The micronutrient genomics project
The micronutrient genomics project is a community effort to build an integrated bioinformatics portal for the evaluation of the micronutrient and health relationship. For each micronutrient, a toolbox is constructed that accesses all relevant information on genetics and visualaizes transcriptome, proteome and metabolome changes in the relevant organs including plasma.
The project is based on volunteer contributions using wiki-based tools. For each micronutrient, a team is or will be created. Anyone (both individual researchers and research projects) is invited to contribute.
Introduction and rationale
The current practice of dietary advice acknowledges that the “one size fits all” concept fails but scientifically solid tools to differentiate are mostly absent. On top of this, micronutrients collaborate in their activities (e.g., maintaining overall homeostasis in metabolism, oxidative and inflammatory processes). Furthermore, It is now apparent that not only lower levels of intake are of individual concern, but also, for many essential nutrients, upper limits need to be established because of long term negative health effects (examples are antioxidant vitamins and death rate, folate and colon cancer recurrence).
With the advance of systems biology, the possibility to assess the activity on a single micronutrient in its complete biological context becomes feasible. Genetic variation is ever more taken into account in the assessment of sub-population vulnerability. Transcriptome studies are empoyed to unravell the mechanisms of action. Many researcher collect fragments of information (relavant SNPs, biological interactions, etc) which are not stored systematially and thus not optimally disseminated.
By creating an toolbox for all "omics" information and evaluation of micronutrient & health studies, we aim at facilitating a conceptual breakthrough in micronutrient research. This will depend not just on the inclusion of new technologies, but much more on allowing a really integrated and "systems" (multi-level and multi-function) view on all relevant processes.
The core of the project will focus on access to and visualisation of genetic, transcriptomic, proteomic and metabolomic aspects. A series of additional features (modeling, flux analysis, etc) are envisaged and can be added, depending on needs, vision and progress.
For each micronutrient, an expert group is established combining the various relevant areas (genetics, nutrition, biochemistry, and epidemiology). Each expert group will
i) collect all available knowledge,
ii) collaborate with the core bioinformatics team towards constructing the pathways and biological networks,
iii) produce a review according to a preset format that describes the initial state of the art on their micronutrient and genetics,
iv) provide continued updating and support, a.o. by updating each review every 5 years. For this purpose, the journal “Genes and Nutrition” has been adopted.
The activities will be coordinated by a team supported by the European Nutrigenomics Organization.The project is coordinated in a transparent manner, regular meetings are organized and dissemination is arranged through tools, website and dedicated publications.
Now that the human genome variation is being mapped, it is time to go back to genome-environment interaction, and relate genome variation to individual phenotypic responses. Diet is one of the most prominent modulators of genomic response, but in this area, the effect of genomic variation so far could hardly be quantified due to the complexity of the processes involved. Also, diet deals with health and the healthy phenotype is hard to quantify.
Our body needs a series of essential nutrients, i.e. vitamins, trace minerals and some specific fatty acids. For almost all of these, a complex mechanism of absorption, storage, metabolism and efficacy is known, with many genetic variations involved. On one hand of the spectrum, monogenic disorders like Wilsons diseaseare well known from clinical genetics. On the other extreme, genetic epidemiology struggles to quantify relative risks attributed to specific genetic variations (example MTHFR) in relation to possible vulnerable subpopulations (in this case pregnant women). In the meantime many micronutrients appear to be involved in a much broader range of biological activities than assumed until recently (examples are Zn, vitamin D).
Assuming that within a foreseeable future the information on the complete (relevant) genomic variation of an individual will become available, it is now time to construct a knowledge basis that will eventually allow for individual optimization of gene-micronutrient interaction and related dietary advice and clinical practice. For this reason, we have started the micronutrient genetics project.
Essentially, the micronutrient genetics project aims at identifying all relevant genetic variations related to the biological activity on a specific micronutrient. In doing so, we will organize this information in a biological perspective, i.e. pathway and biological network oriented visual browsers. Controversially, for many micronutrients the biological knowledge is still fragmented. Thus, a flexible and editable browser with both a wiki-editable and a permanent interface is implemented. The genetic variation on specific genes will be derived from the basic databases embedded in the human variome project. A bioinformatics team is established that will construct and maintain these web-based interfaces.
The use of transcriptomics analysis to investigate the mechanism of action of micronutrients is increasing (e.g. McArdle 2007, Gonzalez 2008, Elliott, 2008). To properly perform this research, pathways visualizing the transcriptome changes centered around specific micronutrients are needed both mostly unavailable. The construction and optimizing of these pathways and related biological networks is performed as part of this project.
Traditionally, plasma biomarkers are used to quantify micronutrient status. With the advent of metabolomics (the application of the measurement of the "complete" set of metabolites in an integrated evaluation of biological activity), a broader use of plasma biomarkers is proposed, linking status biomarkers to health quantification. this concept is further described by Van Ommen et al (2008). The micronutrient genomics project will construct a pathway-based biological network linking intracellular mechanisms related to micronutrient activity to plasma concentrations of all relevant metabolites, and (in a later stage) proteins. Examples for folate and selenium are available in the micronutrient portal of wikipathways.
A community effort
This effort calls for a concerted activity of many researchers. The conditions that allow this collaboration are:
i) this project does not aim to compete with the numerous research activities that currently are undertaken in the area of risk assessment, clinical genetics and nutritional epidemiology but rather will provide a firm basis for these to do a better job,
ii) the contributions will be rewarded by publications,
iii) only limited funding is needed once the basic structure has been agreed upon and the core bioinformatics is on track.
These issues are currently being dealt with by adopting two micronutrients (selenium, folate and beta carotene) as “proof of principle”. We expect to establish teams on all micronutrients later in 2008, and have reports on all micronutrients in 2009. Anyone interested in joining this initiative is invited to contact one of the authors. The micronutrient project is currently supported by 2 European consortia (Eurreca and NuGO), the NTCR division on personalized nutrition and medicine, Tufts University and the Human Variome Project.