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How Data Drives Personalized Prevention

Genes Are Not Our Destiny

2015 - All rights reserved.@DrBonnie360 Presents:

1Welcome, I am Bonnie Feldman, affectionately known as DRbonnie360 and I am delighted to be at the Genomics Festival to speak about why Genes are not our destiny and how we can use data to help drive personalized prevention.

For those of you who want to tweet, my twitter handle is @DRBonnie360

Let me get an idea of who is In the audience. Do you work in Genomics?

Have you ever had your genome sequence?

Has anyone had genomic testing or counseling?

Judy

2To make this topic come to life, I am going to share a story about Judy. Recently, I did a survey (http://bit.ly/20xRCXO) of autoimmune patients, Judy is a compilation of our autoimmune patient survey.

AS we can see here, Judy has several family members with different kinds of autoimmune diseases ranging from Lupus to Crohns, to Psoriasis and others.Who is this room has an autoimmune disease?

Do you have family members with a similar or different kind of autoimmune disease?

diseasesUS populationTop leading cause of death in women less than 64 yrs

There are actually more than 100 different kinds of autoimmune diseases.

Autoimmune is underserved and unrecognized despite the fact that they affect 16% of the US population, more than cancer and heart disease combined! It is one of the top ten leading causes of death in women less than 64 years.

Yet, autoimmune diseases (including T1 diabetes) receive only $1B in NIH funding per year, unlike cancers, which get 7 times as much funding.

Can you believe, it takes on average more than 3.5 years and 5 doctors to get a diagnosis? During this time, 45% of patients were dismissed as hypochondriacs.

Once diagnosed, the available drug treatments are usually applied through a lengthy and frustrating process of trial and error.

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The Lonely Voices of Autoimmune Disease

Having a chronic disease is challenging.

Lets take a moment to learn more as we listen to the lonely voices of autoimmune disease.

Watch Video here: http://bit.ly/X41mMv4

2015 - All rights reserved.

5Coming back to genetics- Genetics and Genomics has been in the news a lot recently with a wide range of topics.Ranging from the Angelina Jolie story which brought awareness to breast cancer, genetics and the possibility of preventive approachesTo the shut down and now reopening of 23 and me by the FDA showing how the agency has the power to regulate genetic startupsGenetic testing for metabolic syndrome turns ROI for AetnaAnd lots in the lay press about the microbiomeNot only the fact that our microbiomes have 100-500 as many genes as our human genes. For every one human gene there are 100 or more microbiome genes.Projects such as American Gut, NIH and Ubiome are all working on mapping and charting the mysteries of the microbiome in both health and disease.We are now beginning to appreciate that: Gut as an organ of immunityBut also, the Brain gut connectionThe composition, the diversity and what causes it to changeOn the technical side, Cost of sequencing has decreased dramatically and new tech such as CRISPR technology which allows gene editing. It is a new faster and cheaper approach to modify DNA.The Presidents precision medicine initiative, which invests 215 million dollars to create a joint project between the FDA, the ONC and NIH. Part of this work will include a 130 M initiative for a million volunteers to form a national research cohort.Other news in cancer and rare disease includes the work of the Genetic Alliance and others working to bring open data and collaboration to solve some of these problems.

2015 - All rights reserved.

The Underpinnings of all these news items goes back to progress in Big DataBig Data has many moving parts include size, variety, variety and velocity

Volume- quantity form terabytes to zettabytesGrowth comes from digitizing existing data and from generating new forms of data. The volume of existing data includes personal medical records, radiology images, clinical trial data, FDA submissions, human genetics and population data. Newer forms of big byte data include genomics and biometric readings all fueling the exponential growth.The Variety of structured and unstructured data in healthcare makes it both interesting and challenging. Structured data is data that can be easily stored, queried, recalled and analyzed by machine. Yet, up to 80% of the data in EHR is unstructured.Velocity- Healthcare data can be at rest and in motionAlthough we think of static paper files, x rays and scrips, healthcare data can also be real time- such as that in an ICU or a NICU. We are now seeing some uses of real time data analytics such using predictive analytics with newborns to avoid complications.Varacity- data varying quality, relevance and meaningThe old adage garbage in, garbage out is important in healthcare because: 1. Life of death decisions may depend on the data and 2. Unstructured data, such as handwritten notes, can be unreadable.

