Genomics and proteomics

By,
Amshumala S
1st year M.tech Bioinformatics
R.V.C.E
A seminar on
 Overview
 Important terms
 Basic understanding
 Hypotheses and goals
 Experimental approaches
 Examples
 Case study
 Future
 References
BASIC
CONCEPTS,
TECHNICAL
TERMS AND
TECHNOLOGY
INVOLVED
APPLICATION
OF
KNOWLEDGE
TO PREVENT
OR CURE
DISEASES
READ,
UNDERSTAND
AND INTERPRET
THE RESEARCH
POTENTIAL
TRANSFORMATION OF
NUTRITION AND DIETIC
PRACTICE AND ITS
IMPLICATIONS
CASE
STUDY CONCLUSION
OVERVIEW OF THE PRESENTATION
IMPORTANT TERMS :
 OMICS : Informally refers to the field of study esp. in biology.
 GENOMICS : The branch of molecular biology concerned with the structure, function,
evolution, and mapping of genomes.
 NUTRIGENOMICS : Application of high-throughput genomics tools in nutrition research.
Promotes an increased understanding of how nutrition influences metabolic pathways and how
this regulation is disturbed in the early phase of a diet-related disease and to what extent
individual genotypes contribute to such diseases.
 GENETICS : Study of genes, heredity, and genetic variation in living organisms.
 NUTRIGENETICS : Branch of nutritional genomics which aims to identify genetic
susceptibility to diseases and genetic variation in the effects of nutrient intake on the genome.
 EPIGENETICS : Processes that regulate how and when certain genes are turned on and off,
while epigenomics pertains to analysis of epigenetic changes in a cell or entire organism.
 SYSTEMS BIOLOGY : Computational and mathematical modeling of complex biological
systems.
EPIDEMIOLOGY : Study of the patterns, causes, and effects of health and disease conditions in
defined populations.
RDA : Recommended dietary allowance
NUTRIGENOMICS AND NUTRIGENETICS : BASIC UNDERSTANDING
Three central factors that justify nutrigenetics and nutrigenomics as an important science are :
There is great
diversity in the
inherited genome
between ethnic
groups and
individuals which
affects nutrient
bioavailability and
metabolism
People differ
greatly in their
food/nutrient
availability and
choices depending
on cultural,
economical,
geographical and
taste perception
differences
Malnutrition (deficiency
or excess) can affect
gene expression &
genome stability. May
cause mutations at the
gene or chromosomal
level causing abnormal
gene dosage and gene
expression leading to
adverse phenotypes
during the various life
stages.
The fundamental hypotheses underpinning the science of
nutrigenetics and nutrigenomics are the following:
1
• Nutrition exerts its impact on health outcomes by directly affecting expression of
genes in critical metabolic pathways and/or indirectly by affecting the incidence
of genetic mutation at the base sequence or chromosomal level which in turn
causes alterations in gene dosage and gene expression.
2
• The health effects of nutrients and nutriomes (nutrient combinations) depend on
inherited genetic variants that alter the uptake and metabolism of nutrients
and/or the molecular interaction of enzymes with their nutrient cofactor and
hence the activity of biochemical reactions
3
• Better health outcomes can be achieved if nutritional requirements are
customized for each individual taking into consideration both his/her inherited
and acquired genetic characteristics depending on life stage, dietary preferences
and health status.
Match the nutriome (i.e. nutrient intake combination)
with the current genome status (i.e. inherited and
acquired genome) so that genome maintenance, gene
expression, metabolism and cell function can occur
normally and in a homeostatically sustainable manner.
Provide better interpretation of data from
epidemiological and clinical intervention studies
regarding health impacts of dietary factors that may
help to revise recommendations for personalized
nutrition.
ULTIMATE GOALS
Nutrigenomics harnesses the following fields
to diagnose health status or disease
trajectory. They are :
• Genome stability
• Epigenome alterations
• micro RNA expression
• Protein expression
• Metabolomics etc
Experimental Approaches and Technologies Used in Studying Nutrigenetics and Nutrigenomics
 Genomics, transcriptomics, proteomics and metabolomics
enables better understanding of effects of bioactive compounds
on human health.
 Invitro, animal, clinical and epidemiologic studies are required
for knowing roles of specific nutrients and foods for optimal
human health.
 OMIC technologies are important along with data on
nutritional, lifestyle, clinical, physiological, demographic and
environmental factors.
 Interactions between the microbiome and host genome.
Eg.gut microflora and its interactions.
Systems biology along with bioinformatics tools are
required for acquisition, management, storage,
retrieval and analysis of such high-throughput
datasets.
