Background Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Methods Using case–control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus–specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. Results A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion–deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. Conclusions A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.)

Galaxy is a mature, browser accessible workbench for scientific computing. It enables scientists to share, analyze and visualize their own data, with minimal technical impediments. A thriving global community continues to use, maintain and contribute to the project, with support from multiple national infrastructure providers that enable freely accessible analysis and training services. The Galaxy Training Network supports free, self-directed, virtual training with >230 integrated tutorials. Project engagement metrics have continued to grow over the last 2 years, including source code contributions, publications, software packages wrapped as tools, registered users and their daily analysis jobs, and new independent specialized servers. Key Galaxy technical developments include an improved user interface for launching large-scale analyses with many files, interactive tools for exploratory data analysis, and a complete suite of machine learning tools. Important scientific developments enabled by Galaxy include Vertebrate Genome Project (VGP) assembly workflows and global SARS-CoV-2 collaborations.

A genome wide association scan of ~6.6 million genotyped or imputed variants in 882 Sardinian Multiple Sclerosis (MS) cases and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (overall P =1.60 × 10-10). CBLB encodes a negative regulator of adaptive immune responses and mice lacking the orthologue are prone to experimental autoimmune encephalomyelitis, the animal model of MS.

Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR—the European infrastructure for biological information—that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.

Summary: End-to-end next-generation sequencing microbiology data analysis requires a diversity of tools covering bacterial resequencing, de novo assembly, scaffolding, bacterial RNA-Seq, gene annotation and metagenomics. However, the construction of computational pipelines that use different software packages is difficult owing to a lack of interoperability, reproducibility and transparency. To overcome these limitations we present Orione, a Galaxy-based framework consisting of publicly available research software and specifically designed pipelines to build complex, reproducible workflows for next-generation sequencing microbiology data analysis. Enabling microbiology researchers to conduct their own custom analysis and data manipulation without software installation or programming, Orione provides new opportunities for data-intensive computational analyses in microbiology and metagenomics.Availability and implementation: Orione is available online at http://orione.crs4.it.Contact: gianmauro.cuccuru@crs4.itSupplementary information: Supplementary data are available at Bioinformatics online.