An Independent Assessment of a Commercial Clinical Interpretation Software Indicates That Software Can Mitigate Variation in Human Assessment

Abstract

Comprehensive next-generation sequencing (NGS) panels for cancer diagnostics create a bottleneck for interpretation. QIAGEN Clinical Insights Interpret One (QCI) is a clinical decision support software that supports molecular pathologists in the classification of oncology-related variants. This study compares variant assessments by QCI to assessments utilizing current laboratory methods. Eight laboratories were recruited by the external quality assessment organization GenQA. The laboratories submitted VCFs from sequencing studies performed on both hematological disorders and solid tumors for analysis by QCI and an independent laboratory. Results were compared and conflicts were resolved using a panel of experts. In total, 14/149 variants (9%) reported as Tier 1 or Tier 2 by either QCI or the submitting laboratory were found to be discordant after expert panel review. In contrast, 41/149 variants (28%) reflected discrepancy among human reviewers. The expert panel was unable to reach resolution on eight variants. QCI demonstrates high concordance in the classification of actionable mutations with independent laboratory methods and expert assessment. The rate of disagreement among laboratories and the expert panel was greater than the disagreement between QCI and expert assessment. Disagreement among experts highlights the subjectivity of classifying variants. The study demonstrates that QCI interpretation supports streamlining and standardization of NGS variant interpretation.

Keywords

• interpretation
• sequencing
• mutation
• Tier