Recommendations from the COST action CA17116 (SPRINT) for the standardization of perinatal derivative preparation and in vitro testing.

Many preclinical studies have shown that birth-associated tissues, cells and their secreted factors, otherwise known as perinatal derivatives (PnD), possess various biological properties that make them suitable therapeutic candidates for the treatment of numerous pathological conditions. Nevertheless, in the field of PnD research, there is a lack of critical evaluation of the PnD standardization process: from preparation to in vitro testing, an issue that may ultimately delay clinical translation. In this paper, we present the PnD e-questionnaire developed to assess the current state of the art of methods used in the published literature for the procurement, isolation, culturing preservation and characterization of PnD in vitro. Furthermore, we also propose a consensus for the scientific community on the minimal criteria that should be reported to facilitate standardization, reproducibility and transparency of data in PnD research. Lastly, based on the data from the PnD e-questionnaire, we recommend to provide adequate information on the characterization of the PnD. The PnD e-questionnaire is now freely available to the scientific community in order to guide researchers on the minimal criteria that should be clearly reported in their manuscripts. This review is a collaborative effort from the COST SPRINT action (CA17116), which aims to guide future research to facilitate the translation of basic research findings on PnD into clinical practice.

TiO2 Nanoparticles and Their Effects on Eukaryotic Cells: A Double-Edged Sword.

Nanoparticulate TiO2 (TiO2 NPs) is a widely used material, whose potential toxicity towards eukaryotic cells has been addressed by multiple studies. TiO2 NPs are considered toxic due to their production of reactive oxygen species (ROS), which can, among others, lead to cellular damage, inflammatory responses, and differences in gene expression. TiO2 NPs exhibited toxicity in multiple organs in animals, generating potential health risks also in humans, such as developing tumors or progress of preexisting cancer processes. On the other hand, the capability of TiO2 NPs to induce cell death has found application in photodynamic therapy of cancers. In aquatic environments, much has been done in understanding the impact of TiO2 on bivalves, in which an effect on hemocytes, among others, is reported. Adversities are also reported from other aquatic organisms, including primary producers. These are affected also on land and though some potential benefit might exist when it comes to agricultural plants, TiO2 can also lead to cellular damage and should be considered when it comes to transfer along the food chain towards human consumers. In general, much work still needs to be done to unravel the delicate balance between beneficial and detrimental effects of TiO2 NPs on eukaryotic cells.

The Carniolan Honeybee from Slovenia-A Complete and Annotated Mitochondrial Genome with Comparisons to Closely Related Apis mellifera Subspecies.

The complete mitochondrial genome of the Carniolan honeybee (Apis mellifera carnica) from Slovenia, a homeland of this subspecies, was acquired in two contigs from WGS data and annotated. The newly obtained mitochondrial genome is a circular closed loop of 16,447 bp. It comprises 37 genes (13 protein coding genes, 22 tRNA genes, and 2 rRNA genes) and an AT-rich control region. The order of the tRNA genes resembles the order characteristic of A. mellifera. The mitogenomic sequence of A. m. carnica from Slovenia contains 44 uniquely coded sites in comparison to the closely related subspecies A. m. ligustica and to A. m. carnica from Austria. Furthermore, 24 differences were recognised in comparison between A. m. carnica and A. m. ligustica subspecies. Among them, there are three SNPs that affect translation in the nd2, nd4, and cox2 genes, respectively. The phylogenetic placement of A. m. carnica from Slovenia within C lineage deviates from the expected position and changes the perspective on relationship between C and O lineages. The results of this study represent a valuable addition to the information available in the phylogenomic studies of A. mellifera-a pollinator species of worldwide importance. Such genomic information is essential for this local subspecies' conservation and preservation as well as its breeding and selection.

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.

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine.

Single cell RNA sequencing (scRNA-seq) represents a new large scale and high throughput technique allowing analysis of the whole transcriptome at the resolution of an individual cell. It has emerged as an imperative method in life science research, uncovering complex cellular networks and providing indices that will eventually lead to the development of more targeted and personalized therapies. The importance of scRNA-seq has been particularly highlighted through the analysis of complex biological systems, in which cellular heterogeneity is a key aspect, such as the immune system. Autoimmune inflammatory rheumatic diseases represent a group of disorders, associated with a dysregulated immune system and high patient heterogeneity in both pathophysiological and clinical aspects. This complicates the complete understanding of underlying pathological mechanisms, associated with limited therapeutic options available and their long-term inefficiency and even toxicity. There is an unmet need to investigate, in depth, the cellular and molecular mechanisms driving the pathogenesis of rheumatic diseases and drug resistance, identify novel therapeutic targets, as well as make a step forward in using stratified and informed therapeutic decisions, which could now be achieved with the use of single cell approaches. This review summarizes the current use of scRNA-seq in studying different rheumatic diseases, based on recent findings from published in vitro, in vivo, and clinical studies, as well as discusses the potential implementation of scRNA-seq in the development of precision medicine in rheumatology.

