the ivdr concept and its use in biobanks, view on ... · 6. nmr can show resiliance/permanent...
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M.Spraul, H.Schäfer, C.Cannet, F.Fang
Bruker BioSpin Biobank Webinar 2018
The IVDr Concept and its Use in Biobanks,View on Personalized Metabolic Profiles
The IVDr Concept
IVDr= In Vitro Diagnostic Research
IVDr:
Offering a completely standardized push button concept based on the IVDrPlatform and its embedded solutions for Clinical and Translational Research allowing:
- integration of results from different user groups all over the world, forminga sofar unthinkable reservoir of completely compatible spectral data andanalysis results
- Speed up translation to future diagnostic methods, be it for personalizedmedicine or populationwide studies on phenotypes and associated riskfactors.
- Development of future diagnostic routines with unmatched specificity andsensitivity
- Enabling tools for quantification of a large number of compound
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IVDr-Platform +Tools3
The IVDr Platform concept
External Partner 1
Cardiovascular
Diseases
In progress
External Partner 2
Prostate Cancer in
progress
External Partner 3
Obesity/Diabetes
Metabolic Syndrome
In progress
External developments in
R&D Ecosystem
IVDr-Platform and Standardization : Allows to combine solutions, developed byBruker BioSpin and/or external partners
• FoodScreener
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e.g. Addressing CVD risk worldwide
Note: Bodyfluid spectral databases only make sense, when data
implemented are run identically (SOPs)
Currently > 65 groups worldwide operate under Bruker NMR SOPs
Data
Analysis
Operation based on complete standardization
guarantees unrestricted exchangeability of
data worldwide
Innovation with Integrity
Longitudinal NMR Reproducibilityringtest on 11 IVDr platforms in 5 organizations on lipoprotein analysisDoi: 10.1021/acs.analchem.8b02412
NCEP Criteria for Lipid and Lipoprotein Testing
Instrument specific variance in QC samples
5 Lipoprotein Ringtest
Biobanks and NMR
NMR can provide added
value to biobanks:
Extensive QC ofIncoming samples
Offer metadata
Selected spectra
from inventory
Support Clinical trials
with spectra instead
of aliquots to
measure
Build compatible
spectra inventory
To other biobanks ww
Build compatible Spectra base withPhenome centers
QC processGenerates NMRData for storage in the biobank
Add AnalysisResults to spectraAnd metadata: e.g.Urine Quant. LipoproteinSubclass Analysis
Sort outAliquots withLow quality
Support developmentOf new diagnosticroutines
NMR for Biobanks
Gain new funding possibilities
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Biobank WorkflowB.I.Methods – Spectrum – B.I.BioBankTool– QC results
B.I.Methods
B.I.
BioBank
Tool
7 NMR for Biobanks
Biobank QC in Plasma/Serum and Urine
Criteria Plasma/Serum Criteria Urine
Matrix Identity Test Matrix Identity Test
Matrix Integrity Test Matrix Integrity Test
Matrix Contamination Test Matrix ContaminationTest
NMR preparation NMR preparation
NMR measurement NMR measurement
Medication Test
Protein Background Test
Test for further indicative parameters
8 NMR for Biobanks
B.I.BioBankToolQC report urineProtein Background
Protein in Urine can have different reasons:
• Kidney damage
• Diabetes
• High blood pressure
• Eating too much protein supplements
• Fever
• Stress
• Preeclampsia
Can be compared to metadata
Visualization of protein backgroundDistribution In 13.000 urine spectraused for validation
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Biobank Input
Quality Control by NMR
Examples
10 NMR for Biobanks
Also Citrate Plasma, Heparine Plasma
Matrix Identity Test MatrixContaminationTests
Biobank QC passed successfullyTransfer of spectrum into BiobankTransfer of quantification data into Biobank
B.I.QUANT-UR
B.I.QUANT-PSB.I.LISA
NMR for Biobanks11
Classical Organization of a Clinical Trialgenerating cohorts:NMR can provide a better way
Group organizingClinical Trial
Groups and Biobanks participating
In Clinical Trial
?
NMR for Biobanks12
Reduce the number of samples to be generated for a clinical trial by adding metadata selected Biobank NMR spectra instead of samples
Group organizingClinical Trial
providing andmeasuring Samples
Groups and Biobanksparticipating
In Clinical TrialProviding samples
NMR Spectra
NMR Spectra NMR Spectra
NMR for Biobanks13
• Some results with relevance for precisionmedicine and precision nutrition
Back to precision medicine
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Person specific self-referencing fingerprints allowHealth assessment from metabolic trajectories
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40
60
80
time
‚Invariant‘
How to solve high urine variabilityUse several snap shots per person!
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Several spectra per person allow the definitionof an invariant metabolic profile per person
22 Volunteers (25-50J.)
40 Samples / person
3 Month collection
- Strip off daily
variation
- Identification of
invariant patterns
original
invariant
Bertini, I. et al., PNAS Feb. 5, 2008
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Person prediction accuracy depending onhealth status, recovery and permanentchanges
DOi : 10.1021/acs.jproteom.5b0275
AS and BV had relocation
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Persons with strong deviations:explanations
AG female 2 pregnancies, in 2014 breastfeeding,
profile changes in lactose, glycine up (reported for
pregnancy and lactating phase)
back to high recognition rate in 2015
AW Male prolonged antibiotic treatment
secondary lactose intolerance in 2014
withdraw fresh dairy from diet, gut microbiom changes
trigonelline, hippuric acid and Hydroxyisobutyrate,
ascorbic acid down, longterm stress
2015 dairy resumed, no antibiotics
Back to high recognition rate 2015
BD 2 pregnancies, not lactating at collections
2014 Total thyroid removal due to cancer,
thyroidal hormon treatment afterwards
permanent distortion of metabolic profile
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Control sample Donor had cardiovascular event 3 days after blood collection
Use Lipoprotein subclass analysis tooptimize treatment on a personalized basis
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Use longitudinal NMR based screening to select and optimize treatment in PKU on a personal basis compared to healthy and disease cohort
Classification model:PCA-DA
Projection of the scores of the patients treated with sapropterindihydrochloride(Kuvan®) treatment (n=12) to the classification model
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Summary
1. NMR supports biobanking by comprehensive quality control
2. NMR can add important information to be stored in biobanks, spectra, analysis results
like quantification of small molecule metabolites and lipoprotein subclass analysis
3. NMR can help to reduce cost and time in clinical trials by using spectra/analysis from various
biobanks instead of generation of new samples
4. NMR can differentiate persons by their invariant metabolic profile
5. NMR can follow invariant personal metabolic profiles and show early deviations
6. NMR can show resiliance/permanent change of the personalized metabolic profile after
disease events
7. NMR can be used to identify best treatment and optimize it, revealing dose response
differences
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Thank you
• M.Nauck et al Greifswald University Hospital Germany
• F.Trefz, J.Okun, G.Hofmann Heidelberg Hospital PediatricsGermany
• J.Nicholson, J.Lindon, E.Holmes, B.Jimenez Imperial College London UK
• C.Luchinat et al CERM, Florence Italy
• S.Aygen INFAI, Cologne Germany
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