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Indirect reference intervals using an R pipeline.

Dustin R Bunch1,2

  • 1Nationwide Children's Hospital, Department of Pathology and Laboratory Medicine, 700 Children's Dr, Columbus, OH 43205, United States.

Journal of Mass Spectrometry and Advances in the Clinical Lab
|March 7, 2022
PubMed
Summary
This summary is machine-generated.

This study demonstrates that R programming can create a robust pipeline for statistical reference intervals. This method effectively separates healthy and pathological values for analytes like testosterone and AST.

Keywords:
ANOVA, Analysis of varianceAST, aspartate aminotransferaseCLSI, Clinical Laboratory Standards InstituteEHR, electronic health recordIFCC, International Federation of Clinical Chemistry and Laboratory MedicineLC-MS/MS, Liquid chromatography tandem mass spectrometryLIS, Laboratory informatics systemMixtoolsR markdown tutorialRI, reference intervalReference intervalSDI, Standard deviation indexSDR, Standard deviation ratioTesto, TestosteroneTukeyHSD, Tukey multiple pairwise-comparisonsz5, Critical z-score

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Area of Science:

  • Clinical Chemistry
  • Biostatistics
  • Computational Biology

Background:

  • Establishing accurate reference intervals (RIs) is crucial for distinguishing healthy from pathological analyte values.
  • Robust statistical methodologies are essential for developing reliable indirect RIs.
  • The R statistical programming language offers a flexible platform for creating such data pipelines.

Purpose of the Study:

  • To develop and validate a data pipeline using R for the estimation of indirect reference intervals.
  • To apply the pipeline to large-scale datasets for testosterone and aspartate aminotransferase.
  • To assess the utility and limitations of the R-based pipeline for RI determination.

Main Methods:

  • An R data pipeline was designed to process large datasets (NHANES).
  • The pipeline included steps for data ingestion, partitioning, normalization, and outlier removal.
  • Reference intervals were identified for testosterone (n=7,207) and aspartate aminotransferase (n=5,882).

Main Results:

  • The pipeline generated reference interval estimates for AST and testosterone that closely approximated existing RIs.
  • The accuracy of the estimated RIs was influenced by analyte pathology and the characteristics of the dataset used.
  • The study highlights the need for careful consideration of these factors when applying the pipeline.

Conclusions:

  • A robust statistical pipeline for indirect reference interval estimation can be successfully implemented using R.
  • The developed R pipeline provides a valuable tool for clinical laboratories and researchers.
  • Further refinement may be necessary depending on specific analytical and dataset considerations.