A framework to assess the quality and impact of bioinformatics training across ELIXIR.

ELIXIR is a pan-European intergovernmental organisation for life science that aims to coordinate bioinformatics resources in a single infrastructure across Europe; bioinformatics training is central to its strategy, which aims to develop a training community that spans all ELIXIR member states. In an evidence-based approach for strengthening bioinformatics training programmes across Europe, the ELIXIR Training Platform, led by the ELIXIR EXCELERATE Quality and Impact Assessment Subtask in collaboration with the ELIXIR Training Coordinators Group, has implemented an assessment strategy to measure quality and impact of its entire training portfolio. Here, we present ELIXIR's framework for assessing training quality and impact, which includes the following: specifying assessment aims, determining what data to collect in order to address these aims, and our strategy for centralised data collection to allow for ELIXIR-wide analyses. In addition, we present an overview of the ELIXIR training data collected over the past 4 years. We highlight the importance of a coordinated and consistent data collection approach and the relevance of defining specific metrics and answer scales for consortium-wide analyses as well as for comparison of data across iterations of the same course.

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 human 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.

Author Correction: Leveraging European infrastructures to access 1 million human genomes by 2022.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The bio.tools registry of software tools and data resources for the life sciences.

Bioinformaticians and biologists rely increasingly upon workflows for the flexible utilization of the many life science tools that are needed to optimally convert data into knowledge. We outline a pan-European enterprise to provide a catalogue ( https://bio.tools ) of tools and databases that can be used in these workflows. bio.tools not only lists where to find resources, but also provides a wide variety of practical information.

Leveraging European infrastructures to access 1 million human genomes by 2022.

Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.

Training bioinformaticians in High Performance Computing.

In the last decade, bioinformatics has become an indispensable branch of modern science research, experiencing an explosion in financial support, developed applications and data collection. The growth of the datasets that are emerging from research laboratories, industry, the health sector, etc., are increasingly raising the levels of demand in computing power and storage. Processing biological data, in the large scales of these datasets, often requires the use of High Performance Computing (HPC) resources, especially when dealing with certain types of omics data, such as genomic and metagenomic data. Such computational resources not only require substantial investments, but they also involve high maintenance costs. More importantly, in order to keep good returns from the investments, specific training needs to be put in place to ensure that wasting is minimized. Furthermore, given that bioinformatics is a highly interdisciplinary field where several other domains intersect (such as biology, chemistry, physics and computer science), researchers from these areas also require bioinformatics-specific training in HPC, in order to fully take advantage of supercomputing centers. In this document, we describe our experience in training researchers from several different disciplines in HPC, as applied to bioinformatics under the framework of the leading European bioinformatics platform ELIXIR, and analyze both the content and outcomes of the course.

Predicting potential drug-drug interactions on topological and semantic similarity features using statistical learning.

Drug-drug interaction (DDI) is a change in the effect of a drug when patient takes another drug. Characterizing DDIs is extremely important to avoid potential adverse drug reactions. We represent DDIs as a complex network in which nodes refer to drugs and links refer to their potential interactions. Recently, the problem of link prediction has attracted much consideration in scientific community. We represent the process of link prediction as a binary classification task on networks of potential DDIs. We use link prediction techniques for predicting unknown interactions between drugs in five arbitrary chosen large-scale DDI databases, namely DrugBank, KEGG, NDF-RT, SemMedDB, and Twosides. We estimated the performance of link prediction using a series of experiments on DDI networks. We performed link prediction using unsupervised and supervised approach including classification tree, k-nearest neighbors, support vector machine, random forest, and gradient boosting machine classifiers based on topological and semantic similarity features. Supervised approach clearly outperforms unsupervised approach. The Twosides network gained the best prediction performance regarding the area under the precision-recall curve (0.93 for both random forests and gradient boosting machine). The applied methodology can be used as a tool to help researchers to identify potential DDIs. The supervised link prediction approach proved to be promising for potential DDIs prediction and may facilitate the identification of potential DDIs in clinical research.

Ten steps to get started in Genome Assembly and Annotation.

As a part of the ELIXIR-EXCELERATE efforts in capacity building, we present here 10 steps to facilitate researchers getting started in genome assembly and genome annotation. The guidelines given are broadly applicable, intended to be stable over time, and cover all aspects from start to finish of a general assembly and annotation project. Intrinsic properties of genomes are discussed, as is the importance of using high quality DNA. Different sequencing technologies and generally applicable workflows for genome assembly are also detailed. We cover structural and functional annotation and encourage readers to also annotate transposable elements, something that is often omitted from annotation workflows. The importance of data management is stressed, and we give advice on where to submit data and how to make your results Findable, Accessible, Interoperable, and Reusable (FAIR).

Four simple recommendations to encourage best practices in research software.

