handouts metabolomics
TRANSCRIPT
-
7/30/2019 Handouts Metabolomics
1/39
Metabolomics by
NMR
Multivariate AnalysisPrincipalComponent Analysis
PLS
Regression AnalysisApplications toNMR
-
7/30/2019 Handouts Metabolomics
2/39
Multivariateanalysis
Allowsustoanalysemanyvariablesatthe
sametime
Necessarywhenwehavehundreds(or
thousands)
of
variables Alsoveryusefulforuncoveringhidden
relationships
-
7/30/2019 Handouts Metabolomics
3/39
PCA(Principal
Component Analysis)
Finds underlying (hidden)datastructures inotherwise
uninterpretable data
Advanced statistical method
Allows grouping ofdataafter combinations ofvariables
-
7/30/2019 Handouts Metabolomics
4/39
PrincipalComponents
=Axis of
Biggest Spread
Figs from:KimH.Esbensen,Multivariate DataAnalysis inPractice,5th edition,Camo Process ASOslo,2004
-
7/30/2019 Handouts Metabolomics
5/39
Asimple
example
studenthrlngde[cm]
sko-strrelse
1 50 37
2 10 46
3 2 42
4 30 395 40 39
6 1.5 45
7 0.6 45
8 3 43
9 40 37
10 4 40
11 1.5 43
12 1.8 43
13 3 43
14 2 43
15 25 43
16 30 39
17 25 38
18 45 41
19 3.5 42
20 1 41
21 2 42
22 50 38
23 30 36
24 55 39
25 40 43
26 2 43
27 40 38
28 1.5 43
29 30 37
30 33 39
31 30 38
32 33 35
-
7/30/2019 Handouts Metabolomics
6/39
First PCisthevector through thedata
with theleast sum
of
square residuals
Shoe size
Hairlength
[cm]
-
7/30/2019 Handouts Metabolomics
7/39
Rotate tomake Trendline
NewXaxis
Scoreplot
-
7/30/2019 Handouts Metabolomics
8/39
PC1
PC2
Centerofdata
isused asorigin ofPC
coordinate system
This distance
represents the
scoreofsample
X onto PC1
X
This distance
represents the
scoreofsample
X onto PC2
Thedirection ofthePCaxes isgivenby
theloadings,i.e.relativeweights,of
thevariables
-
7/30/2019 Handouts Metabolomics
9/39
PCAanalysis yields
-
7/30/2019 Handouts Metabolomics
10/39
Some math.
X = t1
p1
+ + + E
p2
t2
Your data First principalcomponent
loadings
Second principalcomponent
Residuals
loadings
-
7/30/2019 Handouts Metabolomics
11/39
Asimple example
Europeandatafrom2006:
Healthylife
expectancy
(by
gender)
Grossdomesticproduct
Percentagesmokers(byage/gender)
Percentageoverweight(byage/gender)
Hospitalbedsper100000
Datafromhttp://ec.europa.eu/eurostat
-
7/30/2019 Handouts Metabolomics
12/39
Thedata
-
7/30/2019 Handouts Metabolomics
13/39
3Dplots
reveal nothing
%maleswith overweight
-
7/30/2019 Handouts Metabolomics
14/39
2Dplotscan reveal some connections
Healthy life yrs.vs.Smoker % Healthy life yrs.vs.overweight%
Some grouping ofcountries can be observed,butthepicture isnotclear
Correlation stronger forsmoker%than foroverweight%
-
7/30/2019 Handouts Metabolomics
15/39
PCA
brings some order into the
chaos
-
7/30/2019 Handouts Metabolomics
16/39
Loading plotlets us know the
interdependence ofthe
variables
We findtheexpected anticorrelation between healthy life years andsmoke /overweight.
Again,correlation is
stronger for
smoke%
than for
overweight%.
-
7/30/2019 Handouts Metabolomics
17/39
Remember
The
data
16
variables!!!
