Selecting predictive biomarkers from genomic data

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Biomarkers
  • Genetic Markers
  • Genomics*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Prognosis

Substances

  • Biomarkers
  • Genetic Markers

Grants and funding

PS and FK were supported by the European Union’s 7th Framework Programme for research, technological development and demonstration under Grant Agreement no 602552, https://ec.europa.eu/growth/sectors/space/research/fp7_en PS and FK were co-financed by the Polish Ministry of Science and Higher Education under Grant Agreement 2932/7.PR/2013/2. https://www.gov.pl/web/science MB gratefully gratefully acknowledges the support by the grant Nr 2016/23/B/ST1/00454 of the Polish National Center of Science. https://ncn.gov.pl/?language=en The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.