A Workflow For Integrated Processing of Multi-Cohort Untargeted 1H NMR Metabolomics Data In Large Scale Metabolic Epidemiology

Ibrahim Karaman, Diana Dos Santos Ferreira, John Lindon, Claire Boulangé, Manuja Kaluarachchi, David Herrington, Anthony Dona, Raphaële Castagné, Alireza Moayyeri, Benjamin Lehne, Marie Loh, Paul S. de Vries, Abbas Dehghan, Oscar Franco, Albert Hofman, Evangelos Evangelou, Ioanna Tzoulaki, Paul Elliott, Timothy Ebbels

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)
185 Downloads (Pure)


Large-scale metabolomics studies involving thousands of samples present multiple challenges in data analysis, particularly when an untargeted platform is used. Studies with multiple cohorts and analysis platforms exacerbate existing problems such as peak alignment and normalization. Therefore, there is a
need for robust processing pipelines which can ensure reliable data for statistical analysis. The COMBIBIO project incorporates serum from approximately 8000 individuals, in 3 cohorts, profiled by 6 assays in 2 phases using both 1H-NMR and UPLC-MS. Here we present the COMBI-BIO NMR analysis pipeline and demonstrate its fitness for purpose using representative quality control (QC) samples. NMR spectra were first aligned and normalized. After eliminating interfering signals, outliers identified using Hotelling’s T2 were removed and a cohort/phase adjustment was applied, resulting in two NMR datasets (CPMG and NOESY). Alignment of the NMR data was shown to increase the correlation-based alignment quality measure from 0.319 to 0.391 for CPMG and from 0.536 to 0.586 for NOESY, showing that the improvement was present across both large and small peaks. End-to-end quality assessment of the pipeline was achieved using Hotelling’s T2 distributions. For CPMG spectra, the interquartile range decreased from 1.425 in raw QC data to 0.679 in processed spectra, while the corresponding change for NOESY spectra was from 0.795 to 0.636 indicating an improvement in precision following processing. PCA indicated that gross phase and cohort differences were no longer present. These results illustrate that the pipeline produces robust and reproducible data, successfully addressing the methodological challenges of this large multi-faceted study.
Original languageEnglish
Pages (from-to)4188-4194
Number of pages7
JournalJournal of Proteome Research
Issue number12
Early online date12 Sept 2016
Publication statusPublished - 2 Dec 2016


  • metabolomics
  • NMR
  • epidemiology
  • large scale
  • preprocessing
  • normalization
  • alignment
  • quality control
  • multicohort


Dive into the research topics of 'A Workflow For Integrated Processing of Multi-Cohort Untargeted 1H NMR Metabolomics Data In Large Scale Metabolic Epidemiology'. Together they form a unique fingerprint.

Cite this