The maternal serum metabolome by multisegment injection-capillary electrophoresis-mass spectrometry: a high-throughput platform and standardized data workflow for large-scale epidemiological studies.
Meera ShanmuganathanZachary KroezenBiban GillSandi AzabRussell J de SouzaKoon K TeoStephanie A AtkinsonPadmaja SubbaraoDipika DesaiSonia S AnandPhilip Britz-McKibbinPublished in: Nature protocols (2021)
A standardized data workflow is described for large-scale serum metabolomic studies using multisegment injection-capillary electrophoresis-mass spectrometry. Multiplexed separations increase throughput (<4 min/sample) for quantitative determination of 66 polar/ionic metabolites in serum filtrates consistently detected (coefficient of variance (CV) <30%) with high frequency (>75%) from a multi-ethnic cohort of pregnant women (n = 1,004). We outline a validated protocol implemented in four batches over a 7-month period that includes details on preventive maintenance, sample workup, data preprocessing and metabolite authentication. We achieve stringent quality control (QC) and robust batch correction of long-term signal drift with good mutual agreement for a wide range of metabolites, including serum glucose as compared to a clinical chemistry analyzer (mean bias = 11%, n = 668). Control charts for a recovery standard (mean CV = 12%, n = 2,412) and serum metabolites in QC samples (median CV = 13%, n = 202) demonstrate acceptable intermediate precision with a median intraclass coefficient of 0.87. We also report reference intervals for 53 serum metabolites from a diverse population of women in their second trimester of pregnancy.
Keyphrases
- capillary electrophoresis
- mass spectrometry
- high frequency
- pregnant women
- electronic health record
- high throughput
- ms ms
- pregnancy outcomes
- liquid chromatography
- quality control
- high resolution
- randomized controlled trial
- transcranial magnetic stimulation
- computed tomography
- magnetic resonance imaging
- preterm birth
- polycystic ovary syndrome
- data analysis
- gas chromatography
- body mass index
- tandem mass spectrometry
- deep learning
- case control
- blood glucose
- birth weight
- adipose tissue