Titel "Korte inhoud" "Belgian Medical Genomics Initiative (BeMGI)" "Het doel van het BeMGI project is om:(i) inzicht in de biologie van de ziekte te verwerven door de meest geavanceerde genomische hulpmiddelen.(ii) het voorspellen van de klinische uitkomst van genomische informatie en genomische informatie integreren in de klinische zorg in België.(iii) de voorbereiding van de volgende generatie genomics onderzoekers, het informeren van artsen en publiek." "Multidisciplinaire expertise integreren in een lerend en adaptief Europees systeem voor paraatheid bij pandemieën" "Nico Vandaele" "Faculteit Economie en Bedrijfswetenschappen, Campus Kulak Kortrijk, Laboratorium Klinische en Epidemiologische Virologie (Rega Instituut)" "The COVID-19 pandemic has exposed a global need for accelerating research, improving surveillance, and efficiently developing countermeasures against pathogens with epidemic and pandemic potential. LEAPS aims to demonstrate the value and feasibility of a pro-active policy-supporting strategy for genomic surveillance and for pandemic preparedness and response, by delivering a system-wide stakeholder-validated proof of concept, validated in 4 EU countries, of a learning and adaptive European pandemic preparedness system against pathogen X. LEAPS will fill the gaps observed by global, EU (HERA) and national stakeholders in pandemic response by demonstrating the feasibility of combining genomic One Health surveillance, with genomic epidemiologic modeling for detailed pathogen understanding and precise public health intervention design. LEAPS formalizes dynamic health emergency threat assessment linked to the initiation of governance mechanisms to enable timely decisions in crucial, early stages of an outbreak.  LEAPS will develop protocols and models for accelerated medical countermeasure development, availability and accessibility. Based on resulting highly effective intervention strategies, timely countermeasure access and governance mechanisms, model-based policy support is proposed to health authorities for effective, implementable, stakeholder co-created epidemic response scenarios against pathogen X. Scenarios are evaluated on health, socio-economic, and sustainability impact.LEAPS brings together a unique multidisciplinary team with optimal complementary expertise and experience. LEAPS will interact regularly with medical and scientific communities, HERA and health authorities in order to disseminate relevant and accessible information, and during non-emergency periods LEAPS will validate a roadmap for large-scale implementation of LEAPS methodology by EU level, and national authorities and stakeholders in an ecosystem of interlinked actors." "Europese geavanceerde infrastructuur voor innovatieve genomica" "Joris Vermeesch" "Departement Menselijke Erfelijkheid, Laboratorium voor Groeicontrole en Kankeronderzoek (VIB-KU Leuven), Laboratorium voor Cytogenetica en Genoomonderzoek" "Next-generation sequencing (NGS) has taken modern research by storm and consequently is one of the most important tools of modern biological and biomedical research. However, the high cost of instrumentation and reagents, the multifaceted expertise required for correct use and the legal and ethical issues hamper access to NGS technologies for many researchers. EASI-Genomics addresses those challenges by unifying the major European genome centers that provide external access to their facilities. The mission of EASI-Genomics is to facilitate access to cutting-edge DNA sequencing technologies to researchers from both academia and industry, within a framework that ensures compliance with ethical and legal requirements, as well as FAIR and secure data management. EASI-Genomics will provide fully funded access to more than 150 transnational access projects, selected through public calls and a rigorous, fair and transparent peer-review process. Each funded study will be supported from design, through sequencing, to data analysis. EASI-Genomics will provide more than 100 Tb of sequence and more than 25,000 hours of bioinformatic, analytical and data management support to the user community. As outlined in the call, EASI-Genomics will provide access to advanced methods that go beyond what is commercially available. The focus will be on more complex procedures involving short-reads, long-reads, in