This action might not be possible to undo. Are you sure you want to continue?
Journal compilation © 2007 The International Association for the Study of Obesity? 20078••7781Review ArticleNutrigenomic approaches for obesity research R. M. Elliott & I. T. Johnson
Nutrigenomic approaches for obesity research
R. M. Elliott and I. T. Johnson
Institute of Food Research, Colney, Norwich, UK
Keywords: Genetics, genomics, nutrition, obesity.
Accepted 27 November 2006
Address for correspondence: Dr RM Elliott and Professor IT Johnson, Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, UK. E-mail: firstname.lastname@example.org; email@example.com
OnlineOpen: This article is available free online at www.blackwell-synergy.com
obesity reviews (2007) 8 (Suppl. 1), 77–81
At the individual level, weight gain is essentially the result of energy intake exceeding expenditure for signiﬁcant periods of time, but this obvious truth provides no insight into the strategies needed to deal with the ever-increasing problem of obesity in Western populations. It is equally obvious, however, that certain individuals are more prone to developing obesity than others. This phenomenon invites the nutrition research community to explore the physiological basis for such differences and ultimately to design more targeted and personalized approaches to the control of body weight (1). Novel research strategies are required to understand the molecular mechanisms controlling energy balance. In parallel with such studies, there is still much to be learned about the metabolic consequences that follow when an appropriate energy balance is not maintained, and how this relates to risks of diseases such as hypertension, heart disease, stroke, diabetes and certain cancers. The developing ﬁelds of nutrigenetics and nutrigenomics, with their accompanying battery of high-throughput technologies, provide an unprecedented opportunity to cope with the complexity of this condition and to develop the knowledge base required.
interactions). Although the term ‘nutrigenomics’, in its broadest sense, encompasses nutrigenetics, more commonly the main focus of nutrigenomics is considered to be on how diet regulates gene function (transcription and translation) and metabolism (i.e. diet → gene interactions) (2).
Nutrigenetics and obesity
Genetic differences play an important role in the development of obesity, although it is clear that these are by no means the only contributing factors. Environmental and social factors are also very important. The relative contributions of genetic and socioeconomic factors to the development of obesity, and the ways in which these interact in human societies, are largely unknown. The genetic code (DNA sequence) carried by any two unrelated people is approximately 99.9% identical. It is the variation in the sequence of the remaining 0.1% that determines the genetic component of inter-individual differences in disease risk, and presumably also their differing responses to the nutritional environment. Sites in the DNA where the sequences of individuals differ commonly (e.g. in at least 1% of the population) are called polymorphisms; the most common form being a single letter change in the code termed a ‘single nucleotide polymorphism’ (SNP). As each cell contains two copies of every gene (except those present on the sex chromosomes), one individual may carry various combinations of a polymorphism. The term ‘genotype’ refers to the combination of sequences in the two copies of a gene for a particular polymorphism.
Terminology: nutrigenetics and nutrigenomics
The term ‘nutrigenetics’ is generally used to refer to the impact of genetic variation on optimal dietary requirements for an individual (i.e. in the simplest terms: gene → diet
This paper was commissioned by the Foresight programme of the Ofﬁce of Science and Innovation, Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO; published with permission Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 77–81
M. Transcriptomics is performed using microarray technology.org/) (5). syndromes of obesity because of single-gene mutations have been described for at least 10 different genes. markers and chromosomal regions that have been associated or linked with human obesity. A set of such associated SNPs is termed a ‘haplotype’ and it turns out that most chromosome regions have only a few common haplotypes. some combinations of genotypes may interact to enhance or reduce risk to a greater extent than the sum of the effect of each genotype considered in isolation. However. More limited work has been performed with samples from human subjects. appears a truly daunting task. However. characterizing all the genes involved in obesity. obesity reviews 8 (Suppl. Appropriate study design and improved statistical approaches will be vital (8–10). and the fact that many more may yet be identiﬁed. bringing together the large and well-deﬁned cohorts of human subjects that have already been established. This potential is now starting to be realized. rather than inevitably leading to severe and intractable weight gain. For example.18). Their effects are more difﬁcult to detect reliably in a diverse population with varied lifestyles.edu/) (3). most notably appetite. proteomics and metabolomics) in nutrition has been reviewed extensively (12–16). and the avoidance of false positives. 1). So. such syndromes are extremely rare and therefore of limited relevance to the majority of obese individuals. Ultimately. Some regional differences in gene expression within different fat depots have been described and a number of studies have examined the effects of weight loss/caloric restriction on patterns of gene expression in adipose tissue from obese subjects (19). that inﬂuence the development of obesity. which enables the transcript levels for many tens of thousands of genes to be studied simultaneously. the history of genetic association studies addressing subtle and complex associations indicates that the reliable detection of true associations. while a chromosome region may contain many SNPs. it is possible that analysing only a few ‘tag’ SNPs can provide most of the information on the pattern of genetic variation in that region. To date. In spite of the rapid pace of technical developments. and more are added to this list with each update (http://obesitygene. some recent developments help to make this work more feasible. will continue to be a signiﬁcant challenge (6. Preliminary studies have also been performed on the patterns of gene expression in regions of the human brain that are known to show differential responses to nutritional stimuli in obese vs. published with permission Journal compilation © 2007 The International Association for the Study of Obesity. the effects of each polymorphism are more subtle. this type of work will require studies involving very large numbers of human subjects. and to their contributions to key processes. This scale currently still exceeds the capacity of the new platform technologies. Nutrigenomics and obesity The potential impact of functional genomic approaches (transcriptomics. particular combinations of genotypes may cancel each other out. There are currently more than 600 genes. interactions between genotypes for obesity-linked genes may be important. but SNPs that are located close together in the DNA sequence on the same chromosome tend to be inherited together. revealing characteristic and tissue-speciﬁc alterations in the expression of genes involved in adipogenesis. This technology is ideally suited to the study of the metabolic syndrome and the associated inﬂammatory signals that underlie many of the comorbidities linked to the obese state.78 Nutrigenomic approaches for obesity research R. Second. Microarrays have been used to deﬁne the changes in patterns of gene expression at the level of RNA in the adipose and other tissues of different strains of lean and obese mice. Johnson obesity reviews The most recent update of the human obesity gene map emphasizes just how complex the genetic component of obesity alone is. First. These types of studies provide a much broader perspective on the effects of obesity than was possible before the development of microarrays and a wealth of new information and research leads.7). These include the development of technologies capable of parallel genotyping analysis for hundreds of thousands of SNPs from a single small blood or tissue sample (4). with the publication of an increasing ﬂow of nutrigenomic studies each giving new mechanistic insights. Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO. a more comprehensive and focused programme will be required to obtain a robust overview for the changes in gene expression related to obesity and their biological signiﬁcance in relation to health.pbrc. lean individuals (20). Given the number of genes implicated so far. It is estimated that there are about 10 million SNPs in human populations. The effects of the common genetic polymorphisms associated with ‘sporadic’ obesity at the population level are much harder to study for two main reasons. inﬂammation and gluconeogenesis (17. generally modulating the risk of developing obesity by perhaps a few percent. However. 77–81 . T. There is therefore an obvious need to promote new international collaborations. These cases provide immensely valuable insights into the roles of these genes.hapmap. Alternatively. let alone examining their possible interactions. to achieve the study power necessary (11). Transcriptomics The transcriptome is the complete collection of RNA transcripts produced from the DNA in a genome. This paper was commissioned by the Foresight programme of the Ofﬁce of Science and Innovation. Deﬁning these haplotype blocks and the most reliable tag SNPs are the goals of the International HapMap Project (http://www. Elliott & I. Realizing these goals will help to bring the complexity of genetic studies down towards a level that may be manageable.
