Omics Innovations and Applications for Public Health Nutrition
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42 OMICS INNOVATIONS AND APPLICATIONS FOR PUBLIC HEALTH NUTRITION Omics Innovatons and Applicatons for Public Health Nutiton An integrated view Sun Eun Lee Introduction Center for Human Nutrition, Department of Let’s assume that you have been taken to a place you have nev- International Health, Johns Hopkins Bloomberg School er been before, and are not sure how you got there. The frst of Public Health, Baltimore, MD, USA thing you might do is look at a Google map, which may reveal several roads leading to the place, each with outlying inter- sections and roads fom other towns. Diferent overlays may reveal varying terrain, weather or road conditions throughout Key messages the region leading to your destination. Now, imagine a health problem afecting a population at your destination, and the > Omics technologies comprise sets of molecular mapping plexus of pathways (routes), biochemical networks (towns), tools that can help us understand and navigate to or fnction (trafc fow) and other infuential conditions (ter- from states of health, including nutriture. rain, road upkeep, weather, etc.) that may lead to the health problem, overlaid on the map. Omics technologies comprise > Single omics studies explore sets of genes, epigenetic sets of molecular mapping tools for each overlay that can marks, transcripts, proteins, or metabolites, as well as help us understand and navigate to or fom states of health, microbial communities, in an unbiased manner. including nutriture. This breakthrough approach has become possible due to advances in the development and application > Trans-omics studies ofer opportunities to connect, of high-throughput technologies, which allow us to analyze integrate, and map a group of molecules across multiple large-scale biological data to form new molecular maps to omics layers to identify pathways, interactions and health and disease. feedback loops that may more fully reveal the biology and, likely, suites of diagnostic markers, therapeutic targets “ Omics technologies can help and pathways to and from disease states. us understand and navigate to or > Omics approaches are transitioning from the theoretical fom states of health” level to the level of practical application to beneft vulnerable populations. Conventional hypothesis-driven studies typically focus on a > Human studies need to be greatly expanded few specifc molecules of interest based on prior knowledge: a in number and breadth and rigorously designed to nutritional defciency or excess may set into motion a genomic overcome methodological, analytical and biological aberration or epigenetic change that afects RNA expression, complexities in omics data. protein synthesis, metabolite production, or certain bacterial growth (Figure 1A). Single omics studies explore sets (individ- ual overlays) of genes, epigenetic marks, transcripts, proteins, or metabolites, or microbial communities, in an unbiased man- ner. They are data-driven and provide opportunities to discov- SIGHT AND LIFE | VOL. 31(2) | 2017 OMICS INNOVATIONS AND APPLICATIONS FOR PUBLIC HEALTH NUTRITION 43 figure 1: Simplifed fameworks in molecular nutrition studies Nutritional defciency or excess Genome Epigenome | Transcriptome Proteome State of health Metabolome Microbiome A B C Conventional disease Single (“planar”)-omics Trans-omics pathway search biomarker exploration pathways to health Each layer represents the genome, epigenome, transcriptome, proteome, metabolome, or microbiome, and circles or rounded rectangles indicate genes, epigenetic marks, transcripts, proteins, metabolites, or microorganisms, depending on the layer. Solid and dashed arrows represent associations within and across layers, respectively. Please note that the epigenome and transcriptome, which are separate omics-layers, are combined for the sake of simplicity. Modifed fgure fom Yugi et al.1 Reproduced with permission obtained fom the publisher. er unknown factors and biological networks at each molecular Genome level associated with a phenotype (Figure 1B). There has been a growing interest in understanding efects of A limited but increasing number of trans-omics studies genetic variation on child health, enabled by genotyping sin- ofer opportunities to connect, integrate and map a group of gle nucleotide polymorphisms that may predispose biological molecules across multiple omics layers to identif pathways, pathways to misfre. For example, a genome-wide association interactions and feedback loops that may more flly reveal the meta-analysis study reported that the secretor genotype of the biology and, likely, suites of diagnostic markers, therapeutic FUT2 gene, which encodes an enzyme for histo-blood group targets and pathways to and fom