Prof. Wim Van Criekinge, profile picture
Uploaded byProf. Wim Van Criekinge
PPT, PDF1,267 views

2013 10 23_dna_for_dummies_v_presented

This document provides an overview of bioinformatics and computational genomics. It discusses key topics including DNA structure and function, genetic code, DNA replication, mutations, epigenetics, chromatin structure, histone modifications, DNA methylation, cancer stem cells, personalized medicine using biomarkers, and molecular profiling. The document contains diagrams explaining concepts like DNA packaging into chromatin, basic epigenetic mechanisms involving histone modifications and DNA methylation, and how epigenetic changes can alter chromatin structure and regulate gene expression.

Embed presentation

Downloaded 51 times
Wim Van Criekinge Antwerpen 24 oktober 2013
Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
biobix wvcrieki biobix.be bioinformatics.be 3
EUKARYOTES PROKARYOTES All organisms: 1 or more cells
Lab for Bioinformatics and computational genomics Cell Theory • All organisms are composed of one or more cells. • Cells are the smallest living units of all living organisms. • Cells arise only by division of a previously existing cell.
Each human cell contains 46 chromosomes (except sperm or egg cells)
Lab for Bioinformatics and computational genomics Genetic code DNA
Lab for Bioinformatics and computational genomics
Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body)
Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters
Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters That is the equivalent of nearly 70 trips from the earth to the sun and back.
Genetic information is stored in the DNA
DNA encodes proteins
“Genes” encode proteins
DNA replication
DNA synthesis and proofreading
Mutations: possible cause of diseases and disfunctionalities
Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
Microbes are all over us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Lab for Bioinformatics and computational genomics Defining Epigenetics Genome DNA • Reversible changes in gene expression/function • Without changes in DNA sequence Chromatin Epigenome Gene Expression Phenotype • Can be inherited from precursor cells • Epigenetic information is included in the epigenome • Allows to integrate intrinsic with environmental signals (including diet)
Lab for Bioinformatics and computational genomics Chromatin is a Key Component of Epigenetic Mechanisms
Lab for Bioinformatics and computational genomics Chromatin is a Key Component of Epigenetic Mechanisms Cellular DNA is packaged into a structure called chromatin The unit of chromatin is the nucleosome, a complex of a histone tetramer with approx. 125 bp of DNA wound around it nucleosome histone DNA chromatin • Chromatin organizes genes to be accessible for transcription, replication, and repair
Lab for Bioinformatics and computational genomics Basic Epigenetic Mechanisms: Post Translational Modifications to Histones and Base Changes in DNA • Epigenetic modifications of histones and DNA include: – Histone acetylation and methylation, and DNA methylation Histone Acetylation Ac Histone Methylation Me Me Me DNA Methylation
Lab for Bioinformatics and computational genomics Epigenetic Changes can Alter Chromatin Structure and Regulate Gene Expression TF TF Ac Ac Ac Ac Ac Ac Ac Ac Ac Gene expression • • Gene expression Gene expression (transcription) requires DNA to be physically accessible to transcription factors (TF) Epigenetic changes alter the structure of the chromatin, which determines whether DNA is accessible – Open chromatin allows gene expression – Closed chromatin prevents gene expression
Lab for Bioinformatics and computational genomics
Actionable Epigenome
Lab for Bioinformatics and computational genomics Epigenetics • Epigenetics is essentially the study of how our environment impacts traits acquired within our lifetimes, altering certain gene expressions which may then be passed on to future generations • That is, what we do to our own bodies may affect our children & grandchildren more than we thought. 30
Lab for Bioinformatics and computational genomics Epigenetic (meta)information = stem cells
Lab for Bioinformatics and computational genomics Translational Research towards Personalised Medicine • • DNA diagnostic tests can be used to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to: – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements
Lab for Bioinformatics and computational genomics Historically, Cancer Was Considered to be Driven Mostly by Genetic Changes GENETIC • • • • Example: Replication errors X X Mutations in p53 Activating mutations in RAS Mutations or amplifications of the HER-2 gene Chromosomal translocations in myeloid cells and the generation of the BCR-ABL fusion protein Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor
Lab for Bioinformatics and computational genomics Recent Evidence Shows that Epigenetic Changes are Also Important in Causing Cancer GENETIC EPIGENETIC Example: Chromatin modification errors Example: Replication errors X X Altered chromatin structure Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor Altered levels of mRNA/proteins
Lab for Bioinformatics and computational genomics Biology uses methylation extensively as a “regulatory checkpoint” in (cancer) development Schuebel et al 2007
Methylation of MGMT in GBM Kaplan-Meier Estimates of Overall Survival in GBM, According to MGMT Promoter Methylation Status Hegi et al. NEJM 2005, 352(10):997-1003 3
Lab for Bioinformatics and computational genomics Cancer Stem Cell Theory: the ‘Root’ of Cancer Growth Tumor Tumor Development and Growth Epigenetically altered, selfrenewing cancer stem cells
Lab for Bioinformatics and computational genomics Gene-specific Epigenetic reprogramming
Personalized Medicine • • • The use of diagnostic tests (aka biomarkers) to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements Potential uses of biomarkers – Risk assessment – Initial/early detection – Prognosis – Prediction/therapy selection – Response assessment – Monitoring for recurrence
Biomarker First used in 1971 … An objective and « predictive » measure … at the molecular level … of normal and pathogenic processes and responses to therapeutic interventions Characteristic that is objectively measured and evaluated as an indicator of normal biologic or pathogenic processes or pharmacologic response to a drug A biomarker is valid if: – It can be measured in a test system with well established performance characteristics – Evidence for its clinical significance has been established
Rationale 1: Why now ? Regulatory path becoming more clear There is more at stake than efficient drug development. FDA « critical path initiative » Pharmacogenomics guideline Biomarkers are the foundation of « evidence based medicine » - who should be treated, how and with what. Without Biomarkers advances in targeted therapy will be limited and treatment remain largely emperical. It is imperative that Biomarker development be accelarated along with therapeutics
Why now ? First and maturing second generation molecular profiling methodologies allow to stratify clinical trial participants to include those most likely to benefit from the drug candidate—and exclude those who likely will not—pharmacogenomicsbased Clinical trials should attain more specific results with smaller numbers of patients. Smaller numbers mean fewer costs (factor 2-10) An additional benefit for trial participants and internal review boards (IRBs) is that stratification, given the correct biomarker, may reduce or eliminate adverse events.
Molecular Profiling The study of specific patterns (fingerprints) of proteins, DNA, and/or mRNA and how these patterns correlate with an individual's physical characteristics or symptoms of disease.
Generic Health advice •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
Genetics Instrument and Assay providers G E N E T I C Whole-genome sequencing Enrichment seq (Exome) Enrichment Targeted Panels PCR bp Full genome 109 108 107 106 105 104 103 CLIA Lab service providers Confidential Information | ©2013 MDxHealth Inc. All rights reserved. 102 101 1
Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
Wobblebase Mission provide tools to both specialists (researchers, bioinformaticians, health care providers) and individual consumers that unlock the power of genomic data to the USER enable personalized genomics today by simplifying the way we organize, visualize and manage genomic data.
PGM: Personal Genomics Manifesto Everybody who wants to get his genome sequenced has the human right to do so. No third party can own your genetic data, your genetic data is exclusively yours. Nobody can be forced to get his genome analyzed or to reveal his genome to a third party. Your genome should allways be treated as confidential, private information. People should be advised not to share their identity AND their entire genome on a public forum. People should be advised to use secure technologies that allow to maximally protect phenotypic and/or genotype data. People should be able to actively explore, manage and get updated interpretation on their genomic data.
Wobblebase Mission • change the diagnostic/healthcare industry forever by setting a new standard and empowering the user
Choosing the Red Pill The Technical Feasibility Argument The Quality Argument The Price Argument The Logistics around the sample on howto manage the data Argument The Ethical debate The Privacy/Security concern
Notifications Updates are the single moste important feature of Wobblebase
#Rs1805007
Bioinformatics Analysis pipelines Social network twitter Wobblebase Updates Notifications eHealth (fixed vocabulary) Comparison
The Human Microbiome Christine Rodriguez, Ph.D. Harvard Outreach 2012 Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Microbes are all over us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
What is the Human Microbiome? Microbe: tiny living organism, such as bacterium, fungus, protozoan, or virus Microbiome: collectively all the microbes in the human body; a community of microbes Biofilm: a community of microbes that live together on a surface Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Microbes in the Human Microbiome include species from each major domain “Extremophile” Archaebacteria Bacteria Fungi http://en.wikipedia.org/wiki/File:Aspergillus_niger_01.jpg http://en.wikipedia.org/wiki/File:SalmonellaNIAID.jpg http://en.wikipedia.org/wiki/File:Grand_prismatic_spring.jpg http://commons.wikimedia.org/wiki/File:Tree_of_life.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
