Tranquility

Tranquility
Setting new standards
of healthcare
Vuk Devrnja
International Medical Officer | Genoma
Non-Invasive
Prenatal Testing
Genoma’s
mission
(NIPT)
• Premium Swiss Quality – cutting-edge technologies and
Noninvasive
prenatal
(NIPT) processes
is a screening
scientific
knowledge
on testing
its automated
to deliver the
method
forinformation
detecting certain
specificpreventive
chromosomal
vital
genetic
that enables
and
abnormalities
in a developing baby.
personalised
medicine
Noninvasive
testing -istransformative
a sophisticated
blood test
• Innovation
andprenatal
Developments
research
and
that examines
DNAbenefits
in the maternal
bloodstream
to
translating
it into fetal
tangible
for society:
technology
determine whether
a baby
is at riskEurope
of Down
advancement
accessible
throughout
atsyndrome,
an affordable
extra sequences of chromosome 13 (trisomy 13), extra
price
sequences of chromosome 18 (trisomy 18) or a sex
chromosome
as Turner
syndrome.
• Local
presence abnormality,
and Support such
with close
proximity
to clients and
medical community
• Very high throughput platform (over 100’000 samples/year)
Non-Invasive
Prenatal Testing (NIPT)
Genoma’s mission
NIPT:Quality – cutting-edge technologies and
•Principle
PremiumofSwiss
<scientific
1 % of total
DNA in on
maternal
circulation
is fetal to deliver the
knowledge
its automated
processes
5-30
% of cell-free
DNAthat
in maternal
blood stream
vital
genetic
information
enables preventive
andis fetal
personalised medicine
NIPT
utilises these
in
• Innovation
and Developments
- transformative research and
order
to determine
translating
it into tangible benefits for society: technology
potential
chromosomal
advancement
accessible throughout Europe at an affordable
abnormalities
without
price
exposing the mother or
child
to risk
of
• Local
presence
and Support with close proximity to clients and
miscarriage
of invasive
medical community
diagnostic techniques.
• Very high throughput platform (over 100’000 samples/year)
Prenatal testing methods not based on
DNA
Combined first-trimester testing (Triple
Test):
Blood test – weeks 9-13
Ultrasound – weeks 11-12 of gestation
Factors influencing Triple Test:
Gestational age, maternal weight, multiple
pregnancy, IDDM, gravidity/parity, previous
pregnancy
Invasive testing based on DNA
Chorion Villus Sampling
Amniocentesis
Analysis method
Cytogenetics:
• Karyotype
• Fluorescence in Sito Hybridation
(FISH)
Molecular:
Performed after 10-13 weeks of
gestation
Performed after 14 weeks of
gestation
Risks:
Vaginal bleeding
Amniotic fluid leakage
Infections
Chorio-amnionitis
Fetal loss: 0.5%
Risks:
Transient vaginal spotting: 1-2%
Amniotic fluid leakage: 1-2%
Chorio-amnionitis: < 0.1%
Needle injuries to the fetus (rare
when
ultrasonographic guidance is used)
• Quantitative Fluorescence Polymerase chain reaction (QF-PCR)
• Multiplex Ligation-Dependent Probe
Amplification (MLPA)
• Comparative Genomic Hybridization
(aCGH) and Single Nucleotide
Polymorphism (SNP array)
Aneuploidies screening objectives
 Increased sensitivity
 Reduced fetal invasion
 Fewer fetal losses
 Reduce the anxiety of the couple
 Early
 Lower cost
Tranquility®
- CE-IVD certified
Genoma’s mission
- Tranquility is a non-invasive test of fetal
•DNA
Premium
Swiss Quality
– cutting-edge
technologies and
with CE-IVD
certification
for
scientific21,
knowledge
on(also
its automated
processes to deliver the
trisomies
18 and 13
allows
vitalsex
genetic
information that enables preventive and
fetal
determination).
