Control Charting Genomic Data

Area of Science:

• Genomics
• Clinical Laboratory Science
• Quality Assurance

Background:

• Traditional clinical laboratory testing utilizes control charting for quality assurance.
• Genomic tests, specifically next-generation sequencing (NGS) assays, are not routinely managed using control charting.
• This study investigates the application of control charting for monitoring clinical NGS assay performance.

Purpose of the Study:

• To evaluate the utility of control charting for quality assurance in clinical genomic testing.
• To assess the impact of reagent lot changes on sequencing coverage in genomic regions.
• To determine the correlation between control material and clinical sample performance.

Main Methods:

• Retrospective analysis of 3 years of control material (NA12878) data from clinical genomic epilepsy testing.
• Utilization of Levey-Jennings plots to visualize sequencing coverage depth in targeted genomic regions.
• Correlation analysis of coverage depth changes with capture probe reagent lot changes and clinical sample data.

Main Results:

• Lot changes in capture probe reagents significantly altered average and minimum sequencing coverage in numerous genomic regions.
• Sensitivity to lot-to-lot variation differed between average and minimum coverage metrics.
• Levey-Jennings plots effectively visualized coverage differences across reagent lots, with moderate correlation (r² = 0.45) between control material and clinical samples.

Conclusions:

• Genomic control charting is a viable and routine method for clinical laboratories.
• It enables effective monitoring of assay performance and ensures the quality of genomic testing.
• Implementation of control charting enhances the reliability of clinical genomic data.