Var2GO: a web-based tool for gene variants selection.

BACKGROUND: One of the most challenging issue in the variant calling process is handling the resulting data, and filtering the genes retaining only the ones strictly related to the topic of interest. Several tools permit to gather annotations at different levels of complexity for the detected genes and to group them according to the pathways and/or processes they belong to. However, it might be a time consuming and frustrating task. This is partly due to the size of the file, that might contain many thousands of genes, and to the search of associated variants that requires a gene-by-gene investigation and annotation approach. As a consequence, the initial gene list is often reduced exploiting the knowledge of variants effect, novelty and genotype, with the potential risk of losing meaningful pieces of information. RESULTS: Here we present Var2GO, a new web-based tool to support the annotation and filtering of variants and genes coming from variant calling of high-throughput sequencing data. Var2GO permits to upload either the unprocessed Variant Calling Format file or a table containing the annotated variants. The raw data undergo a preliminary step of variants annotation, using the SnpEff tool, and are converted to a table format. The table is then uploaded into an on the fly generated database. Genes associated to the variants are automatically annotated with the corresponding Gene Ontology terms covering the three GO domains. Using the web interface it is then possible to filter and extract, from the whole list, genes having annotations in the domain of interest, by simply specifying filtering parameters and one or more keywords. The relevance of this tool is demonstrated on exome sequencing data. CONCLUSIONS: Var2GO is a novel tool that implements a topic-based approach, expressly designed to help biologists in narrowing the search of relevant genes coming from variant calling analysis. Its main purpose is to support non-bioinformaticians in handling and processing raw variant calling data through an intuitive web interface. Furthermore, Var2GO offers a complete pipeline that, starting from the raw VCF file, allows to annotate both variants and associated genes and supports the extraction of relevant biological knowledge.

CytReD: A database collecting human cytokinome information.

UNLABELLED: The cytokines/related receptors system represents a complex regulatory network that is involved in those chronic inflammatory processes which lead to many diseases as cancers. We developed a Cytokine Receptor Database (CytReD) to collect information on cytokine receptors related to their biological activity, gene data, protein structures and diseases in which these and their ligands are implicated. This large set of information may be used by researchers as well as by physicians or clinicians to identify which cytokines, reported in the literature, are important in a given disease and, therefore, useful for purposes of diagnosis or prognostic. AVAILABILITY: The database is available for free at http://www.cro-m.eu/CytReD/

Structural and functional similarities between osmotin from Nicotiana tabacum seeds and human adiponectin.

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the ß-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico.

CytokineDB: a database collecting biological information.

Cytokines are subdivided in 12 sub-families and are described as multi-functional molecules that play an important biological activity in host defense system against pathogens, in homeostasis, tissue repair, cell growth and development. CytokineDB is an annotated database that collects biological information regarding the cytokines family in human and will be periodically updated by including new biological information. This database is freely available online and can be accessed at the URL: http://www.cro-m.eu/CytokineDB/