A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

Diversification of histone variants is marked by the acquisition of distinct motifs and functional properties through convergent evolution.1–4 H2A variants are distinguished by specific C-terminal motifs and tend to be segregated within defined domains of the genome.5,6 Whether evolution of these motifs pre-dated the evolution of segregation mechanisms or vice versa has remained unclear. A suitable model to address this question is the variant H2A.W, which evolved in plants through acquisition of a KSPK motif7 and is tightly associated with heterochromatin.4 We used fission yeast, where chromatin is naturally devoid of H2A.W, to study the impact of engineered chimeras combining yeast H2A with the KSPK motif. Biochemical assays showed that the KSPK motif conferred nucleosomes with specific properties. Despite uniform incorporation of the engineered H2A chimeras in the yeast genome, the KSPK motif specifically affected heterochromatin composition and function. We conclude that the KSPK motif promotes chromatin properties in yeast that are comparable to the properties and function of H2A.W in plant heterochromatin. We propose that the selection of functional motifs confer histone variants with properties that impact primarily a specific chromatin state. The association between a new histone variant and a preferred chromatin state can thus provide a setting for the evolution of mechanisms that segregate the new variant to this state, thereby enhancing the impact of the selected properties of the variant on genome activity.Fil: Lei, Bingkun. Gregor Mendel Institute; AustriaFil: Capella, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Montgomery, Sean A.. Gregor Mendel Institute; AustriaFil: Borg, Michael. Gregor Mendel Institute; AustriaFil: Osakabe, Akihisa. Gregor Mendel Institute; AustriaFil: Goiser, Malgorzata. Gregor Mendel Institute; AustriaFil: Muhammad, Abubakar. Universitat Technical Zu Munich; AlemaniaFil: Braun, Sigurd. Universitat Technical Zu Munich; AlemaniaFil: Berger, Frédéric. Gregor Mendel Institute; Austri

Recording provenance of workflow runs with RO-Crate

Recording the provenance of scientific computation results is key to the support of traceability, reproducibility and quality assessment of data products.Several data models have been explored to address this need, providing representations of workflow plans and their executions as well as means of packaging the resulting information for archiving and sharing.However, existing approaches tend to lack interoperable adoption across workflow management systems.In this work we present Workflow Run RO-Crate, an extension of RO-Crate (Research Object Crate) and Schema.org to capture the provenance of the execution of computational workflows at different levels of granularity and bundle together all their associated objects (inputs, outputs, code, etc.).The model is supported by a diverse, open community that runs regular meetings, discussing development, maintenance and adoption aspects.Workflow Run RO-Crate is already implemented by several workflow management systems, allowing interoperable comparisons between workflow runs from heterogeneous systems.We describe the model, its alignment to standards such as W3C PROV, and its implementation in six workflow systems.Finally, we illustrate the application of Workflow Run RO-Crate in two use cases of machine learning in the digital image analysis domain.A corresponding RO-Crate for this article is at https://w3id.org/ro/doi/10.5281/zenodo.1036898

Population gene introgression and high genome plasticity for the zoonotic pathogen Streptococcus agalactiae

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacteria populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated twelve major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan-genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of eleven populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation

Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation

Background: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. Methods and Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase δ chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. Conclusions: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The "unnatural" history of colorectal cancer in Lynch syndrome : Lessons from colonoscopy surveillance

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and of immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.Peer reviewe

The ELIXIR Human Copy Number Variations Community:building bioinformatics infrastructure for research

Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While 'High-Throughput' sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim of this white paper is to provide a guiding framework for the future contributions of ELIXIR's recently established h uman CNV Community, with implications beyond human disease diagnostics and population genomics. This white paper is the direct result of a strategy meeting that took place in September 2018 in Hinxton (UK) and involved representatives of 11 ELIXIR Nodes. The meeting led to the definition of priority objectives and tasks, to address a wide range of CNV-related challenges ranging from detection and interpretation to sharing and training. Here, we provide suggestions on how to align these tasks within the ELIXIR Platforms strategy, and on how to frame the activities of this new ELIXIR Community in the international context

Comparison of the high energy models for neutral meson photoproduction and the related hadronic processes

To critically compare the Michigan and Argonne models we perform simultaneus fits to the high-energy data for [pi]0 and [nu] photoproduction together with that for the related hadronic vector meson production reactions, in particular that for [pi]+n --> [omega]p. Thus all constraints on these models are considered simultaneously. Particular attention is given to the strength of absoptive cuts in both models, and to the role of the B-meson exchange in filling dips in the Argonne model. We find that the [varrho]-Pomeron cuts (i.e. cuts associated with large helicity flip at the N vertex) are essential to introducing unnatural parity exchange in the Michigan model, and that the B-meson contribution is incapable of filling unwanted dips which appear in any model with nonsense wrong signature zeros as required by exchange degeneracy. The flip and non-flip [varrho] and [omega] coupling strengths at the N vertex are determined. Predictions are made for various polarization asymmetries for [gamma]p --> [pi]0p and [gamma]p --> [eta]p. The differential cross section for KL0p --> KS0p is calculated and compared with the existing data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33569/1/0000070.pd

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

New implementation of data standards for AI research in precision oncology. Experience from EuCanImage

An unprecedented amount of personal health data, with the potential to revolutionise precision medicine, is generated at healthcare institutions worldwide. The exploitation of such data using artificial intelligence relies on the ability to combine heterogeneous, multicentric, multimodal and multiparametric data, as well as thoughtful representation of knowledge and data availability. Despite these possibilities, significant methodological challenges and ethico-legal constraints still impede the real-world implementation of data models. The EuCanImage is an international consortium aimed at developing AI algorithms for precision medicine in oncology and enabling secondary use of the data based on necessary ethical approvals. The use of well-defined clinical data standards to allow interoperability was a central element within the initiative. The consortium is focused on three different cancer types and addresses seven unmet clinical needs. This article synthesises our experience and procedures for healthcare data interoperability and standardisation.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 952103.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThis study describes a new process to harmonize and standardize clinical data. The data will be available upon request to the authors