Pathology orgs issue recommendations for in silico approaches for validating NGS analysis pipelines

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The Association for Molecular Pathology (AMP) on Tuesday announced the publication of consensus recommendations for the use of in silico approaches for validating next-generation sequencing (NGS) data analysis pipelines.

The manuscript, "Recommendations for the Use of In Silico Approaches for Next Generation Sequencing Bioinformatic Pipeline Validation: A Joint Report of the Association for Molecular Pathology, Association for Pathology Informatics, and College of American Pathologists," was released online ahead of publication in The Journal of Molecular Diagnostics.

 “As more laboratories around the country use in silico data to simulate variants to help validate the performance of clinical NGS data analysis pipelines, clinical laboratory professionals may need an aid for understanding both the value these methods bring and the important nuances and limitations of these approaches,” Justin Zook, cochair of the AMP In Silico Pipeline Validation Working Group and coleader of the Biomarker and Genomic Sciences Group at the National Institute of Standards and Technology, said in a statement.

To develop the recommendations, a panel of subject matter experts from AMP, Association for Pathology Informatics, and College of American Pathologists explored the advantages and disadvantages of various types of in silico data.

The panel reviewed the available published literature, analyzing the different types of in silico data and how they can be used in the clinical molecular diagnostic laboratory. 

The new report also presents survey data on current use cases and highlights potential future applications.

In silico approaches for next generation sequencing (NGS) data modeling have utility in the clinical laboratory as a tool for clinical assay validation,” the authors wrote in the published study. “In silico NGS data can take a variety of forms, including pure simulated data or manipulated data files in which variants are inserted into existing data files.”

The team offered the following expert consensus opinion general recommendations based on these findings:

  • The laboratory may use in silico data files to supplement NGS analytical validation, particularly to assess analytical sensitivity or false negative rates for specific variants; however, in silico data files cannot supplant the use of physical samples (e.g., patient samples).
  • The laboratory should understand the functional limitations of the type(s) of in silico data being utilized.
  • The laboratory should understand the limitations of most in silico data for assessing performance in particular genome contexts and variant types susceptible to systematic sequencing and mapping errors.
  • The laboratory may consider using in silico samples for minor updates to clinical bioinformatics software pipelines.
  • Commercial vendors and internal pipeline developers should include options in their analysis pipelines to facilitate easier in silico data file import and analysis by clinical laboratories.

The group intends to review and update the consensus recommendations as new data and other in silico methods become available.

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