personalised medicine
• Innovation and Developments - transformative research and
- The
entire process
connected
to for society: technology
translating
it into tangible
benefits
trisomies
21, 18accessible
and 13 (collection,
advancement
throughout Europe at an affordable
preparation,
sequencing, bioinformatic
price
analysis and report) are in accordance
•with:
Local presence and Support with close proximity to clients and
medical community
In Vitro Diagnostics Directive (98/79/EC)
• Very high throughput platform (over 100’000 samples/year)
Tranquility
Technology and expertise
Genoma’s–mission
• Premium Swiss Quality – cutting-edge technologies and
Tranquility
is knowledge
based on whole
scientific
on its automated processes to deliver the
genome
sequencing,
using Next
vital genetic
information
that enables preventive and
Generation
Sequencing
(NGS)
personalised
medicine
platforms.
• Innovation and Developments - transformative research and
translating
it into tangible
Test is performed
in thebenefits for society: technology
advancement accessible throughout Europe at an affordable
Genoma Swiss Biotechnology
price
laboratories in Geneva.
• Local presence and Support with close proximity to clients and
community
Thismedical
is the largest
clinical genetics
laboratory in Europe.
• Very high throughput platform (over 100’000 samples/year)
Tranquility mission
– availability
Genoma’s
• Premium Swiss Quality – cutting-edge technologies and
scientific knowledge
on its automated processes to deliver the
- Tranquility
can be performed
vital genetic information that enables preventive and
any day of the week,
personalised medicine
365 days a year
gestational
week in
•10th
Innovation
and Developments
- transformative research and
translatingpregnancies
it into tangible benefits for society: technology
singleton
advancement
accessible
12th
gestational
week in throughout Europe at an affordable
price
multigestational
pregnancies
• Local presence and Support with close proximity to clients and
- Results
available 5 working
medicalare
community
days after sample arrival to the
•laboratory
Very high throughput platform (over 100’000 samples/year)
What is detected?
Genoma’s
mission
• Premium
Swiss Quality
– cutting-edge
Chromosomal
Aneuploidies
Gender technologies and
scientific knowledge on its automated processes to deliver the
Trisomy 21
Male
vital genetic information that enables preventive and
Trisomy 18
Female
personalised
medicine
Trisomy 13
• Innovation and Developments - transformative research and
Microdeletions
Sex Chromosome Disorders
translating it into tangible benefits for society: technology
Angelman accessible
Syndrome throughout
Triple XEurope
Syndrome
advancement
at (XXX)
an affordable
price Cri Du Chat Syndrome
Jacobs Syndrome (XYY)
DiGeorge Syndrome
Klinefelter Syndrome (XXY)
• Local presence and Support with close proximity to clients and
Prader-Willi
Syndrome
Turner Syndrome (45 X)
medical
community
2q33.1 deletion Syndrome
• Very high throughput platform (over 100’000 samples/year)
Microdeletion syndromes
Microdeletion syndrome
DiGeorge syndrome
Cri-du-chat Syndrome (5p-)
location
22q11.2 deletion
5p15.2
Size deleted
Incidence
>3Mb (~85% of cases) 1/4,000
Clinical features
• Variable intellectual disability,
• Heart defects (74% of individuals),
• Palatal abnormalities
• Immune deficiency
• Normal lifespan.
3.2 Mb – 30 Mb
1 in 20,000-50,000 • Significant intellectual disability,
• Cat-like cry, dysmorphic features
• 10% mortality in first year
Prader-Willi Syndrome
15q11.2-q13
5-6Mb
1 in 10,000-25,000 • Severe hypotonia
• Feeding difficulties in early infancy, followed by
excessive eating leading to morbid obesity.