obesity reviews Nutrigenomic approaches for obesity research R. Reﬁnements to these data capture systems are likely to include appropriate data-quality metrics and specialty-speciﬁc metadata. Epigenetic marks have recently been shown to change in response to environmental factors over an individual’s lifetime (32). both as causes and possible consequences of obesity. These approaches have already been demonstrated to be sensitive enough to detect the often subtle effects of dietary modiﬁcation. http:// www. tic/classiﬁcation analyses. both between individuals with differing susceptibilities to chronic weight gain. etc. It is ideally suited. Before this concept can be developed further. The use of protein expression patterns as ‘biomarkers of vulnerability’ to obesity-related diseases such as colorectal cancer is one approach (22).). As the massive task of mapping the human epigenome progresses. and is the newest of the ‘omic’ technologies.g.nugo. the absence of the full range of identiﬁed metabolites limits the biological interpretation of the data. M. physical activity and gut microﬂora) has to be deﬁned. The next challenge is to develop tools to integrate the different types of data and start to realize the vision of nutritional systems biology. it has proven possible not only to obtain lists of gene products and metabolites that change in response under deﬁned conditions but also to gain insights into the overall biological processes involved. The challenges and potential of nutrigenomics and nutrigenetics The potential of nutrigenomic and nutrigenetic approaches is starting to be realized. A great deal of progress has already been made and. by applying new analytical tools to the data already generated. gender. Standardization of data capture for microarray studies has already been addressed (33) and equivalent procedures are in development for proteomic and metabolomic studies (34. an organ. Studies relating directly to the physiology and biochemistry of obesity have examined patterns of protein expression in adipocytes during differentiation (23. rather than drown in the ﬂood. For example. the inﬂuence of potential confounding factors (e.24). The mass spectrometry and nuclear magnetic resonance techniques that are used to analyse the composition of these ﬂuids are capable of very high sample throughput at comparatively low cost (after the initial set-up of the machinery). or in body ﬂuids. including all subsequent modiﬁcations that the proteins may undergo. Continuing development of improved statistical and bioinformatic tools means that the conclusions of the data analyses are becoming more robust and sensitive. and within individuals who are undergoing signiﬁcant changes in body weight and adiposity (28. Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO. This can be deﬁned as the study of heritable epigenetic signals. While these proﬁles may be used with multivariate statistical tools for diagnos- This paper was commissioned by the Foresight programme of the Ofﬁce of Science and Innovation. Not least among the many challenges are the needs for quality control. Johnson 79 Proteomics The proteome is the full complement of proteins produced from the transcriptome.org) is working to identify bottlenecks and emerging technical requirements and seeking solutions to them. The ‘omic’ tools produce vast quantities of data rapidly. age. To date. data capture and storage of nutrigenomic and nutrigenetic data. standardization. In addition to its use in the analysis of gene expression in tissues. Another emerging challenge that may well carry implications for the development of obesity research is that of ‘epigenomics’. the European Nutrigenomics Organization (NuGO. It is therefore possible to generate large datasets very fast. proteomics has been used less extensively in nutrigenomic studies than transcriptomics but it has just as much potential (21). If we are to make use of this information. encoded in patterns of DNA methylation and histone acetylation within the chromatin. There is also increasing interest in the use of metabolomic proﬁles as markers of dietary habits and as a descriptor of nutritional phenotype (30). 77–81 . it will become possible to explore the role of epigenetic effects. proteomics provides a possible route for the identiﬁcation and validation of new protein biomarkers that can be detected in plasma. T. The international HuPO Plasma Proteome Project is providing new resources (protein databases and optimized experimental standards) that will be essential for this kind of work (27).29). published with permission Journal compilation © 2007 The International Association for the Study of Obesity. New text-mining tools are starting to make it easier to interrogate the full body of scientiﬁc literature and thus to place new ﬁndings within the context of current scientiﬁc knowledge. both from a technical and scientiﬁc standpoint. the effects of a high-fat diet on protein expression in different target tissues in mice (25) and have compared skeletal muscle of lean and obese women (26). to the global analysis of metabolite patterns in body ﬂuids (plasma/serum/urine. that modulate the expression of genes (31). NuGO is working with international organiza- Metabolomics Metabolomics is the study of the sum total of endogenous and exogenous metabolites in a cell. Another challenge is that present metabolomic technologies generate metabolite proﬁles for which the majority of signals are not immediately identiﬁed. obesity reviews 8 (Suppl.35). it is essential that the data collected are of high quality and are captured in a manner that enables them to be stored and exchanged readily. In all these areas. and should lend themselves readily to the detection of metabolic differences. ethnicity. so even identical twins may ultimately develop differing susceptibilities to adverse environmental factors. Elliott & I. 1). which are comparatively easy to access in human volunteers.