Scientific research relies on computer software, yet software is not always developed following practices that ensure its quality and sustainability. This manuscript does not aim to propose new software development best practices, but rather to provide simple recommendations that encourage the adoption of existing best practices. Software development best practices promote better quality software, and better quality software improves the reproducibility and reusability of research. These recommendations are designed around Open Source values, and provide practical suggestions that contribute to making research software and its source code more discoverable, reusable and transparent. This manuscript is aimed at developers, but also at organisations, projects, journals and funders that can increase the quality and sustainability of research software by encouraging the adoption of these recommendations.

Top 10 metrics for life science software good practices.

Metrics for assessing adoption of good development practices are a useful way to ensure that software is sustainable, reusable and functional. Sustainability means that the software used today will be available - and continue to be improved and supported - in the future. We report here an initial set of metrics that measure good practices in software development. This initiative differs from previously developed efforts in being a community-driven grassroots approach where experts from different organisations propose good software practices that have reasonable potential to be adopted by the communities they represent. We not only focus our efforts on understanding and prioritising good practices, we assess their feasibility for implementation and publish them here.

Lightweight application for generating clinical research information systems: MAGIC.

BACKGROUND: Our purpose was to build and test a lightweight solution for generating clinical research information systems (CRIS) that would allow non-IT professionals with basic knowledge of computer usage to quickly define and build a ready-to-use, safe and secure web-based clinical research system for data management. We use the acronym MAGIC (Medical Application Generator InteraCtive) for the system. METHODS: The generated CRIS should be very easy to build and use, so a common LAMP (Linux Apache MySQL Perl) platform was used, which also enables short development cycles. The application was built and tested using eXtreme Programming (XP) principles by a small development team consisting of one informatics specialist, one physician and one graphical designer/programmer. RESULTS: The parameter and graphical user interface (GUI) definitions for the CRIS can be made by non-IT professionals using an intuitive English-language-like formalism called application definition language (ADL). From these definitions, the MAGIC builds an end-user CRIS that can be used on a wide variety of platforms (from standard workstations to hand-held devices). A working example of a national health-care-quality assessment program is presented to illustrate this process. CONCLUSION: The lightweight application for generating CRIS (MAGIC) has proven to be useful for both clinical and analytical users in real working environment. To achieve better performance and interoperability, we are planning to recompile the application using XML schemas (XSD) in HL7 CDA or openEHR archetypes formats used for parameters definition and for data interchange between different information systems.

Prevalence of isolated systolic hypertension (ISH) in Slovene hypertensive patients: insights from the "Quality of Healthcare in Slovenia" project.

OBJECTIVES: The aim of the present study was mainly to evaluate age- and gender-dependent isolated systolic hypertension (ISH) prevalence before and during antihypertensive treatment, and to evaluate pulse pressure (PP) distributions during antihypertensive treatment in almost 20,000 Slovene hypertensive patients. METHODS: The study was conducted as part of the "Quality of Healthcare in Slovenia" project, in agreement with the National Medical Ethics Committee of the Republic of Slovenia. Appropriate statistical analyses and evaluations were performed. RESULTS: The prevalence of ISH before the treatment was 19.6 % (17.0 % for men and 21.4 % for women) and it was significantly (p < 0.001) higher during the treatment (29.6 %; 26.4 % for men and 31.9 % for women). The mean PP before the treatment for the whole study patient sample was (71.2 ± 16.9) mmHg and was significantly (p < 0.001) reduced during the treatment to (57.4 ± 12.5) mmHg. CONCLUSION: With regard to high ISH in treated Slovene hypertensive patients, quality of ISH control may not be optimal and should be improved. On the other hand, the adequate arterial hypertension (AH) control (systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg) was achieved in 55.6 % of patients. Our observations may have useful therapeutic implications in the management of AH, particularly ISH in the elderly.

A multiscale model of the electrohysterogram the BioModUE_PTL project.

The electrohysterogram (EHG) is a promising means of monitoring pregnancy and of detecting a risk of preterm labor. To improve our understanding of the EHG as well as its relationship with the physiologic phenomena involved in uterine contractility, we plan to model these phenomena in terms of generation and propagation of uterine electrical activity. This activity can be realistically modeled by representing the principal ionic dynamics at the cell level, the propagation of electrical activity at the tissue level and then the way it is reflected on the skin surface through the intervening tissue. We present in this paper the different steps leading to the development and validation of a biophysics based multiscale model of the EHG, going from the cell to the electrical signal measured on the abdomen.

Telepharmacology in clinical practice?

The role and collaboration of a pharmacologist with other members of the health care team is very important with his/her knowledge about prescribing, administration and pharmacodynamics of drugs as well as about using the existing drug related information systems. It seems optimal for a health care system to use telepharmacology which means a special pharmacological team (and information system) on duty available 24h to different medical specialists via remote multimedia link.