ArticleComputational and structural biotechnology journal2019
Accounting for biological variation with linear mixed-effects modelling improves the quality of clinical metabolomics data.
Article in Computational and structural biotechnology journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Flavonoids fromJournal of enzyme inhibition and medicinal chemistry · 2026Article
- Breastfeeding type is associated with urinary metabolic changes in early life: influence of sex and early weight gain in healthy term infants.Molecular and cellular pediatrics · 2026Article
- Application of Mass Spectrometry-Based Metabolomics and Machine Learning in the Diagnostics of Lyme Neuroborreliosis.ACS omega · 2026Article
- The Constrained Disorder Principle: A Paradigm Shift for Accurate Interactome Mapping and Information Analysis in Complex Biological Systems.Bioengineering (Basel, Switzerland) · 2025Review
- Integrating Advanced Metabolomics and Machine Learning for Anti-Doping in Human Athletes.Metabolites · 2025Review
- A Comprehensive Model for Separating Systematic Bias and Noise in Metabolomic Timecourse Data-A Nonlinear B-Spline Mixed-Effects Approach.Biotechnology and bioengineering · 2025Article
- A Comparison of the Treatment Effects of a Risperidone Solution, an Equal Ratio of DHA/ARA, and a Larger Ratio of Omega-6 PUFA Added to Omega-3 PUFA: An Open-Label Clinical Trial.Current issues in molecular biology · 2025Article
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- Unraveling Metabolic Changes following Stroke: Insights from a Urinary Metabolomics Analysis.Metabolites · 2024Article
- Host-derived organic acids enable gut colonization of the honey bee symbiont Snodgrassella alvi.Nature microbiology · 2024Article
- Metabolomics in Preclinical Drug Safety Assessment: Current Status and Future Trends.Metabolites · 2024Review
- Data processing solutions to render metabolomics more quantitative: case studies in food and clinical metabolomics using Metabox 2.0.GigaScience · 2024Article
- Targeted quantitative metabolomics with a linear mixed-effect model for analysis of urinary nucleosides and deoxynucleosides from bladder cancer patients before and after tumor resection.Analytical and bioanalytical chemistry · 2023Article
- Metabolomics meets systems immunology.EMBO reports · 2023Review
- Plasma carnitine concentrations in Medium-chain acyl-CoA dehydrogenase deficiency: lessons from an observational cohort study.Journal of inherited metabolic disease · 2022Observational
- Serum Bile Acid Profiling and Mixed Model Analysis Reveal Biomarkers Associated with Pruritus Reduction in Maralixibat-Treated Patients with BSEP Deficiency.Metabolites · 2022Article
- GC × GC-TOFMS metabolomics analysis identifies elevated levels of plasma sugars and sugar alcohols in diabetic mellitus patients with kidney failure.The Journal of biological chemistry · 2022Article
- The gut microbiota affects the social network of honeybees.Nature ecology & evolution · 2022Article
- Promoter hypermethylation of GALR1 acts as an early epigenetic susceptibility event in colorectal carcinogenesis.Journal of human genetics · 2022Article
- Metabolomics in clinical and forensic toxicology, sports anti-doping and veterinary residues.Drug testing and analysis · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolite profiles from biological samples suffer from both technical variations and subject-specific variants. To improve the quality of metabolomics data, conventional data processing methods can be employed to remove technical variations. These methods do not consider sources of subject variation as separate factors from biological factors of interest. This can be a significant issue when performing quantitative metabolomics in clinical trials or screening for a potential biomarker in early-stage disease, because changes in metabolism or a desired-metabolite signal are small compared to the total metabolite signals. As a result, inter-individual variability can interfere subsequent statistical analyses. Here, we propose an additional data processing step using linear mixed-effects modelling to readjust an individual metabolite signal prior to multivariate analyses. Published clinical metabolomics data was used to demonstrate and evaluate the proposed method. We observed a substantial reduction in variation of each metabolite signal after model fitting. A comparison with other strategies showed that our proposed method contributed to improved classification accuracy, precision, sensitivity and specificity. Moreover, we highlight the importance of patient metadata as it contains rich information of subject characteristics, which can be used to model and normalize metabolite abundances. The proposed method is available as an R package lmm2met.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.