 Diet-gene studies benefits individuals seeking
personalised dietary advice and helps improve public
health recommendations.
Metabolomics and proteomics are used to identify
biomarkers of exposure and to distinguish between
individuals with different dietary habits.
 Epidemiologic studies are of particular interest
because they examine the effects of a dietary
exposure and genetic variants in humans.
EXAMPLE ON HOW NUTRIGENOMICS CLARIFIES ROLE OF SPECIFIC DIETARY FACTORS
Caffeinated-coffee was found to increase the risk of a heart attack among individuals
who carry a version of a gene that makes them ‘slow’ caffeine metabolisers, but has no
effect among individuals who are ‘fast’ caffeine metabolisers.
Evidence derived from epidemiological studies has suggested that high fruit and
vegetable intake is associated with a reduced risk of a variety of cancers and
cardiovascular diseases.
However, a protective role has not been established conclusively in
clinical studies.
Variations in genes affecting phytochemical absorption, distribution, utilization,
biotransformation and excretion potentially influence nutrient exposure at the
tissue level
Same goes with……………………..
Nutrigenetics and Nutrigenomics in Optimizing Well-Being and Performance
General assumptions in nutritional research are based on :
What should also be taken into consideration are :
Nutritional experts are learning to analyse information on genes and genetic variants, diet,
lifestyle and environment, in order to develop nutritional strategies based on genetic makeup,
typically but not exclusively in the form of SNPs and lifestyle.
Coeliac disease is one example for which personalised nutrition is currently being used.
A disease in which the small intestine is hypersensitive to gluten, leading to difficulty
in digesting food.
It appears that several genetic changes are involved, the most consistent of which are
genetic variants in the HLA-DQ (DQ2 and/or DQ8) genes. Such changes are necessary
but not sufficient for the development of the disease. However, measurement of such
changes indicates a high level of risk with a high degree of probability.
The only sustainable treatment for coeliac disease is a strict, lifelong gluten-free diet
that avoids wheat, rye, barley and related products.
Obesity is one of the diseases with potential for improved prevention using nutrigenetics
Arkadianos et al. developed a personalised calorie-controlled diet, using
24 variants in 19 genes that were involved in metabolism to a weight reduction programme.
They compared weight loss and weight loss maintenance in 50 individuals who
received exercise and dietary advice tailored to their genotype to optimise nutrient intake
during weight loss and 43 control individuals who were given only generic diet and exercise
advice. They were able to show that the group receiving personalised dietary advice not only
performed better but also in weight loss retention over the following
year.
In general, surveys found that consumers primarily select food according
to convenience, appearance, price, taste and social engagement. Health still appears
to be relatively low on the average consumer’s list of priorities.
Nutrigenetics in Cardiovascular and Metabolic Disease Prevention and Control as
Illustrated in an Ethnically Diverse Developed Country – The Case of Singapore
Inter individual variability in
the response to a diet is
particularly evident.
•Genetic differences
• Cultural differences
Increase in life expectancy has given rise to an epidemiologic transition such that
mortality from infection and malnutrition has largely been replaced by chronic non
communicable diseases, such as cardiovascular disease and cancer.
Asian Indians > Malay > Chinese…………………. Cardio vascular disease
Elevated insulin resistance
Diabetes mellitus
Low HDL levels
Malays have high levels of hypertension
•Genetic variant at the FTO (fat mass- and obesity-associated gene), the rs9939609 SNP
• It is associated with increased risk of obesity and type 2 diabetes in multiple populations.
• The presence of the FTO variant may relate susceptibility to obesity in an environment where
food (particularly foods of high energy density) is readily available and low physical activity is
common, which is precisely the environment that most urban settings provide.
Follow up was conducted on children who were given unlimited supply of food.
• Further, they examined relationship between obesity and insulin resistance.
• It is evident that obesity does not fully explain the variation in insulin resistance in human
populations. Body mass index only explains a small proportion of the variance in insulin
resistance . The insulin resistance can occur in the absence of obesity, and that
despite the absence of obesity, it is still associated with an increased risk of cardiovascular
disease.
It seems reasonable to hypothesize that different
individuals can take different routes to obesity and
insulin resistance.
Application of ‘Omic’ Technologies in Nutritional Sciences to Understand
Mechanisms of Action of Dietary Factors and Metabolites
OMIC technologies provide the opportunity for global transcript and protein analyses, and
bioinformatics analysis can be used to identify novel gene, protein and nutrient interactions or
to uncover potentially novel mechanisms in disease progression.
