OpenGenomeBrowser: a versatile, dataset-independent and scalable web platform for genome data management and comparative genomics.

BACKGROUND As the amount of genomic data continues to grow, there is an increasing need for systematic ways to organize, explore, compare, analyze and share this data. Despite this, there is a lack of suitable platforms to meet this need. RESULTS OpenGenomeBrowser is a self-hostable, open-source platform to manage access to genomic data and drastically simplifying comparative genomics analyses. It enables users to interactively generate phylogenetic trees, compare gene loci, browse biochemical pathways, perform gene trait matching, create dot plots, execute BLAST searches, and access the data. It features a flexible user management system, and its modular folder structure enables the organization of genomic data and metadata, and to automate analyses. We tested OpenGenomeBrowser with bacterial, archaeal and yeast genomes. We provide a docker container to make installation and hosting simple. The source code, documentation, tutorials for OpenGenomeBrowser are available at opengenomebrowser.github.io and a demo server is freely accessible at opengenomebrowser.bioinformatics.unibe.ch . CONCLUSIONS To our knowledge, OpenGenomeBrowser is the first self-hostable, database-independent comparative genome browser. It drastically simplifies commonly used bioinformatics workflows and enables convenient as well as fast data exploration

A chromosome-scale genome assembly reveals a highly dynamic effector repertoire of wheat powdery mildew

Blumeria graminis f. sp. tritici (B.g. tritici) is the causal agent of the wheat powdery mildew disease. The highly fragmented B.g. tritici genome available so far has prevented a systematic analysis of effector genes that are known to be involved in host adaptation. To study the diversity and evolution of effector genes we produced a chromosome‐scale assembly of the B.g. tritici genome. The genome assembly and annotation was achieved by combining long‐read sequencing with high‐density genetic mapping, bacterial artificial chromosome fingerprinting and transcriptomics. We found that the 166.6 Mb B.g. tritici genome encodes 844 candidate effector genes, over 40% more than previously reported. Candidate effector genes have characteristic local genomic organization such as gene clustering and enrichment for recombination‐active regions and certain transposable element families. A large group of 412 candidate effector genes shows high plasticity in terms of copy number variation in a global set of 36 isolates and of transcription levels. Our data suggest that copy number variation and transcriptional flexibility are the main drivers for adaptation in B.g. tritici. The high repeat content may play a role in providing a genomic environment that allows rapid evolution of effector genes with selection as the driving force

A reference sequence for Blumeria graminis f. sp. tritici (wheat powdery mildew) and its application for comparative and evolutionary genomics

