Research project P7/43 (Research action P7)
PERSPECTIVE
Genomics emerged as a new discipline in the 80-ies from the convergence of genetics, molecular biology, informatics and robotics. Since then, genomics has culminated in (i) the availability of the complete sequence of the human genome and that of a growing number of other organisms, (ii) a catalogue of all common and low frequency genetic variants in human, (iii) an expanding list of functional genome elements identified on the basis of evolutionary conservation, epigenome and transcriptome profiling, and (iv) an arsenal of rapidly improving genome exploration tools including next generation sequencing.
Genomics has fundamentally changed the practice of biomedical research. Bioinformatic mining of existing databases in conjunction with the generation of –omic scale data have become indispensable tools to make significant contributions in deciphering normal and pathological biological processes. Genomic approaches have led to the identification of > 3,000 genes causing monogenic Mendelian diseases, > 900 loci influencing inherited predisposition to common complex diseases, loci influencing the risk of adverse or ineffective drug response, to the stratification of cancers on the basis of expression or somatic mutation profile, and to the correlation of microbiome composition and disease status. Drug development is increasingly guided by information accrued from genomic approaches. Relying on demanding technology, genomics is hardly compatible with traditional cottage-style approach to biomedical research, but requires collaborative efforts to achieve critical mass for the acquisition as well as exploitation of high throughput platforms, and establishment of consortia to collect and characterize large patient cohorts.
Recent developments in sequencing technology (“NGS: Next Generation Sequencing”) herald a new era of “personal genomes”: it is highly likely that our children and certainly grandchildren will have access to their complete personal genome sequence. These advances will have a major impact on (i) our ability to dissect the molecular mechanisms leading to disease and hence to uncover novel therapeutic targets, and (ii) the integration of genomic information in clinical decision-making, i.e. genomic medicine is an imminent transition. Consequently, roads towards genomic medicine are actively being charted in the most advanced countries in the world (e.g. Green et al. Nature 470:204, 2011). The integration of genomic information in clinical practice raises important societal, legal and public policy issues that need to be proactively addressed.
OBJECTIVES
The aim of the BeMGI project is to establish a vibrant network devoted to medical genomics, including Belgian top scientists active in the field of human genetics, in order to:
(i) Boost individual research efforts towards understanding the biology of disease by promoting collaborative exploitation of the most advanced genomic tools.
(ii) Develop approaches to predict clinical outcome from genomic information and fulfill a pilot role towards concerted integration of genomic information in clinical care in Belgium.
(iii) Play a catalyzing role in preparing the next generation of genomics researchers, informing medical practitioners about evolving trends in medical genomics, and conducting public outreach.
WORKPACKAGES
Accordingly, BeMGI comprises three sections respectively devoted to:
Section 1: Understanding the biology of disease
Workpackage 1.1: Rare heterogeneous monogenic disorders Workpackage 1.2: Oligogenic disorders – searching for modifier loci Workpackage 1.3: Common polygenic disorders
Section 2: Predicting clinical outcome from genomic information.
Workpackage 2.1: Developing quasi-infiinitesimal genome-wide predictors of disease predisposition, severity and treatment response Workpackage 2.2: Integrating personal genome information in clinical genetics Workpackage 2.3: Societal, legal and public policy issues
Section 3: Training and education in medical genomics
Workpackage 3.1: BeMGI graduate and advanced courses in medical genomics Workpackage 3.2: Informing the medical community about medical genomics Workpackage 3.3: Informing the general public about medical genomics
DELIVERABLES
Anticipated deliverables include:
1. High-profile collaborative publications reporting findings of the consortium with regards to genetic causes and pathogenesis of monogenic, oligogenic and polygenic diseases.
2. Genome-wide predictors of individual predisposition to common complex diseases, disease severity and treatment response.
3. Approaches for the diagnostic use of resequencing information in clinical genetic centres.
4. A sustainable Belgian program of graduate and advanced courses in medical genomics.
5. The concerted establishment of biobanks that will nourish future competitive research efforts in Belgium.
NETWORK
Belgian partners. BeMGI involves eight partners from six Belgian Universities (three Flemish-speaking, three French-speaking), all with internationally recognized expertise in the field of medical genomics. It includes five of the seven recognized academic clinical genetic centres in Belgium. It includes all members of the Belgian IBD consortium, a very successful partnership that has made internationally recognized contributions to the study of Inflammatory Bowel Disease.
International partners. BeMGI includes (i) Prof. GertJan van Ommen who is playing a leading role in the Netherlands Genomic Initiative that shares common objectives with BeMGI, and (ii) Prof. Peter Visscher, from the Queensland Institute in Medical Research and the University of Queensland Diamantina Institute, who is the world’s leading expert in quasi-infinitesimal modelling of complex diseases.
Interaction with other IUAP networks. The BeMGI IUAP will establish close ties and interactions with the BIOMAGNET bioinformatics IUAP.
