ELIXIR Luxembourg Node, a data hub for Translational Medicine (ELIXIR-LU)

ELIXIR, the European infrastructure for life science information, aims to provide long-term access to bioinformatics tools and biological data. ELIXIR-LU, the national ELIXIR node, focuses on long-term sustainability of tools and data for translational medicine, the combination between the clinical and experimental environment. On the national level, support in standardising and electronic capture of clinical data is provided together with hosting and analysis pipelines. Internationally, translational medicine data is hosted by the Bioinformatics Core and support is given in the curation and standardisation of data sets to improve the reusability and value of the data for the research community.

Coordinator: Head of Node: Reinhard Schneider, Luxembourg Centre for Systems Biomedicine, University of Luxembourg

Official website: https://elixir-luxembourg.org/ 

FAIRification of IMI and EFPIA data (FAIRplus)

Wide sharing of knowledge and data drives the progression of science. Shared data allows other researchers to reproduce  findings and benchmark quality of experiments. Sharing data so that other researchers can Find, Access and Interoperate – i.e. integrate the data with the outcomes of their own experiments - allows Reuse and an opportunity to build the large aggregated cohorts we need to detect rare signals and manage the many confounding factors in translational research. This project will develop the guidelines and tools needed to make data FAIR. Through worked examples using IMI and EFPIA data and application and extension of existing methods we will improve the level of discovery, accessibility, interoperability and reusability of selected IMI and EFPIA data. In addition, through disseminated guidelines and tailored training for data handlers in academia, SMEs and pharmaceuticals, data management culture will change and be sustained and datasets will be reused by pharmaceutical companies, academia and SMEs. Our FAIR SME & Innovation programme will enable wide data reuse and foster an innovation ecosystem around these data that power future re-use, knowledge generation, and societal benefit. We call this approach ‘FAIRplus’.

Funding body: Innovative Medicines Initiative (IMI-JU)

Coordinator: Serena Scollen, ELIXIR-Europe, United Kingdom

Official website: https://fairplus-project.eu/

Citizen-centred EU-eHR exchange for personalised health (Smart4Health)

Smart4Health will enable the citizen-centred EU EHR exchange for personalised health. This will pave the way for the full
deployment of citizen-centred solutions and services in a digital single market for wellbeing and healthcare. It will provide for
interoperability, complementarity and cooperativity with profiles that are currently used e.g. by Member States and regions.
Smart4Health will enable the bridging between the diverse EU EHR data and citizen-generated health data. It will connect
citizens to science and personalised health services.

The European Commission 2017 review of the Digital Single Market lists three priorities:

1. Citizens´ secure access to electronic health records and the possibility to share it across borders
2. Supporting data infrastructure, to advance research, disease prevention and personalised health and care
3. Facilitating feedback and interaction between patients and healthcare providers, to support prevention and citizen empowerment as well as quality and patient-centred care.

Smart4Health addresses these priorities with an outstanding consortium that develops, tests and validates a platform
prototype for the Smart4Health citizen-centred health record EU-EHR exchange. Smart4Health provides an easy-to-use,
secure, constantly accessible and portable health data and services prototype, thus advancing citizen health and wellbeing,
and digital health innovation.
Smart4Health builds on the strength of the European infrastructures CEF, ELIXIR, the EIT Health, BBMRI-ERIC, the
European Virtual Laboratory for Enterprise Interoperability (I-VLab), the experience and knowledge gained and generated,
the EU/US collaboration in eHealth, e.g. the Icahn School of Medicine at Mount Sinai, the momentum of initiatives in the
Member States, e.g. 'Medizininformatik Initiative' of the BMBF in Germany. Smart4Health enables citizens to manage and
bridge their own health data throughout the EU and beyond, advancing own and societal health and wellbeing.

