A Laboratory-Adaptive Dynamic Quality Control Framework Reduces Targeted Capture Sequencing Failure in Solid Tumors...

High failure rates in targeted capture sequencing of solid tumors-especially from formalin-fixed, paraffin-embedded samples-limit the clinical application of next-generation sequencing. Current wet-laboratory quality control (QC) relies on rigid, predefined thresholds, which are not adaptable to the heterogeneity of clinical samples and contribute significantly to sequencing failures. Retrospective analysis of QC parameters from 1146 tumor samples (425-gene panel; 2021 to 2023) identified five independent predictors of failure: total DNA amount, nucleic acid quality, DNA input, prelibrary total DNA, and prelibrary input (all P < 0.05). On the basis of these findings, the first laboratory-adaptive dynamic QC framework was developed to utilize sample-specific QC metrics for real-time adjustment of wet-laboratory workflows. Prospective validation in 2687 consecutive samples (March 2023 to the present) demonstrated a >90% reduction in sequencing failures, lowering the failure rate from 4.2% to 0.3% (P < 0.001), with significant improvements for high-risk samples. This approach also reduced projected costs by 257 RMB (Renminbi; Chinese Yuan) per sample, saving >230,000 RMB annually. By replacing static cutoffs with a dynamic, sample-specific strategy, this framework offers a scalable and cost-efficient solution, providing a paradigm shift in wet-laboratory QC for heterogeneous clinical specimens.