situ sequencing and single-cell analysis. Complex integrative projects and projects on non-human samples will also be highlighted. Finally, EASI-Genomics will support the wider NGS community to improve their quality control processes by offering open inter-laboratory comparisons allowing them to obtain ISO certification and accreditation in line with many of the EASI-Genomic partners. The EASI-Genomics project aims to build a community of practice, which leverages advanced sequencing technologies beyond country and sector borders to tackle global challenges in science." "Genomische diagnostiek voorbij de sequentie." "Johan Hofkens" "Moleculaire Visualisatie en Fotonica" "Cytogenetic diagnostic approaches provide information on the single-chromosome level but suffer from low resolution and throughput. In contrast, next generation sequencing (NGS) based diagnostics provides single base resolution and high throughput but suffer from short reads that prevent analysis of large genomic aberrations as well as being prone to PCR-amplification bias and erasure of epigenetic information. This proposal aims to bridge the gap between these domains by analyzing long individual DNA molecules without PCR-amplification via utilization of emerging optical DNA mapping technologies. We specifically address three types of challenges to current genomic based diagnostics:Loss of relevant information such as DNA damage lesions, rare mutations or epigenetic markers following PCR amplification.Limitations in resolving long-range variations in genomic layout and correlating them with single point mutations, preventing large scale screens.Limitations imposed by the sample such as low sample amounts (micro biopsy, circulating tumor DNA) or inhomogeneous/highly variable samples (bacterial cultures).We will develop a robust toolbox for integrated genetic and epigenetic profiling of single DNA molecules that will include automated sample preparation of native unamplified DNA as well as the hardware and software platforms and analysis tools for readout, extraction and quantification of medically relevant genomic information. This technology will be used to develop a set of specific, proof of principle diagnostic assays based on optical barcoding of individual DNA molecules. These assays will address:Bacterial infections and antibiotic resistanceDiagnosis/prognosis tools for hematological malignanciesSpinal Muscular AtrophyEarly diagnosis of colorectal and lung cancer.Ultimately our project will provide reagents, prototype DNA barcoding devices and data analysis software ready for large scale validation and early stage commercialization." "Belgisch medisch genomica initiatief (BeMGI)." "Guy Van Camp" "Medische genetica van obesitas en skeletaandoeningen (MGENOS), Menselijke moleculaire genetica" "Het doel van het BeMGI project is een actief en ondernemend network op te starten om werk te maken van 'medical genomics'. Het network bestaat uit een aantal Belgische onderzoekers en onderzoeksgroepen die actief zijn in het domein van de menselijke genetica, en die o.a. de volgende objectieven nastreven:(i) Individuele en collaboratieve onderzoeksactiviteiten rond genetica en de pathogenese van erfelijke ziekten ondersteunen met alle mogelijke middelen die de laatste genomische technologie biedt.(ii) Een aanpak ontwikkelen die het mogelijk maakt het klinisch effect en nut van genomische informative over te brengen, door middel van het opzetten van een piloot project voor de integratie van genomica in de geneeskundige zorg in België.(iii) Zorgen dat er generatie jonge 'genomische' onderzoekers wordt opgeleid, die kunnen omgaan met deze technologie en de informatica die er bijhoort, en tegelijk zorgen dat de huidige generatie artsen en zorgverleners – en het publiek – uitleg krijgt over de mogelijkheden en beperkingen van de genomische geneeskunde." "SAL-O5_Asses the variation in lipopolysaccharide structure in circulating African invasive Salmonella Typhimurium isolates to predict vaccine coverage" "Sandra Van Puyvelde" "University of Oxford, Instituut voor Tropische Geneeskunde Antwerpen (ITG), Institut Nationale de la Recherche Biomédicale (INRB), Universiteit van Kaapstad, Università degli Studi di Trieste, Laboratorium voor Medische Microbiologie (LMM)" "In sub-Saharan Africa, invasive non-typhoidal