Funding body: Horizon 2020

Coordinator: Ricardo Goncalves, UNINOVA, Portugal

Official website: https://www.smart4health.eu/ 

Develop the organisation, connectivity and impact of ELIXIR Nodes to align Europe’s infrastructure roadmaps for long-term FAIR life science data (ELIXIR-CONVERGE)

Long-term sustainability of a distributed research infrastructure rests on a foundation of stable national Nodes. ELIXIR’s long-term sustainability plan sets out a range of actions to secure operations and provide the scientific capabilities needed to support cutting-edge research. Several components of our long-term sustainability plan are already on-going and *this project* is designed to drive significant progress against the major, complex and outstanding issue of aligning national data management practice, impact assessments and national roadmap positioning. Thus, the focus of *This project* is on strengthening the national ELIXIR Nodes. *this project* will harmonise toolkits, operations and monitoring indicators. The long-term operation of a pan-European network that delivers national and transnational data management requires the development of business models, funding strategies and service agreements that ensure long-term operations of national Nodes. Specifically we aim to achieve this transformation by delivering results against four project objectives:

• Objective 1: Develop a sustainable and scalable operating model for transnational life-science data management support by leveraging national capabilities in ELIXIR Nodes
• Objective 2:Strengthen Europe’s data management capacity through a comprehensive training programme delivered throughout the European Research Area
• Objective 3:Align national data management standards, tools and services into a long-term sustainable, scalable and cost-effective toolkit
• Objective 4:Building on national investments in both Nodes and the joint ELIXIR Programme to drive harmonised monitoring and impact assessments, increasing the global influence of ELIXIR.

Funding body: Horizon 2020

Coordinator: Niklas Blomberg, ELIXIR-Europe, United Kingdom

Official website: https://elixir-europe.org/about-us/how-funded/eu-projects/converge

Beyond 1+Million Genomes (B1MG)

It can take less than one day to sequence a whole human genome. This technical prowess, unthinkable just a few decades ago, has opened up new possibilities for improving human health, from preventative medicine (based on genetic predisposition) and faster and more accurate diagnosis, to the development of pharmacogenomics (more efficient treatments with reduced harmful side effects). Unleashing the potential of personalised medicine, a healthcare approach that takes into account a person’s genetic make-up, is expected to bring significant socio-economic benefits, including more efficient national health systems, leading to better health and quality of life of patients, and increased life expectancy. This is, however, uncharted territory where common mechanisms to securely share the required information have yet to be designed, agreed and implemented, at national, European and international levels, so that genomic and phenotypic (clinical, lifestyle) data can be searched and accessed, within and across national jurisdictions. Europe is uniquely placed to take on this challenge and position itself as a global leader in this field..
Until recently, genomic data have predominantly been generated, curated and used in research settings, with health care systems lacking the necessary processes to bring in this genomic knowledge into their daily practice. Notably, it is the lack of integration of genomic and clinical data that represents a major bottleneck, both in research and health settings. Furthermore, it is generally complex to share genomic data within and across national jurisdictions - this reduces sample sizes and hence the statistical power required for adequate research and clinical decisions to happen, of particular relevance to rare diseases, the understanding of polygenic diseases, and minority ethnic groups. Working in partnership with European countries that have signed, or not, the 'Towards access to at least 1 million sequenced genomes in the EU by 2022' Declaration, as well as national health care providers, patient organisations, research infrastructures and the industry, the B1MG (Beyond 1 Million Genome) project aims to bridge the gap between research and practice, to accelerate translation into improved healthcare. This will be achieved by collaboratively developing a roadmap for the integration of genomic data with phenotypic data across borders using demonstrators from different medical areas.

Funding body: Horizon 2020

Coordinator: Serena Scollen, ELIXIR-Europe, United Kingdom

Official website: https://b1mg-project.eu/

HealthyCloud - Health Research & Innovation Cloud

HealthyCloud’s strategic agenda will lay the foundations for the establishment of a trusted and decentralised European computational system for the use and better exploitation of health data by humans and machines. This project will be built upon 4 strategic objectives

• Objective #1 - Impulse a dialogue with a broad range of stakeholders for identifying needs, challenges and opportunities so they can be modelled and prioritized in the HealthyCloud’s strategic agenda.
• Objective #2 - Overcoming legal and administrative barriers of a borderless sharing of human data in Europe and establishing a robust and trustable governance that combines efficient support for research with full endorsement of citizens’ rights and interests.
• Objective #3 - Provide recommendations, guidelines and best practices to enable accessing, using and reusing health data for better research outcomes across Europe within an ethically sound and legally compliant framework.
• Objective #4 - Drive the adoption of mechanisms for the sustainable use of European capabilities on computational systems including both Cloud and High Performance Computing.

