Normalization
to account for variation in urinary dilution is crucial
for interpretation of urine metabolic profiles. Probabilistic quotient
normalization (PQN) is used routinely in metabolomics but is sensitive
to systematic variation shared across a large proportion of the spectral
profile (>50%). Where
1
H nuclear magnetic resonance
(NMR)
spectroscopy is employed, the presence of urinary protein can elevate
the spectral baseline and substantially impact the resulting profile.
Using
1
H NMR profile measurements of spot urine samples
collected from hospitalized COVID-19 patients in the ISARIC 4C study,
we determined that PQN coefficients are significantly correlated with
observed protein levels (
r
2
= 0.423,
p
< 2.2 × 10
–16
). This correlation
was significantly reduced (
r
2
= 0.163,
p
< 2.2 × 10
–16
) when using a
computational method for suppression of macromolecular signals known
as small molecule enhancement spectroscopy (SMolESY) for proteinic
baseline removal prior to PQN. These results highlight proteinuria
as a common yet overlooked source of bias in
1
H NMR metabolic
profiling studies which can be effectively mitigated using SMolESY
or other macromolecular signal suppression methods before estimation
of normalization coefficients.
Objectives: Peptide tyrosine tyrosine (PYY) exists as two species, PYY 1-36 and PYY 3-36 , with distinct effects on insulin secretion and appetite regulation. The detailed effects of bariatric surgery on PYY 1-36 and PYY 3-36 secretion are not known as previous studies have used nonspecific immunoassays to measure total PYY. Our objective was to characterize the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on fasting and postprandial PYY 1-36 and PYY 3-36 secretion using a newly developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.Design and Subjects: Observational study in 10 healthy nonobese volunteers and 30 participants with obesity who underwent RYGB (n = 24) or SG (n = 6) at the Imperial Weight Centre [NCT01945840]. Participants were studied using a standardized mixed meal test (MMT) before and 1 year after surgery. The outcome measures were PYY 1-36 and PYY 3-36 concentrations.
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