What features distinguish the microbial domains? Bacteria •Have no nucleus or membrane bound organelles •Often sphere (cocci) or rod (bacillus) shape, but others as well Generalized bacteria and archaebacteria cell Archeabacteria •Have no nucleus or membrane bound organelles •Can look similar to bacteria or drastically different shapes, such as flat and square •Have some metabolic similarities to eukaryotes Eukaryotes •Have a true nucleus and membrane bound organelles •Wide variety of shapes. For this presentation, we will focus on fungi •Fungi are unique since they have a cell wall and form spores during reproduction eneralized eukaryotic cell http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=CELL006B&File_type=GIF http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=BACT003B&File_type=GIF Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Microbes are normally found in and on the human body The following sites are “hotspots” for microbial life Some microbes are native, normally found in the body Let’s explore these five regions Some microbes are introduced, suddenly arriving at a new residence in the body http://nihroadmap.nih.gov/hmp/ Summer 2012 Workshop in Biology and Multimedia for High School Teachers
What’s Happening in the Nose? Cilia and mucous lining trap inhaled microbes The nose is a primary defender against inhaled pathogens Inflammation from viral infection and allergic reactions Inhaled medicines and oral antibiotics There is a delicate balance of microbes that are maintained to keep that environment healthy. Weakened immune systems can throw off that balance and allow the wrong microbes to grow out of control. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg
Nose The interior lining of the nose contains mucous secreting glands. A wide variety of microbes are normally found there. Here’s a few: • Staphylococcus epidermidis bacteria forms a biofilm that coats the mucosal lining • Staphylococcus aureus bacteria is fine when kept under control by a protease found in S. epidermidis, but if left to grow out of control, S. aureus can become pathogenic and cause infection Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:MRSA7820.jpg http://en.wikipedia.org/wiki/File:Staphylococcus_epidermidis_01.png
Nose • Aspergillus fungal spores are often inhaled through the nose. If the immune system fails to clear these, mold can grow in the lungs •Corneybacterium accolens bacteria is rarely a pathogen, but if it enters the bloodstream due to a torn blood vessel, it can cause serious infections Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:Corynebacterium_ulcerans_01.jpg http://en.wikipedia.org/wiki/File:Aspergillus.jpg http://en.wikipedia.org/wiki/File:Aspergillus_fumigatus_Invasive_Disease_Mechanism_Diagram.jpg
What’s Happening in the Oral Cavity? A wide variety of microbes regularly enter the oral cavity Brushing and flossing teeth clears some built up biofilm saliva, pH, temperature, immune system prevent many species from surviving Oral antibiotics inhibit growth Symbiosis of the oral microbes that are able to survive these conditions form an elaborate scaffold that lives on the tooth enamel and at the interface with the gums. It forms a barrier for incoming bacteria. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg
Oral Cavity The oral cavity has a wide variety of microbes normally found there. Here’s a few: Fusobacterium sp. bacteria is a larger bacteria that helps form a scaffold for many other bacteria in the oral biofilm http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Streptococcus mitis bacteria typically forms a biofilm on the hard enamel surfaces of the teeth. If gums get inflamed, it can enter the bloodstream and cause infection
Oral Cavity •Prevotella sp. bacteria have natural antibiotic resistance genes. They can attach to epithelial cells or other bacteria and cause larger infections in inflamed areas. • Candida albicans fungus can cause oral infection known as thrush http://microbewiki.kenyon.edu/index.php/File:P_ruminicola.jpg http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Thrush.JPG http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
What’s Happening on the Skin? There are several skin environments: oily, dry, moist. Some microbes prefer one over another. The skin has natural defenses including slightly acidic sweat and antimicrobial peptides. Microbes hide in crevices to recolonize skin after washing with soap Antibiotic washes and oral antibiotics disturb normal balance of microbes on the skin There is a normal balance of microbes on the skin that protect introduced microbes from harming us. Damaged skin gives opportunities for microbes to invade the bloodstream and cause serious illness. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg
Skin • Propionibacterium acnes bacteria colonizes healthy pores, but if pores become clogged, it grows out of control • Staphylococcus epidermidis bacteria normally colonizes on the skin. But when P. acnes clogs pores, S. epidermidis also grows out of control in the infected pores • Staphylococcus aureus bacteria can also infect clogged pores like Staph epidermidis. Even worse, many antibiotic resistant strains of Staph aureus make it difficult to treat the infection. http://microbewiki.kenyon.edu/index.php/File:Lesionsmicro.jpg http://microbewiki.kenyon.edu/index.php/File:Lesionsclosed.jpg http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Skin Trichophyton and Microsporum fungi feast on keratin in the skin and cause ringworm fungal infections http://en.wikipedia.org/wiki/File:Yeartinfection.JPG http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
What’s Happening in the Gut? Major barriers for microbes entering the gut: •low pH •Saliva and Bile •Immune system •Finding a place to attach to intestinal wall •Surviving a widely varied diet For those microbes that manage to colonize the gut: •gut flora perform regular tasks of digestion, vitamin production, many others • Gene transfer between the myriad of species in the gut can generate new combinations of drug resistant “superbugs” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Gut Bacteroides thetaiotaomicron bacteria ferments simple carbohydrates in the gut, releasing hydrogen and CO2. + carbohydrates CO2 and H2 Methanobrevibacter smithii archeabacteria consumes hydrogen gas from Bacteroides and produces methane, which is lost from gut as “gas” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers CH4 Methane Gas
Gut Ruminococcus sp. bacteria can be found in significantly high numbers in the gut flora. They break down cellulose in the gut, helping with digestion. Helicobacter pylori bacteria has a helical shape and colonizes the stomach and upper G.I. tract. It is known to be a major cause of stomach ulcers, although many with H. pylori do not get ulcers. http://microbewiki.kenyon.edu/index.php/File:G_reaction1.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Helicobacter_pylori_diagram.png
What’s Happening in the Urogenital Tract? Urinary system almost sterile due to urea and other chemicals Introducing a catheter into the urethra can introduce microbes directly into the bladder, where a biofilm can grow and cause bladder infection Urine often flushes out microbes that find their way in The vagina has a low pH due to Lactobacillus secreting lactic acid and hydrogen peroxide. Let’s explore the microbiome of this region further. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg
Urogenital Lactobacillus normally maintain low pH while other species are kept in small numbers in the vagina Candida albicans can take over and cause a yeast infection If Lactobacillus decreases from antibiotics… Lactobacillus and vaginal epithelial cell G. vaginalis and vaginal epithelial cell Gardnerella vaginalis can grow too much and cause bacterial vaginosis. http://commons.wikimedia.org/wiki/File:Lactobacillus_sp_01.png http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
Urogenital The urinary tract is normally sterile due to urine flushing out the tract. Urine sample infected with E. coli Urine sample infected with E. coli But, Escherichia coli from GI tract can infect urinary tract due to poor hygiene and contamination from nearby GI tract opening. http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:E_choli_Gram.JPG http://commons.wikimedia.org/wiki/File:Pyuria2011.JPG
Interplay Between Medicine and Microbes Antibiotics Chemotherapy drugs Kills infectious bacteria but also disrupts natural flora. Can result in yeast infections, digestive problems, etc. http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:NOVAMOXIN_antibiotic.jpg Gut flora has been shown to modify some drugs during metabolism. This causes many side effects, including upset stomach. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Use of Antimicrobial Products How many do we really need? But do we need some natural exposure to germs to keep our normal flora around? Products kill germs to reduce infection http://commons.wikimedia.org/wiki/File:Afwasmiddel.jpg http://commons.wikimedia.org/wiki/File:Tissue.jpg http://commons.wikimedia.org/wiki/File:Refill_soap.jpg http://commons.wikimedia.org/wiki/File:Toothpaste.jpg http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Will this allow “superbugs” that can barely survive these treatments to grow and become more prevalent…causing problems for the future?
Is My Gut Microbiome the Same as Yours? The number and amount of the many different microbes can vary greatly from person to person. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Relative amounts of species Research in the Human Microbiome Project is starting to identify the relative amount of each microbe present at different locations in the body. The Microbiome of one person can be different than others in species and relative amounts Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Skin_Microbiome20169-300.jpg
So many new questions to answer about the Human Microbiome… How does the gut flora modify drugs, and how can we minimize side effects? Are we making germs more resistant to anitmicrobials? What happens when the germs are resistant to all of the drugs in our arsenal? Why does my gut flora look different than yours? How does that affect obesity, food allergies, and ability to fight disease? What do you want to know? http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
Lab for Bioinformatics and computational genomics …$

