Systemic body

odor diseases
Private exome
sequencing pilot in
cooperation with the
Institute of Medical
Genetics and Applied
Genomics Tbingen
(Germany)
For any contact please send
a mail to
danny.kunz@gmx.de
Thank you!
 IGEL offer overview

Available (IGEL) offer

(for Germany only currently)
Exome sequencing WES (650)
https://en.wikipedia.org/wiki/Exome_sequencing

Exome sequencing + RNA expression

analysis (1100)
Whole genome sequencing WGS (1300)
https://en.wikipedia.org/wiki/Whole_genome_sequencing
 Overview

Overview about the private

pilot exome sequencing
What are the details of the offer?
What does an exome sequencing mean?
Why an exome sequencing for Bromhidrosis /
TMAU 2 / fecal body odor?
Who pays for that?
How can a patient apply to the offer?
 Details of the offer

What are the details of the

offer?
Based on our research
(https://www.researchgate.net/profile/Danny
_Kunz/projects) the Institute of Medical
Genetics and Applied Genomics Tbingen
does offer patients having Bromhidrosis or
TMAU2 or fecal body odor, which are
connected to us, the possibility of a pilot
exome sequencing
The offering is an IGEL service (the patient has
to privatly pay for it)
What are the details of
the offer?
 Details of the offer

What are the details of the

offer?
The offer of the medical genetics institute
includes the mandatory genetic counseling,
the exom sequencing and analysis
Additionally you get the raw sequence data
which represents the genetic code of
proteine encoding parts of you DNA handed
over
You are then free to hand over your raw
sequence data to any further private service
or research teams to get further analysis done
on top of that. Thats your free choice.
 Details of the offer

What are the details of the

offer?
Be aware:
The Medical Genetics Institute does NOT
investigate into the relationship between
Bromhidrosis/TMAU2/... with the probably
detected genetic mutations or genetic faults; they
are there to get a raw analysis done on the
genes, they have no expertise on the details of
those diseases
In other words:
they are experts in scanning the whole genome,
but not necessarily what the results mean in detail.
Those details then get elaborated by follow up
investigations of reasearch teams
 Details of the offer

What are the details of the

offer?
Additional hint:
On request the Institute in Tbingen is able to
cooperate with other medical genetics
institutions germany wide
Patients which are not located in the south of
Germany may receive further addresses of
institutions which will provide the genetic
counselling service for them
 Details of the offer

What are the details of the

offer?
The recommended approach from the Medical Institute of
Tbingen is a first exome sequencing (WES)
They additonally offer a whole genome sequencing (WGS) or a
combination with an RNA expression analysis
The WGS cover more regions of the DNA (so called non proteine
coding regions/ Introns ), but due to the lack of current
understanding of those regions, they are not yet able to analyze
those for defects.
Nevertheless does the current ongoing research in all medical
fields show, that those Intron regions are important as well for a
lot of diesease AND due to the fact that the gentic code of your
DNA does not change over lifetime, it is possible to include those
regions in the sequencing, to have the data for the future when
intron regions are better understood and can be associated to
diseases (genetic code sequencing is a one time action done in
the life)
What does an exome
sequencing mean?
 Exome sequencing

What does an exome

sequencing mean?
The most modern development of medicine is the
use of DNA high troughput sequencing machines
(like the ILLUMINA line; https://www.illumina.com/)
The DNA consists of coding regions which do
contain the plan of creating an enzyme proteine,
or a transporter proteine e.g.
Based on the findings of the over the years
ongoing human genome projects
(https://en.wikipedia.org/wiki/Human_Genome_Pr
oject) those regions can today be compared and
analyzed with very adanced software methods
 Exome sequencing

What does an exome

sequencing mean?
As a result it is today possible to analyze a
probe of your DNA by sequencing it, locating
the proteine coding regions with modern
software analysis and comparing those with
the reference proteins known for enzymes
e.g.
And with those findings of defect coding
regions of an enzyme e.g., you can draw a
picture of its impact on the human
metabolism
Why an exome sequencing
for Bromhidrosis / TMAU 2 /
fecal body odor?
 Exome sequencing