Funding body: Horizon 2020

Coordinator: Juan Gonzalez, Instituto Aragones de Ciencias Salud, Spain

Official website: https://healthycloud.eu/

Exascale Centre of Excellence in Personalised Medicine (PerMedCoE)

This HPC centre of excellence optimises codes for cell-level simulations in HPC/Exascale and bridges the gap between organ and molecular simulations, thus contributing to the European Personalised Medicine Roadmap.

The centre will become the entry point to Exascale-ready cell-level simulation software, able to transform personal omics data into actionable mechanistic models of medical relevance, supporting developers and end-users with know-how and best practices. It will connect simulation software developers with HPC, HTC and HPDA experts at centres of excellence such as POP and HiDALGO. PerMedCoE will also work with other biomedical consortia such as ELIXIR and LifeTime, connecting pre-exascale infrastructures hosted by supercomputing centres such as the Barcelona Supercomputing Center and CSC–IT Center for Science.

The LCSB is one of the 12 partners from across Europe participating in this project. The Bioinformatics Core is in charge of developing and optimising a pre exascale cell level simulation software and leads the development of guidelines for data protection and privacy preservation in an exascale HPC environment.

Funding body: Horizon 2020

Coordinator: Alfonso Valencia, Barcelona Supercomputing Center (BSC), Spain

Official website: www.permedcoe.eu

A Systems medicine approach to chronic inflammatory disease (SYSCID)

The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique "core disease signatures” which are associated with the disease state and independent of temporal variation, (ii) the generation of "predictive models of disease outcome"- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) "reprogramming disease"- will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool. Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.

Funding body: Horizon 2020

Coordinator: Philip Rosenstiel, Christian-Albrechts-Universität zu Kiel, Germany

Official website: https://syscid.eu/

Biomarkers in Atopic Dermatitis and Psoriasis (BIOMAP)

Our objective is to provide a taxonomic and predictive systems medicine model of Atopic Dermatitis and Psoriasis based on
clinical and molecular profiling to (i) identify determinants of clinically relevant outcomes (disease manifestation, progression,
comorbidity development and treatment response) (ii) improve understanding on shared and distinct disease mechanism(s)
and associated signatures, and their relative importance in patient subpopulations and (iii) deliver biomarkers that identify
disease trajectories and treatment response for use in drug development and clinical practice. BIOMAP will create a
biospecimen and data resource of unprecedented scale and depth accessible via a central, open-source data and analysis
portal, harmonizing diverse, high quality, multi-dimensional datasets on skin and blood (whole and single cell), large scale
population-based and trial data alongside clinical research infrastructure delivering supplementary material flexible to the
needs of the consortium. This resource will be systematically analyzed using state-of-the-art methodologies in epidemiology,
molecular profiling, skin biology and mathematical modelling to define disease and drug endotypes and how these interact
with lifestyle and environmental factors. Selected, highly discriminatory, associated biomarkers will pass through a
diagnostics pipeline (novel in-silico trial methods and assay development), ready for immediate translation. BIOMAP is
expected to drive drug discovery to target causal mechanisms, shorten drug development pathways, and fundamentally
change the diagnosis and management paradigm, from re-active to pro-active strategies that encompass disease biology
and life-time trajectory, matching the intervention (prevention, modification of risk factors, therapeutics) with endotypes.
Clinically annotated endotypes and associated biomarkers will identify when, in whom and how to intervene to minimize
disease impact and improve outcomes.

Funding body: Innovative Medicines Initiative (IMI-JU)

Coordinator: Stephan Weidinger, University Kiel, Germany

Official website: https://www.biomap-imi.eu/

Better control and treatment of immune-mediated diseases by exploring the universe of microenvironment imposed tissue signatures and their correlates in liquid biopsies (ImmUniverse)