Applying these large data sets it becomes apparent that the average patient will by definition mistreat a significant portion of the population. As we learn more applying genomics to personalized medicine we are now appreciating how important it is to focus on the underlying veracity ( truthfulness, relevance and predictive value of the data) in order to realize the potential of big data analytics and personalized medicine.

GenomicsOmics Enables Systems BiologyEpigenomics

Proteomics

TranscriptomicsMetabolomics

Advances in the ability to collect, store, move and analyze large data sets haveIgnited the growth of new fields collectively called omicsOmics information is one of the many types of data sets contributing to big data in biological research.Genomics is what can happen to DNA. The Genes are hardwired and can only be altered by mutations. It is the study of genes, how they are expressed in cells and the role they play in biologyThe Human Genome ProjectEpigenomics are environmental influences on the DNA. These influences are exciting because new research shows we can modify our gate.Transcriptomics- what appears to be happening at the RNA levelProteomics is what makes it happen on the protein level, where proteins from mRNA modulate cellular metabolismMetabolomics- all this comes together as cellular metabolismTaken together, comprehensive omics based strategies will give us a systems biology approach to better understanding health and disease.7

Judy is lost and alone

Coming back to Judy. She has GI symptoms that come and go as well as pelvic and hip pain. After a frustrating experience with many different doctors over several years, she is finally told she has IBD. The cause of her pelvic/hip pain is still not known.

You will recall that she has a family history of autoimmune disease.

Untangling the difference between innate and adaptive immunity at the molecular level is hard. We need to tease out what provokes autoimmunity, produces clinical disease and then perpetuates chronicity.

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Judy realizes shes preautoimmune

Progress in defining the genetics of autoimmunity has been enhanced by large scale genetic studies. Genome wide approaches examine large numbers of cases and has increased our understanding of the genetic risk signature

Large scale GWAS studies as well as new tools have improved our understanding of autoimmune disease. But has not given us a complete picture. Our ability to collect omics data is ahead of our capability to give meaning to the data.

Hope lies in a better understanding of the epigenomics because Total risk is made up of environmental and genetic contributions.

The concept of the environment has expanded from exogenous triggers such as infections and toxins to endogenous triggers harbored in the microbiome.

EWAS Epigenomics of Autoimmunity gives us some clues about environmental changes such as that in DNA methylation.

We are now beginning to look at some of the results of EWAS studies.

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2014 - All rights reserved.Judy wonders how do environmental triggers work for her?

The news has had lots about food. It seems like everyday there is a new diet recommendation. What is good versus what is not? Most recently, it was hotdogs and processed meats, while at other times it has been coffee.

Judy finds out about the work of Larry Smarr. He did 3 levels of monitoring. First is macro monitoring of nutrients, food, exercise, sleep and stress. At the next level is systems biology that looks at proteins and metabolic products from blood, saliva and stool test. Third is measuring the microbiome, metagenome and its proteins, and metabolomics products via stool tests. Noteworthy, he was able to identify a latency period. Using these approaches He has published a time series biomarker analysis and looks curiously at his explanation of a time when his data showed early signs of disease but he did not know much about it.

She then does some scientific research and finds several journal article describing the timeline for autoimmunity which includes a time when there may be opportunities to modify her triggers and prevent her health from getting worse.

Judy wonders why none of her doctors have talked about pre-autoimmune prevention or a latency period?10

Judy needsPersonalized Prevention for Pre-autoimmune

11Personalized Lifestyle medicine mixed with QS

She goes on line and finds lots of information as well as summits- The Autoimmune Summit, the Paleo summit, the gluten free summit.

Does she want to try a gluten free diet, a paleo diet, a paleo atuoimmune diet, a low Fodmap diet or a low carbohydrate diet.

The internet is filled with advice from Western trained physicians who have had their own autoimmune diseases with symptoms alleviated from lifestyle changes, including diet.

Judy seeks tailored lifestyle modification

12GWAS studies have implicated over 60 genes in IBD. These pathways suggest that specific dietary intervention could be useful, depending on the genes involved. Epigenetics and the gut microbiome are also responsive to dietary interventions.

Nutrigenetic recognizes the genetic variation on nutrition requirements may lead to personalized nutrition.

While nutrigenomics covers the nutrition regulation of gene expression. may help understand the nature of the disease and individual response to nutrients.

New research on epigenetics and the gut microbiota are beginning to show us how the 160 genes associated with these diseases fall into pathways largely related to microbiome, immune response and intestinal barrier function.