Why an exome sequencing for

Bromhidrosis / TMAU 2 / fecal body
odor?
With two software prototypes which operate
on the data set of the major international
enzyme/genome databases, we were able to
reduce the possible causes of Bromhidrosis
and TMAU 2 and the fecal body odor types to
a certain small subset of the metabolic
pathways of the human intestinal metabolism,
with the result of several enzyme targets as
disease causes
Those enzyme gene targets are part of the
exome sequencing analysis
 General impact overview

Core disease pattern

 General impact overview

Core disease pattern

Malabsorptions of
Tryptophan, Tyrosine,
Phenylalanine and
Histidin in the ileum
of the intestinal tract
Various causes are
enzyme defects
inhibiting major
enzyme layers for
aromatic amino acid
degradation
 General impact overview

Core disease pattern

Low intensity but
widespread
degradation failure of
amino acids lead to
activation of several
tight junction
regulating receptors
(H1,H2, M1,...)
This leads to gut
dysbiosis which
actually increase
pressure on to the
already deficient
enzymes which makes
the disease persistent
 Exome sequencing

Why an exome sequencing for

Bromhidrosis / TMAU 2 / fecal body
odor?
With an pilot exome analysis per body odor type we
intend to support our data analysis with a first explorative
paper published in a medical journal
If successful, this would shift the view of the
TMAU2 disease to be caused by a bacterial dysbiosis in the
gut to a disease which is caused by a degradation failure of
certain amino acids (which results in gut dysbiosis as a
symptom and not as a cause)
Bromhidrosis disease to not be caused by malfunctions of
eccrine or apocrine sweat glands (or bacterias on skin; which
is actually already proved to be wrong), instead being
caused by the emergency malregulation of the tight junctions
in the ileum/intestinal tract
Fecal body odor type and Bromhidrosis patients share the
degradation failure of the same amino acids and that they
span an own disease group, where Bromhidrosis patients have
stronger tight junction impacts and the others stronger
malabsorption impacts
 Exome sequencing

Why an exome sequencing for

Bromhidrosis / TMAU 2 / fecal body
odor?
So for every body odor patient supporting our
research with the anonymous donation of
exome sequencing data we would be closer
to etablish the Bromhidrosis/TMAU2 diseases in
the medical field as what they are
After the first exome analysis with a sucessful
finding of a defect within our proposed
pathways and the resulting medical paper
being published, it would be a lot easier to
get medical units towards providing accurate
support for patients
 Exome sequencing

Why an exome sequencing for

Bromhidrosis / TMAU 2 / fecal body
odor?
And for every body odor patient supporting
our research with the anonymous donation of
exome sequencing data we would also be
able to render prelimitary pictures where the
defects of the patients genome are located
in our pathways, what the proposed
interactions are
Additionally we are able to render related
food diet lists automatically (adapted to the
enzyme defect location) right now, which
might the patients help to identify the
harming foods much more easier
 Exome sequencing for
Bromhidrosis / TMAU2 / ...

Who pays for that?

 Costs

Who pays for that?

The Institute of Tbingen provides its offer as
IGEL service, which the patient has privately
to pay for (public health insurances do not
cover those)
The exom sequencing would cost 650
The service will be immediately available in
Germany as fast as our patient organized
support group provides the lists of patients to
the institute of Tbingen (which should take
about 2 months or immediately as soon as
five or more patients are found)
 Costs

Who pays for that?

