Showing posts with label proteomics. Show all posts
Showing posts with label proteomics. Show all posts

Thursday, April 1, 2010

The World of Nutritional Omics

Proteomics and Metabolomics are still lagging behind Genomics, promising to catch up in 5 or 10 years.

Nutriproteomics and Nutrimetabolomics (aka Nutritional Proteomics and Nutritional Metabolomics) may be following the same trend. According to Medline these terms are temporarily forgotten and not yet ready for the prime time.

Nutrigenomics (Nutritional Genomics) is the discipline studying the effects of food on gene expression, thought to bring technologies on tailoring diets to genetic makeups. Many researchers believe that it will also lead to creating foods (so called 'functional foods') that will prevent an individual's genes from expressing disease.

The 2006 report by GeneWatch called nutrigenomics a spin-off from the Human Genome Project created to sell the idea of 'wellness', not for improving health. This report claims that 'Personalized nutrition' is a false solution to the problem of diet-related disease. Most genetic association studies later turn out to be wrong. Genes could contribute to a person's health risks, but the number of other different factors might be overwhelming. According to this report, future health is likely to be much harder to predict than the weather is and basing diets on misleading health predictions could do more harm than good.

With the exception of the major food intolerances (for example, to milk, peanuts, fava beans and alcohol) the body's ability to respond to different diets is complex and likely to be extremely hard to predict from a person's genetic make-up. Aurametrix agrees on this with GeneWatch, but why are the weathermen still employed?.. Aurametrix bases its predictions on the body response to food intake - not only the kind that can be measured by omics technologies, but is acknowledging the importance of genome, proteome and metabolome-based diagnostics.

Like blood pressure and cholesterol levels, but unlike genetic make-up, measurements of gene expression or a person's proteome and metabolome change with time. Researchers are busily tackling transcriptome responses to foods - Dutch ServiceXS, for example, uses microarrays designed by the European Nutrigenomics Organization (NuGo) and manufactured by Affymetrix to study nutrition and genomics.
Nutrition research, on the other hand, is mostly about the isolation and analysis of bioactive components (or nutraceuticals) in foods. At first, it was focused on low molecular weight compounds and single proteins. The rapid growth of molecular biology shifted the focus to DNA, but the great expectations of solving all health-related issues by cracking the genome remained unanswered.

Genes expression does depend on diets, but mRNAs need to be translated into proteins - their sole presence does not guarantee that proteins will be present and working. Genomics fan club defines nutrigenomics as inclusive of all omics disciplines - gene, protein and metabolic profiling, but these are disciplines of their own.
Nutriproteomics studies how diets change expression, modification, distribution and interactions of proteins in the human body. It identifies the protein targets of foods and allows to more accurately than genomics address individual differences in terms of response to diet and food preference. It also helps to assess quality and authenticity of food and is useful for food allergy prevention.
Nutriproteomics addresses not only the qualitative analysis of proteomics interesting to the nutrition scientist, but also protein structures and interactions with other molecules, proteomes specific to body fluids and their localization in tissues.

In our previous blogs, we talked about metabolomics, genomics and molecular dietetics. Nutrimetabolomics focuses on the metabolomic aspect of nutritional phenotype, exploring the human response to different nutritional situations. It is estimated that there are 6,500 individual metabolites produced in the human body. Subtle disruptions in metabolic processes are evident in easily accessed body fluids and vapors. Nutrimetabolomics is nothing short of biochemical oracle for nutrition promising to accelerate the discovery of new markers and diet-related pathways. Quantitative measures of small molecules or metabolites can tell about deficiencies of digestive enzymes, microbiome health, best nutrition methods to improve individual health. Individual metabolic phenotypes do exist and can be defined from multiple measurements after eliminating the daily "noise".

The “Nutritional Phenotype database” (dbNP) was proposed to integrate and interrogate genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition data, tailored to nutrition research and embedded in an environment of standard procedures and protocols, curated by the Nutrigenomics Organisation (NuGo). dbNP is extensively described in a publication in Genes & Nutrition 2010. It's based on micronutrient data sheets, comprehensive pathways (see examples for folate and selenium in the micronutrient portal ), ontologies and other knowledge engineering and analytic technologies.