More Related Content

PPTX
Personalized Medicine and the Omics Revolution by Professor Mike Snyder
byThe Hive
 
PPT
Brian_Strahl 2013_class_on_genomics_and_proteomics
byUniversity of North Carolina Chapel Hill (UNC)
 
PPTX
Genome sequencing and undiagnosed disease
byStephen Guthery, MD
 
PPTX
Applications of genomics and proteomics ppt
byIbad khan
 
PPTX
Genes, Genomics and Proteomics
byGarry D. Lasaga
 
PPT
Building a Program in Personalized Medicine
byDana-Farber Cancer Institute
 
PDF
Genomics and proteomics (Bioinformatics)
bySchool of Biosciences, MACFAST College, Tiruvalla, Kerala, India
 
PDF
The 'omics' revolution: How will it improve our understanding of infections a...
byWAidid
 
Personalized Medicine and the Omics Revolution by Professor Mike Snyder
byThe Hive
 
Brian_Strahl 2013_class_on_genomics_and_proteomics
byUniversity of North Carolina Chapel Hill (UNC)
 
Genome sequencing and undiagnosed disease
byStephen Guthery, MD
 
Applications of genomics and proteomics ppt
byIbad khan
 
Genes, Genomics and Proteomics
byGarry D. Lasaga
 
Building a Program in Personalized Medicine
byDana-Farber Cancer Institute
 
Genomics and proteomics (Bioinformatics)
bySchool of Biosciences, MACFAST College, Tiruvalla, Kerala, India
 
The 'omics' revolution: How will it improve our understanding of infections a...
byWAidid
 

What's hot

PPTX
Genomics experimental-methods
byProf. Wim Van Criekinge
 
PDF
Transcriptomics and metabolomics
bySukhjinder Singh
 
PPTX
Genetic polymorphism
byDandu Prasad Reddy
 
PPTX
Genomics, Transcriptomics, Proteomics, Metabolomics - Basic concepts for clin...
byPrasenjit Mitra
 
PPTX
Genome sequencing in vegetable crops
byBommesh
 
PDF
Exome sequence analysis
byPubudu Samarakoon
 
PPTX
Plant system biology
bySubaParanie
 
PPT
Genome sequencing
byanita devi
 
PPTX
Bioinformatics final
byRainu Rajeev
 
PPTX
Whole genome sequencing of arabidopsis thaliana
byBhavya Sree
 
PPTX
Genetic toxicology
byinam arif
 
PPT
Vijay protiomics current
byRohit Bisht
 
PPTX
Applications of Genomic and Proteomic Tools
byRaju Paudel
 
PPTX
Ashwini presentation
byAshwani Patil
 
PPT
Genomics seminar copy
bymanjunatha s s
 
PDF
Genomics and proteomics I
byNikolay Vyahhi
 
PPTX
Yeast Genome
byISF COLLEGE OF PHARMACY MOGA
 
PPT
Genomics and Plant Genomics
byHarshvardhan Gaikwad
 
PPTX
Genomics
byKomal Rajgire
 
PPTX
Comparative genomics
byhemantbreeder
 
Genomics experimental-methods
byProf. Wim Van Criekinge
 
Transcriptomics and metabolomics
bySukhjinder Singh
 
Genetic polymorphism
byDandu Prasad Reddy
 
Genomics, Transcriptomics, Proteomics, Metabolomics - Basic concepts for clin...
byPrasenjit Mitra
 
