Dataset Information

Investigation of cross-platform analytical precision in NMR and UPLC-MS based metabolic-phenotyping

ABSTRACT: Dataset of six samples of pooled human urine, aliquoted, and independently prepared and aquired by NMR spectroscopy, and UPLC-MS. Each source sample is seperatly prepared and assayed thirteen times. A pooled QC sample and independent external reference of a compariable matrix is also aquired to assist in assesing analytical precision.

OTHER RELATED OMICS DATASETS IN: PXD018322PXD006154

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR), Liquid Chromatography MS - Positive (LC-MS (Positive))

SUBMITTER: MRC-NIHR National Phenome Centre Jake Pearce

PROVIDER: MTBLS694 | MetaboLights | 2018-08-31

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS694	Other
	FILES	Other
	a_MTBLS694_pipelinetest_metabolite_profiling_NMR_spectroscopy.txt	Txt
	a_MTBLS694_pipelinetest_metabolite_profiling_mass_spectrometry.txt	Txt
	i_Investigation.txt	Txt

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Project description:To better understand the molecular mechanisms underpinning physiological variation in human populations, metabolic phenotyping approaches are increasingly being applied to studies involving hundreds and thousands of biofluid samples. Hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) has become a fundamental tool for this purpose. However, the seemingly inevitable need to analyze large studies in multiple analytical batches for UPLC-MS analysis poses a challenge to data quality which has been recognized in the field. Herein, we describe in detail a fit-for-purpose UPLC-MS platform, method set, and sample analysis workflow, capable of sustained analysis on an industrial scale and allowing batch-free operation for large studies. Using complementary reversed-phase chromatography (RPC) and hydrophilic interaction liquid chromatography (HILIC) together with high resolution orthogonal acceleration time-of-flight mass spectrometry (oaTOF-MS), exceptional measurement precision is exemplified with independent epidemiological sample sets of approximately 650 and 1000 participant samples. Evaluation of molecular reference targets in repeated injections of pooled quality control (QC) samples distributed throughout each experiment demonstrates a mean retention time relative standard deviation (RSD) of <0.3% across all assays in both studies and a mean peak area RSD of <15% in the raw data. To more globally assess the quality of the profiling data, untargeted feature extraction was performed followed by data filtration according to feature intensity response to QC sample dilution. Analysis of the remaining features within the repeated QC sample measurements demonstrated median peak area RSD values of <20% for the RPC assays and <25% for the HILIC assays. These values represent the quality of the raw data, as no normalization or feature-specific intensity correction was applied. While the data in each experiment was acquired in a single continuous batch, instances of minor time-dependent intensity drift were observed, highlighting the utility of data correction techniques despite reducing the dependency on them for generating high quality data. These results demonstrate that the platform and methodology presented herein is fit-for-use in large scale metabolic phenotyping studies, challenging the assertion that such screening is inherently limited by batch effects. Details of the pipeline used to generate high quality raw data and mitigate the need for batch correction are provided.

Project description:Introduction:Electronic health record (EHR)-driven phenotyping is a critical first step in generating biomedical knowledge from EHR data. Despite recent progress, current phenotyping approaches are manual, time-consuming, error-prone, and platform-specific. This results in duplication of effort and highly variable results across systems and institutions, and is not scalable or portable. In this work, we investigate how the nascent Clinical Quality Language (CQL) can address these issues and enable high-throughput, cross-platform phenotyping. Methods:We selected a clinically validated heart failure (HF) phenotype definition and translated it into CQL, then developed a CQL execution engine to integrate with the Observational Health Data Sciences and Informatics (OHDSI) platform. We executed the phenotype definition at two large academic medical centers, Northwestern Medicine and Weill Cornell Medicine, and conducted results verification (n = 100) to determine precision and recall. We additionally executed the same phenotype definition against two different data platforms, OHDSI and Fast Healthcare Interoperability Resources (FHIR), using the same underlying dataset and compared the results. Results:CQL is expressive enough to represent the HF phenotype definition, including Boolean and aggregate operators, and temporal relationships between data elements. The language design also enabled the implementation of a custom execution engine with relative ease, and results verification at both sites revealed that precision and recall were both 100%. Cross-platform execution resulted in identical patient cohorts generated by both data platforms. Conclusions:CQL supports the representation of arbitrarily complex phenotype definitions, and our execution engine implementation demonstrated cross-platform execution against two widely used clinical data platforms. The language thus has the potential to help address current limitations with portability in EHR-driven phenotyping and scale in learning health systems.

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Investigation of cross-platform analytical precision in NMR and UPLC-MS based metabolic-phenotyping

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