Some early hints at how to personalize nutrition may involve essential micronutrients such as folate, vitamin B12, selenium and zinc. Other approaches could include enteral nutrition, various antioxidants, plan flavonoids and long chain omega 3 fatty acids. There is also some new research on the use of probiotics and prebiotics.

In addition to food, what type of exercise and stress reduction makes sense?

INDIVIDUALYogaMeditationPsychologistsBiofeedbackCoachesGROUPFamilyFriendsChurchMUSCULOSKELETAL INTEGRITY TEAMPhysical TherapyAcupunctureMassageChiropracticBiofeedbackFOOD AS MEDICINE TEAMNutritionistsCoachesWELL-BEING TEAM

What should Judy do about her other problems? Her Because Judy also has the genetics for osteoporosis along with her current hip pain, she wonders how can apply this proactive approach to her posture.

She is aware of the importance of posture based upon some of the latest articles claiming that sitting is the new smoking, but that does not tell her how to address her skeletal issues.

Without much guidance, Judy is left with experimentation.

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Integrated Autoimmune Medicine

14Given her genetics, she wants to be able to coordinate her care with her Western physician.

But alas, it turns out that is very challenging.

DIY Your Genetic Fate

So, our genes are not our destiny. Each of us is unique. We need to own and appreciate our uniqueness as part of the DIY movement. Each of us can be a maker- a maker of our own health and wellness destiny. Big data is the foundation that spurs progress in omics creation and growth in microbiome research

Use of omics gives us new insights into systems biology, which could enable better biomarkers for complex diseases such as autoimmune disease. With new and improved biomarkers we will be on step closer to personalized medicine.

In the meanwhile, it is up to each of us to be curious experimenters, following those in QS and others like Larry Smarr. In autoimmune disease it is important to look at your genetics as an opportunity to tweak your lifestyle in a way to make your genetics works for you. and not against

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The Genes You Cant Take Off: What is the Relationship between Autoimmunity and Genetics?Ritchie, M., Holzinger, E., Li, R., Pendergrass, S. & Kim, D. Methods of integrating data to uncover genotype-phenotype interactions. Nature Reviews Genetics (2015). http://www.nature.com/nrg/journal/v16/n2/abs/nrg3868.html

Seldin, MF. The genetics of human autoimmune disease: A perspective on progress in the field and future directions. Journal of autoimmunity (2015). http://www.sciencedirect.com/science/article/pii/S0896841115300330

Smilek, D. & Clair, W. Solving the puzzle of autoimmunity: critical questions. F1000Prime Reports 7, (2015). http://www.ncbi.nlm.nih.gov/pubmed/25750735

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Change your Fate: What can Epigenetics do for Autoimmunity?Farh, K. et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518, 33743 (2015). http://www.nature.com/nature/journal/v518/n7539/full/nature13835.html Gupta, B. & Hawkins, D. Epigenomics of autoimmune diseases. Immunol Cell Biol 93, 271276 (2015). http://www.nature.com/icb/journal/v93/n3/full/icb201518a.html Jeffries, MA & Sawalha, AH. Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve? Expert review of clinical (2014). http://www.pubfacts.com/detail/25534978/Autoimmune-disease-in-the-epigenetic-era:-how-has-epigenetics-changed-our-understanding-of-disease-a

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Are We What We Eat Or Is What We Eat Who We Are?: Nutrigenomics and Autoimmunity

Ferguson, LR. Nutrigenetics, nutrigenomics and inflammatory bowel diseases. Expert review of clinical immunology (2013). http://www.ncbi.nlm.nih.gov/pubmed/23971750

Gibson, PR, Varney, J, Malakar, S & Muir, JG. Food Components and Irritable Bowel Syndrome. Gastroenterology (2015). at http://www.sciencedirect.com/science/article/pii/S0016508515001961

Minich, D. M. & Bland, J. S. Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. The Scientific World Journal 2013, (2013). http://www.ncbi.nlm.nih.gov/pubmed/23878520

Xie, G, Li, X, Li, H & Jia, W. Toward personalized nutrition: comprehensive phytoprofiling and metabotyping. Journal of proteome research (2013). http://pubs.acs.org/doi/abs/10.1021/pr301222b

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Our Genes Are Not Our Destiny+1.310.666.5312drbonnie360@gmail.comwww.drbonnie360.com@DrBonnie360 www.facebook.com/YourAutoimmunityConnection

Bonnie Feldman, DDS, MBABusiness Development for Digital Health

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