Powdery mildew is one of the most important cereal diseases. It is caused by fungi of the species Blumeria graminis, which have an obligate-biotrophic lifestyle and are specific for a single host plant species. The topic of this thesis is the molecular analysis of the genome sequence of Blumeria graminis forma specialis tritici (B.g. tritici), the powdery mildew pathogen of wheat, with regard to its biology as a plant pathogen. Powdery mildew of wheat and barley are caused by B.g. tritici and B.g. hordei, respectively. In a pilot study, a comparative analysis of two orthologous loci in the genomes of the two fungi revealed that the orthologous genes are well conserved and synthenic, whereas the intergenic regions are highly diverse and massively populated with transposable elements (TEs). A divergence time estimate based on the sequence alignments indicates that B.g. tritici and B.g. hordei have co-evolved with their hosts. The major part of this work reports on the reference sequence of B.g. tritici (isolate 96224) and its bioinformatic analysis. B.g. tritici was found to be large with a high content of repetititve DNA and TEs. To get an overview of the TE population in the B.g. tritici genome, we produced a repeat library that contains the 56 most abundant TEs. The library was also used to annotate TEs in the genome sequence. As was found in other biotrophic fungi, B.g. tritici lacks a number of genes which code for proteins that are involved in the degradation of cell wall components, carbohydrate transport, nitrate and sulfur metabolism or the production of secondary metabolites. Based on comparative analysis with B.g. hordei, we identified about 600 candidate effector genes that could play a role during the infection process or the determination of host specificity. In addition to the Swiss isolate 96224, we re-sequenced the genomes of three wheat powdery mildew isolates from UK, Israel and Switzerland. Compared to the reference (isolate 96224), the three re-sequenced isolates differ in the absence of certain genes, most of them are effector candidates. Apparently, there is a selective pressure for loosing these genes which makes them candidates for determinants of race specific interactions. Single nucleotide polymorphisms present in the genome of the three isolates compared to the reference were found to be unevenly distributed, which leads to a mosaic structure of these genomes consists of younger and more ancient regions. These highly diverse haplogroups have already existed prior to the domestication of wheat. We hypothesize that the occurrence of bread wheat as a new host for B.g. tritici did not lead to a dramatic loss of genetic diversity in the genome, and that the highly diverse haplotype pool provides a large genetic potential for pathogen variation facilitating its ready adaptation to new host species. Mehltau ist weltweit eine der verheerendsten Getreidekrankheiten. Verursacht wird sie von Pilzen der Art Blumeria graminis, welche eine obligat-biotrophe Lebensweise haben und wirtsspezifisch, also spezialisiert auf eine Pflanzenart sind. Diese Arbeit befasst sich mit der molekularen Analyse der Genomsequenz von Blumeria graminis forma specialis tritici (B.g. tritici), dem Verursacher von Mehltau bei Weizen, hinsichtlich seiner Biologie als Getreidepathogen. Mehltau bei Weizen und Gerste wird von zwei unterschiedlichen Pilzen verursacht, welche jeweils spezifisch für ihre Wirtspflanze sind. Ein Sequenzvergleich zweier orthologer Loci aus den Genomen der beiden Pilze hat gezeigt, dass die orthologen Gene synthenisch und stark konserviert sind, während sich die intergenen Regionen grundlegend unterscheiden und einen sehr hohen Anteil an Transposons enthalten. Der Sequenzvergleich ermöglichte ausserdem eine Schätzung des Zeitpunkts der Trennung der beiden Pathogene von ihrem letzten gemeinsamen Vorfahren, was auf eine Co-evolution der beiden Pathogene mit ihren jeweiligen Wirten hindeutet. Der Hauptteil der Arbeit widmet sich der vollständigen Sequenzierung des Weizenmehltau-Genoms (Isolat 96224) und seiner bioinformatischen Analyse. Mehltaupathogene haben, verglichen mit dem anderen Pilzen, ein relativ grosses Genom, welches reich bevölkert ist mit repetititven Elementen, sogenannten Transposons. Mit dem Ziel einen Überblick über die Transposonpopulation im Weizenmehltaugenom zu erhalten, haben wir eine Transposon-Datenbank mit den 56 häufigsten repetitiven Elemente, welche im Weizenmehltaugenom vorkommen, erstellt. Diese Datenbank wurde benützt um Transposons in der Genomsequenz zu annotieren. Wie schon bei anderen biotrophen Pilzen gefunden wurde, fehlen im B.g. tritici Genom bestimmte Gene, zum Beispiel solche, die für Proteine kodieren, die in den Abbau von Zellwandkomponenten, Kohlenhydrattransport, Nitrat- und Schwefelmetabolismus oder Produktion von Sekundärmetaboliten involvert sind. Mittels vergleichender Studien mit B.g. hordei konnten etwa 600 Gene identifiziert werden, welchen eine tragende Rolle während dem Infektionsprozess oder der Festlegung der Wirtspezifität zugeschrieben wird (sogenannte Effektoren). Zusätzlich zum Schweizer Isolat 96224 wurden noch drei weitere Mehltauisolate sequenziert, welche in Grossbritannien, Israel und der Schweiz gesammelt wurden. Im Vergleich zur Referenz, dem Isolat 96224, fehlen den drei zusätzlich sequenzierten Isolaten einzelne Gene, von denen fast alle Effektorkandidaten sind. Diese Gene, welche offensichtlich einer Selektion bezüglich deren Verlust unterliegen, könnten als entscheidende Faktoren der Rassenspezifität der Isolate wirken. Ausserdem unterscheiden sich die drei re-sequenzierten Isolate im Vergleich zur Referenz auch in einzelnen Basen, sogenannten SNPs (single nucleotide polymorphisms). Diese sind ungleich im Genom verteilt und führen zu einer Mosaikstruktur von "älteren" uns "jüngeren" Bereichen. Diese höchst verschiedenartigen Haplogruppen haben schon vor der Domestikation von Weizen existiert. Wir vermuten, dass die Enstehung von Brotweizen als neue Wirtpflanze nicht zu einer Reduktion der genetischen Vielfalt im B.g. tritici Genom geführt hat, und dass die hohe Vielfalt an Haplotypen ein grosses genetisches Potenzial für Pathogenvariablilität darstellt, welches die schnelle Anpassung an neue Wirtspflanzen begünstigt

Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity.