Genome sequencing in vegetable crops
byBommesh
 
Exome sequence analysis
byPubudu Samarakoon
 
Plant system biology
bySubaParanie
 
Genome sequencing
byanita devi
 
Bioinformatics final
byRainu Rajeev
 
Whole genome sequencing of arabidopsis thaliana
byBhavya Sree
 
Genetic toxicology
byinam arif
 
Vijay protiomics current
byRohit Bisht
 
Applications of Genomic and Proteomic Tools
byRaju Paudel
 
Ashwini presentation
byAshwani Patil
 
Genomics seminar copy
bymanjunatha s s
 
Genomics and proteomics I
byNikolay Vyahhi
 
Yeast Genome
byISF COLLEGE OF PHARMACY MOGA
 
Genomics and Plant Genomics
byHarshvardhan Gaikwad
 
Genomics
byKomal Rajgire
 
Comparative genomics
byhemantbreeder
 

Similar to 2013 10 23_dna_for_dummies_v_presented

PPT
2015 03 13_puurs_v_public
byProf. Wim Van Criekinge
 
PPTX
2014 11 03_bioinformatics_case_studies
byProf. Wim Van Criekinge
 
PPTX
PadminiNarayanan-Intro-2018.pptx
byDESMONDEZIEKE1
 
PPT
2015 04 22_time_labs_shared
byProf. Wim Van Criekinge
 
PDF
Bioengineering Information for Genomic Medicine
byNECST Lab @ Politecnico di Milano
 
PPTX
2015 bioinformatics personal_genomics_wim_vancriekinge
byProf. Wim Van Criekinge
 
PPTX
Epigenesis.pptx
byHiwaAhmed6
 
PPT
Beckman coulter basics of genomics
byBeckmanCoulter
 
PDF
j_pierce_introduction_to_omics_092220-opt.pdf
byMHS72
 
PPTX
2015 09 imec_wim_vancriekinge_v42_to_present
byProf. Wim Van Criekinge
 
PPTX
Epigenetics
byPaul Magbanua
 
PPTX
Van criekinge next_generation_epigenetic_profling_vuppsala
byProf. Wim Van Criekinge
 
PPT
Genomics
byPubudu Gokarella
 
PPTX
Exploring your personal genome with free, online bioinformatics tools
by01archivist
 
DOC
Epigeneticsand methylation
byShubhda Roy
 
PPTX
presentation on epigenomics , and technologies in epigenomics
byyanshikasain13
 
PPTX
HGP, the human genome project
byBahauddin Zakariya University lahore
 
PDF
Bioinformatics-definitionScope.pdf
byMuhammadHammad144434
 
PPT
2014 05 21_personal_genomics_v_n2n_vfinal
byProf. Wim Van Criekinge
 
PPTX
EPIGENETIC ,DNA ,RNA Description and explaination
byCarolin Wijaya
 
2015 03 13_puurs_v_public
byProf. Wim Van Criekinge
 
2014 11 03_bioinformatics_case_studies
byProf. Wim Van Criekinge
 
PadminiNarayanan-Intro-2018.pptx
byDESMONDEZIEKE1
 
2015 04 22_time_labs_shared
byProf. Wim Van Criekinge
 
Bioengineering Information for Genomic Medicine
byNECST Lab @ Politecnico di Milano
 
2015 bioinformatics personal_genomics_wim_vancriekinge
byProf. Wim Van Criekinge
 
Epigenesis.pptx
byHiwaAhmed6
 
Beckman coulter basics of genomics
byBeckmanCoulter
 
j_pierce_introduction_to_omics_092220-opt.pdf
byMHS72
 
2015 09 imec_wim_vancriekinge_v42_to_present
byProf. Wim Van Criekinge
 
Epigenetics
byPaul Magbanua
 
Van criekinge next_generation_epigenetic_profling_vuppsala
byProf. Wim Van Criekinge
 
Genomics
byPubudu Gokarella
 
Exploring your personal genome with free, online bioinformatics tools
by01archivist
 
