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从基因组数据中选择预测生物标志物。

Selecting predictive biomarkers from genomic data.

机构信息

Department of Medical Statistics, CEMSIIS, Medical University of Vienna, Vienna, Austria.

Institute of Mathematics, University of Wroclaw, Wroclaw, Poland.

出版信息

PLoS One. 2022 Jun 16;17(6):e0269369. doi: 10.1371/journal.pone.0269369. eCollection 2022.

Abstract

Recently there have been tremendous efforts to develop statistical procedures which allow to determine subgroups of patients for which certain treatments are effective. This article focuses on the selection of prognostic and predictive genetic biomarkers based on a relatively large number of candidate Single Nucleotide Polymorphisms (SNPs). We consider models which include prognostic markers as main effects and predictive markers as interaction effects with treatment. We compare different high-dimensional selection approaches including adaptive lasso, a Bayesian adaptive version of the Sorted L-One Penalized Estimator (SLOBE) and a modified version of the Bayesian Information Criterion (mBIC2). These are compared with classical multiple testing procedures for individual markers. Having identified predictive markers we consider several different approaches how to specify subgroups susceptible to treatment. Our main conclusion is that selection based on mBIC2 and SLOBE has similar predictive performance as the adaptive lasso while including substantially fewer biomarkers.

摘要

最近,人们付出了巨大的努力来开发统计程序,以确定某些治疗方法对哪些患者群体有效。本文侧重于基于大量候选单核苷酸多态性(SNP)选择预后和预测性遗传生物标志物。我们考虑了包含预后标志物作为主效应和预测标志物作为与治疗相互作用的模型。我们比较了不同的高维选择方法,包括自适应套索、排序 L-One 惩罚估计器(SLOBE)的贝叶斯自适应版本和贝叶斯信息准则(mBIC2)的修改版本。这些方法与个体标志物的经典多重检验程序进行了比较。在确定了预测性生物标志物后,我们考虑了几种不同的方法来指定对治疗敏感的亚组。我们的主要结论是,基于 mBIC2 和 SLOBE 的选择与自适应套索具有相似的预测性能,同时包含的生物标志物要少得多。

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