• Developmental delay
• Hypogonadism, short stature, characteristic
facial features
Angelman Syndrome
15q11.2-q13
5-6Mb
1 in 12,000
• Intellectual disability & developmental delay
• Speech impairment,
• Ataxia, seizures, dysmorphic features
• Normal lifespan
Microdeletion detection challenges
Resolution of the analysis is determined by the number of reads:
Uniquely mapped reads : longer reads have more chances to be unique
Resolution of 3 Mb would require 150M reads
Resolution of 2 Mb would require 192M reads
Resolution of 1 Mb would require 380M reads
-> too expensive for a screening test
Range of currently implemented tests: from 2M to 25M
Tranquilitymission
- process
Genoma’s
• Premium Swiss Quality – cutting-edge technologies and
scientific knowledge on its automated processes to deliver the
vital genetic information that enables preventive and
personalised medicine
• Innovation and Developments - transformative research and
translating it into tangible benefits for society: technology
advancement accessible throughout Europe at an affordable
price
• Local presence and Support with close proximity to clients and
medical community
• Very high throughput platform (over 100’000 samples/year)
Genoma’s
mission
Testing process
Tranquility utilises Next Generation Sequencing (NGS):
• Premium Swiss Quality – cutting-edge technologies and
Innovative high tech method for genome sequencing, which can
scientific knowledge on its automated processes to deliver the
be used
to detect
chromosomal
abnormalities.
vital genetic
information
that enables
preventive and
personalised medicine
In principle, bases of small fragment of DNA are sequentially
identified
fromand
signals
emitted as
each fragment
is re- and
• Innovation
Developments
- transformative
research
synthesised
DNA template
translatingfrom
it intoa tangible
benefitsstrand.
for society: technology
advancement accessible throughout Europe at an affordable
price
NGS
extends across millions of reactions in a massively parallel
fashion, rather than being limited to a single or a few DNA
• Local presence
and Support
with sequencing
close proximity
clients
and
fragments.
This advance
enables
of to
large
stretches
medical
community
of DNA
base
pairs spanning entire genomes, with instruments
capable of producing hundreds of gigabases of data in a single
• Very high throughput platform (over 100’000 samples/year)
sequencing run.
Technology comparisson
Technology comparisson
Technology comparison
Genome-wide MPS (Tranquility)
- Low Assay failure rates
- Faster analysis times
- Ability to add new content to test menu
FetalDNA fractionGenoma’s
missionfactors
• Premium Swiss Quality – cutting-edge technologies and
scientific
on its automated processes to deliver the
Maternal knowledge
weight
genetic
information
that
enables preventive and
The vital
amount
of maternal
cell-free
DNA
personalised
medicine
increases
with an increase
in body weight.
Increased maternal weight may prevent a
satisfiable
isolation
cell-free-fetal DNA
• Innovation
andofDevelopments
- transformative research and
translating it into tangible benefits for society: technology
advancement
accessible throughout Europe at an affordable
Maternal health
price
Certain
health conditions, such as infections,
cancer or other conditions that may require
• Local
presence
blood
transfusion,
alsoand
maySupport
prevent with close proximity to clients and
satisfiable
isolation
of cell-free-fetal DNA.
medical
community
• Very high throughput platform (over 100’000 samples/year)
sis
ation
th
oton
or
Tranquility technical workflow
Bioinformatic analysis and report generation – InKaryo biotechnology
- Data imported automatically from Ion Proton and process on a CE-IVD
certified software
- Calculation of risk of affected or unaffected pregnancy
- Process takes 5-7 minutes per sample
- A validity check based on sequencing data quality, fetal fraction estimate,
number of sequencing reads is performed to ensure the validity of results
Advanced bioinformatics
Genoma’s
mission
An• advanced
is utilised
for
Premiumalgorithm
Swiss Quality
– cutting-edge
technologies and
analysing
sequenced
samples,
scientific
knowledge
on its automated processes to deliver the
evaluating
the chromosome
numbers,
vital genetic
information
that enables preventive and
and other characteristics.
personalised medicine
The
most advanced
bioinformatics- transformative research and
• Innovation
and Developments
platform
used for
analysis
is called
translating
it into
tangible
benefits for society: technology
InKaryo
and is theaccessible
property ofthroughout Europe at an affordable
advancement
Genoma
price Swiss Biotechnology.
