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Editorial

Genomics and Human Health—An Assessment of the State of the Science

, Ph.D. & , Ph.D., DABT
Pages 49-50 | Published online: 09 Oct 2008

Genomics, in a broader sense, is a product of synthesis between biological sciences and information technology and it aims at mapping living organisms at the level of genes. The promise of genomics in developing cures for various diseases as well as facilitating the development of “personalized medicine” and “personalized nutrition” has captured the imagination of scientists and public alike. However, despite real technological progress and much journalistic hyperbole, completion of sequencing of the genomes of humans and other species has not yet radically changed the practice of medicine and nutrition. This is because translating basic research into product development is often not a linear process. Thus, the discovery and development of new products often lags behind the rapid advances in basic research. The disconnect between the hope of quick returns from the evolving science of genomics and the reality of the long-drawn path of finding “cures” may lead to under-appreciation of the progress and achievements of genomics.

The genomic revolution is expected to transform almost all branches of biology and medicine. It has already produced a paradigm-shift in basic research from the traditional hypothesis-driven research to information (data)-driven hypothesis formulation and research. It has been almost a decade since Affymetrix introduced its GeneChip® brand arrays. In these intervening years, scientists from academics, industries, and Government laboratories have been increasingly using microarrays to address a wide variety of scientific issues from basic research to pharmaceutical development as well as addressing food safety, and food defense.

In two special issues of this journal, the state of the science of genomics and its various applications has been discussed in eight articles written by experts who are among the front-line practitioners of genomics. The articles discuss the current application of genomics in various fields of science that have direct relevance to human health, such as, toxicology, drug development, safety assessment, food safety, and food defense.

Lord and colleagues have discussed the evolution of gene expression studies in drug safety assessment, emphasizing the utility and increasing use of toxicogenomics for various purposes, such as drug candidate selection, drug development decision making, and investigative studies aimed at risk assessment. The article by Tong and colleagues has addressed the utility as well as the challenges of developing reliable predictive molecular classifiers from inherently noisy and sometimes biased “omics” datasets through the use of decision forest (DF), a consensus modeling approach. Caba and Aubrecht have discussed the promise of adopting toxicogenomics in predicting genotoxic stress response and obtaining insights into the molecular mechanisms of genotoxicity. Being able to differentiate genotoxic from non-gentoxic mechanisms through the use of toxicogenomics will provide an important component of risk management strategies for compounds with isolated positive findings in mammalian chromosome damage assays. Orr has discussed the current state as well as the future of cross-species biomarker discovery and validation through the use of the “omics” technology and database development. Using data from rat and human tissues, identification of a previously known biomarker of fibrosis (APOA1) and a novel candidate biomarker of fibrosis, FETUB has been demonstrated. Huang and colleagues have discussed FDA's role and current efforts in integrating toxicogenomic data in drug safety assessment paradigm to further ensure the development of more effective, safer, and affordable medicines. This is still a forward-looking and evolving process in which some possible scenarios have been discussed where the toxicogenomic data could be successfully utilized in drug safety assessment. A discussion of the required as well as voluntary genomics data submission (VGDS) also illustrates the progress made in this area so far.

Burns-Naas and colleagues have discussed the utility of the “omics” technologies in immunopharmacology and immunotoxicology, emphasizing on the potential of these technologies to impact chemical hazard identification, risk characterization, and risk assessment as they relate to immunopharmacology and immunotoxicology. The authors have discussed how the “omics” technologies can not only advance our understanding about how chemicals cause toxicity to the immune system, but also help in our understanding of the molecular basis of immune-mediated disease (such as, allergy or autoimmunity) and diseases of the immune system (such as, HIV, cancer), as well as how the immune system may contribute to the development or resolution of infectious diseases and toxicities to non-immune organs. Mukherjee and colleagues have discussed two high throughput approaches, whole-genome genotyping, and whole-cell phenotyping, as useful tools to study microbial diversity. The DNA tiling array discussed in this article allows high-throughput sampling of genomes with single-nucleotide precision. The phenotypic microarray system is useful for differentiating microbial sub-species and might also be used to distinguish subtle differences among closely related isolates within a species grouping. This work emphasizes the utility of novel tools in identifying pathogenic microbes through characterization of strain/isolate-specific genotypic and phenotypic signatures. The knowledge gained from such studies can be successfully applied to food safety and food defense. Bagchi et al. have presented a case study in nutritional genomics. Using microarray, the effects of low-dose oral administration of calcium-potassium salt of (-)-hydroxycitric acid (HCA-SX) on the abdominal fat transcriptome was determined in rats. High-density microarray analysis of 9960 genes and ESTs present in the fat tissue identified changes in the expression profile of a small set of specific genes in response to dietary HCA-SX administration. The last article by Choudhuri is an elaborate epilogue of historical nature. It discusses some major landmarks in the history of DNA research, beginning from the identification of nuclein by Friedrich Miescher in 1869, all the way to the completion of the human genome sequencing.

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