Epigeneticsand methylation
byShubhda Roy
 
presentation on epigenomics , and technologies in epigenomics
byyanshikasain13
 
HGP, the human genome project
byBahauddin Zakariya University lahore
 
Bioinformatics-definitionScope.pdf
byMuhammadHammad144434
 
2014 05 21_personal_genomics_v_n2n_vfinal
byProf. Wim Van Criekinge
 
EPIGENETIC ,DNA ,RNA Description and explaination
byCarolin Wijaya
 

More from Prof. Wim Van Criekinge

PPTX
2020 02 11_biological_databases_part1
byProf. Wim Van Criekinge
 
PPTX
2019 03 05_biological_databases_part5_v_upload
byProf. Wim Van Criekinge
 
PPTX
2019 03 05_biological_databases_part4_v_upload
byProf. Wim Van Criekinge
 
PPTX
2019 03 05_biological_databases_part3_v_upload
byProf. Wim Van Criekinge
 
PPTX
2019 02 21_biological_databases_part2_v_upload
byProf. Wim Van Criekinge
 
PPTX
2019 02 12_biological_databases_part1_v_upload
byProf. Wim Van Criekinge
 
PPTX
P7 2018 biopython3
byProf. Wim Van Criekinge
 
PPTX
P6 2018 biopython2b
byProf. Wim Van Criekinge
 
PPTX
P4 2018 io_functions
byProf. Wim Van Criekinge
 
PPTX
P3 2018 python_regexes
byProf. Wim Van Criekinge
 
PPTX
T1 2018 bioinformatics
byProf. Wim Van Criekinge
 
PPTX
P1 2018 python
byProf. Wim Van Criekinge
 
PDF
Bio ontologies and semantic technologies[2]
byProf. Wim Van Criekinge
 
PPTX
2018 05 08_biological_databases_no_sql
byProf. Wim Van Criekinge
 
PPTX
2018 03 27_biological_databases_part4_v_upload
byProf. Wim Van Criekinge
 
PPTX
2018 03 20_biological_databases_part3
byProf. Wim Van Criekinge
 
PPTX
2018 02 20_biological_databases_part2_v_upload
byProf. Wim Van Criekinge
 
PPTX
2018 02 20_biological_databases_part1_v_upload
byProf. Wim Van Criekinge
 
PPTX
P7 2017 biopython3
byProf. Wim Van Criekinge
 
PPTX
P6 2017 biopython2
byProf. Wim Van Criekinge
 
2020 02 11_biological_databases_part1
byProf. Wim Van Criekinge
 
2019 03 05_biological_databases_part5_v_upload
byProf. Wim Van Criekinge
 
2019 03 05_biological_databases_part4_v_upload
byProf. Wim Van Criekinge
 
2019 03 05_biological_databases_part3_v_upload
byProf. Wim Van Criekinge
 
2019 02 21_biological_databases_part2_v_upload
byProf. Wim Van Criekinge
 
2019 02 12_biological_databases_part1_v_upload
byProf. Wim Van Criekinge
 
P7 2018 biopython3
byProf. Wim Van Criekinge
 
P6 2018 biopython2b
byProf. Wim Van Criekinge
 
P4 2018 io_functions
byProf. Wim Van Criekinge
 
P3 2018 python_regexes
byProf. Wim Van Criekinge
 
T1 2018 bioinformatics
byProf. Wim Van Criekinge
 
P1 2018 python
byProf. Wim Van Criekinge
 
Bio ontologies and semantic technologies[2]
byProf. Wim Van Criekinge
 
2018 05 08_biological_databases_no_sql
byProf. Wim Van Criekinge
 
2018 03 27_biological_databases_part4_v_upload
byProf. Wim Van Criekinge
 
2018 03 20_biological_databases_part3
byProf. Wim Van Criekinge
 
2018 02 20_biological_databases_part2_v_upload
byProf. Wim Van Criekinge
 
2018 02 20_biological_databases_part1_v_upload
byProf. Wim Van Criekinge
 
P7 2017 biopython3
byProf. Wim Van Criekinge
 
P6 2017 biopython2
byProf. Wim Van Criekinge
 

Recently uploaded

PPTX
Complete and Detailed Overview of Odoo 18 Contact
byCeline George
 
PDF
Experiment No. 2 To synthesis and submit chlorobutanol.
byPradeep Swarnkar
 
PPTX
STERILITY INDICATOR Pharmaceutical microbiology
byChetana Wagh
 
PPTX
Insertion of Suppositories..........pptx
byAneetaSharma15
 
PPTX
Complete Overview of Shopfloor in Odoo 18
byCeline George
 
PPTX
When UDL is no longer enough: Examining post-UDL reflections on inclusive des...
byFrederic Fovet
 
PDF
Fanatics of LDM a Time Capsule By LDMMIA
by©LDMMIA, ©Reiki Yoga
 
PDF
19 January 2026 Andreas Schleicher Digital Education Outlook 2026.pdf
byEduSkills OECD
 
PPTX
Redox Titration - Oxidation and Reduction
byKhushbu Shah
 
PPTX
Blood, Blood Composition, Blood Groups, Disorders of Blood.pptx
byAshish Umale
 
PPTX
Sci8-Q3-W29-Tides_Science 8 Matatag.pptx
byOliverVillanueva13
 
PDF
Overview of Ethiopian Agriculture: Systems and Economic Impact.pdf
byinebaseifu
 
PDF
To synthesis and submit Benzamide synthesis.pdf
byPradeep Swarnkar
 
PPTX
Electric Charges and Fields 25.pptx notes of lecture 25 by lakshay neet 2026 2.0
byhh3360156
 
PPTX
ANTISEPTICS AND DISINFECTANTS CHAPTER NO.05.pptx
byGanu Gavade
 
PPTX
ANTI-TUSSIVE CHAPTER NO.05 PHARMACOGNOSY
byGanu Gavade
 
PPTX
Report for Prepare Time Management in Odoo 19 POS
byCeline George
 
PDF
Fidelity to Energy: A Critical Analysis of Baz Luhrmann’s Intersemiotic Trans...
byKruti Vyas
 
PPTX
Introduction Pharmacotherapeutics _ PT1 2026.pptx
byRavinandan A P
 
PPTX
Complete Overview of Roles in Odoo 18 Planning
byCeline George
 
Complete and Detailed Overview of Odoo 18 Contact
byCeline George
 
Experiment No. 2 To synthesis and submit chlorobutanol.
byPradeep Swarnkar
 
STERILITY INDICATOR Pharmaceutical microbiology
byChetana Wagh
 
Insertion of Suppositories..........pptx
byAneetaSharma15
 
Complete Overview of Shopfloor in Odoo 18
byCeline George
 
When UDL is no longer enough: Examining post-UDL reflections on inclusive des...
byFrederic Fovet
 
Fanatics of LDM a Time Capsule By LDMMIA
by©LDMMIA, ©Reiki Yoga
 
19 January 2026 Andreas Schleicher Digital Education Outlook 2026.pdf
byEduSkills OECD
 
Redox Titration - Oxidation and Reduction
byKhushbu Shah
 
Blood, Blood Composition, Blood Groups, Disorders of Blood.pptx
byAshish Umale
 
Sci8-Q3-W29-Tides_Science 8 Matatag.pptx
byOliverVillanueva13
 
Overview of Ethiopian Agriculture: Systems and Economic Impact.pdf
byinebaseifu
 
To synthesis and submit Benzamide synthesis.pdf
byPradeep Swarnkar
 
Electric Charges and Fields 25.pptx notes of lecture 25 by lakshay neet 2026 2.0
byhh3360156
 
ANTISEPTICS AND DISINFECTANTS CHAPTER NO.05.pptx
byGanu Gavade
 
ANTI-TUSSIVE CHAPTER NO.05 PHARMACOGNOSY
byGanu Gavade
 
Report for Prepare Time Management in Odoo 19 POS
byCeline George
 
Fidelity to Energy: A Critical Analysis of Baz Luhrmann’s Intersemiotic Trans...
byKruti Vyas
 
