . Contact: jonas.almeida@stonybrookmedicine.edu.

The genome of Anopheles darlingi, the main neotropical malaria vector.

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector-human and vector-parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles-darlingi.

The linked human imprintome v1.0: over 120 genes confirmed as imprinted impose a major review on previous censuses.

The whole set of human imprinted genes, termed imprintome, is here analysed by means of a reasonable, valid application of the Semantic Web and Linked Data approaches to a few structured datasets in order to provide a comprehensive collection of imprinted genes in the human genome. Thus, we have stored, organised, filtered, and analysed massive amounts of existing data on human imprinted genes towards compiling, structuring and linking data to comprise a sharing resource for genome and epigenome interrogated studies. Our datasets of linked data are the actual research outcome of this human imprintome analysis because as genomics become more and more data intensive, due to huge amounts of biological data, so does our needs for more structured data to be easier mined and shared. We present the resulting first version of the Linked Human Imprintome as a project within Linked Open Data (LOD) initiative (http://lod-cloud.net/) through Data Hub (http:// thedatahub.org/en/dataset/a-draft-version-of-the-linked-human-imprintome).

C. pseudotuberculosis Phop confers virulence and may be targeted by natural compounds.

The bacterial two-component system (TCS) regulates genes that are crucial for virulence in several pathogens. One of such TCS, the PhoPR system, consisting of a transmembrane sensory histidine kinase protein (PhoR) and an intracellular response regulator protein (PhoP), has been reported to have a major role in mycobacterial pathogenesis. We knocked out the phoP in C. pseudotuberculosis, the causal organism of caseous lymphadenitis (CLA), and using a combination of in vitro and in vivo mouse system, we showed for the first time, that the PhoP of C. pseudotuberculosis plays an important role in the virulence and pathogenicity of this bacterium. Furthermore, we modeled the PhoP of C. pseudotuberculosis and our docking results showed that several natural compounds including Rhein, an anthraquinone from Rheum undulatum, and some drug-like molecules may target PhoP to inhibit the TCS of C. pseudotuberculosis, and therefore may facilitate a remarkable attenuation of bacterial pathogenicity being the CLA. Experiments are currently underway to validate these in silico docking results.

The effects of the fungus Metarhizium anisopliae var. acridum on different stages of Lutzomyia longipalpis (Diptera: Psychodidae).

The control of Visceral Leishmaniasis (VL) vector is often based on the application of chemical residual insecticide. However, this strategy has not been effective. The continuing search for an appropriate vector control may include the use of biological control. This study evaluates the effects of the fungus Metarhizium anisopliae var. acridum on Lutzomyia longipalpis. Five concentrations of the fungus were utilized, 1 x 10(4) to 1 x 10(8) conidia/ml, accompanied by controls. The unhatched eggs, larvae and dead adults previously exposed to fungi were sown to reisolate the fungi and analysis of parameters of growth. The fungus was subsequently identified by PCR and DNA sequencing. M. anisopliae var. acridum reduced egg hatching by 40%. The mortality of infected larvae was significant. The longevity of infected adults was lower than that of negative controls. The effects of fungal infection on the hatching of eggs laid by infected females were also significant. With respect to fungal growth parameters post-infection, only vegetative growth was not significantly higher than that of the fungi before infection. The revalidation of the identification of the reisolated fungus was confirmed post-passage only from adult insects. In terms of larvae mortality and the fecundity of infected females, the results were significant, proving that the main vector species of VL is susceptible to infection by this entomopathogenic fungus in the adult stage.

Actin-interacting and flagellar proteins in Leishmania spp.: Bioinformatics predictions to functional assignments in phagosome formation.

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.