Quality assurance and quality control reporting in untargeted metabolic phenotyping: mQACC recommendations for analytical quality management

Abstract

Background: Demonstrating that the data produced in metabolic phenotyping investigations (metabolomics/metabonomics) is of good quality is increasingly seen as a key factor in gaining acceptance for the results of such studies. The use of established quality control (QC) protocols, including appropriate QC samples, is an important and evolving aspect of this process. However, inadequate or incorrect reporting of the QA/QC procedures followed in the study may lead to misinterpretation or overemphasis of the findings and prevent future metanalysis of the body of work.

Objective: The aim of this guidance is to provide researchers with a framework that encourages them to describe quality assessment and quality control procedures and outcomes in mass spectrometry and nuclear magnetic resonance spectroscopy-based methods in untargeted metabolomics, with a focus on reporting on QC samples in sufficient detail for them to be understood, trusted and replicated. There is no intent to be proscriptive with regard to analytical best practices; rather, guidance for reporting QA/QC procedures is suggested. A template that can be completed as studies progress to ensure that relevant data is collected, and further documents, are provided as on-line resources.

Key reporting practices: Multiple topics should be considered when reporting QA/QC protocols and outcomes for metabolic phenotyping data. Coverage should include the role(s), sources, types, preparation and uses of the QC materials and samples generally employed in the generation of metabolomic data. Details such as sample matrices and sample preparation, the use of test mixtures and system suitability tests, blanks and technique-specific factors are considered and methods for reporting are discussed, including the importance of reporting the acceptance criteria for the QCs. To this end, the reporting of the QC samples and results are considered at two levels of detail: "minimal" and "best reporting practice" levels.

Keywords: Mass spectrometry (MS); Nuclear magnetic resonance (NMR) spectroscopy; Quality assurance (QA); Quality control (QC); Reporting standards; Untargeted metabolomics.

Fig. 1

One possible QC scheme for the use of QC samples in the analytical section of manuscripts describing untargeted mass spectrometry based metabolic profiling. Clearly a similar one could easily be constructed that covers other methodologies such as e.g., NMR spectroscopy etc.

Fig. 2

Information that should be documented in manuscripts to show the steps that have been taken to ensure the robustness of the analytical stages of a metabolic phenotyping experiment and its resulting data (see also Table OR3)

Fig. 3

The various cumulative levels of analytical reporting for QC samples are depicted in a hierarchy of value and effort. Each layer builds upon lower layers. A The samples that support interlaboratory comparability have the highest value and can be reported in the minimal sense (a qualitative description of the samples in the study) and in a Best Reporting Practice sense where QC metrics are also reported. B Long-term intra-laboratory QC samples represent ongoing efforts in the reporting laboratory to present consistent results across their various projects, and these can also be reported in a Minimal or Best Reporting Practice sense. C Individual project comparability during the analytical phase of the project can be demonstrated by Intra-study QC samples and reported in a minimal or as best reporting practice. D Instrument QC sample reporting demonstrates fitness-for-purpose of the instrument at the time of the project and represents the foundation upon which the other layers rest