Elliott R. Bouchard C. the identity of many genes in which polymorphisms can affect the propensity to develop obesity and related conditions such as diabetes and cardiovascular disease and. 8. Affolter M. beyond the ‘omic’ technologies. The human system is immensely complex and individual variation very diverse. German B. Lanchbury JS. genetic. 2. 63: 145–152. Collins FS. Allen L. Brookes AJ. The power of genome–wide association studies of complex disease genes: statistical limitations of indirect approaches using snp markers. Tokunaga K. Rodriguez RL. a detailed overview of the molecular mechanisms that control energy balance will be available. Barnes S. 437: 1299–1320. 9. Ebbesson SO. Ordovas JM. which may be subtle in the short term but profound over many years or a lifetime. Dawson K. New biomarkers of health. Koletzko B. Cooney CA. Kibbe WA. 58: 250–264. Junien C. Finally. Lauren DR.html). Fairweather-Tait S. Mathers J. Hoh J. Daniel H. Genet Med 2002. The different ‘omic’ and bioinformatic approaches to realize the vision of nutritional systems biology are in the process of integration. Schork NJ. High-throughput snp analysis for genetic association studies. Set association analysis of SNP case-control and microarray data. Felton J. Kaput J. and perhaps 25 years away. Brown KH. A longer time frame (up to 20 years) will see detailed analyses of the basis of individual variation in obese individuals. Zuberi A. Trends Genet 2001. Ames BN. J Biotechnol 2006. Fenech M. Korf BR. Argyropoulos G. Raymond F.80 Nutrigenomic approaches for obesity research R. 4: 45–61. Krempin DW. References 1. Chakravarti A. Coping with this may be difﬁcult. Elliott & I. obesity reviews 8 (Suppl. Sawyer SL. Krauss R. Jobs M. St Clair D. Hartman JL. both through contributions to the design of core modules and through the development of the nutrition-speciﬁc component. Fogg-Johnson N.org/Workgroups/ rsbi/rsbi. Conclusion Thus. Kanter M. Mayne M. 124: 758–787. nutrigenomic/nutrigenetic research in obesity has provided insights in three major areas. Hwang JK. to date. Gillies PJ. Jang Y. Kussmann M. van Ommen B. Joost H. 17: 407–413. 4. Donnelly P. Conﬂict of Interest Statement No conﬂict of interest was declared. Single nucleotide plymorphisms and the future of genetic epidemiology. Ordovas JM. Fredman D. Perusse L. Kornman K. J Comput Biol 2003. Brooks LD. 7. A comprehensive review of genetic association studies. T. Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO. Manica da Cruz IB. 10. The quest for cardiovascular health in the genomic era: nutrigenetics and plasma lipoproteins. Bartholomew A. 77–81 . Nature 2005. Clement K. published with permission Journal compilation © 2007 The International Association for the Study of Obesity. Ott J. as these could prevent such a full exploitation of the potential of nutrigenetics and nutrigenomics. First. epigenetic and dietary factors. http://www. Prince JA. OMICS-driven biomarker discovery in nutrition and health. The human obesity gene map: the 2004 update. In parallel with this. both in the propensity to develop obesity and the propensity to develop associated diseases. Corella D. J Hum Genet 2001. characteristic changes in patterns of gene expression in adipose and other tissues associated with obesity. 13: 381–490. A haplotype map of the human genome. Chadwick R. there is clearly an emerging need for the development of non-invasive techniques that will allow biological processes to be visualized in remote tissues in vivo. Castle D. and interaction between. Proc Nutr Soc 2004. Snyder EE. Cutting-edge work in this area at the moment involves further validation. Finley JW. Clin Genet 2000. 46: 478–482. Birk R. 5. Rankinen T. 1). Altshuler D. 11. However. and non-invasive techniques to facilitate future studies in humans are in development. and the more rigorous characterization of lean and obese phenotypes at the molecular level are being developed. Curr Opin Drug Discov Devel 2003. 6: 317–321. Malyj W. Marnellos G. is the creation of a comprehensive knowledge base to be used for the This paper was commissioned by the Foresight programme of the Ofﬁce of Science and Innovation. it is important to note what the main barriers are in this area of research. second. Chagnon YC.mged. Gibney MJ. Jais JP. optimization and standardization of the ‘omic’ technology platforms and how they are used for nutritional studies as well as the development of improved statistical and bioinformatic methods to enable the full biological meaning of the vast datasets produced to be extracted. In 5– 15 years. Byrne E. Leveille GA. Clarke S. development of targeted strategies to reduce obesity incidence and severity and the burden of chronic disease at the population level. these have provided indications as to the processes involved and their biological consequences. 3. Feuk L. Duster T. SNP association studies in alzheimer’s disease highlight problems for complex disease analysis. He L. Walts B. M. Gustafsson JA. a mechanistic deﬁnition of the metabolic consequences of failure to maintain appropriate energy balance and how this relates to the development of associated diseases is likely. Caetano R. van Bladeren P. Fallin D. Ho Lee J. Lohmueller K. Archer MC. as will designing and executing studies of sufﬁcient power to deﬁne the effects of. 10: 569–574. Lin SJ. Obes Res 2005. Ohashi J. Johnson obesity reviews tions from other specialties on the development of the Reporting Structure for Biological Investigations Tiered Checklist (RSBI-TC. Hirschhorn K. Daly MJ. What could the full exploitation of nutrigenomic/ nutrigenetic approaches provide during the next 25 years? In 5–10 years. Ferguson L. Gill-Garrison R. Emahazion T. Hirschhorn JN. These will be essential for future studies with human volunteers to conﬁrm that the dietary effects characterized in model systems also occur in target tissues in humans in the manner predicted. 6. Langin D. Weisnagel SJ. In turn. Bradford KJ.