Insect bite hypersensitivity (IBH) is a Th-2, IgE-mediated dermatitis of horses caused by bites of insects of the genus Culicoides that has common features with human atopic dermatitis. Together with Th-2 cells, the epithelial barrier plays an important role in development of type I hypersensitivities. In order to elucidate the role of the epithelial barrier and of the skin immune response in IBH we studied the transcriptome of lesional whole skin of IBH-horses (IBH-LE; n = 9) in comparison to non-lesional skin (IBH-NL; n = 8) as well as to skin of healthy control horses (H; n = 9). To study the "baseline state" of the epithelial barrier, we investigated the transcriptome of non-lesional epidermis in IBH-horses (EPI-IBH-NL; n = 10) in comparison with healthy epidermis from controls (EPI-H; n = 9). IBH-LE skin displayed substantial transcriptomic difference compared to H. IBH-LE was characterized by a downregulation of genes involved in tight junction formation, alterations in keratins and substantial immune signature of both Th-1 and Th-2 types with particular upregulation of IL13, as well as involvement of the hypoxic pathway. IBH-NL shared a number of differentially expressed genes (DEGs) with IBH-LE, but was overall more similar to H skin. In the epidermis, genes involved in metabolism of epidermal lipids, pruritus development, as well as IL25, were significantly differentially expressed between EPI-IBH-NL and EPI-H. Taken together, our data suggests an impairment of the epithelial barrier in IBH-affected horses that may act as a predisposing factor for IBH development. Moreover, these new mechanisms could potentially be used as future therapeutic targets. Importantly, many transcriptional features of equine IBH skin are shared with human atopic dermatitis, confirming equine IBH as a natural model of skin allergy

Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis

Pneumococcal meningitis (PM) causes damage to the hippocampus, a brain structure critically involved in learning and memory. Hippocampal injury-which compromises neurofunctional outcome-occurs as apoptosis of progenitor cells and immature neurons of the hippocampal dentate granule cell layer thereby impairing the regenerative capacity of the hippocampal stem cell niche. Repetitive transcranial magnetic stimulation (rTMS) harbours the potential to modulate the proliferative activity of this neuronal stem cell niche. In this study, specific rTMS protocols-namely continuous and intermittent theta burst stimulation (cTBS and iTBS)-were applied on infant rats microbiologically cured from PM by five days of antibiotic treatment. Following two days of exposure to TBS, differential gene expression was analysed by whole transcriptome analysis using RNAseq. cTBS provoked a prominent effect in inducing differential gene expression in the cortex and the hippocampus, whereas iTBS only affect gene expression in the cortex. TBS induced polarisation of microglia and astrocytes towards an inflammatory phenotype, while reducing neurogenesis, neuroplasticity and regeneration. cTBS was further found to induce the release of pro-inflammatory cytokines in vitro. We conclude that cTBS intensified neuroinflammation after PM, which translated into increased release of pro-inflammatory mediators thereby inhibiting neuroregeneration

An unusual case of bovine anthrax in the canton of Jura, Switzerland in 2017.

BACKGROUND Anthrax caused by Bacillus anthracis is a zoonotic disease mainly affecting herbivores. The last Swiss outbreak was over 20 years ago. We describe a recent anthrax outbreak involving two cows from the same herd. One cow was designated as a peracute clinical case with sudden death and typical lung lesions, while the other cow presented with protracted fever and abortion. CASE PRESENTATION On April 29th 2017, a 3.5-year-old Montbéliard dairy cow was found dead while out at pasture with haemorrhage from the nose. The veterinarian suspected pneumonia and performed a necropsy on site. Subsequently, a lung and liver sample were sent to the laboratory. Unexpectedly, Bacillus anthracis was isolated, a pathogen not found in Switzerland for decades. Several days later, a second cow from the same farm showed signs of abortion after protracted fever. Since these symptoms are not typical for anthrax, and the bacteria could not be demonstrated in blood samples from this animal, a necropsy was performed under appropriate biosafety measures. Subsequently, Bacillus anthracis could be isolated from the placenta and the sublumbal lymph nodes but not from the blood, liver, spleen and kidney. The outbreak strain (17OD930) was shown to belong to the lineage B.Br.CNEVA, the same as Swiss strains from previous outbreaks in the region. We speculate that the disease came from a temporarily opened cave system that is connected to an old carcass burial site and was flushed by heavy rainfall preceding the outbreak. CONCLUSION Even in countries like Switzerland, where anthrax is very rare, new cases can occur after unusual weather conditions or ground disturbance. It is important for public officials to be aware of this risk to avoid possible spread