Introduction Pharmacotherapeutics _ PT1 2026.pptx
byRavinandan A P
 
Complete Overview of Roles in Odoo 18 Planning
byCeline George
 

2013 10 23_dna_for_dummies_v_presented

  • 1.
  • 2.
    Lab for Bioinformaticsand computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  • 3.
  • 4.
  • 5.
    Lab for Bioinformaticsand computational genomics Cell Theory • All organisms are composed of one or more cells. • Cells are the smallest living units of all living organisms. • Cells arise only by division of a previously existing cell.
  • 6.
    Each human cellcontains 46 chromosomes (except sperm or egg cells)
  • 7.
    Lab for Bioinformaticsand computational genomics Genetic code DNA
  • 8.
    Lab for Bioinformaticsand computational genomics
  • 9.
    Lab for Bioinformaticsand computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body)
  • 10.
    Lab for Bioinformaticsand computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters
  • 11.
    Lab for Bioinformaticsand computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters That is the equivalent of nearly 70 trips from the earth to the sun and back.
  • 12.
    Genetic information isstored in the DNA
  • 13.
  • 14.
  • 15.
  • 16.
    DNA synthesis andproofreading
  • 17.
    Mutations: possible cause ofdiseases and disfunctionalities
  • 18.
    Lab for Bioinformaticsand computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  • 19.
    Microbes are allover us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 20.
    Lab for Bioinformaticsand computational genomics Defining Epigenetics Genome DNA • Reversible changes in gene expression/function • Without changes in DNA sequence Chromatin Epigenome Gene Expression Phenotype • Can be inherited from precursor cells • Epigenetic information is included in the epigenome • Allows to integrate intrinsic with environmental signals (including diet)
  • 21.
    Lab for Bioinformaticsand computational genomics Chromatin is a Key Component of Epigenetic Mechanisms
  • 22.
    Lab for Bioinformaticsand computational genomics Chromatin is a Key Component of Epigenetic Mechanisms Cellular DNA is packaged into a structure called chromatin The unit of chromatin is the nucleosome, a complex of a histone tetramer with approx. 125 bp of DNA wound around it nucleosome histone DNA chromatin • Chromatin organizes genes to be accessible for transcription, replication, and repair
  • 23.
    Lab for Bioinformaticsand computational genomics Basic Epigenetic Mechanisms: Post Translational Modifications to Histones and Base Changes in DNA • Epigenetic modifications of histones and DNA include: – Histone acetylation and methylation, and DNA methylation Histone Acetylation Ac Histone Methylation Me Me Me DNA Methylation
  • 24.
    Lab for Bioinformaticsand computational genomics Epigenetic Changes can Alter Chromatin Structure and Regulate Gene Expression TF TF Ac Ac Ac Ac Ac Ac Ac Ac Ac Gene expression • • Gene expression Gene expression (transcription) requires DNA to be physically accessible to transcription factors (TF) Epigenetic changes alter the structure of the chromatin, which determines whether DNA is accessible – Open chromatin allows gene expression – Closed chromatin prevents gene expression
  • 28.
    Lab for Bioinformaticsand computational genomics
  • 29.
  • 30.
    Lab for Bioinformaticsand computational genomics Epigenetics • Epigenetics is essentially the study of how our environment impacts traits acquired within our lifetimes, altering certain gene expressions which may then be passed on to future generations • That is, what we do to our own bodies may affect our children & grandchildren more than we thought. 30
  • 31.
    Lab for Bioinformaticsand computational genomics Epigenetic (meta)information = stem cells
  • 32.
    Lab for Bioinformaticsand computational genomics Translational Research towards Personalised Medicine • • DNA diagnostic tests can be used to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to: – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements
  • 33.
    Lab for Bioinformaticsand computational genomics Historically, Cancer Was Considered to be Driven Mostly by Genetic Changes GENETIC • • • • Example: Replication errors X X Mutations in p53 Activating mutations in RAS Mutations or amplifications of the HER-2 gene Chromosomal translocations in myeloid cells and the generation of the BCR-ABL fusion protein Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor
  • 34.
    Lab for Bioinformaticsand computational genomics Recent Evidence Shows that Epigenetic Changes are Also Important in Causing Cancer GENETIC EPIGENETIC Example: Chromatin modification errors Example: Replication errors X X Altered chromatin structure Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor Altered levels of mRNA/proteins
  • 35.
    Lab for Bioinformaticsand computational genomics Biology uses methylation extensively as a “regulatory checkpoint” in (cancer) development Schuebel et al 2007
  • 36.
    Methylation of MGMTin GBM Kaplan-Meier Estimates of Overall Survival in GBM, According to MGMT Promoter Methylation Status Hegi et al. NEJM 2005, 352(10):997-1003 3
  • 37.
    Lab for Bioinformaticsand computational genomics Cancer Stem Cell Theory: the ‘Root’ of Cancer Growth Tumor Tumor Development and Growth Epigenetically altered, selfrenewing cancer stem cells
  • 38.
    Lab for Bioinformaticsand computational genomics Gene-specific Epigenetic reprogramming
  • 44.
    Personalized Medicine • • • The useof diagnostic tests (aka biomarkers) to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements Potential uses of biomarkers – Risk assessment – Initial/early detection – Prognosis – Prediction/therapy selection – Response assessment – Monitoring for recurrence
  • 45.
    Biomarker First used in1971 … An objective and « predictive » measure … at the molecular level … of normal and pathogenic processes and responses to therapeutic interventions Characteristic that is objectively measured and evaluated as an indicator of normal biologic or pathogenic processes or pharmacologic response to a drug A biomarker is valid if: – It can be measured in a test system with well established performance characteristics – Evidence for its clinical significance has been established
  • 46.
    Rationale 1: Why now? Regulatory path becoming more clear There is more at stake than efficient drug development. FDA « critical path initiative » Pharmacogenomics guideline Biomarkers are the foundation of « evidence based medicine » - who should be treated, how and with what. Without Biomarkers advances in targeted therapy will be limited and treatment remain largely emperical. It is imperative that Biomarker development be accelarated along with therapeutics
  • 47.
    Why now ? Firstand maturing second generation molecular profiling methodologies allow to stratify clinical trial participants to include those most likely to benefit from the drug candidate—and exclude those who likely will not—pharmacogenomicsbased Clinical trials should attain more specific results with smaller numbers of patients. Smaller numbers mean fewer costs (factor 2-10) An additional benefit for trial participants and internal review boards (IRBs) is that stratification, given the correct biomarker, may reduce or eliminate adverse events.
  • 48.
    Molecular Profiling The studyof specific patterns (fingerprints) of proteins, DNA, and/or mRNA and how these patterns correlate with an individual's physical characteristics or symptoms of disease.
  • 49.
    Generic Health advice •Exercise(Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  • 50.
    Generic Health advice(UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  • 51.
    Generic Health advice(UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  • 52.
    Generic Health advice(UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  • 53.
    Lab for Bioinformaticsand computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  • 54.
    Genetics Instrument and Assayproviders G E N E T I C Whole-genome sequencing Enrichment seq (Exome) Enrichment Targeted Panels PCR bp Full genome 109 108 107 106 105 104 103 CLIA Lab service providers Confidential Information | ©2013 MDxHealth Inc. All rights reserved. 102 101 1
  • 55.
    Lab for Bioinformaticsand computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  • 56.
    Wobblebase Mission provide toolsto both specialists (researchers, bioinformaticians, health care providers) and individual consumers that unlock the power of genomic data to the USER enable personalized genomics today by simplifying the way we organize, visualize and manage genomic data.
  • 57.
    PGM: Personal GenomicsManifesto Everybody who wants to get his genome sequenced has the human right to do so. No third party can own your genetic data, your genetic data is exclusively yours. Nobody can be forced to get his genome analyzed or to reveal his genome to a third party. Your genome should allways be treated as confidential, private information. People should be advised not to share their identity AND their entire genome on a public forum. People should be advised to use secure technologies that allow to maximally protect phenotypic and/or genotype data. People should be able to actively explore, manage and get updated interpretation on their genomic data.
  • 58.
    Wobblebase Mission • change the diagnostic/healthcareindustry forever by setting a new standard and empowering the user
  • 59.
    Choosing the RedPill The Technical Feasibility Argument The Quality Argument The Price Argument The Logistics around the sample on howto manage the data Argument The Ethical debate The Privacy/Security concern
  • 60.
    Notifications Updates are thesingle moste important feature of Wobblebase
  • 61.
  • 62.
  • 64.
    The Human Microbiome ChristineRodriguez, Ph.D. Harvard Outreach 2012 Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 65.
    Microbes are allover us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 66.
    What is theHuman Microbiome? Microbe: tiny living organism, such as bacterium, fungus, protozoan, or virus Microbiome: collectively all the microbes in the human body; a community of microbes Biofilm: a community of microbes that live together on a surface Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 67.
    Microbes in theHuman Microbiome include species from each major domain “Extremophile” Archaebacteria Bacteria Fungi http://en.wikipedia.org/wiki/File:Aspergillus_niger_01.jpg http://en.wikipedia.org/wiki/File:SalmonellaNIAID.jpg http://en.wikipedia.org/wiki/File:Grand_prismatic_spring.jpg http://commons.wikimedia.org/wiki/File:Tree_of_life.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 68.