disease states (Figure 1C).1 antigen production (a host defense mechanism), portends a Omics technologies are now poised to fll gaps in biological higher risk of diarrheal disease in children.2 The fnding illus- knowledge and provide roadmaps to prevention strategies in trates the potential importance of genetic variants in the FUT2 public health nutrition. gene that may identif children susceptible to enteropathogen- In the “Frontiers in Nutrition” edition of Sight and Life ic organisms. (1/2015), the principles of each omics technology and emerging In contrast to inherited genetic predispositions, studies of opportunity were discussed. The aim of this article is to highlight DNA damage biomarkers have revealed genome integrity can some of the recent progress and innovations in omics, mainly be modifed by nutritional status and diet early in life. Micro- focusing on infant and child nutrition and health (Table 1). In nucleated cells, which indicate missing genetic information and addition, this review will project the translation of omics-based chromosomal damage, have been observed more fequently in discovery into potential public health applications, drawing on malnourished than well-nourished Egyptian children.3 Large plasma proteomics as an example. birth size has also been associated with increased cytogenetic 44 OMICS INNOVATIONS AND APPLICATIONS FOR PUBLIC HEALTH NUTRITION DNA damage biomarkers in the cord blood lymphocytes of oth- numerous immunologic responses and impaired mucosal repair. erwise well-nourished Australian infants.4 Telomere length attri- This study provides potential biomarker candidates of gut fnc- tion is considered a genomic marker of chromosomal instability tion and a noninvasive approach that can be used in the fture and fture disease risk. In Latino preschool children, exclusive to elucidate host-microbiota dynamics in the gastrointestinal breastfeeding and infant obesity were respectively negative- environment. ly and positively associated with telomere shortening.5 In the same study, soda consumption was associated with shortened Proteome telomere length. Thus, nutritional imbalance – leading to def- A plasma proteomics project using tandem mass spectrometry ciency or excess – may be deleterious to genome health early was initiated, motivated by the need for a strategy to assess in life. Among fture challenges are the need to establish causal multiple nutritional defciencies in populations on a single an- relationships between nutritional exposures and DNA damage, alytic platform.10 Assuming that nutrient metabolism is coordi- efcacies of dietary interventions to attenuate or reverse DNA nately associated with a network of measurable proteins, and damage, short- and long-term health efects of early-life genome that such proteins possess sufcient variability to predict nutri- damage, and wider use of genome health assays in nutritional ent status, plasma nutriproteomes have been reported to date epidemiology and population science. for vitamins A, D, E and K and selenium, comprising plasma transporters, immune and tissue repair proteins, and numerous “ Nutritional imbalance may metabolic homeostatic factors in a population of school-aged Nepalese children.11–15 be deleterious to genome health The utility of plasma proteomics has been frther extend- early in life” ed to quantif clusters of proteins associated with attained stature and arm muscle mass, but not fat mass, refecting a lean, generally undernourished phenotype.16 Proteins asso- Epigenome and Transcriptome ciated with child height have included insulin-like growth Gene expression is regulated by chemical modifcations of his- factor (IGF)-1 and its three binding proteins, likely refecting tones and DNA without changing the underlying DNA sequence. the major role of IGF regulation in linear growth. Nearly 100 Maternal nutritional or other exposures during embryo-fetal plasma proteins originating in the liver and peripheral tissues development can lead to epigenetic changes in fetal DNA that involved in host defense, nutrient metabolism, and tissue re- may infuence disease risk later in life. The hypothesis of diet- pair have been linked to α₁-acid glycoprotein, a generalized epigenome interaction was tested in a rural Gambian population, infammatory biomarker, revealing a dynamic and informa- examining seasonal variations in maternal levels of nutrients in- tive proteome of subclinical infammation.17 Six stable and volved in methyl-donor pathways. The study revealed that DNA constitutive protein biomarkers of infammation have been methylation of infants difered by season of conception at spe- associated with intelligence test scores measured a year af- cifc metastable epialleles, which refect systemic (tissue-wide) ter blood collection, possibly refecting both chronicity and epigenetic