Immune-mediated diseases (IMIDs) are an increasing medical burden in industrialized countries worldwide. IMIDs are characterized by an enormous heterogeneity with regard to disease outcome and response to targeted therapies, which currently cannot be adequately anticipated to tailor individual patient management. Hence, mechanistic understanding of this heterogeneity and biomarkers predictive for disease control and therapy response over time are important prerequisites of a future precision medicine in IMIDs. ImmUniverse has been formed as a European transdisciplinary consortium to tackle these unmet needs and to understand the role of the crosstalk between tissue microenvironment and immune cells in disease progression and response to therapy of four different IMIDs: ulcerative colitis, Crohn’s disease, Psoriasis and atopic dermatitis. Following this unique cross-disease approach ImmUniverse will fill the gap and the limitations of current studies, which do not systematically compare the complex interactions between recirculating immune cells and the respective tissue microenvironment. The consortium will combine analysis of tissue-derived signatures with “circulating signatures” detectable in liquid biopsies, employing state-of-the-art profiling technologies corresponding to multi-Omics datasets. The project will also bring diagnostics in IMID to a new level by implementing disruptive non-invasive liquid-biopsy methodology in combination with novel, validated circulating biomarker assays which are expected to improve diagnosis, inform early in the clinical course on disease severity and progression and enable treatment response monitoring. The identified signature will be validated to monitor state/progression and response to therapy in prospective observational cohorts. Realization of these objectives will result in improvement of patient management, lead to increased patient well-being and will significantly reduce the socioeconomic burden of these diseases.

Funding body: Innovative Medicines Initiative (IMI-JU)

Coordinator: Silvio Danese, HUMANITAS MIRASOLE SPA, Italy

Official website: https://www.immuniverse.eu/

Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies (imSAVAR)

The vision of Immune Safety Avatar (imSAVAR) is to develop a platform for integrated nonclinical assessments of
immunomodulatory therapy safety and efficacy. Existing nonclinical models do not adequately represent the complexity of the immune system and its interactions in both immunoncology and immunmediated diseases. They also do not accurately reflect the diversity of response to new therapies that is seen in clinical medicine. We will, thus, constantly refine existing and develop new nonclinical models with the final goal of validation aiming at:

1. understanding the value of nonclinical models for predicting efficacy and safety of immunomodulators incorporating cellular high throughput assays, complex organisms models and micro physiological systems
2. developing new endpoints and better monitoring approaches for immune function tests
3. designing cellular and molecular biomarkers for early detection of adverse effects.

The platform imSAVAR will be based upon case studies for prioritized therapeutic modalities
and has been built around institutes of the Fraunhofer-Gesellschaft which has strong track records in applied science and in particular toxicology. The consortium will improve the prediction of the transferability of safety and efficacy of
immunomodulators from pre-clinical models to first-in-human studies in collaboration with the private sector, pharma,
regulators and technology providers. We will share experience on customized models that can be deployed (w.r.t. the 3Rs
principles), establish the necessary infrastructure, conduct the analyses and provide wider disease domain expertise. This
conjoint effort assures that the platform imSAVAR constantly benefits the field of immune safety evaluation, and will generate opportunities for European businesses. A guiding principle of this consortium is the meaningful engagement of
multiple stakeholders including patients and regulators.

Funding body: Innovative Medicines Initiative (IMI-JU)

Coordinator: Peter Loskill, Fraunhofer, Germany

Official website: https://imsavar.eu/

Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis (MIRIADE)

Dementia is currently diagnosed largely based on cognitive decline, while pathology starts years before symptom onset. To make progress in the development of effective drugs for dementia, there is an urgent need for biomarkers to enable precision health: for early and specific diagnosis and objective monitoring of disease progression.
With its multidisciplinary team of scientists from academia, industry, and patient organisations, MIRIADE aims to train a new generation of scientists able to optimise and accelerate development of novel biomarkers for dementia.
MIRIADE will integrate biomarker discovery data from multiple platforms and develop a Dementia Disease Map to enhance biomarker identification (WP1). We will develop assays for prioritized biomarkers (WP2), and selected markers will be clinically validated (WP3). We will study pre-analytical stability and validate against regulatory requirements (WP4) and develop a roadmap for optimal biomarker development (WP5). MIRIADE will thus establish an innovative biomarkerfocussed cross-sectoral research and training programme that will equip ESRs with a unique combination of skills in big data analysis, biomarker assay development, innovation management, and a thorough understanding of medical needs. This programme will provide a new task force of scientists that are optimally trained to the accelerate the biomarker development for dementias and able to progress effective biomarker tools to the clinic.

