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Stressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”.

RNA editing by A-to-I deamination is a relevant co/posttranscriptional modification carried out by ADAR enzymes. In humans, it has pivotal cellular effects and its deregulation has been linked to a variety of human disorders including neurological and neurodegenerative diseases and cancer. Despite its biological relevance, the detection of RNA editing variants in large transcriptome sequencing experiments (RNAseq) is yet a challenging computational task. To drastically reduce computing times we have developed a novel REDItools version able to identify A-to-I events in huge amount of RNAseq data employing High Performance Computing (HPC) infrastructures.Here we show how to use REDItools v2 in HPC systems.

RNA editing is a relevant epitranscriptome phenomenon able to increase the transcriptome and proteome diversity of eukaryotic organisms. ADAR mediated RNA editing is widespread in humans in which millions of A-to-I changes modify thousands of primary transcripts. RNA editing has pivotal roles in the regulation of gene expression or modulation of the innate immune response or functioning of several neurotransmitter receptors. Massive transcriptome sequencing has fostered the research in this field. Nonetheless, different aspects of the RNA editing biology are still unknown and need to be elucidated. To support the study of A-to-I RNA editing we have updated our REDIportal catalogue raising its content to about 16 millions of events detected in 9642 human RNAseq samples from the GTEx project by using a dedicated pipeline based on the HPC version of the REDItools software. REDIportal now allows searches at sample level, provides overviews of RNA editing profiles per each RNAseq experiment, implements a Gene View module to look at individual events in their genic context and hosts the CLAIRE database. Starting from this novel version, REDIportal will start collecting non-human RNA editing changes for comparative genomics investigations. The database is freely available at http://srv00.recas.ba.infn.it/atlas/index.html.

Background RNA editing is a widespread co-/post-transcriptional mechanism that alters primary RNA sequences through the modification of specific nucleotides and it can increase both the transcriptome and proteome diversity. The automatic detection of RNA-editing from RNA-seq data is computational intensive and limited to small data sets, thus preventing a reliable genome-wide characterisation of such process. Results In this work we introduce HPC-REDItools, an upgraded tool for accurate RNA-editing events discovery from large dataset repositories. Availability: https://github.com/BioinfoUNIBA/REDItools2. Conclusions HPC-REDItools is dramatically faster than the previous version, REDItools, enabling big-data analysis by means of a MPI-based implementation and scaling almost linearly with the number of available cores.

Background The advent of Next Generation Sequencing (NGS) technologies and the concomitant reduction in sequencing costs allows unprecedented high throughput profiling of biological systems in a cost-efficient manner. Modern biological experiments are increasingly becoming both data and computationally intensive and the wealth of publicly available biological data is introducing bioinformatics into the “Big Data” era. For these reasons, the effective application of High Performance Computing (HPC) architectures is becoming progressively more recognized also by bioinformaticians. Here we describe HPC resources provisioning pilot programs dedicated to bioinformaticians, run by the Italian Node of ELIXIR (ELIXIR-IT) in collaboration with CINECA, the main Italian supercomputing center. Results Starting from April 2016, CINECA and ELIXIR-IT launched the pilot Call “ELIXIR-IT HPC@CINECA”, offering streamlined access to HPC resources for bioinformatics. Resources are made available either through web front-ends to dedicated workflows developed at CINECA or by providing direct access to the High Performance Computing systems through a standard command-line interface tailored for bioinformatics data analysis. This allows to offer to the biomedical research community a production scale environment, continuously updated with the latest available versions of publicly available reference datasets and bioinformatic tools. Currently, 63 research projects have gained access to the HPC@CINECA program, for a total handout of ~ 8 Millions of CPU/hours and, for data storage, ~ 100 TB of permanent and ~ 300 TB of temporary space. Conclusions Three years after the beginning of the ELIXIR-IT HPC@CINECA program, we can appreciate its impact over the Italian bioinformatics community and draw some considerations. Several Italian researchers who applied to the program have gained access to one of the top-ranking public scientific supercomputing facilities in Europe. Those investigators had the opportunity to sensibly reduce computational turnaround times in their research projects and to process massive amounts of data, pursuing research approaches that would have been otherwise difficult or impossible to undertake. Moreover, by taking advantage of the wealth of documentation and training material provided by CINECA, participants had the opportunity to improve their skills in the usage of HPC systems and be better positioned to apply to similar EU programs of greater scale, such as PRACE. To illustrate the effective usage and impact of the resources awarded by the program - in different research applications - we report five successful use cases, which have already published their findings in peer-reviewed journals.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with unknown etiology. Recent experimental evidences suggest the contribution of non-coding RNAs (ncRNAs) in the pathophysiology of ASD. In this work, we aimed to investigate the expression profile of the ncRNA class of circular RNAs (circRNAs) in the hippocampus of the BTBR T + tf/J (BTBR) mouse model and age-matched C57BL/6J (B6) mice. Alongside, we analyzed BTBR hippocampal gene expression profile to evaluate possible correlations between the differential abundance of circular and linear gene products. From RNA sequencing data, we identified circRNAs highly modulated in BTBR mice. Thirteen circRNAs and their corresponding linear isoforms were validated by RT-qPCR analysis. The BTBR-regulated circCdh9 was better characterized in terms of molecular structure and expression, highlighting altered levels not only in the hippocampus, but also in the cerebellum, prefrontal cortex, and amygdala. Finally, gene expression analysis of the BTBR hippocampus pinpointed altered biological and molecular pathways relevant for the ASD phenotype. By comparison of circRNA and gene expression profiles, we identified 6 genes significantly regulated at either circRNA or mRNA gene products, suggesting low overall correlation between circRNA and host gene expression. In conclusion, our results indicate a consistent deregulation of circRNA expression in the hippocampus of BTBR mice. ASD-related circRNAs should be considered in functional studies to identify their contribution to the etiology of the disorder. In addition, as abundant and highly stable molecules, circRNAs represent interesting potential biomarkers for autism.