Salmonella (iNTS) is the major cause of bacterial bloodstream infections among young children and disease management is jeopardised by increasing antimicrobial resistance (AMR). The O-antigen portion of Salmonella lipopolysaccharide (LPS) is recognised as key target antigen for protective immunity and O-antigen-based vaccines covering the main serovars Salmonella Typhimurium and Enteritidis are in development. Some of the vaccine candidates are about to enter phase 1 clinical trials; however, efficacy in Africa will not be tested for several years. O-antigen structural variability can have an impact on the protective immunity of corresponding vaccines. Serotyping and genomic investigation of recent iNTS isolates from the Democratic Republic of the Congo (DRC) have shown increasing rates of iNTS isolates with variation in O-antigen structure. In particular, more than 45 % of the recent Salmonella Typhimurium isolates do not present O:5 specificity, associated to O-antigen O-acetylation. In this project, we will analyse the genomic variation of O-antigen of Salmonella Typhimurium DRC isolates within the African context. The genomic basis of differences in O-antigenic structure will be proven by mutagenesis experiments. We will determine the O-antigen structure from a panel of Salmonella Typhimurium isolates recently collected in DRC, ascertaining the nature of the O-antigen genomic variations. The coverage of current O-antigen based vaccines against iNTS is likely to be impacted by the O-antigen structural variability, and this project will yield key insights on how to improve the current vaccines" "Reconstructie en computermodellering voor erfelijke stofwisselingsziekten" "Peter Witters" "Vrouw en Kind" "Our overall objectives are to accelerate the diagnosis, and enable personalised management, of inherited metabolic diseases (IMDs). Established academic technology for statistical genomic analysis, deep learning-based prediction of protein structure, and whole-body metabolic network modelling shall be applied to generate personalised computational models, given patient-derived genomic, transcriptomic, proteomic and metabolomic data. To train diagnostic models, a comprehensive clinical team will recruit 1,945 diagnosed patients with a wide variety of IMDs, then validate the clinical utility of personalised computational models on a set of 685 undiagnosed patients. An enhanced human metabolic network reconstruction, especially for lipid metabolism, reaction kinetics and inherited metabolic disease pathways, will increase the predictive capacity of cellular and whole-body metabolic network models. As an exemplar for other IMDs, personalised computational modelling will be used to identify compensatory and aggravating mechanisms that associate with clinical severity in Gaucher disease. The predictive capacity of personalised models will be validated by comparison with additional empirical investigations of protein structure and function as well as metabolomics, tracer-based metabolomics and proteomics of patient-derived in vitro disease models. To maximise the potential for impact, personalised modelling software will be developed to be generally applicable to a broad variety of IMDs, and implemented in a way that is both accessible to clinicians and admissible to regulatory authorities. Sustainability will be promoted by development of a roadmap for a European foundation to aid personalised diagnosis and management of IMDs, informed by broad stakeholder consultation. This is a unique opportunity to realise the potential of personalised computational modelling for a broad set of rare diseases, which is a field where European collaboration is an essential for progress." "Crowdsourced medische gegevens verzameld via smartphones voor biomedisch onderzoek: Een analyse van de ethische, legale en gezondheidsbeleid aspecten" "Mahsa Shabani" "Vakgroep Criminologie, Strafrecht en Sociaal Recht" "Smartphone-applicaties worden steeds vaker gebruikt als eenplatform voor het verzamelen van grote hoeveelheden persoonlijkedata die gegenereerd worden door middel van crowdsourcing. Dezekunnen ingezet worden voor biomedisch onderzoek en hetontwikkelen van algoritmes. Daarnaast kunnen burgers toegangverkrijgen tot hun eigen genetische data via genetische zelftests.Alhoewel het gebruik van smartphones