Funding body: Marie Sklodowska Curie Actions Innovative Training Networks

Coordinator: Charlotte Teunissen, VUMC (NL)

Official website: https://miriade.eu/

diagnostic test to improve surveillance and care of COVID-19 patients (COVIRNA)

Coronavirus disease 2019 (COVID-19) caused by infection with SARS coronavirus 2 (SARS-CoV-2) has reached pandemic proportions with more than 7 million people infected and 0.4 million people killed worldwide. Death rates are accentuated by
cardiovascular comorbidities and arrhythmias leading to unexpected major cardiovascular events. Being able to identify COVID-19 patients at risk of developing cardiovascular events leading to death would allow improving surveillance and care.
Currently, there is no accurate method to predict outcome of COVID-19 patients. COVIRNA is a patient-centered Innovation Action aiming to satisfy this urgent and unmet need. COVIRNA will complete and deploy a prognostic system based on
cardiovascular biomarkers of COVID-19 clinical outcomes combined with digital tools and artificial intelligence analytics (i.e. prediction model). Complementary expertise of 15 EU partners from the healthcare sector, academia, association and
industry will allow conducting a large retrospective study on existing cohorts of COVID-19 patients. By upscaling the already validated and patented research use only FIMICS panel of cardiac-enriched long noncoding RNA biomarkers into an in-vitro
diagnostic test (COVIRNA) adapted to COVID-19 patients, the project will quickly deliver a minimally-invasive, simple yet robust and affordable prognosis tool that can be used in the context of the current COVID-19 crisis as well as in further major
health issues. By tackling the cardiovascular complications in COVID-19, known to contribute significantly to mortality, the project outputs are expected to have a major impact on the pandemic outcomes. The COVIRNA test will be CE-marked and
prepared for commercialization, allowing to risk stratify patients, adapt therapies and to inform drug design.

Funding body: Horizon 2020

Coordinator: Yvan Devaux (LIH), Luxembourg

Official website: https://covirna.eu/

Exploiting GLIOblastoma intractability to address European research TRAINing needs in translational brain tumour research, cancer systems medicine and integrative multi-omics (GLIOTRAIN)

Glioblastoma (GBM) is the most frequent, aggressive and lethal of all brain tumours. It has a universally fatal prognosis with
85% of patients dying within two years. New treatment options and effective precision medicine therapies are urgently
required. This can only be achieved by focused multi-sectoral industry-academia collaborations in newly emerging,
innovative research disciplines. GLIOTRAIN will exploit the intractability of GBM to address European applied biomedical
research training needs. The ETN, which comprises 9 beneficiaries and 14 partner organisations from 8 countries, will train
15 innovative, creative and entrepreneurial ESRs. The research objective of GLIOTRAIN is to identify novel therapeutic
strategies for application in GBM, while implementing state of the art next generation sequencing, systems medicine and
integrative multi-omics to unravel disease resistance mechanisms. Research activities incorporate applied systems medicine, integrative multi-omics leveraging state of the art platform technologies, and translational cancer biology
implementing the latest clinically relevant models. The consortium brings together leading European and international
academics, clinicians, private sector and not-for-profit partners across GBM fields of tumour biology, multi-omics, drug
development, clinical research, bioinformatics, computational modelling and systems biology. Thus, GLIOTRAIN will address currently unmet translational research and clinical needs in the GBM field by interrogating innovative therapeutic strategies
and improving the mechanistic understanding of disease resistance. The GLIOTRAIN ETN addresses current needs in
academia and the private sector for researchers that have been trained in an environment that spans translational research,
medicine and computational biology, and that can navigate confidently between clinical, academic and private sector
environments to progress applied research findings towards improved patient outcomes.

