Targeted metabolomics by Bevital
Learn more about Bevital´s targeted metabolomics solution
Why Targeted?
During the last 20 years Bevital´s scientists and technicians have specialized in targeted metabolomics and we believe that our targeted metabolomics solutions will suite for many research questions and projects, even if untargeted or semi-targeted approaches seem to be a good fit.
Untargeted, semi-targeted, and targeted metabolomics are three distinct strategies for studying metabolites. Selecting the most suitable approach depends on various factors, such as the research objectives and the study hypothesis.
Untargeted Metabolomics
Untargeted Metabolomics
Untargeted metabolomics is a hypothesis generating approach, analyzing as many metabolites as possible without prior knowledge of their identity. It’s used for broad, comprehensive profiling and discovery of new or unexpected metabolites.
Semi-Targeted Metabolomics
Semi-Targeted Metabolomics
Semi-targeted metabolomics focuses on a subset of metabolites, often from a specific pathway or class, but without the strict quantification requirements of targeted approaches. It combines some level of metabolite selection with exploratory analysis.
Targeted Metabolomics
Targeted Metabolomics
Targeted metabolomics specifically quantifies a predefined set of known metabolites. It is highly sensitive and precise, often used for hypothesis-driven research or validation of known metabolic pathways.
General Comparison
General Comparison
Targeted approaches are typically used for hypothesis testing, whereas untargeted methods are employed to generate hypotheses and discover new or unknown metabolites (Table 1). As a result, targeted metabolomics usually covers a limited range of analytes, typically around 50-200 metabolites, while untargeted approaches provide broader data, often identifying more than 10,000 so-called features.
When it comes to data quality, targeted approaches generally surpass untargeted methods for several reasons. Untargeted metabolomics only provides relative quantification, limiting the ability to compare data across different experiments, labs, cohorts, or studies. In contrast, targeted metabolomics delivers absolute quantification (typically in nmol/L or µg/mL), which is essential for clinical diagnostics and especially valuable when validation and regulatory approval are required. Additionally, untargeted methods lack standardization, leading to lower assay reproducibility and often resulting in inconsistent findings across studies. Targeted approaches also typically offer higher specificity and sensitivity, as they are optimized for a defined set of well-characterized analytes. As a result, automation is more feasible in targeted workflows, with analytes measured under well-established parameters. Finally, data interpretation is faster and more cost-effective with targeted approaches, while untargeted methods require extensive and costly statistical analysis tools.
| Targeted | Untargeted | |
|---|---|---|
| Discovery | Hypothesis testing | Hypothesis generating |
| Coverage | Low | High |
| Quantification | Absolute and relative | Relative |
| Standardisable | Yes | No |
| Reproducibility | High | Low |
| Specificity | High | Low |
| Sensitivity | High | Low |
| Automation | Fast | Slow |
| Data interpretation | Cheap & fast | Expensive & demanding |
Tab.1: General comparison of targeted and untargeted metabolomics.
Semi-targeted metabolomics is a middle ground, suitable when researchers need both breadth and specificity, typically around defined biochemical pathways. It doesn’t fully replicate the discovery power of untargeted or the precision of targeted metabolomics, but it’s a versatile approach for studies with defined focus.
For a more detailed comparison of targeted and untargeted metabolomics we recommend the talk of Dr. David S. Wishart from October 2022: Why targeted metabolomics is essential for population health.
Targeted Metabolomics by Bevital
Targeted Metabolomics by Bevital
Isotope-labeled internal standards (ILIS) are considered the gold standard for quantification in metabolomics. However, because authentic ILIS are either unavailable or very expensive for certain metabolites, most targeted approaches and metabolomics labs use non-authentic ILIS for many of their analytes. In contrast, Bevital’s methods exclusively rely on authentic ILIS for each analyte, enabling us to provide both relative and absolute metabolite quantification of the highest quality, consistently validated through participation in external quality programs. As demonstrated by figure 1, authentic ILIS offer significantly higher precision, with 3-7 times lower CVs (Ulvik et al.), which is especially crucial in small cohort studies with often suffer from limited statistical power to detect true biological differences. Additionally, internal data from our group indicate that quantifying various analytes using non-authentic ILIS can lead to false-positive results. These artifacts, known as spurious correlations since described by Karl Pearson in 1897, can be avoided only through targeted approaches specifically designed to quantify each analyte using authentic ILIS.
Fig.1: Comparison of CV (%) of selected analytes by use of authentic and non-authentic ILIS.
In addition to assay precision and accuracy, Bevital’s diverse analytical platforms are designed to be both analytically and biologically complementary, established across dedicated GC- and LC-MS/MS systems. As a result, our metabolomic platforms enable quantification of a wide range of related metabolite classes, spanning both low- and high-abundance compounds within physiologically relevant dynamic ranges from pmol/L to mmol/L. Unlike untargeted approaches, which often produce missing data for metabolites below their detection limits, our highly sensitive methods allow us to “dive into the deep sea of metabolomics and catch the fish we are hunting for” (Fig. 2).
Fig.2: Exploring the “Deep Sea of Metabolomics” by targeted metabolomics