Background Gene fusions derive from chromosomal rearrangements. The resulting chimeric transcripts are often endowed with oncogenic potential. Furthermore, they serve as diagnostic tools for the clinical classification of cancer subgroups with different prognosis and, in some cases, they can provide specific drug targets. To date, many efforts have been carried out to study gene fusion events occurring in tumor samples. In recent years, the availability of a comprehensive next-generation sequencing dataset for all existing human tumor cell lines has provided the opportunity to further investigate these data in order to identify novel and still uncharacterized gene fusion events. Results In our work, we have extensively reanalyzed 935 paired-end RNA-sequencing experiments downloaded from the Cancer Cell Line Encyclopedia repository, aiming at addressing novel putative cell-line specific gene fusion events in human malignancies. The bioinformatics analysis has been performed by the execution of four gene fusion detection algorithms. The results have been further prioritized by running a Bayesian classifier that makes an in silico validation. The collection of fusion events supported by all of the predictive software results in a robust set of ∼1,700 in silico predicted novel candidates suitable for downstream analyses. Given the huge amount of data and information produced, computational results have been systematized in a database named LiGeA. The database can be browsed through a dynamic and interactive web portal, further integrated with validated data from other well-known repositories. Taking advantage of the intuitive query forms, the users can easily access, navigate, filter, and select the putative gene fusions for further validations and studies. They can also find suitable experimental models for a given fusion of interest. Conclusions We believe that the LiGeA resource can represent not only the first compendium of both known and putative novel gene fusion events in the catalog of all of the human malignant cell lines but it can also become a handy starting point for wet-lab biologists who wish to investigate novel cancer biomarkers and specific drug targets.

Applying next-generation sequencing (NGS) technologies to species of agricultural interest has the potential to accelerate the understanding and exploration of genetic resources. The storage, availability and maintenance of huge quantities of NGS-generated data remains a major challenge. The PeachVar-DB portal, available at http://hpc-bioinformatics.cineca.it/peach, is an open-source catalog of genetic variants present in peach (Prunus persica L. Batsch) and wild-related species of Prunus genera, annotated from 146 samples publicly released on the Sequence Read Archive (SRA). We designed a user-friendly web-based interface of the database, providing search tools to retrieve single nucleotide polymorphism (SNP) and InDel variants, along with useful statistics and information. PeachVar-DB results are linked to the Genome Database for Rosaceae (GDR) and the Phytozome database to allow easy access to other external useful plant-oriented resources. In order to extend the genetic diversity covered by the PeachVar-DB further, and to allow increasingly powerful comparative analysis, we will progressively integrate newly released data.

A previous genome scan on 323 Piedmontese individuals identified a cluster of 13 SNPs significantly associated with direct calving ease and centred on the three genes LAP3, LCORL and NCAPG in chromosome 6. We investigated missense mutations affecting calving ease in Piedmontese cattle in the identified region using sequences from the whole exome in eight Piedmontese individuals chosen from the extremes of the direct calving ease estimated breeding values distribution for this trait. The present study has not found missense variants in LAP3 and LCORL, while two were identified on NCAPG by three different variant calling methods. Other gene candidates in the same region harbour missense mutations, such as PPM1K, PKD2, SPP1 and MEPE, but both SIFT analysis and chi-square test on frequency of alleles make us hypothesise that NCAPG is the single gene responsible for the trait variation. The two SNPs on NCAPG are in complete linkage disequilibrium in our samples; therefore, further investigations are needed in order to discriminate their role.

