2023/05/16 by Liuyi Lan, Xuanjin Cheng, Lan, Liuyi +4
Biochemistry, Genetics and Molecular Biology · Mathematics · #Cancer Genomics and Diagnostics #FOS: Computer and information sciences #Gene expression and cancer classification #Methodology (stat.ME) #Statistical Methods in Clinical Trials
paper · pdf · doi:10.48550/arxiv.2305.09090
openalex publication_date 2023/05/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Motivation: Precision medicine is a major trend in the future of medicine. It aims to provide tailored medical treatment and prevention strategies based on an individual's unique characteristics and needs. Biomarker is the primary source of patients' unique features used in precision medicine. We often need to investigate many cutoff values of a continuous biomarker to find the optimal one and test if it can help segment patients into two groups with significantly different clinical outcomes. This requires multiple testing adjustments on tests conducted on overlapped data. The permutation-based approach is often a preferred solution, since it does not suffer the limitations of state-of-art theoretical methods. However, permutation is computationally expensive and limits its application scenarios, such as web applications requiring a fast response or the analysis of genomic study requiring to repeat analysis many times on tens of thousands of genes. Results: We proposed a novel method BOSS, Biomarker Optimal Segmentation System, to solve this problem. In simulation studies, we found BOSS's statistical power and type I error control are both non-inferior to the permutation approach, and it is hundreds of times faster than permutation. To illustrate our method, we applied BOSS to real data and revealed potentially converging biomarkers that have referential importance in exploring synergy and target-matched therapies in lung adenocarcinoma. Availability: An R package, boss, is being developed and will be available on CRAN