Illustration : Gene and protein expression (i.e. transcriptomic and proteomic) studies in
colorectal cancer cell lines investigating the impact of butyrate, a metabolite generated in the
colon by bacterial fermentation of dietary fibre or resistant starch.
Dietary fibre, esp. digestion-resistant starch, promotes bowel health, and has potential
protection against the development of colorectal cancer.
Butyrate, one of the predominant short-chain fatty acids produced from the
fermentation of resistant starch by the gut bacteria, may be responsible for the physiological
effects of colorectal cancer.
In colorectal cancer cell lines, they have shown that butyrate treatment induces apoptosis
and inhibits proliferation after 48 h.
Proteomics and gene expression arrays were used to identify the mechanisms underlying
butyrate-induced apoptosis using HT29 cells as the model system.
Using proteomics (2D-DIGE and mass spectrometry), they detected 1,347 proteins, including
protein isoforms and modifications, and identified 139
proteins which are potentially involved in the apoptotic response to butyrate.
Butyrate also affected the following cellular functions :
•Remodeling of the actin cytoskeleton;
• increased expression of oncogenic proteins;
• enhanced cell stress response;
• negative regulation of protein biosynthesis;
• negative regulation of cell growth, and
• inhibition of the glycolytic pathway (Warburg effect).
According to parallel gene expression studies using Affymetrix array, It was found that 2550
genes were modulated by butyrate. (~10% of human gene).
These genes were found to be involved in DNA repair
and transcription, cell cycle progression, cell metabolism and signal transduction.
OMIC technologies along with bioinformatics and statistical tools gives a
deep understanding of the mechanisms by which nutrient exerts its
effects on the genome based on genetic background.
FUTURE OF NUTRIGENOMICS AND NUTRIGENETICS
Taking care of the enormous
public health implications
associated and to carry out
research extensively.
Scrutinizing the evidence- based
approach continuously.
Combining nutrigenetics-based
advice with ‘omic’ biomarkers
for validation of the personalized
recommendation given for
nutritional change and health
benefit within the individual
Educating the dieticians and
medical practitioners as well as
geneticists for aiding the optimal
use of nutrigenomics data and to
prevent abuse.
ASSOCIATED QUERIES
BIBLIOGRAPHY
1. Fenech M, El-Sohemy A, Cahill L, et al. Nutrigenetics and Nutrigenomics:
Viewpoints on the Current Status and Applications in Nutrition Research and
Practice. Journal of Nutrigenetics and Nutrigenomics. 2011;4(2):69-89.
doi:10.1159/000327772.
Genomics and proteomics
Genomics and proteomics
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Genomics and proteomics

  • 1. By, Amshumala S 1st year M.tech Bioinformatics R.V.C.E A seminar on
  • 2.  Overview  Important terms  Basic understanding  Hypotheses and goals  Experimental approaches  Examples  Case study  Future  References
  • 3. BASIC CONCEPTS, TECHNICAL TERMS AND TECHNOLOGY INVOLVED APPLICATION OF KNOWLEDGE TO PREVENT OR CURE DISEASES READ, UNDERSTAND AND INTERPRET THE RESEARCH POTENTIAL TRANSFORMATION OF NUTRITION AND DIETIC PRACTICE AND ITS IMPLICATIONS CASE STUDY CONCLUSION OVERVIEW OF THE PRESENTATION
  • 4. IMPORTANT TERMS :  OMICS : Informally refers to the field of study esp. in biology.  GENOMICS : The branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes.  NUTRIGENOMICS : Application of high-throughput genomics tools in nutrition research. Promotes an increased understanding of how nutrition influences metabolic pathways and how this regulation is disturbed in the early phase of a diet-related disease and to what extent individual genotypes contribute to such diseases.  GENETICS : Study of genes, heredity, and genetic variation in living organisms.  NUTRIGENETICS : Branch of nutritional genomics which aims to identify genetic susceptibility to diseases and genetic variation in the effects of nutrient intake on the genome.  EPIGENETICS : Processes that regulate how and when certain genes are turned on and off, while epigenomics pertains to analysis of epigenetic changes in a cell or entire organism.  SYSTEMS BIOLOGY : Computational and mathematical modeling of complex biological systems. EPIDEMIOLOGY : Study of the patterns, causes, and effects of health and disease conditions in defined populations. RDA : Recommended dietary allowance
  • 5. NUTRIGENOMICS AND NUTRIGENETICS : BASIC UNDERSTANDING Three central factors that justify nutrigenetics and nutrigenomics as an important science are : There is great diversity in the inherited genome between ethnic groups and individuals which affects nutrient bioavailability and metabolism People differ greatly in their food/nutrient availability and choices depending on cultural, economical, geographical and taste perception differences Malnutrition (deficiency or excess) can affect gene expression & genome stability. May cause mutations at the gene or chromosomal level causing abnormal gene dosage and gene expression leading to adverse phenotypes during the various life stages.
