A research data management (RDM) community for ELIXIR.

Research data management (RDM) is central to the implementation of the FAIR (Findable Accessible, Interoperable, Reusable) and Open Science principles. Recognising the importance of RDM, ELIXIR Platforms and Nodes have invested in RDM and launched various projects and initiatives to ensure good data management practices for scientific excellence. These projects have resulted in a rich set of tools and resources highly valuable for FAIR data management. However, these resources remain scattered across projects and ELIXIR structures, making their dissemination and application challenging. Therefore, it becomes imminent to coordinate these efforts for sustainable and harmonised RDM practices with dedicated forums for RDM professionals to exchange knowledge and share resources. The proposed ELIXIR RDM Community will bring together RDM experts to develop ELIXIR's vision and coordinate its activities, taking advantage of the available assets. It aims to coordinate RDM best practices and illustrate how to use the existing ELIXIR RDM services. The Community will be built around three integral pillars, namely, a network of RDM professionals, RDM knowledge management and RDM training expertise and resources. It will also engage with external stakeholders to leverage benefits and provide a forum to RDM professionals for regular knowledge exchange, capacity building and development of harmonised RDM practices, keeping in line with the overall scope of the RDM Community. In the short term, the Community aims to build upon the existing resources and ensure that the content of these remain up to date and fit for purpose. In the long run, the Community will aim to strengthen the skills and knowledge of its RDM professionals to support the emerging needs of the scientific community. The Community will also devise an effective strategy to engage with other ELIXIR structures and international stakeholders to influence and align with developments and solutions in the RDM field.

Validation of automatic bone age determination in children with congenital adrenal hyperplasia.

BACKGROUND: Determination of bone age is routinely used for following up substitution therapy in congenital adrenal hyperplasia (CAH) but today is a procedure with significant subjectivity. OBJECTIVE: The aim was to test the performance of automatic bone age rating by the BoneXpert software package in all radiographs of children with CAH seen at our clinic from 1975 to 2006. MATERIALS AND METHODS: Eight hundred and ninety-two left-hand radiographs from 100 children aged 0 to 17 years were presented to a human rater and BoneXpert for bone age rating. Images where ratings differed by more than 1.5 years were each rerated by four human raters. RESULTS: Rerating was necessary in 20 images and the rerating result was closer to the BoneXpert result than to the original manual rating in 18/20 (90 %). Bone age rating precision based on the smoothness of longitudinal curves comprising a total of 327 data triplets spanning less than 1.7 years showed BoneXpert to be more precise (P<0.001). CONCLUSION: BoneXpert performs reliable bone age ratings in children with CAH.

The ELIXIR Biodiversity Community: Understanding short- and long-term changes in biodiversity.

Biodiversity loss is now recognised as one of the major challenges for humankind to address over the next few decades. Unless major actions are taken, the sixth mass extinction will lead to catastrophic effects on the Earth's biosphere and human health and well-being. ELIXIR can help address the technical challenges of biodiversity science, through leveraging its suite of services and expertise to enable data management and analysis activities that enhance our understanding of life on Earth and facilitate biodiversity preservation and restoration. This white paper, prepared by the ELIXIR Biodiversity Community, summarises the current status and responses, and presents a set of plans, both technical and community-oriented, that should both enhance how ELIXIR Services are applied in the biodiversity field and how ELIXIR builds connections across the many other infrastructures active in this area. We discuss the areas of highest 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 a Biodiversity Community in ELIXIR and is an appeal to identify and involve new stakeholders.

Systems Biology in ELIXIR: modelling in the spotlight.

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases.

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

A unified resource and configurable model of the synapse proteome and its role in disease.

Genes encoding synaptic proteins are highly associated with neuronal disorders many of which show clinical co-morbidity. We integrated 58 published synaptic proteomic datasets that describe over 8000 proteins and combined them with direct protein-protein interactions and functional metadata to build a network resource that reveals the shared and unique protein components that underpin multiple disorders. All the data are provided in a flexible and accessible format to encourage custom use.

Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity: The EarlyCause project.

INTRODUCTION: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. METHODS AND ANALYSIS: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

History of maltreatment and mental health problems in foster children: a review of the literature.

OBJECTIVE: Foster children often experience compromising situations such as neglect, physical abuse, or sexual abuse before out-of-home placement. This article aims to give a literature review related to the development and mental health of foster children with special consideration of trauma history. METHODS: A computer-based literature search was conducted in the databases Medline, PsycINFO, PSYNDEXplus, and SCOPUS. We determined a time frame from 1998 to 2009. RESULTS: The literature search resulted in 32 articles reporting empirical data about development and mental health in foster children. Very high rates of exposure to maltreatment, developmental delays and mental disorders were found. A broad spectrum of externalizing as well as internalizing symptoms and a high prevalence of comorbid mental disorders were found. CONCLUSIONS: Foster children exhibit a broad pattern of developmental problems and psychopathology. The etiology of these disorders is discussed in the context of multiple risk factors, especially that of persistent maltreatment.

Rule-based modelling provides an extendable framework for comparing candidate mechanisms underpinning clathrin polymerisation.

Polymerisation of clathrin is a key process that underlies clathrin-mediated endocytosis. Clathrin-coated vesicles are responsible for cell internalization of external substances required for normal homeostasis and life -sustaining activity. There are several hypotheses describing formation of closed clathrin structures. According to one of the proposed mechanisms cage formation may start from a flat lattice buildup on the cellular membrane, which is later transformed into a curved structure. Creation of the curved surface requires rearrangement of the lattice, induced by additional molecular mechanisms. Different potential mechanisms require a modeling framework that can be easily modified to compare between them. We created an extendable rule-based model that describes polymerisation of clathrin molecules and various scenarios of cage formation. Using Global Sensitivity Analysis (GSA) we obtained parameter sets describing clathrin pentagon closure and the emergence/production and closure of large-size clathrin cages/vesicles. We were able to demonstrate that the model can reproduce budding of the clathrin cage from an initial flat array.