1. A new pipeline for the normalization and pooling of metabolomics data
- Author
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Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, and Sub Inorganic Chemistry and Catalysis
- Subjects
Normalization (statistics) ,Pooling ,Computer science ,Pipeline (computing) ,Endocrinology, Diabetes and Metabolism ,computer.software_genre ,Microbiology ,Biochemistry ,Generalized linear mixed model ,Statistical power ,Article ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Cancer epidemiology ,Metabolites ,Metabolomics ,Imputation (statistics) ,Càncer ,Molecular Biology ,030304 developmental biology ,Cancer ,0303 health sciences ,Cancer och onkologi ,Bioinformatics (Computational Biology) ,Normalization ,Technical variability ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,Missing data ,QR1-502 ,3. Good health ,Diabetes and Metabolism ,Metabolòmica ,030220 oncology & carcinogenesis ,Cancer and Oncology ,Outlier ,Bioinformatik (beräkningsbiologi) ,Data mining ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,computer - Abstract
Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers, imputation of missing data, (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis, (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.
- Published
- 2021