The reduction in sequencing costs associated with next generation sequencing technologies (NGS) has led to a rapid upsurge in the amount of genome re-sequencing data, paving the way for the advent of personalized genomics and precision medicine. Accurate genotyping is crucial for effective analyses of these data, and in particular for the correct identification of candidate causal mutations in diagnostic screenings. The body of genome resequencing data will likely see exponential growth in the next few years, underlining the need for publicly available, accurate and time-effective bioinformatics systems for data analysis. Ideally, such systems should be easy to use and constantly updated as new genomes and software tools are released. Here we present IVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. IVaCS offers state of the art tools for variant calling and annotation along with expert made pipelines for the analysis of whole genome sequencing (WGS), whole-exome sequencing (WES) and targeted resequencing (TGS) data, performing all steps from quality trimming to variant annotation. The system is specifically designed to assist users with little or no bioinformatics skills and all the pipelines are available through a user friendly web interface. The final output is provided in the form of a dynamic web page where variants can be selected on the base of user defined hard filters. A comprehensive report containing detailed information and statistics concerning the execution of each step of the pipelines is also generated. Extensive tests on publicly available genome resequencing data (Illumina platinum genome NA12878), show that our system recovers a slightly better sensitivity and a higher specificity than the commercial Illumina VCAT 2.0 software. IVaCS is implemented with a modular architecture and each module (quality trimming, reads mapping, variant calling, variant annotation) can be used independently. IVaCS may manage all the major commercial kits for exome sequencing, such as Illumina, Agilent or Nimblegen, along with a comprehensive collection of reference genomes (all the Illumina genomes, including human, mouse and cow, among the others) with corresponding genomic annotations. Finally, the software leverages an ensemble of publicly available resources (e.g., dbSNP, OMIM, COSMIC and ClinVar among others) for the functional annotation of human variants. Advanced users needing more control over the single steps might also request the command-line version of the software which is more flexible and easy to customize. IVaCS has a very active and growing community. The system is under constant development and new reference genomes, databases and bioinformatics tools are added to IvaCS on a regular basis. IVACS is available at: https://bioinformatics.cineca.it/ivacs

We present MultiWiBi, an approach to the automatic creation of two integrated taxonomies for Wikipedia pages and categories written in different languages. In order to create both taxonomies in an arbitrary language, we first build them in English and then project the two taxonomies to other languages automatically, without the help of language-specific resources or tools. The process crucially leverages a novel algorithm which exploits the information available in either one of the taxonomies to reinforce the creation of the other taxonomy. Our experiments show that the taxonomical information in MultiWiBi is characterized by a higher quality and coverage than state-of-the-art resources like DBpedia, YAGO, MENTA, WikiNet, LHD and WikiTaxonomy, also across languages. MultiWiBi is available online at http://wibitaxonomy.org/multiwibi .

Bilingual machine-readable dictionaries are knowledge resources useful in many automatic tasks. However, compared to monolingual computational lexicons like WordNet, bilingual dictionaries typically provide a lower amount of structured information, such as lexical and semantic relations, and often do not cover the entire range of possible translations for a word of interest. In this paper we present Cycles and Quasi-Cycles (CQC), a novel algorithm for the automated disambiguation of ambiguous translations in the lexical entries of a bilingual machine-readable dictionary. The dictionary is represented as a graph, and cyclic patterns are sought in the graph to assign an appropriate sense tag to each translation in a lexical entry. Further, we use the algorithm's output to improve the quality of the dictionary itself, by suggesting accurate solutions to structural problems such as misalignments, partial alignments and missing entries. Finally, we successfully apply CQC to the task of synonym extraction.

Recently, experts and practitioners in language resources have started recognizing the benefits of the linked data (LD) paradigm for the representation and exploitation of linguistic data on the Web. The adoption of the LD principles is leading to an emerging ecosystem of multilingual open resources that conform to the Linguistic Linked Open Data Cloud, in which datasets of linguistic data are interconnected and represented following common vocabularies, which facilitates linguistic information discovery, integration and access. In order to contribute to this initiative, this paper summarizes several key aspects of the representation of linguistic information as linked data from a practical perspective. The main goal of this document is to provide the basic ideas and tools for migrating language resources (lexicons, corpora, etc.) as LD on the Web and to develop some useful NLP tasks with them (e.g., word sense disambiguation). Such material was the basis of a tutorial imparted at the EKAW’14 conference, which is also reported in the paper.

We present WiBi, an approach to the automatic creation of a bitaxonomy for Wikipedia, that is, an integrated taxonomy of Wikipage pages and categories. We leverage the information available in either one of the taxonomies to reinforce the creation of the other taxonomy. Our experiments show higher quality and coverage than state-of-the-art resources like DBpedia, YAGO, MENTA, WikiNet and WikiTaxonomy. WiBi is available at http://wibitaxonomy.org.