Research projects
This section introduces all current projects of the Bioinformatics Core group.
Improving knowledge management and data sustainability
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/ |
European Translational Information and Knowlegde Management Services (eTRIKS) |
eTRIKS is an Innovative Medicines Initiative (IMI) project addressing the knowledge management (KM) needs of the other IMI projects. IMI is Europe’s largest public-private partnership that is focused on accelerating the development of better and safer medicines for patients. Many of the IMI projects are targeting data intensive translational research requiring a KM environment that allows storing data and facilitates combined analysis of different data types. The main goal of eTRIKS is to develop a sustainable IMI translational research/KM platform and to implement a sustainable KM service for the IMI data. tranSMART was chosen as the software basis for the development of an open eTRIKS KM platform. In addition to the software platform, we provide guidelines and data curation services as well as selection of appropriate ontologies and terminologies. This allows standardizing the data in a homogenous way and and thus guarantees better cross-study comparability. One of the goals of eTRIKS is to improve the operational efficiency in translational research by providing an adapted software and data storage environment as well as data standards. Funding body: Innovative Medicines Initiative (IMI-JU) Coordinator: Yi-Ke Guo, Imperial College, London, United Kingdom Official website: http://www.etriks.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 Funding body: Horizon 2020 Coordinator: Ricardo Goncalves, UNINOVA, Portugal Official website: https://www.smart4health.eu/ |
Harmonising standardisation strategies to increase efficiency and competitiveness of European life-science research (CHARME) |
Biotechnology is an enabling technology that alone, or in combination with cognate technologies, provides the capacity to spur huge leaps in the performance and capabilities of numerous sectors, such as healthcare and medicine, agricultural production, and industrial production. In this context, a prerequisite for modern R&D is a high quality of the research data. By enabling re-use of research assets, research is made considerably more efficient and economical. Funding body: COST Coordinator: Susanne Hollmann, Institute of Biochemistry and Biology, University of Potsdam, Germany Official website: https://www.cost-charme.eu/ |
Redefinition of diseases on the molecular level
Organising Knowledge about Neurodegenerative Disease Mechanisms for the Improvement of Drug Development and Therapy (AETIONOMY) |
In January 2014 the AETIONOMY consortium started a project aiming to develop a new way to classify Alzheimer’s and Parkinson’s disease. The 5-year-project is funded by the Innovative Medicines Initiative (IMI), a joint undertaking between the European Union and the pharmaceutical industry association EFPIA. The new classification will be generated using data derived from a wide range of new biological approaches and will be based on the underlying causes of the disease. Currently, Alzheimer’s disease and Parkinson’s disease are classified by their symptoms and severity but it is clear that this does not represent the many different causes of these diseases. It has been widely recognised that within these broad disease groups there are sub-groups where the different causes result in the symptoms of memory loss or movement disorder. Funding body: Innovative Medicines Initiative (IMI-JU) Coordinator: Duncan McHale, UCB Pharma, Belgium Website: https://www.aetionomy.eu/
|
Data integration across disease and disciplines
PerMedCoE: HPC/Exascale Centre of Excellence in Personalised Medicine |
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: European Commission - Horizon 2020 research and innovation programme Coordinator: Barcelona Supercomputing Center (BSC), Spain Official website: www.permedcoe.eu |
Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCOG) |
Postoperative delirium (POD) is characterized by the progressive deterioration of sensory/cognitive function after surgery with incidences of up to 30-80%. It is frequently followed by postoperative cognitive dysfunction (POCD) which tends to persist over time. In elderly patients, POCD resembles chronic dementia and appears to accelerate the cognitive decline in Alzheimer dementia. POD is strongly associated with subsequent dementia after 3.2 and 5.0 years of follow-up: odds ratio = 12.52 [95% CI, 1.86-84.21] corrected for baseline dementia, severity of illness, age. In an aging society like the EU, the socioeconomic implications of POD/POCD are therefore profound. At present no treatment exists and there are no established molecular or imaging biomarkers that allow risk and clinical outcome prediction. We will establish valid biomarkers panels for risk and clinical outcome prediction of POD/POCD in N=1200 surgical patients according to the regulatory requirements of the European Medicines Agency. Thus, a valuable database will be created not yet existing worldwide. Funding body: The European Union Seventh Framework Programme (FP7) Coordinator: Georg Winterer, Charité Berlin, Germany Official website: www.biocog.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 Funding body: Innovative Medicines Initiative (IMI-JU) Coordinator: Stephan Weidinger, University Kiel, Germany
|
Scalable Machine Learning And Reservoir Computing Platform for Analyzing Temporal Data Sets in the Context of Parkinson's Disease and Biomedicine |
A myriad of computational and biomedical data flow through time with strong dependencies on the previous states. In Parkinson's research, well-established longitudinal studies generate sufficient snapshots of patients' phenotypes, omics, and imaging data so they could be treated as time series. More profoundly, phone applications and wearables capturing patient's gait and tremor, daily or as a continuous stream, make a strong case for performant and general-purpose temporal analysis. To predict disease progression and to obtain an immediate feedback on the therapeutic efficiency would allow to closely follow individual patient's trajectories and quickly adjust their treatments. Funding body: Michael J Fox Foundation
|
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 Funding body: Marie Sklodowska Curie Actions Innovative Training Networks Coordinator: Annette Byrne, Royal College of Surgeons in Ireland, Ireland Website: https://www.gliotrain.eu/
|
Text and data mining
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/ |
Genomic Analysis
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: 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 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. 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
|