-
7/30/2019 Handouts Metabolomics
18/39
PCAwith
all
16
variables
-
7/30/2019 Handouts Metabolomics
19/39
Loading
plot
of
all
16
variables
-
7/30/2019 Handouts Metabolomics
20/39
Multivariate Modelling (PLSR)
Partial Least SquaresRegression
Model
Predict
-
7/30/2019 Handouts Metabolomics
21/39
PLSR finding theparametersbest
describing aproperty
-
7/30/2019 Handouts Metabolomics
22/39
PLSRon females showsunexpected
coincidence
-
7/30/2019 Handouts Metabolomics
23/39
Modelling based on PLS
R
Healthlife years (realdata)
-
7/30/2019 Handouts Metabolomics
24/39
What hasitgot todowith NMR???the
hell
-
7/30/2019 Handouts Metabolomics
25/39
NMR
of
blood serum
Complicated spectrum with thousands oflines
How toget started???
-
7/30/2019 Handouts Metabolomics
26/39
NMR
data
as
X
matrix
-
7/30/2019 Handouts Metabolomics
27/39
NMRdataasXmatrix
Thesame
like any other data
-
7/30/2019 Handouts Metabolomics
28/39
Rapidandnoninvasive diagnosisofthepresenceandseverityofcoronaryheart
diseaseusing
1HNMRbasedmetabonomics
BrindleJ,Antti H,HolmesE,etal.
NatureMedicine,December2002
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
29/39
Study
DesignDiagnosis study
36patientswithprovenCHD
30patients
with
normal
coronary
arteries
Exclusionsincludedpatientswithhighbloodpressure,diabetesorvalve
disease.
OnedimensionalprotonNMR
Principalcomponentanalysis(PCA)
Partial
least
squares
discriminantanalysis(PLSDA)
OrthogonalPLSDA
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
30/39
Study
DesignSeverity study
28
patients
with
single
vessel
disease
20patientswithdoublevesseldisease
28
patients
with
triple
vessel
disease
Similaranalysisasdiagnosis
study
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
31/39
Diagnosis Study
Results
2nd
and
3
rd
principal
componentsofPLSDA
showsomeclustering(PCA
notshown)
OPLS
DA
analysis
gives
a
clearerseparation
triple
vessel
disease
normal
angio
Key:
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
32/39
Diagnosis Study
Results Spectralpeakscorrelated
with
disease: 0.86ppm lipidCH3 1.26,1.30,1.34ppm lipid
CH2
Spectralpeakscorrelatedwithhealth:
1.22ppm lipidCH2 3.22ppm choline
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
33/39
Diagnosis Study
Results PLSDAmodel:
92%sensitivity
93%specificity
triple
vessel
disease
normal
angio
testset
Key:
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
34/39
Severity Study
Results
triplevessel
disease
singlevessel
disease
doublevessel
disease
Key:
Onlypartialseparationofgroupsbasedonseverityofdisease(but
muchbetterthanachievedcurrentlybyusingriskfactors)
MunsoorA.
Hanifa
-
7/30/2019 Handouts Metabolomics
35/39
Application toFoodAnalysis
Fruit Juices
http://www.brukerbiospin.com/metabolomics_food.html
-
7/30/2019 Handouts Metabolomics
36/39
Take Nfruit juicesamples
runNMR
spectra on all
of
them
Processing,data
pre
treatment
PCAhttp://www.brukerbiospin.com/fileadmin/be_user/general/public/sgfprofiling0810.pdf
-
7/30/2019 Handouts Metabolomics
37/39
Authentification of
Origin
http://www.brukerbiospin.com/fileadmin/be_user/general/public/sgf
profiling
0810.pdf
3Dscoresplot
-
7/30/2019 Handouts Metabolomics
38/39
Cheating with the
Juice?RealJuiceor Concentrate?
http://www.brukerbiospin.com/fileadmin/be_user/nmr/JuiceScreener/BrukerJuiceScreenerEditorial0108.pdf
Extra peak fromhydroxymethyl
furfural
Stemsfromexcessiveheattreatment
Less fruit content than promised?
-
7/30/2019 Handouts Metabolomics
39/39
And
now for
the
data
on you