Funding body: Marie Sklodowska Curie Actions Innovative Training Networks

Coordinator: Annette Byrne, Royal College of Surgeons in Ireland, Ireland

Website: https://www.gliotrain.eu/

HeartMed: an ICT platform combining preclinical and clinical information for enhancing translational medicine and patient specific modelling in cardiovascular diseases (HeartMed)

Heart failure, the number 1 reason for death in the EU, is a disease with complex aetiology (e.g. volume dependent heart failure, ischemic heart disease, hypertension, etc. ) and varying severity (HFpEF, HFrEF). As these influencing factors vary between patients, individual treatment options are urgently needed. This heterogeneity also often prevents the transfer of mono-causal animal models to humans as the shared and disliked features are unknown.
The availability of bio-medical data on individual patients (imaging, sensors, omics) has increased dramatically in recent years and deep-phenomapping has the potential to better classify patients based on heterogeneous data sets. Furthermore, mechanistic models have matured to clinical application enabling molecular understanding of complex pathophysiological processes if data quality is sufficient.
Here we propose a novel concept (the HeartMed platform) to enhance translational medicine and support personalized medical decision making.
HeartMed will compile heterogeneous data of animal models and human patients and perform deep-phenomapping to identify heart failure subclasses and assess conformities and differences between pre- and clinical phenotypes.
For patient specific modelling models have to be parameterized with data of sufficient high quality, that are difficult and expensive to obtain from patients (e.g. omics from myocardial tissue). This results in so called “missing data”. Based on the phenomapping classification, HeartMed will combine pre-/clinical information for complementing missing data to enable patient specific mechanistic modelling for a broader class of patients.
In a Clinical proof-of-concept study of patients with heart failure (retrospective data), we will use the HeartMed platform to improve patient classification, determine transferability of animal models and use animal data to improve patient specific modelling with metabolic and hemodynamic models.

Funding body: ERA PerMed (FNR INTER)

Coordinator: Titus Kühne, Charité, Germany

Identification of personalized inflammatory profiles of aging and senescence which are modified specifically by risk factors of dementia modulating the pre-dementia speed of symptomatic progression (PREADAPT)

Age represents by far the highest risk factor for dementia, including Alzheimer’s disease (AD). However, not every person will develop dementia during aging, indicating that age-related processes may not inescapably lead to dementia. The elucidation of the fundamental processes occurring in aging is likely to prevent or postpone the development of dementia. One such key mechanism is cellular senescence, which causes chronic inflammation through the release senescence-associated secretory phenotype (SASP) profile of mediators. PREADAPT will build on the hypothesis that chronic systemic- and neuroinflammation, quantified through a set of SASP mediators, affects the basal trajectory of the senescence occurring in the aging brain, thus allowing to predict future cognitive decline and dementia. The levels and changes of SASP mediators during aging are modulated by different genetic and environmental factors defining thereby a personalized risk for progressing to dementia. Importantly, research has identified that SASP mediators are also altered in cerebrospinal fluid of AD patients. Moreover, SASP together with genetics, known AD biomarkers, and other comorbidities define a combined Risk Profile which provides personalized information on the risk of progressing to dementia. To achieve these goals, PREADAPT has gathered a team of leading experts in the field of neuroinflammation, epidemiology, genetics, epigenetics, neuropsychology, and clinical research. PREADAPT has access to state-of-the-art methodology and knowhow on inflammatory markers to define a set of SASP mediators which derived from PREADAPT own preliminary research. PREADAPT has also access to large epidemiological and clinical follow-up studies that are characterized in-depth using neuroimaging, genomics, and proteomics. This unique configuration will enable PREADAPT to identify, already at pre-dementia stages, age-related profiles informing on the personalized future risk to decline cognitively and to progress to dementia. From a translational perspective, PREADAPT will provide first evidence showing that a SASP personalized risk profile responds to specific intervention depending on the profile of an individuum.

Funding body: JPND (FNR INTER)

Coordinator: Alfredo Ramirez, University of Cologne, Germany

moleculaR -based, Data -driven drug REpurposing for bladder Cancer (ReDiRECt)

ReDiRECt targets to introduce in the pharmaceutical company sector (the market) candidates for drug repurposing in bladder cancer (BC) (the products). An in silico drug repurposing based on the comparison of the molecular signature of BC against the molecular signature of drugs will be applied. The BC signature will be derived from integration of proteomics data with publicly available transcriptomics and literature- mined data. The most promising findings will be tested in model systems.