om medische gegevens teverzamelen een meerwaarde kan betekenen voor biomedischonderzoek, roepen deze mogelijkheden vragen op met betrekking totonderzoeksethiek, dataprotectie en verantwoordelijkheden van appontwikkelaars en onderzoekers. In dit project plannen wij om deethische, juridische en gezondheidsbeleid-gerelateerde uitdagingenkritisch onder de loep te nemen vanuit een interdisciplinairperspectief. Bovendien wensen we aanbevelingen te ontwikkelenzodat het gebruik van dergelijke toepassingen op een veilige enmaatschappelijk aanvaardbare manier gebeurt." "Super-resolutie genomische mapping voor het microbioom" "Johan Hofkens" "Moleculaire Visualisatie en Fotonica" "Animals and bacteria have been working together for about as long as they have co-existed, long before the advent of mankind. The bodies of our ancient ancestors offered protected, nutrient-rich habitats for bacteria. In return, animals could take an evolutionary short-cut to developing new capabilities by ‘borrowing’ bacterial genes. Indeed, when gut bacteria assist with the digestion of e.g. dietary fiber, the resulting metabolites will subsequently exert an influence on an intricate network of host molecular pathways. Gut microbiota, in addition to host genetics, can therefore constitute a major factor in the etiology of complex disorders, ranging from obesity, cardiovascular disease, autoimmune disease (multiple sclerosis, rheumatoid arthrosis), inflammation (inflammatory bowel disease, Crohn’s) to neurological conditions.Although such a key role for the human microbiomes had been postulated for some time, many details on the delicate interplay between flora and host remained unknown, largely because suitable methods for uncovering these host-guest interactions were simply not available. These technological barriers keep the diagnostic and therapeutic potential of the microbiome largely untapped. In this project, we will validate the FLUROCODE genomic mapping technology as an alternative to shotgun sequencing and amplicon based techniques for microbiome studies. This will extend the benefits of genomic mapping techniques to complex sample analysis. Through a head-to-head comparison with the state of the art in metagenomic analysis, the POC data will serve as a key enabler for the transfer of the technology platform into a separate venture, working towards diagnostic applications and developing METAMAPPER based microbiome screening as a routine medical tool. The METAMAPPER microbiome readout technology is be perfectly placed to be part of the evolution of microbiome analysis to clinical application." "Ontrafelen van de genetische architectuur van periphere zenuwen: een bijdrage van overerfbare periphere neuropathieën." "Albena Jordanova" "Bogaziçi University, University of Belgrade, Medical University Sofia, VIB CMN - Moleculaire Neurogenomica" "Charcot-Marie-Tooth (CMT) neuropathieën, de meest gemeenschappelijke genetische aandoening onder PNs, zijn ernstige en ongeneesbare aandoeningen. Autosomaal recessieve CMT vormen (ARCMT) hebben een vroegere aanvangsleeftijd en erger ziekteverloop. De moleculaire genetica en biologie van ARCMT, net als CMT, is schaars begrepen vanwege de extreme genetische en pathophysiologische heterogeniteit. De diversiteit van de reeds gekende functies maken van CMT een ideaal paradigma om de homeostasis en disfunctie van periphere zenuwen te bestuderen. We zullen een cohort van 135 ARCMT families bestuderen gebruik makend van exome sequencing, positionele clonering, bioinformatica en functionele genomica in Drosophila modellen, om mogelijks nieuwe ARCMT genen en hun interactiepatronen te bestuderen. Onze bevindingen zullen: i) genen lokaliseren die bijdragen tot PNS homeostasis; ii) de relaties tussen causale genen accentueren; iii) nieuwe pathomechanismen van neurodegeneratie ontrafelen of de reeds gekende versterken; iv) helpen om de variabele fenotypische uitkomsten als gevolg van verschillende genetische achtergronden te voorspellen; v) ziektemodellen leveren die geschikt zijn voor therapeutische applicaties; iv) de moleculaire diagnosis, prognosis en preventie van CMT neuropathieën verbeteren. De vergaarde kennis zal relevant zijn voor CMT, maar ook een bredere bijdrage leveren tot het begrijpen en behandelen van andere overerfbare of verworven neurodegeneratieve ziekten."