Federal Regulation of Clinical Laboratories and the Clinical Laboratory Improvement Amendments of 1988-Part II

Bachner, Paul; Hamlin, William B.

doi:10.1016/s0272-2712(18)30421-9

Cited by 17 publications

(1 citation statement)

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“…For an NGS assay, the National Institute of Standards and Technology (NIST) reference sample, NA12878, is a gold standard sample that has been sequenced as part of the NIST Genome in a Bottle (GIAB) initiative and part of the Illumina Platinum Genome project. 87 This sample has been well studied and established as a standard of truth distributed by the GIAB consortium and Illumina. Using high-confidence regions of this genome, the sensitivity and specificity of germ-line variant detection can be evaluated for a bioinformatics pipeline.…”

Section: Validation Step 1: Reference Sample Engineered Samples Andmentioning

confidence: 99%

Assembling and Validating Bioinformatic Pipelines for Next-Generation Sequencing Clinical Assays

SoRelle

Wachsmann

Cantarel

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Clinical next-generation sequencing (NGS) is being rapidly adopted, but analysis and interpretation of large data sets prompt new challenges for a clinical lab setting. Clinical NGS results rely heavily on the bioinformatics pipeline for identifying genetic variation in complex samples. The choice of bioinformatics algorithms, genome assembly, and genetic annotation databases are important for determining genetic alterations associated with disease. The analysis methods are often tuned to the assay to maximize accuracy. Once a pipeline has been developed, it must be validated to determine accuracy and reproducibility for samples similar to real-world cases. In silico proficiency testing or institutional data exchange will ensure consistency among clinical laboratories. Objective.— To provide molecular pathologists a step-by-step guide to bioinformatics analysis and validation design in order to navigate the regulatory and validation standards of implementing a bioinformatic pipelines as a part of a new clinical NGS assay. Data Sources.— This guide uses published studies on genomic analysis, bioinformatics methods, and methods comparison studies to inform the reader on what resources, including open source software tools and databases, are available for genetic variant detection and interpretation. Conclusions.— This review covers 4 key concepts: (1) bioinformatic analysis design for detecting genetic variation, (2) the resources for assessing genetic effects, (3) analysis validation assessment experiments and data sets, including a diverse set of samples to mimic real-world challenges that assess accuracy and reproducibility, and (4) if concordance between clinical laboratories will be improved by proficiency testing designed to test bioinformatic pipelines.

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Section: Validation Step 1: Reference Sample Engineered Samples Andmentioning

confidence: 99%