    What features distinguishthe microbial domains? Bacteria •Have no nucleus or membrane bound organelles •Often sphere (cocci) or rod (bacillus) shape, but others as well Generalized bacteria and archaebacteria cell Archeabacteria •Have no nucleus or membrane bound organelles •Can look similar to bacteria or drastically different shapes, such as flat and square •Have some metabolic similarities to eukaryotes Eukaryotes •Have a true nucleus and membrane bound organelles •Wide variety of shapes. For this presentation, we will focus on fungi •Fungi are unique since they have a cell wall and form spores during reproduction eneralized eukaryotic cell http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=CELL006B&File_type=GIF http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=BACT003B&File_type=GIF Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 69.
    Microbes are normallyfound in and on the human body The following sites are “hotspots” for microbial life Some microbes are native, normally found in the body Let’s explore these five regions Some microbes are introduced, suddenly arriving at a new residence in the body http://nihroadmap.nih.gov/hmp/ Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 70.
    What’s Happening in theNose? Cilia and mucous lining trap inhaled microbes The nose is a primary defender against inhaled pathogens Inflammation from viral infection and allergic reactions Inhaled medicines and oral antibiotics There is a delicate balance of microbes that are maintained to keep that environment healthy. Weakened immune systems can throw off that balance and allow the wrong microbes to grow out of control. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg
  • 71.
    Nose The interior liningof the nose contains mucous secreting glands. A wide variety of microbes are normally found there. Here’s a few: • Staphylococcus epidermidis bacteria forms a biofilm that coats the mucosal lining • Staphylococcus aureus bacteria is fine when kept under control by a protease found in S. epidermidis, but if left to grow out of control, S. aureus can become pathogenic and cause infection Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:MRSA7820.jpg http://en.wikipedia.org/wiki/File:Staphylococcus_epidermidis_01.png
  • 72.
    Nose • Aspergillus fungalspores are often inhaled through the nose. If the immune system fails to clear these, mold can grow in the lungs •Corneybacterium accolens bacteria is rarely a pathogen, but if it enters the bloodstream due to a torn blood vessel, it can cause serious infections Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:Corynebacterium_ulcerans_01.jpg http://en.wikipedia.org/wiki/File:Aspergillus.jpg http://en.wikipedia.org/wiki/File:Aspergillus_fumigatus_Invasive_Disease_Mechanism_Diagram.jpg
  • 73.
    What’s Happening in theOral Cavity? A wide variety of microbes regularly enter the oral cavity Brushing and flossing teeth clears some built up biofilm saliva, pH, temperature, immune system prevent many species from surviving Oral antibiotics inhibit growth Symbiosis of the oral microbes that are able to survive these conditions form an elaborate scaffold that lives on the tooth enamel and at the interface with the gums. It forms a barrier for incoming bacteria. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg
  • 74.
    Oral Cavity The oralcavity has a wide variety of microbes normally found there. Here’s a few: Fusobacterium sp. bacteria is a larger bacteria that helps form a scaffold for many other bacteria in the oral biofilm http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Streptococcus mitis bacteria typically forms a biofilm on the hard enamel surfaces of the teeth. If gums get inflamed, it can enter the bloodstream and cause infection
  • 75.
    Oral Cavity •Prevotella sp.bacteria have natural antibiotic resistance genes. They can attach to epithelial cells or other bacteria and cause larger infections in inflamed areas. • Candida albicans fungus can cause oral infection known as thrush http://microbewiki.kenyon.edu/index.php/File:P_ruminicola.jpg http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Thrush.JPG http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
  • 76.
    What’s Happening on theSkin? There are several skin environments: oily, dry, moist. Some microbes prefer one over another. The skin has natural defenses including slightly acidic sweat and antimicrobial peptides. Microbes hide in crevices to recolonize skin after washing with soap Antibiotic washes and oral antibiotics disturb normal balance of microbes on the skin There is a normal balance of microbes on the skin that protect introduced microbes from harming us. Damaged skin gives opportunities for microbes to invade the bloodstream and cause serious illness. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg
  • 77.
    Skin • Propionibacterium acnesbacteria colonizes healthy pores, but if pores become clogged, it grows out of control • Staphylococcus epidermidis bacteria normally colonizes on the skin. But when P. acnes clogs pores, S. epidermidis also grows out of control in the infected pores • Staphylococcus aureus bacteria can also infect clogged pores like Staph epidermidis. Even worse, many antibiotic resistant strains of Staph aureus make it difficult to treat the infection. http://microbewiki.kenyon.edu/index.php/File:Lesionsmicro.jpg http://microbewiki.kenyon.edu/index.php/File:Lesionsclosed.jpg http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 78.
    Skin Trichophyton and Microsporumfungi feast on keratin in the skin and cause ringworm fungal infections http://en.wikipedia.org/wiki/File:Yeartinfection.JPG http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 79.
    What’s Happening in theGut? Major barriers for microbes entering the gut: •low pH •Saliva and Bile •Immune system •Finding a place to attach to intestinal wall •Surviving a widely varied diet For those microbes that manage to colonize the gut: •gut flora perform regular tasks of digestion, vitamin production, many others • Gene transfer between the myriad of species in the gut can generate new combinations of drug resistant “superbugs” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 80.
    Gut Bacteroides thetaiotaomicron bacteria fermentssimple carbohydrates in the gut, releasing hydrogen and CO2. + carbohydrates CO2 and H2 Methanobrevibacter smithii archeabacteria consumes hydrogen gas from Bacteroides and produces methane, which is lost from gut as “gas” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers CH4 Methane Gas
  • 81.
    Gut Ruminococcus sp. bacteriacan be found in significantly high numbers in the gut flora. They break down cellulose in the gut, helping with digestion. Helicobacter pylori bacteria has a helical shape and colonizes the stomach and upper G.I. tract. It is known to be a major cause of stomach ulcers, although many with H. pylori do not get ulcers. http://microbewiki.kenyon.edu/index.php/File:G_reaction1.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Helicobacter_pylori_diagram.png
  • 82.
    What’s Happening inthe Urogenital Tract? Urinary system almost sterile due to urea and other chemicals Introducing a catheter into the urethra can introduce microbes directly into the bladder, where a biofilm can grow and cause bladder infection Urine often flushes out microbes that find their way in The vagina has a low pH due to Lactobacillus secreting lactic acid and hydrogen peroxide. Let’s explore the microbiome of this region further. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg
  • 83.
    Urogenital Lactobacillus normally maintain low pHwhile other species are kept in small numbers in the vagina Candida albicans can take over and cause a yeast infection If Lactobacillus decreases from antibiotics… Lactobacillus and vaginal epithelial cell G. vaginalis and vaginal epithelial cell Gardnerella vaginalis can grow too much and cause bacterial vaginosis. http://commons.wikimedia.org/wiki/File:Lactobacillus_sp_01.png http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
  • 84.
    Urogenital The urinary tractis normally sterile due to urine flushing out the tract. Urine sample infected with E. coli Urine sample infected with E. coli But, Escherichia coli from GI tract can infect urinary tract due to poor hygiene and contamination from nearby GI tract opening. http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:E_choli_Gram.JPG http://commons.wikimedia.org/wiki/File:Pyuria2011.JPG
  • 85.
    Interplay Between Medicine andMicrobes Antibiotics Chemotherapy drugs Kills infectious bacteria but also disrupts natural flora. Can result in yeast infections, digestive problems, etc. http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:NOVAMOXIN_antibiotic.jpg Gut flora has been shown to modify some drugs during metabolism. This causes many side effects, including upset stomach. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 86.
    Use of AntimicrobialProducts How many do we really need? But do we need some natural exposure to germs to keep our normal flora around? Products kill germs to reduce infection http://commons.wikimedia.org/wiki/File:Afwasmiddel.jpg http://commons.wikimedia.org/wiki/File:Tissue.jpg http://commons.wikimedia.org/wiki/File:Refill_soap.jpg http://commons.wikimedia.org/wiki/File:Toothpaste.jpg http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Will this allow “superbugs” that can barely survive these treatments to grow and become more prevalent…causing problems for the future?
  • 87.
    Is My GutMicrobiome the Same as Yours? The number and amount of the many different microbes can vary greatly from person to person. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 88.
    Relative amounts ofspecies Research in the Human Microbiome Project is starting to identify the relative amount of each microbe present at different locations in the body. The Microbiome of one person can be different than others in species and relative amounts Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Skin_Microbiome20169-300.jpg
  • 89.
    So many newquestions to answer about the Human Microbiome… How does the gut flora modify drugs, and how can we minimize side effects? Are we making germs more resistant to anitmicrobials? What happens when the germs are resistant to all of the drugs in our arsenal? Why does my gut flora look different than yours? How does that affect obesity, food allergies, and ability to fight disease? What do you want to know? http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  • 90.
    Lab for Bioinformaticsand computational genomics …$

