Design and analytical validation of clinical DNA sequencing assays

Arch Pathol Lab Med. 2012 Jan;136(1):41-6. doi: 10.5858/arpa.2010-0623-OA.

Abstract

Context: DNA sequencing is the method of choice for mutation detection in many genes.

Objectives: To demonstrate the analytical accuracy and reliability of DNA sequencing assays developed in clinical laboratories. Only general guidelines exist for the validation of these tests. We provide examples of assay validation strategies for DNA sequencing tests.

Design: We discuss important design and validation considerations.

Results: The validation examples include an accuracy study to evaluate concordance between results obtained by the newly designed assay and analyzed by another method or laboratory. Precision (reproducibility) studies are performed to determine the robustness of the assay. To assess the quality of sequencing assays, several sequence quality measures are available. In addition, assessing the ability of primers to specifically and robustly amplify target regions before sequencing is important.

Conclusion: Protocols for validation of laboratory-developed sequencing assays may vary between laboratories. An example summary of a validation is provided.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Checkpoint Kinase 2
  • Hamartoma Syndrome, Multiple / diagnosis*
  • Hamartoma Syndrome, Multiple / genetics
  • Humans
  • Molecular Diagnostic Techniques / standards*
  • PTEN Phosphohydrolase / genetics*
  • Protein Serine-Threonine Kinases / genetics
  • Reproducibility of Results
  • Saccharomyces cerevisiae Proteins / genetics
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Smad4 Protein / genetics
  • United States
  • United States Food and Drug Administration

Substances

  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • Smad4 Protein
  • Checkpoint Kinase 2
  • Protein Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae
  • PTEN Phosphohydrolase