  • 6. The fundamental hypotheses underpinning the science of nutrigenetics and nutrigenomics are the following: 1 • Nutrition exerts its impact on health outcomes by directly affecting expression of genes in critical metabolic pathways and/or indirectly by affecting the incidence of genetic mutation at the base sequence or chromosomal level which in turn causes alterations in gene dosage and gene expression. 2 • The health effects of nutrients and nutriomes (nutrient combinations) depend on inherited genetic variants that alter the uptake and metabolism of nutrients and/or the molecular interaction of enzymes with their nutrient cofactor and hence the activity of biochemical reactions 3 • Better health outcomes can be achieved if nutritional requirements are customized for each individual taking into consideration both his/her inherited and acquired genetic characteristics depending on life stage, dietary preferences and health status.
  • 7. Match the nutriome (i.e. nutrient intake combination) with the current genome status (i.e. inherited and acquired genome) so that genome maintenance, gene expression, metabolism and cell function can occur normally and in a homeostatically sustainable manner. Provide better interpretation of data from epidemiological and clinical intervention studies regarding health impacts of dietary factors that may help to revise recommendations for personalized nutrition. ULTIMATE GOALS Nutrigenomics harnesses the following fields to diagnose health status or disease trajectory. They are : • Genome stability • Epigenome alterations • micro RNA expression • Protein expression • Metabolomics etc
  • 8. Experimental Approaches and Technologies Used in Studying Nutrigenetics and Nutrigenomics  Genomics, transcriptomics, proteomics and metabolomics enables better understanding of effects of bioactive compounds on human health.  Invitro, animal, clinical and epidemiologic studies are required for knowing roles of specific nutrients and foods for optimal human health.  OMIC technologies are important along with data on nutritional, lifestyle, clinical, physiological, demographic and environmental factors.  Interactions between the microbiome and host genome. Eg.gut microflora and its interactions.
  • 9. Systems biology along with bioinformatics tools are required for acquisition, management, storage, retrieval and analysis of such high-throughput datasets.  Diet-gene studies benefits individuals seeking personalised dietary advice and helps improve public health recommendations. Metabolomics and proteomics are used to identify biomarkers of exposure and to distinguish between individuals with different dietary habits.  Epidemiologic studies are of particular interest because they examine the effects of a dietary exposure and genetic variants in humans.
  • 10. EXAMPLE ON HOW NUTRIGENOMICS CLARIFIES ROLE OF SPECIFIC DIETARY FACTORS Caffeinated-coffee was found to increase the risk of a heart attack among individuals who carry a version of a gene that makes them ‘slow’ caffeine metabolisers, but has no effect among individuals who are ‘fast’ caffeine metabolisers.
  • 11. Evidence derived from epidemiological studies has suggested that high fruit and vegetable intake is associated with a reduced risk of a variety of cancers and cardiovascular diseases. However, a protective role has not been established conclusively in clinical studies. Variations in genes affecting phytochemical absorption, distribution, utilization, biotransformation and excretion potentially influence nutrient exposure at the tissue level
  • 13. Nutrigenetics and Nutrigenomics in Optimizing Well-Being and Performance General assumptions in nutritional research are based on : What should also be taken into consideration are : Nutritional experts are learning to analyse information on genes and genetic variants, diet, lifestyle and environment, in order to develop nutritional strategies based on genetic makeup, typically but not exclusively in the form of SNPs and lifestyle.
  • 14. Coeliac disease is one example for which personalised nutrition is currently being used. A disease in which the small intestine is hypersensitive to gluten, leading to difficulty in digesting food. It appears that several genetic changes are involved, the most consistent of which are genetic variants in the HLA-DQ (DQ2 and/or DQ8) genes. Such changes are necessary but not sufficient for the development of the disease. However, measurement of such changes indicates a high level of risk with a high degree of probability. The only sustainable treatment for coeliac disease is a strict, lifelong gluten-free diet that avoids wheat, rye, barley and related products.