If the community is able to get crowdfundings on
the way, it might be possible to get one or two
cases crowdfunded
BUT:
Crowdfunding needs additional time of regularly
about 6 Months
AND for one patient analysis about 20 people have
to make a 50 donation (you have some
crowdfunding fees and marketing fees normally)
AND we need as much exomes as possible, since
we have more than one enzyme target per body
odor type!
How can a patient apply
to the offering?
 Applying for an exome sequencing

How can a patient apply to the

offering?
The patient applies directly to us in a first step per email to
danny.kunz@gmx.de
We need only the full name of a patient and its rough location in
Germany (a larger city named which is close to the patient is sufficient)
but NOT the full address
We handle this data and propagate the collected patient names for
patients applying to the exome sequencing to the medical genetics
insitute of Tbingen
They will process those patient lists and propagate those to the genetic
counseling services at their location (or on request to the same services
of a closer located institute to the patients location);
That step is necessary, since such services (for the given price) is only
available by our arrangement with the institute
As soon as we get feedback from the institute, that the counseling service
is informed, the patients can directly contact the genetic counseling
services at the institution of Tbingen
At that point, we are out of play. All medical relevant information is only
handled by the institution of Tbingen in its proper way, we do not have
access to any medical information you give to them or the resulting
exome data
 Applying for an exome sequencing

How can a patient apply to the

offering?
How do we come into play again afterwards?
At the end of the exome screening process, the
patient will get the full raw data of the exome
sequencing hes free to do with what he wants
If he decides to provide us his data (anonymously),
we can investigate into it for research purposes as
far as our current understanding goes
But important: no patient is forced to provide us his
data (its a completely free decision)
Nevertheless will the raw data (and raw analysis)
being to limited information or practically no
information for non experts, so it makes less sense to
apply to the offering without our expertise (or
expertise of other research groups in that field)
 Applying for an exome sequencing

How can a patient apply to the

offering?
Soin short the roles we take over in the
process
We do organize the collection of patients willing
to apply to an exome analysis
The institute of medical genetics in Tbingen
does the genetic counseling and exome
analysis work
We do the visualization and research work
regarding the body odor diseases
We do take the role of a patient organized
support group for body odor patients
Additional information
 Project link

Research gate project

Please find the project log under the following link:
https://www.researchgate.net/profile/Danny_Kunz/projects
 Prototype

Scalable metabolic simulation

prototype
Metabolic pathway simulation
Core enzyme data is based on the KEGG database
(http://www.genome.jp/kegg/)
Supports
Enzyme to gene/mRNA interaction
Gene expression to enzyme location mapping in the body
Gene expression to enzyme location mapping in the cell
Integration
Urine metabolite database integration
HMDB Human metabolic database (http://www.hmdb.ca/)
Gene database integration
KEGG (http://www.genome.jp/kegg/ )
Proteine atlas (http://www.proteinatlas.org/)
Drug interaction database integration
IUPHAR (http://www.guidetopharmacology.org/)
Drugbank partially (https://www.drugbank.ca/)
Food to Nutrient database
USDA Food Composition database (https://ndb.nal.usda.gov/ndb/)
 Prototype

Scalable metabolic simulation

prototype
Simulation allows us to visualize any
metabolic pathway
Possible to input altered levels of any
metabolite from any test (urine, blood,
skin surface) and mRNA expressions
Possible to trace impacts on the
metabolic pathways
Possible to triangulate enzyme
deficiencies
 Prototype

Scalable metabolic simulation

prototype
We are able to
simulate human
as well as
microbiological
pathways
 Prototype

Scalable metabolic simulation

prototype
With different cell
locations and
locations within a
cell
> 6900 enzymes
> 10500 reactions
> 18000 chemical
compounds
 Prototype

Metabolites to receptor to
drug interactions clustering
 Prototype

Metabolites to receptor to
drug interactions clustering
 Research areas
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Metabolic pathway simulations
danny.kunz@gmx.de
Candida pathogenicity in
Bromhidrosis
Candida pathogenicity in
Bromhidrosis
Candida pathogenicity in
Bromhidrosis
Candida pathogenicity in
Bromhidrosis
Tight junction counterflux and
amino acid transporters
Antifungal effect in Bromhidrosis