pr9b00535_si_001.pdf (4.89 MB)
Untargeted Serum Metabolic Profiling by Comprehensive Two-Dimensional Gas Chromatography–High-Resolution Time-of-Flight Mass Spectrometry
journal contribution
posted on 2019-12-13, 13:35 authored by Nicolas Di Giovanni, Marie-Alice Meuwis, Edouard Louis, Jean-François FocantWhile many laboratories take appropriate care, there
are still
cases where the performances of untargeted profiling methods suffer
from a lack of design, control, and articulation of the various steps
involved. This is particularly harmful to modern comprehensive analytical
instrumentations that otherwise provide an unprecedented coverage
of complex matrices. In this work, we present a global analytical
workflow based on comprehensive two-dimensional gas chromatography
coupled to high-resolution time-of-flight mass spectrometry. It was
optimized for sample preparation and chromatographic separation and
validated on in-house quality control (QC) and NIST SRM 1950 samples.
It also includes a QC procedure, a multiapproach data (pre)processing
workflow, and an original bias control procedure. Compounds of interest
were identified using mass, retention, and biological information.
As a proof of concept, 35 serum samples representing three subgroups
of Crohn’s disease (with high, low, and quiescent endoscopic
activity) were analyzed along with 33 healthy controls. This led to
the selection of 33 unique candidate biomarkers able to classify the
Crohn’s disease and healthy samples with an orthogonal partial
least-squares discriminant analysis Q2 of 0.48 and a receiver-operating-characteristic area under the curve
of 0.85 (100% sensitivity and 82% specificity in cross validation).
Fifteen of these 33 candidates were reliably annotated (Metabolomics
Standards Initiative level 2).
History
Usage metrics
Categories
Keywords
33 candidatesquality controlmultiapproach dataCrohnendoscopic activitytime-of-flight mass spectrometrybias control procedurecandidate biomarkersreceiver-operating-characteristic areaworkflowleast-squares discriminant analysis Q 2Untargeted Serum Metabolic Profilinggas chromatography35 serum samplesQC proceduresample preparationNIST SRM 1950 samples
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC