MRDadaptis: self-adaptive parameter configuration enhances minimal residual disease detection in heterogeneous ctDNA samples

作者：Tianci Wang, Xin Lai, Shenjie Wang, Zhengfa Xue, Yuqian Liu, Xiaoyan Zhu, Xiaonan Wang, Zhili Chang, Yang Shao, Xian Zhang, Jiayin Wang · 发表于：Briefings in Bioinformatics · 年份：2025 · DOI：10.1093/bib/bbaf529 · 被引用次数：1 · 研究领域：Cancer Genomics and Diagnostics、Genomics and Phylogenetic Studies、Molecular Biology Techniques and Applications

Detection of structural variations (SVs) through circulating tumor DNA (ctDNA) has become a key method for detecting minimal residual disease (MRD). However, the heterogeneity of ctDNA samples, characterized by variable limits of detection (LOD) and diverse structural variant types, significantly impacts detection stability and performance, posing persistent challenges for conventional SV detection tools such as Delly and Manta. These widely used methods require extensive manual parameter tuning, hindered by the combinatorial complexity of multiple parameters and heterogeneous sequencing data. To address this, we propose MRDadaptis, a novel SV detection tool that uniquely incorporates a self-adaptive parameter optimization mechanism. MRDadaptis distinguishes itself by integrating Bayesian optimization with meta-learning techniques to dynamically adjust detection parameters automatically, based on intrinsic features derived from the ctDNA sequencing data itself. This innovative approach not only reduces manual intervention but also effectively captures sample-specific characteristics, significantly improving detection stability, and detection performance. Extensive validation experiments using both simulated and real-world ctDNA datasets demonstrates it distinct advantages, including markedly improved average F1-scores and superior stability (reduced variance, lower RMSE, increased kurtosis). These results highlight the significant advantages of MRDadaptis in addressing sample...