Cancello R. Poulsen P. Leung KY. Nikolsky Y. Kramer K. Nadler ST. Proteome analysis of skeletal muscle from obese and morbidly obese women. Proteomics in nutrition and health. Carlsson E. 66: 6553–6562. Towne B. Reily MD. Simopoulos AP. Glenisson P. Milner JA. Paz MF. Johansson E. Summary recommendations for standardization and reporting of metabolic analyses. Sansone SA. Aebersold R. Yoo JS. Hathout Y. BMJ 2002. Thomas C. 54: 1283–1288. Holmes E. 29: 365–371. Schulze-Kremer S. Nutrigenomics: the impact of biomics technology on nutrition research. Zhao-Wilson X. Sarkans U. Cantor GH. Sherlock G. Kell DB. Robertson DG. Pelto GH. Stich V. Proc Natl Acad Sci USA 2005. The case for strategic international alliances to harness nutritional genomics for public and personal health. Pin C. Schuster G. Nutrigenomics: exploiting systems biology in the nutrition and health arena. Lehman-McKeeman L. Hancock WS. Gene expression proﬁles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility. Elliott R. Jonsson P. 28. Kapp EA. 35. Burrin DG. Brown AJ. Pisano M. Eng J. Zeisel SH. Transcriptomics applied to obesity and caloric restriction.) ingestion. Admon A. Ferre P. 19. Park T. Attie AD. and disseminating proteomics experimental data. Wu YZ. 22. Nutritional genomics. Omenn GS. published with permission Journal compilation © 2007 The International Association for the Study of Obesity. Milner JA. Nutrition 2004. Moritz RL. Geurts JM. Gaskell SJ. Warden C. Hylands PJ. Zvonic S. Converset V. Taylor R. Paton NW. Earll M. Hardy N. Cancer Res 2006. 4: 2270–2282. Proteomic analysis of primary cultures of human adipose-derived stem cells: modulation by adipogenesis. Urioste M. Simpson RJ. Yandell BS. Qiu J. Kim IF. Schaefer H. Polley AC. A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L. Pandey A. Ong TJ. Apweiler R. Hochstrasser DF. Davis A. Spellman P. obesity reviews 8 (Suppl. 16: 236– 244. Ansorge W. Ball CA. Deery MJ. 62: 492–503. Klein S. 5: 3226–3245. Elliott & I. 21. generating a core dataset of 3. 16: 166–177. Nadler ST. Kirby PD. Haab BB. Cigudosa JC. Sanchez-Aguilera A. 135: 1613–1616. Mohammed S. Morgan P. Mariman E. Riba-Garcia I. Cash P. Markowitz V. Sanchez JC. Lindberg J. 87: 117–123. Curr Opin Biotechnol 2002. Proteomic analysis reveals ﬁeldwide changes in protein expression in the morphologically normal mucosa of patients with colorectal neoplasia. Johnson 81 McNabb W. Verheij ER. Beer I. Stierum R. Permana PA. Hingamp P. Ward M. 27.obesity reviews Nutrigenomic approaches for obesity research R. Zeng R. Wu CY. Gimble JM. German JB.020 proteins and a publicly available database. Please pass the chips: genomic insights into obesity and diabetes. 14. Gravois A. Senn H. 15. 12. Visek WJ. 25. Poutanen K. Hittel DS. Sennitt MV. Beckwith-Hall BM. 4: 731–740. A systematic approach to modeling. 18. J Nutr 2001. Chan DW. Mathers JC. Meyer H. 8: 679– 696. Wiencke J. Ferguson LR. van Ommen B. Uauy R. Vaag A. Fraga MF. Evelo C. Stewart J. The nutritional phenotype in the age of metabolomics. Freake HC. 23. Speicher DW. Shelling AN. Walter N. Powell J. 131: 2078–2081. Spraul M. Zou F. Antti H. Nutrigenomics: integrating genomic approaches into nutrition research. J Nutr 2005. Muller M. Diabetes 2003. 