Bridging Targeted and Untargeted Mass Spectrometry-Based Metabolomics via Hybrid Approaches

Abstract

This mini-review aims to discuss the development and applications of mass spectrometry (MS)-based hybrid approaches in metabolomics. Several recently developed hybrid approaches are introduced. Then, the overall workflow, frequently used instruments, data handling strategies, and applications are compared and their pros and cons are summarized. Overall, the improved repeatability and quantitative capability in large-scale MS-based metabolomics studies are demonstrated, in comparison to either targeted or untargeted metabolomics approaches alone. In summary, we expect this review to serve as a first attempt to highlight the development and applications of emerging hybrid approaches in metabolomics, and we believe that hybrid metabolomics approaches could have great potential in many future studies.

The History of Gene Hunting in Hereditary Spinocerebellar Degeneration: Lessons From the Past and Future Perspectives

“…Metabolomics is the closest omics layer to the phenotype and could have central roles in validating the newly discovered Mendelian genes ( Feussner and Polle, 2015 ; Graham et al, 2018 ; Almontashiri et al, 2020 ). Metabolomics studies are conducted using two main approaches: a hypothesis-directed approach that studies a predetermined set of metabolites (targeted metabolomics) and a hypothesis-free comprehensive approach that aims to analyze the whole set of metabolites within a system (untargeted or global metabolomics; Almontashiri et al, 2020 ; Chen et al, 2020 ). Global metabolomics is gaining momentum over targeted approaches in clinical settings ( Almontashiri et al, 2020 ).…”

Recurrent Topics in Mass Spectrometry-Based Metabolomics and Lipidomics—Standardization, Coverage, and Throughput

“… 1 , 97 Recently, hybrid MS approaches emerged which offer attractive ways bridging the concepts of targeted and nontargeted analysis. 20 These workflows successfully exploit the power for accurate relative quantification by QqQ-MS, without omitting a discovery step. The “discovery” is realized through optimizing the MRM transitions based on a sample matrix representative for the large-scale study.…”

“…Recent applications resort to small scale studies for hypothesis generation, followed by a (wide) targeted large scale study for hypothesis validation. 20 …”

Comparison of Targeted and Untargeted Approaches in Breath Analysis for the Discrimination of Lung Cancer from Benign Pulmonary Diseases and Healthy Persons

“…In contrast to the targeted strategy, the lack of absolute quantification makes it difficult to assess variations in metabolite levels between groups, to normalize the acquired data and even to make interlaboratory comparisons of the results [ 7 , 8 ]. These weaknesses of the non-targeted approach are, at the same time, the strengths of the targeted approach and, recently, hybrid approaches bridging them have been developed [ 8 , 9 ]. In this study, we make a retrospective non-targeted analysis of full scan data previously acquired [ 10 ] in targeted analysis of the breath samples from lung cancer (Ca+) and benign pulmonary disease (Ca−) patients and healthy controls (HC).…”