Other Links
Aurametrix goal is to provide powerful solutions at your fingertips to help you manage your health. The company is initially focusing on relief for those suffering from digestive problems.
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Wednesday, November 4, 2009

Thoughts on the Future of Dx



Workflow, procedures and organization of diagnostic laboratories have changed little since the end of the 19th century. Technology improved quality and safety, lead to higher throughput and allowed private electronic access to patients' lab test results - at least partially, but other than that not much has changed.

The introduction of first generation transcriptome technologies in the mid 1990s (Schena et al., 1995; DeRisi et al., 1996) has led to a phenomenal ability to simultaneously measure thousands of genes, create molecular profiles of cancers, all other diseases and conditions.

Proteomics - coined a couple of years later (James, 1997) - was accepted as an even more promising technique for effective diagnostics of diseases. Figure on the left, however, demonstrates that it too faces many challenges from discovery of biomarkers to their verification and approval. After more than a decade (Oliver et al., 1998), metabolomics has been accepted as - at least - an equally promising technique, but it still lagging behin genomics and proteomics.

All these techniques will have significant impact on the business model of diagnostics. Multiplexing (measuring multiple biomarkers at once) is obviously much more cost-effective. Diagnostics industry is historically very resistant to disruptive technological change, but potential cost advantages should outweigh this, leading to novel business models in health management.

A change will also come from the growing near patient testing (NPT) sector. NPT is already finding a role in wellness monitoring. Existing self tests - such as cholesterol kits - may not be very accurate, but with the advent of inexpensive multiplexing assays this will be overcome. Even when blood testing is done by trained professionals in a lab, there can be significant variability in test results. Same applies to blood pressure measurements - you may need to do three measurements per day for five days in order to get a decent baseline. This only justifies the need to have inexpensive tests that can be done more often.

But lets go back to metabolomics and its potential to provide noninvasive inexpensive diagnostics. Are there any clinical trials attempting to translate it into clinical practice?
Here are our favorite ones:

CANCER
NCT00757952: Diagnosing ovarian cancer in exhaled breath. (Pine Street Foundation & University of Maine)
NCT00898209: Diagnosing Lung cancer in exhaled breath. (Vanderbilt-Ingram Cancer Center)
NCT00898209: Exhaled breath analyzed for lung cancer. (Vanderbilt-Ingram Cancer Center)
NCT00639067: Breath test for early detection of lung cancer (Menssana Research)
NCT00873366: Breath tests to access effectiveness of breast cancer treatment (Mayo Clinic and National Cancer Institute (NCI))

OTHER
NCT00330603: Metabolomic breath analysis to predict treatment for chronic cough (University of Virginia)
NCT00632307: Breath analysis to diagnose COPD; lung cancer; airway infection; interstitial lung disease, sleep apnea; pulmonary disorders with pleural infusions; sarcoidosis (Lung Clinic Hemer, Germany)
NCT00294489: Breath analysis to diagnose Hepatitis C (Hadassah Medical Organization, Jerusalem, Israel)


References
Schena M, Shalon D, Davis RW, Brown PO 1995 Quantitative monitoring of gene expression patterns with complementary DNA microarray. Science 270 : 467 –470[Abstract/Free Full Text]

DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA
1996 Use of a cDNA microarray to analyze gene expression patterns in human cancer. Nat Genet 14 : 457 –460[CrossRef][Medline]

James P 1997 Protein identification in the post-genome era: the rapid rise of proteomics.". Quarterly reviews of biophysics 30 (4): 279–331. doi:10.1017/S0033583597003399. PMID 9634650.

Oliver SG, Winson MK, Kell DB, Baganz F. 1998. Systematic functional analysis of the yeast genome. Trends in Biotechnology 16: 373-378.

Aurametrix is conducting research to develop next-generation diagnostics to help you evaluate your personal health risks and benefits. Better tools for a healthier world.
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