• Local presence
and Support
with close proximity to clients and
Calculating
the fetal fraction
and
incorporating
it into the bioinformatics
medical community
algorithm allows Tranquility the highest
levels
of analytical
performance
as well
• Very
high throughput
platform
(over 100’000 samples/year)
as reliability and reproducibility.
Evolution of Cytogenetic Testing
• Highlights in e-karyotyping development
Karyotyping
~1950
Microscope
FISH
~1998
DNA Label
CMA
~2004
Array
eKaryotype™
2013
Next-gen sequencing
- From analog to digital
- NGS performance exceeds that of Chromosomal MicroArrays
(CMA)
- Cost inflection point is occurring now
Genoma’s
mission workflow
InKaryo eKaryotype
Karyotype Specific Massive Parallel Shotgun Sequencing (KS-MPSS)
• Premium Swiss Quality – cutting-edge technologies and
scientific knowledge on its automated processes to deliver the
vital genetic information that enables preventive and
personalised medicine
Sample and Developments
Library- transformative research
Shotgun and
• Innovation
Requisition
Preparation
Sequencing
translating it into tangible benefits for society: technology
advancement accessible throughout Europe at an affordable
price
• Local presence and Support with close proximity to clients and
Proprietary
Bioinformatics
medical
community
• Very high throughput platform
(over 100’000 samples/year)
eKaryotyping
Bioinformatics
eKaryotype
InKaryo eKaryotype:
CGH Array Karyotype:
The central grey band almost becomes a line, indicating
The width of the central grey band represents the noise for quantifying
significant noise reduction in quantifying the 2 copies of
2 copies of chromosome
chromosome bins.
Results
Genoma’s
mission
• Premium Swiss Quality – cutting-edge technologies and
scientific knowledge on its automated processes to deliver the
vital genetic information that enables preventive and
personalised medicine
• Innovation and Developments - transformative research and
translating it into tangible benefits for society: technology
advancement accessible throughout Europe at an affordable
price
• Local presence and Support with close proximity to clients and
medical community
• Very high throughput platform (over 100’000 samples/year)
Results
Genoma’s
mission
Results of Tranquility present the absence of
• Premium Swiss Quality – cutting-edge technologies and
risk that the fetus carries a chromosomal
scientific knowledge on its automated processes to deliver the
aneuploidy or microdeletion. If requested sex
vital genetic information that enables preventive and
determination will be performed as well.
personalised medicine
In twin pregnancies Tranquility will determine
• Innovation and Developments - transformative research and
the risk of one of the feti having a trisomy 21,
translating it into tangible benefits for society: technology
18 or 13. If requested. Presence of Y
advancement
chromosome
will be accessible
determined. throughout Europe at an affordable
price
Chromosome 21, 18, 13 (CE-IVD):
• Local presence and Support with close proximity to clients and
- “Aneuploidy
detected”
medical not
community
- “Aneuploidy
• Very highdetected”
throughput platform (over 100’000 samples/year)
Results
Genoma’s
mission
Sex chromosome aneuploidies:
• Premium Swiss Quality – cutting-edge technologies and
- “Results consistent with two sex
scientific knowledge on its automated processes to deliver the
chromosomes” – based on country
vital genetic information that enables preventive and
- “Result consistent with sex chromosome
personalised medicine
aneuploidy”
- Aneuploidy detected will be listed as:
• Innovation and Developments - transformative research and
XXY, XXX, X, XYY.
translating it into tangible benefits for society: technology
advancement accessible throughout Europe at an affordable
Microdeletions:
price
“Detected” - one or more microdeletions has
been
detected.
The and
reportSupport
will contain
the proximity to clients and
• Local
presence
with close
genomic
position
and size of microdeletion
medical
community
on a chromosome. If the microdeletion has
previously been associated with the specific
• Very high throughput platform (over 100’000 samples/year)
syndrome, such designation will be provided.
[email protected]
Genoma SA
12, Chemin des Aulx
1228 Plan Les Ouates, Geneva
www.genoma.com