  • 15. Obesity is one of the diseases with potential for improved prevention using nutrigenetics Arkadianos et al. developed a personalised calorie-controlled diet, using 24 variants in 19 genes that were involved in metabolism to a weight reduction programme. They compared weight loss and weight loss maintenance in 50 individuals who received exercise and dietary advice tailored to their genotype to optimise nutrient intake during weight loss and 43 control individuals who were given only generic diet and exercise advice. They were able to show that the group receiving personalised dietary advice not only performed better but also in weight loss retention over the following year. In general, surveys found that consumers primarily select food according to convenience, appearance, price, taste and social engagement. Health still appears to be relatively low on the average consumer’s list of priorities.
  • 16. Nutrigenetics in Cardiovascular and Metabolic Disease Prevention and Control as Illustrated in an Ethnically Diverse Developed Country – The Case of Singapore Inter individual variability in the response to a diet is particularly evident. •Genetic differences • Cultural differences Increase in life expectancy has given rise to an epidemiologic transition such that mortality from infection and malnutrition has largely been replaced by chronic non communicable diseases, such as cardiovascular disease and cancer. Asian Indians > Malay > Chinese…………………. Cardio vascular disease Elevated insulin resistance Diabetes mellitus Low HDL levels Malays have high levels of hypertension
  • 17. •Genetic variant at the FTO (fat mass- and obesity-associated gene), the rs9939609 SNP • It is associated with increased risk of obesity and type 2 diabetes in multiple populations. • The presence of the FTO variant may relate susceptibility to obesity in an environment where food (particularly foods of high energy density) is readily available and low physical activity is common, which is precisely the environment that most urban settings provide. Follow up was conducted on children who were given unlimited supply of food. • Further, they examined relationship between obesity and insulin resistance. • It is evident that obesity does not fully explain the variation in insulin resistance in human populations. Body mass index only explains a small proportion of the variance in insulin resistance . The insulin resistance can occur in the absence of obesity, and that despite the absence of obesity, it is still associated with an increased risk of cardiovascular disease. It seems reasonable to hypothesize that different individuals can take different routes to obesity and insulin resistance.
  • 18. Application of ‘Omic’ Technologies in Nutritional Sciences to Understand Mechanisms of Action of Dietary Factors and Metabolites OMIC technologies provide the opportunity for global transcript and protein analyses, and bioinformatics analysis can be used to identify novel gene, protein and nutrient interactions or to uncover potentially novel mechanisms in disease progression. Illustration : Gene and protein expression (i.e. transcriptomic and proteomic) studies in colorectal cancer cell lines investigating the impact of butyrate, a metabolite generated in the colon by bacterial fermentation of dietary fibre or resistant starch. Dietary fibre, esp. digestion-resistant starch, promotes bowel health, and has potential protection against the development of colorectal cancer. Butyrate, one of the predominant short-chain fatty acids produced from the fermentation of resistant starch by the gut bacteria, may be responsible for the physiological effects of colorectal cancer. In colorectal cancer cell lines, they have shown that butyrate treatment induces apoptosis and inhibits proliferation after 48 h.
  • 19. Proteomics and gene expression arrays were used to identify the mechanisms underlying butyrate-induced apoptosis using HT29 cells as the model system. Using proteomics (2D-DIGE and mass spectrometry), they detected 1,347 proteins, including protein isoforms and modifications, and identified 139 proteins which are potentially involved in the apoptotic response to butyrate. Butyrate also affected the following cellular functions : •Remodeling of the actin cytoskeleton; • increased expression of oncogenic proteins; • enhanced cell stress response; • negative regulation of protein biosynthesis; • negative regulation of cell growth, and • inhibition of the glycolytic pathway (Warburg effect). According to parallel gene expression studies using Affymetrix array, It was found that 2550 genes were modulated by butyrate. (~10% of human gene). These genes were found to be involved in DNA repair and transcription, cell cycle progression, cell metabolism and signal transduction. OMIC technologies along with bioinformatics and statistical tools gives a deep understanding of the mechanisms by which nutrient exerts its effects on the genome based on genetic background.
  • 20. FUTURE OF NUTRIGENOMICS AND NUTRIGENETICS Taking care of the enormous public health implications associated and to carry out research extensively. Scrutinizing the evidence- based approach continuously. Combining nutrigenetics-based advice with ‘omic’ biomarkers for validation of the personalized recommendation given for nutritional change and health benefit within the individual Educating the dieticians and medical practitioners as well as geneticists for aiding the optimal use of nutrigenomics data and to prevent abuse.
  • 22. BIBLIOGRAPHY 1. Fenech M, El-Sohemy A, Cahill L, et al. Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice. Journal of Nutrigenetics and Nutrigenomics. 2011;4(2):69-89. doi:10.1159/000327772.