Welcome,

I am Bonnie Feldman, aec2onately known as DRbonnie360 and I am

delighted to be at the Genomics Fes2val to speak about why Genes are not our
des2ny and how we can use data to help drive personalized preven2on.

For those of you who want to tweet, my twiHer 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 tes2ng or counseling?


To make this topic come to life, I am going to share a story about Judy. Recently, I did

a survey (hHp://bit.ly/20xRCXO) of autoimmune pa2ents, Judy is a compila2on of our
autoimmune pa2ent survey.

AS we can see here, Judy has several family members with dierent 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 dierent kind of autoimmune disease?

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

Autoimmune is underserved and unrecognized despite the fact that they aect 16%
of the US popula2on, 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 2mes as much funding.

Can you believe, it takes on average more than 3.5 years and 5 doctors to get a
diagnosis? During this 2me, 45% of pa2ents were dismissed as hypochondriacs.

Once diagnosed, the available drug treatments are usually applied through a lengthy
and frustra2ng process of trial and error.

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: hHp://bit.ly/X41mMv

Coming back to gene2cs- Gene2cs 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, gene2cs and the
possibility of preven2ve approaches

To the shut down and now reopening of 23 and me by the FDA showing how the agency has the
power to regulate gene2c startups
Gene2c tes2ng for metabolic syndrome turns ROI for Aetna
And lots in the lay press about the microbiome
Not 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 char2ng the
mysteries of the microbiome in both health and disease.
We are now beginning to appreciate that:
Gut as an organ of immunity
But also, the Brain gut connec2on
The composi2on, the diversity and what causes it to change
On the technical side, Cost of sequencing has decreased drama2cally and new tech such as CRISPR
technology which allows gene edi2ng. It is a new faster and cheaper approach to modify DNA.
The Presidents precision medicine ini2a2ve, 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 ini2a2ve for a million
volunteers to form a na2onal research cohort.
Other news in cancer and rare disease includes the work of the Gene2c Alliance and others working to
bring open data and collabora2on to solve some of these problems.

The Underpinnings of all these news items goes back to progress in Big Data

Big Data has many moving parts include size, variety, variety and velocity


Volume- quan2ty form terabytes to zeHabytes

Growth comes from digi2zing exis2ng data and from genera2ng new forms of data. The volume of

exis2ng data includes personal medical records, radiology images, clinical trial data, FDA submissions,
human gene2cs and popula2on data. Newer forms of big byte data include genomics and biometric
readings all fueling the exponen2al growth.
The Variety of structured and unstructured data in healthcare makes it both interes2ng 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 mo2on
Although we think of sta2c paper les, x rays and scrips, healthcare data can also be real 2me- such as
that in an ICU or a NICU. We are now seeing some uses of real 2me data analy2cs such using predic2ve
analy2cs with newborns to avoid complica2ons.
Varacity- data varying quality, relevance and meaning
The 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 handwriHen notes, can be unreadable.

Applying these large data sets it becomes apparent that the average pa2ent will by deni2on mistreat a
signicant por2on of the popula2on. As we learn more applying genomics to personalized medicine we
are now apprecia2ng how important it is to focus on the underlying veracity ( truthfulness, relevance
and predic2ve value of the data) in order to realize the poten2al of big data analy2cs and personalized
medicine.



Advances in the ability to collect, store, move and analyze large data sets have
Ignited the growth of new elds collec2vely called omics
Omics informa2on is one of the many types of data sets contribu2ng to big data in
biological research.
Genomics is what can happen to DNA. The Genes are hardwired and can only be
altered by muta2ons. It is the study of genes, how they are expressed in cells and the
role they play in biology
The Human Genome Project
Epigenomics are environmental inuences on the DNA. These inuences are exci2ng
because new research shows we can modify our gate.
Transcriptomics- what appears to be happening at the RNA level
Proteomics is what makes it happen on the protein level, where proteins from mRNA
modulate cellular metabolism
Metabolomics- all this comes together as cellular metabolism
Taken together, comprehensive omics based strategies will give us a systems biology
approach to beHer understanding health and disease.

Coming back to Judy. She has GI symptoms that come and go as well as pelvic and hip pain.
Aper a frustra2ng experience with many dierent doctors over several years, she is nally told
she has IBD. The cause of her pelvic/hip pain is s2ll not known.

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

Untangling the dierence between innate and adap2ve immunity at the molecular level is
hard. We need to tease out what provokes autoimmunity, produces clinical disease and then
perpetuates chronicity.

Progress in dening the gene2cs of autoimmunity has been enhanced by large scale
gene2c studies. Genome wide approaches examine large numbers of cases and has
increased our understanding of the gene2c 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 beHer understanding of the epigenomics because Total risk is made up
of environmental and gene2c contribu2ons.

The concept of the environment has expanded from exogenous triggers such as
infec2ons 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 methyla2on.

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



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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 recommenda2on.
What is good versus what is not? Most recently, it was hotdogs and processed meats, while at
other 2mes it has been coee.

Judy nds 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 iden2fy a latency period. Using these approaches He has published
a 2me series biomarker analysis and looks curiously at his explana2on of a 2me when his data
showed early signs of disease but he did not know much about it.

She then does some scien2c research and nds several journal ar2cle describing the 2meline
for autoimmunity which includes a 2me when there may be opportuni2es to modify her
triggers and prevent her health from gerng worse.

Judy wonders why none of her doctors have talked about pre-autoimmune preven2on or a

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Personalized Lifestyle medicine mixed with QS

She goes on line and nds lots of informa2on 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 lled with advice from Western trained physicians who have had their
own autoimmune diseases with symptoms alleviated from lifestyle changes, including
diet.

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 GWAS studies have implicated over 60 genes in IBD. These pathways suggest that
specic dietary interven2on could be useful, depending on the genes involved.
Epigene2cs and the gut microbiome are also responsive to dietary interven2ons.



Nutrigene2c recognizes the gene2c varia2on on nutri2on requirements may lead to

personalized nutri2on.

While nutrigenomics covers the nutri2on regula2on of gene expression. may help
understand the nature of the disease and individual response to nutrients.

New research on epigene2cs 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 intes2nal barrier func2on.

Some early hints at how to personalize nutri2on may involve essen2al micronutrients
such as folate, vitamin B12, selenium and zinc. Other approaches could include
enteral nutri2on, various an2oxidants, plan avonoids and long chain omega 3 faHy
acids. There is also some new research on the use of probio2cs and prebio2cs.

In addi2on to food, what type of exercise and stress reduc2on makes sense?

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What should Judy do about her other problems? Her Because Judy also has the
gene2cs for osteoporosis along with her current hip pain, she wonders how can apply
this proac2ve approach to her posture.

She is aware of the importance of posture based upon some of the latest ar2cles
claiming that sirng is the new smoking, but that does not tell her how to address her
skeletal issues.

Without much guidance, Judy is lep with experimenta2on.

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Given her gene2cs, she wants to be able to coordinate her care with her Western
physician.

But alas, it turns out that is very challenging.

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So, our genes are not our des2ny. 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 des2ny. Big
data is the founda2on that spurs progress in omics crea2on and growth
in microbiome research

Use of omics gives us new insights into systems biology, which could
enable beHer 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 gene2cs as an opportunity to
tweak your lifestyle in a way to make your gene2cs works for you. and
not against

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