Editor's Notes

  • #21 Here, we define epigenetics and depict the relationship between the genome and the epigenome The genome is hereditary information encoded in the DNA and the epigenome is the way cells express the encoded information1 The epigenome is a ‘bridge’ between genotype and phenotype (epigenetics governs genotype and phenotype) Epigenetic information is included in the genome of a cell but is not encoded by the DNA1,2 Epigenetic information may be inherited from precursor cells1 Epigenetic changes affect chromosome structure to alter gene expression1,2 References Goldberg AD et al. Cell 2007;128:635–8. Bernstein BE et al. Cell 2007;128:669–81.
  • #23 This slide shows the histone and DNA components and the nucleosome subunits of chromatin, located in the cell nucleus1 Chromatin consists of repeating units of nucleosomes: DNA wrapped around histone octamers, which consist of two copies each of histones H2A, H2B, H3, and H41 The function of chromatin is to package DNA and to organize and arrange genes to be accessible to factors involved in transcription, replication, and repair1 Epigenetic mechanisms involve modifications of DNA and histone proteins which affect chromatin structure1 References Wang GG et al. Trends Mol Med 2007;13:363–72.
  • #24 This slide illustrates the epigenetic modifications of histones and DNA that are discussed in this slide set Epigenetic modifications change the chemical interactions of histones and DNA, which leads to changes in chromatin structure1 Of all of the known types of histone modifications, acetylation and methylation are among the best characterized2 Histones can also be modified by phosphorylation, isoprenylation, ubiquitination, sumoylation and poly(ADP) ribosylation2 Epigenetic modification of DNA involves methylation of cytosine residues3 References Jones PA, Baylin SB. Cell 2007;128:683–92. Kouzarides T. Cell 2007;128:693–705. Esteller M. Nat Rev Genet 2007;8:286–98.
  • #25 Here we illustrate one way in which changes in chromatin structure affect gene expression Gene expression (transcription) requires DNA to be physically accessible to transcription factors (TF)1,2 The compactness of the chromatin structure – or degree of wrapping of DNA – determines whether DNA is accessible Epigenetic modifications to histones and DNA can change chromatin structure, which regulates gene expression1,2 The panel on the left of the slide depicts an ‘open’ chromatin structure, which may allow transcription factor binding and gene expression The panel on the right depicts a ‘closed’ chromatin structure, which may block transcription factor binding and inhibit gene expression References Kouzarides T. Cell 2007;128:693–705. Drummond DC. Annu Rev Pharmacol Toxicol 2005;45:495–528.
  • #34 This slide outlines the role of genetic changes in the development of cancer Traditionally, cancer has been considered a disease of genetic defects, such as gene mutations, deletions, and chromosomal abnormalities1 On the left of this slide, we see that mutations in DNA sequence result in production of mRNA and proteins with altered function Mutation of proteins involved in cell growth and death can lead to deregulated cell proliferation and survival, resulting in cancer2 Examples: Mutations in p532 Activating mutations in RAS2 Mutations or amplifications of the HER-2 gene3 Chromosomal translocations in myeloid cells and the generation of the BCR-ABL fusion protein3 References Bolden JE et al. Nat Rev Drug Discov 2006;5:769–84. Rieger PT Semin Oncol Nurs 2004;20:145–54. Croce CM N Engl J Med 2008;358:502–11.
  • #35 There is growing evidence that epigenetic modifications are also crucial to the onset and progression of cancer1 On the right of the slide, we see that changes in gene expression due to chromatin modifications (e.g. histone acetylation, DNA methylation) lead to altered levels of mRNA and proteins Altered levels of proteins involved in cell growth and death can lead to deregulated cell proliferation and survival, resulting in cancer 2 Examples: Silencing of p15 tumor suppressor gene expression3 Aberrant expression of IGF24 Silencing of ER-α gene expression3 References Bolden JE et al. Nat Rev Drug Discov 2006;5:769–84. Miranda E et al. Br J Cancer 2006;95:1101–7. Esteller M. N Engl J Med 2008;358:1148–59. Feinberg AP. Nature 2007;447:433–40.
  • #38 The involvement of epigenetics in cancer development has led researchers to propose the cancer stem cell, or malignant progenitor cancer cell, theory1,2: Self renewal and differentiation of stem cells are largely governed by epigenetic programs Occasionally, some stem cells acquire heritable epigenetic and genetic changes that result in the malignant phenotype Malignant stem cells “seed” highly proliferative and transformed cells that cause cancer Evidence in support of an epigenetic cancer stem cell model for anti-tumor therapy1: Studies of tumor cells show that epigenetic deregulation is reversible Global epigenetic changes are often found to precede genetic mutations in cancer and are found in benign neoplasia as well as tumors Most of the properties of tumor cells are epigenetically controlled and can be reprogrammed to follow normal development Since the viability and differentiation of malignant stem cells is highly governed by epigenetic mechanisms, targeting epigenetic regulators may offer a more complete approach for the treatment of cancer1 The importance of epigenetics in cancer can be conceptualized as a tree, where epigenetic therapy may affect both ‘branches’ (full blown tumor cells) and ‘roots’ (malignant stem cells), as shown in the following slides References Jones PA, Baylin SB. Cell 2007;128:683–92. Feinberg AP et al. Nat Rev Genet 2006;7:21–33.