21: 247–254. Nicholson JK. T. Walker J. Microarray gene expression proﬁling in obesity and insulin resistance. adipose tissues. Robben J. Rodriguez RL. Mol Cell Proteomics 2005. Krotzky A. Renes J. Rai AJ. Baunsgaard D. Oliver SG. Rabaglia ME. 29. van Ommen B. Plumb R. Plass C. 441: 143–145. Epigenetic differences arise during the lifetime of monozygotic twins. Tammen H. Tataranni PA. Nutritional genomics: the next frontier in the postgenomic era. Poitou C. and liver of C57BL/6 mice. Hoffman EP. Matese JC. Cell Mol Life Sci 2005. Bier DM. Schuppe-Koistinen I. Zhao X. Bege RD. J Nutr Biochem 2005. Nicholson JK. Lilley KS. Kussmann M. Amberg A. Parkinson H. Gaasterland T. Rasmussen KM. Johnson IT. Affolter M. Haselden JN. Qian X. 26. Bauman DE. Lindon JC. Selway L. Hanash SM. 324: 1438–1442. Nature 2006. Sampson J. Roberts M. Ropero S. Biochimie 2005. Smith A. States DJ. Holmes E. Wolff GL. Adkins J. Williams EA. Ling C. capturing. 10: 101–108. Daykin C. Mills SJ. Deutsch EW. Aebersold R. Br J Nutr 2005. Nat Biotechnol 2003. Protein proﬁling of 3T3-L1 adipocyte differentiation and (tumor necrosis factor alpha-mediated) starvation. 23: 833–838. 32. Aach J. 13. Bruce SJ. Muller M. Wasinger V. Vingron M. Winkler J. DeLany JP. Overview of the HUPO plasma proteome project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups. 102: 10604–10609. 1). Kochhar S. Viguerie N. 17. 16. Kilroy G. Garwood KL. Stoeckert C. Marquis GS. Del Parigi A. den Dunnen JT. Epigenetics: unﬁnished symphony. 53: 191–196. Solanky KS. Navarange M. Cassidy A. Stead DA. Andrews P. 30. Howard JA. Southon S. Ballestar E. 52: 688–700. Physiol Genomics 2004. Nicholson JK. van der Ouderaa F. Adamski M. Tang H. Yates JR 3rd. Ann Nutr Metab 2005. Zucker JD. Roepstorff P. Pensel N. Bingham S. 94: 623–632. Tsugita A. Ballestar ML. Vilo J. Nat Genet 2001. Comb Chem High Throughput Screen 2005. 13: 517–521. Benitez J. Schueler KL. Spector TD. Dunkley T. Perez-Jimenez F. Schmid GM. Reiners E. Stoehr JP. Corthesy-Theulaz I. Minimum information about a microarray experiment (MIAME): toward standards for microarray data. Clement K. 31. Wold S. Wu X. Causton HC. Blackwell TW. Ping P. Tai ES. Hubbard SJ. 20. Wang R. van der Ouderaa F. Lefevre M. Effect of high-fat diet on the expression of proteins in muscle. Proteomics 2004. Menon R. 33. M. Brazma A. Pearce JT. Paik YK. Houmard JA. Yin Z. Robinson A. Bradburn DM. Mol Diagn Ther 2006. Heine-Suner D. Esteller M. Craig A. Mulholland F. Pounds J. Noben JP. Stephan Z. Brass A. Byers H. Lan H. Nat Biotechnol 2005. Hermjakob H. Kaput J. Saris WH. 24. This paper was commissioned by the Foresight programme of the Ofﬁce of Science and Innovation. Trayhurn P. Diabetes 2005. Bouwman F. 20: 134–138. 77–81 . Weiss R. 34. Holmes E. Quackenbush J. J Agric Food Chem 2005. 49: 355–365. Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO. Wilson ID. Floyd ZE. BoixChornet M. Fay LB. Hefta SA. Setien F. Bailey NJ. Taylor CF. Holstege FC. Cawthorne MA. Keun HC. Attie AD. van Belzen N. Archakov A. Bioﬂuid 1H NMR-based metabonomic techniques in nutrition research – metabolic effects of dietary isoﬂavones in humans. Proteomics 2005. Eddes JS. Wang Y. Langin D.
This action might not be possible to undo. Are you sure you want to continue?