BOSS -- Biomarker Optimal Segmentation System

TL;DR

BOSS is a fast, permutation-based method for optimal biomarker segmentation that maintains statistical power and error control, enabling efficient analysis in precision medicine applications.

Contribution

We introduce BOSS, a novel, computationally efficient approach for biomarker cutoff optimization that rivals permutation tests in accuracy and is suitable for large-scale genomic studies.

Findings

BOSS achieves similar power and error control as permutation tests.

BOSS is hundreds of times faster than permutation methods.

Application to lung adenocarcinoma data identified key biomarkers.

Abstract

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