Funding body: EUROSTARS (FNR INTER)

Coordinator: Harald Mischak, Mosaiques Diagnostics, Germany

PD Map

Please find the PD map here.                                                                                                                                                                                                          

BioKB

BioKB platform, a pipeline which, by exploiting text mining and semantic technologies, helps researchers easily access semantic content of thousands of abstracts and full text articles. The text mining component analyzes the articles content and extracts relations between a wide variety of concepts, extending the scope from proteins, chemicals and pathologies to biological processes and molecular functions. Extracted knowledge is stored in a knowledge base publicly available for both, human and machine access, via this web application and SPARQL endpoint.

Website: http://biokb.lcsb.uni.lu/

National Centre of Excellence in Research: Early diagnosis and stratification of Parkinson’s Disease (NCER-PD)

NCER-PD represents a joint effort between 4 partners in Luxembourg that unite their expertise in Parkinson’s disease. In order to answer the urgent questions surrounding the occurance of Parkinson’s disease, researchers need to analyse clinical data and samples from hundreds of patients and healthy control persons. Our group provides NCER-PD with our competences and technology for the integration, curation and analysis of multidimensional data. To this end, the Data and Computation platform will establish secure and anonymized data ows among other NCER-PD platforms. Well-grounded machine learning and computational modeling approaches will enable data analysis and interpretation. 

Funding body: Fonds National de la Recherche

Coordinator: Rejko Krüger, University of Luxembourg

Official website: https://www.parkinson.lu

Using Whole Genome Sequencing data from LRRK2 families to identify novel rare variants of LRRK2 associated Parkinson's disease

The age of onset and penetrance (likelihood of disease) of individuals with the LRRK2 G2019S mutation varies considerably, the latter ranging in some families from as high as 100 percent to as low as 22 percent. This variation suggests that genetic modifiers contribute to LRRK2 pathogenesis in Parkinson’s disease (PD). The objective of this project is to collect and sequence the genomes of multiple LRRK2 families and use innovative technology and computational approaches to identify and validate novel genetic modifiers of LRRK2-mediated neurodegeneration. The overarching goal is to identify genetic modifiers of LRRK2 G2019S–induced neurodegeneration in PD. To do this, researchers propose a four phase plan:
1. identification and collection of samples from LRRK2 families
2. integrating analysis of existing genetic data on PD patients with LRRK2 G2019S mutations to confirm the identity of candidate genetic modifiers
3. whole genome sequencing data on LRRK2 G2019S families to identify novel genetic modifiers
4. funneled into a validation scheme to directly test potential genetic modifiers for modifying LRRK2 G2019S-induced neurodegeneration in induced pluripotent stem cell (iPSC)-derived neurons from patients with the LRRK2 G2019S mutation.
This project hopes to identify genes that are important for the progression of LRRK2 associated PD. By sequencing the genomes of individuals from many families harboring LRRK2 mutations, investigators will use computational approaches to pinpoint specific genetic mutations that either enhance or lessen the onset and/or progression of LRRK2-associated PD. They will then use neurons, derived from patients with LRRK2 mutations, to validate and understand the role of these genetic mutations within cells. This work would not only increase understanding of what goes wrong in the cells of LRRK2 patients, but also help with genetic testing and in identifying potential therapeutic targets.

Funding body: Michael J Fox Foundation

Coordinator: Rudi Balling, University of Luxembourg

Epi25 Collaborative for Large-Scale Whole Genome Sequencing in Epilepsy (Epi25 Collaborative)  

Epi25  is a collaborative of more than 200 partners from 40 research cohorts from around the world. More than 14,000 exomes have been sequenced as part of this collaborative effort. We expect to find evidence that accurate and detailed phenotypic data reduces genetic heterogeneity, allows for identification of a well-matched replication cohort, and clarifies the phenotypic spectrum associated with a gene.  This approach will help us address fundamental questions about the importance of rare variants, common variants, or de novo changes as the basis for specific forms of epilepsy. 

