Overcoming Sample Matrix Effect in Quantitative Blood Metabolomics Using Chemical Isotope Labeling Liquid Chromatography Mass Spectrometry
Bibliographic record
Abstract
Blood is widely used for discovery metabolomics to search for disease biomarkers. However, blood sample matrix can have a profound effect on metabolome analysis, which can impose an undesirable restriction on the type of blood collection tubes that can be used for blood metabolomics. We investigated the effect of blood sample matrix on metabolome analysis using a high-coverage and quantitative metabolome profiling technique based on differential chemical isotope labeling (CIL) LC-MS. We used 12 C-/ 13 C-dansylation LC-MS to perform relative quantification of the amine/phenol submetabolomes of four types of samples (i.e., serum, EDTA plasma, heparin plasma, and citrate plasma) collected from healthy individuals and compare their metabolomic results. From the analysis of 80 plasma and serum samples in experimental triplicate, we detected a total of 3651 metabolites with an average of 1818 metabolites per run ( n = 240). The number of metabolites detected and the precision and accuracy of relative quantification were found to be independent of the sample type. Within each sample type, the metabolome data set could reveal biological variation (e.g., sex separation). Although the relative concentrations of some individual metabolites might be different in the four types of samples, for sex separation, all 66 significant metabolites with larger fold-changes (FC ≥ 2 and p < 0.05) found in at least one sample type could be found in the other types of samples with similar or somewhat reduced, but still significant, fold-changes. Our results indicate that CIL LC-MS could overcome the sample matrix effect, thereby greatly broadening the scope of blood metabolomics; any blood samples properly collected in routine clinical settings, including those in biobanks originally used for other purposes, can potentially be used for discovery metabolomics.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".