Improving global feature detectabilities through scan range splitting for untargeted metabolomics by high-performance liquid chromatography-Orbitrap mass spectrometry

Ranninger, Christina; Schmidt, Lukas; Rurik, Marc; Limonciel, Alice; Jennings, Paul; Kohlbacher, Oliver; Huber, Christian G.

doi:10.1016/j.aca.2016.05.017

Cited by 22 publications

(20 citation statements)

References 30 publications

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“…The reached scaling efficiency of~88% indicates remarkable performance achieved on generic cloud providers. Furthermore, although our results in positive ionization model was slightly different to that of Ranninger et al (13) , the results of our analysis were reproducible regardless of the platform used to perform the computations, indicating a level of replicability of study results and reusability of workflows in the analysis that -to the best of our knowledge -has never been reported before in metabolomics data analysis.…”

Section: Discussioncontrasting

confidence: 52%

Interoperable and scalable data analysis with microservices: Applications in Metabolomics

Khoonsari

Moreno

Bergmann

et al. 2017

Preprint

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Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task.We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed in parallel using the Kubernetes container orchestrator. The access point is a virtual research environment which can be launched on-demand on cloud resources and desktop computers.IT-expertise requirements on the user side are kept to a minimum, and established workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry studies, one nuclear magnetic resonance spectroscopy study and one fluxomics study, showing that the method scales dynamically with increasing availability of computational resources. We achieved a complete integration of the major software suites resulting in the first turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, multivariate statistics, and metabolite identification.Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science.2 peer-reviewed)

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Section: Discussioncontrasting

confidence: 52%

Interoperable and scalable data analysis with microservices: Applications in Metabolomics

Khoonsari

Moreno

Bergmann

et al. 2017

Preprint

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“…We then assessed metabolomic signatures measured by a new untargeted UHPLC–ESI–HR-MS quantification method, which has been shown to provide high-quality quantification results (55–57). Metabolic patterns and their responses to nutritional, viral, or xenobiotic challenges have been studied in primary rodent hepatocytes and human hepatic cell lines, such as HepG2, Huh7.5, and HepaRG, and such approaches have been used for mechanistic investigations and to predict DILI (58–62).…”

Section: Discussionmentioning

confidence: 99%

Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long‐term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics

et al. 2017

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Adverse reactions or lack of response to medications are important concerns for drug development programs. However, faithful predictions of drug metabolism and toxicity are difficult because animal models show only limited translatability to humans. Furthermore, current in vitro systems, such as hepatic cell lines or primary human hepatocyte (PHH) 2-dimensional (2D) monolayer cultures, can be used only for acute toxicity tests because of their immature phenotypes and inherent instability. Therefore, the migration to novel phenotypically stable models is of prime importance for the pharmaceutical industry. Novel 3-dimensional (3D) culture systems have been shown to accurately mimic in vivo hepatic phenotypes on transcriptomic and proteomic level, but information about their metabolic stability is lacking. Using a combination of targeted and untargeted high-resolution mass spectrometry, we found that PHHs in 3D spheroid cultures remained metabolically stable for multiple weeks, whereas metabolic patterns of PHHs from the same donors cultured as conventional 2D monolayers rapidly deteriorated. Furthermore, pharmacokinetic differences between donors were maintained in 3D spheroid cultures, enabling studies of interindividual variability in drug metabolism and toxicity. We conclude that the 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long-term drug metabolism and pharmacokinetics.—Vorrink, S. U., Ullah, S., Schmid, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman-Sundberg, M., Lauschke, V. M. Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics.

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“…It is a good habit to look at the ion injection time across the whole chromatographic time range where analytes elute. Sections with very short ion injection times are not ideal (low sensitivity in the matrix) and may call for the definition of a narrower scan range or the setting up of targeted experiments.…”

Section: Resultsmentioning

confidence: 99%

Analytical performance of the various acquisition modes in Orbitrap MS and MS/MS

Kaufmann¹

2018

J Mass Spectrom

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Quadrupole Orbitrap instruments (Q Orbitrap) permit high-resolution mass spectrometry-based full scan acquisitions and have a number of acquisition modes where the quadrupole isolates a particular mass range prior to a possible fragmentation and high-resolution mass spectrometry-based acquisition. Selecting the proper acquisition mode(s) is essential if trace analytes are to be quantified in complex matrix extracts. Depending on the particular requirements, such as sensitivity, selectivity of detection, linear dynamic range, and speed of analysis, different acquisition modes may have to be chosen. This is particularly important in the field of multi-residue analysis (eg, pesticides or veterinary drugs in food samples) where a large number of analytes within a complex matrix have to be detected and reliably quantified. Meeting the specific detection and quantification performance criteria for every targeted compound may be challenging. It is the aim of this paper to describe the strengths and the limitations of the currently available Q Orbitrap acquisition modes. In addition, the incorporation of targeted acquisitions between full scan experiments is discussed. This approach is intended to integrate compounds that require an additional degree of sensitivity or selectivity into multi-residue methods.

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Improving global feature detectabilities through scan range splitting for untargeted metabolomics by high-performance liquid chromatography-Orbitrap mass spectrometry

Cited by 22 publications

References 30 publications

Interoperable and scalable data analysis with microservices: Applications in Metabolomics

Interoperable and scalable data analysis with microservices: Applications in Metabolomics

Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long‐term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics

Analytical performance of the various acquisition modes in Orbitrap MS and MS/MS

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