Funding body: NHGRI

Website: http://epi-25.org/                                         

Epileptogenesis of genetic epilepsies (FOR 2715)

Epilepsy is a common, severe, and disabling condition with a significant disease burden worldwide. Despite
many available treatment options, the seizures are not well controlled in one third of all patients with epilepsy.
Gene discovery and first functional analyses of genetic defects have been major drivers to unravel disease
mechanisms in the last 20 years and have brought about the first personalized treatment options. However,
most of the genetic alterations underlying epilepsy remain to be elucidated and the mechanisms driving a
healthy into an epileptic brain are not well understood. A common feature of genetic epilepsies is the typical
age dependency the origin of which is largely unknown and which differs between syndromes. Therefore,
developmental factors are likely to play a pivotal role for epileptogenesis of genetic epilepsies. In this Research
Unit (RU), we aim to investigate if and how genetic mutations induce a cascade of multidimensional
epileptogenic processes, such as transcriptional, cellular (morphological, neurophysiological), and network
changes, and how these interact with developmental processes which likely contribute to the age‐dependent
manifestation of seizure and behavioral phenotypes in genetic epilepsies.

Funding body: DFG Research Unit (FNR co-funded)

Coordinator: Holger Lerche, University of Tübingen, Germany                                                                                                                                                         

Mitochondrial Risk factors in Parkinson's Disease (MiRisk-PD)

Mitochondria play an essential role in neuronal function and survival. Maintaining the functional integrity of mitochondria is important for cell survival. Extensive prior data generated by use of genotyping arrays and/or exome sequencing approaches in monogenetic and sporadic forms of PD has unequivocally implicated mitochondrial dysfunction as one of the central pathophysiological pathways in PD. Nevertheless, there remains an appreciable gap in deciphering the missing heritability in PD. Primarily, this may result from a dominating focus on understanding the impact of common and rare variants encoded by nuclear genes in PD. By contrast, emerging evidence suggests that genetic variability within mitochondrial DNA may explain missing heritability which, hitherto, cannot be deciphered by nuclear encoded genes alone. This hypothesis is supported by various genetic studies which have shown the involvement of mitochondrial “haplogroups” in causing disease susceptibility for PD. However, results have remained inconclusive so far due to inadequate sample sizes.
In the proposed project, MiRisk-PD, we will implement an integrative approach to understand the role and impact of both nuclear encoded mitochondrial genes and the mitochondrial genome in explaining the missing heritability in PD. This new integrative strategy will be based on (i) a large exome repository of clinically well-defined PD cohort (4500 cases and 5500 controls) within Parkinson disease Genomics Sequencing Consortium (PDGSC) to define nuclear encoded “mitochondrial-network map”; (ii) a unique collection of families with autosomal dominant and autosomal recessive PD (for mitochondrial genome sequencing) and (iii) a large cohort of clinically well-defined sporadic PD patients (45,000 cases and 40,000 controls) from the Genetic Epidemiology of Parkinson disease (GEoPD) consortium, covering different populations worldwide for genetic studies that will translate into (iv) functional validation studies in patient-derived cellular models.
The multisystem approach, as outlined in our MiRisk-PD proposal, will identify stratified cohorts based on the genomic profile to identify and explore novel therapeutic targets, paving the way for a personalized medicine program for PD.

Funding body: Fonds National de la Recherche

Coordinator: Rejko Krüger, University of Luxembourg

New Therapies for Neurological Ion Channel and Transporter Disorders (Treat-ION)

Treat-ION represents a network of clinicians and scientists across Germany to advance the knowledge about recognizing and treating rare neurological ion channel and transporter disorders. Those comprise a variety of neuropsychiatric diseases and symptoms including developmental delay, epilepsy, episodic and chronic ataxia, migraine and others, which often occur in combination or are caused by mutations in the same channels. Due to the common fundamental function of channels and transporters to regulate neuronal excitability and ionic homeostasis, pathophysiological and therapeutic principles are shared across diseases. The main goal of this grant application is to translate findings from genetic and pathophysio- logical studies into rational, individualized therapies. We will therefore focus on therapeutic studies in cellular, animal and human models, which will be complemented by in silico searches for new treatments, better predictions for the functional consequences of mutations for therapeutic purposes and cellular drug screens. We will focus our efforts on approved and available ‘repurposed’ drugs. As a proof-of-principle, we successfully have been per- forming n-of-1 trials and established three investigator-initiated trials in specific rare channel disorders with other funding, which will be of great value for the network. The results of our research and the knowledge of experts will be systematically and directly delivered to patients through a structured molecular therapeutic board attached to the German academy of rare neurological diseases (DASNE).

Funding body: BMBF Individualisierte Medizin

Coordinator: Holger Lerche, University of Tübingen, Germany