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Identifying Prognostic SNPs in Clinical Cohorts: Complementing Univariate Analyses by Resampling and Multivariable Modeling

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  • Stefanie Hieke
  • Axel Benner
  • Richard F Schlenk
  • Martin Schumacher
  • Lars Bullinger
  • Harald Binder

Abstract

Clinical cohorts with time-to-event endpoints are increasingly characterized by measurements of a number of single nucleotide polymorphisms that is by a magnitude larger than the number of measurements typically considered at the gene level. At the same time, the size of clinical cohorts often is still limited, calling for novel analysis strategies for identifying potentially prognostic SNPs that can help to better characterize disease processes. We propose such a strategy, drawing on univariate testing ideas from epidemiological case-controls studies on the one hand, and multivariable regression techniques as developed for gene expression data on the other hand. In particular, we focus on stable selection of a small set of SNPs and corresponding genes for subsequent validation. For univariate analysis, a permutation-based approach is proposed to test at the gene level. We use regularized multivariable regression models for considering all SNPs simultaneously and selecting a small set of potentially important prognostic SNPs. Stability is judged according to resampling inclusion frequencies for both the univariate and the multivariable approach. The overall strategy is illustrated with data from a cohort of acute myeloid leukemia patients and explored in a simulation study. The multivariable approach is seen to automatically focus on a smaller set of SNPs compared to the univariate approach, roughly in line with blocks of correlated SNPs. This more targeted extraction of SNPs results in more stable selection at the SNP as well as at the gene level. Thus, the multivariable regression approach with resampling provides a perspective in the proposed analysis strategy for SNP data in clinical cohorts highlighting what can be added by regularized regression techniques compared to univariate analyses.

Suggested Citation

  • Stefanie Hieke & Axel Benner & Richard F Schlenk & Martin Schumacher & Lars Bullinger & Harald Binder, 2016. "Identifying Prognostic SNPs in Clinical Cohorts: Complementing Univariate Analyses by Resampling and Multivariable Modeling," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-18, May.
  • Handle: RePEc:plo:pone00:0155226
    DOI: 10.1371/journal.pone.0155226
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    References listed on IDEAS

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    1. van Wieringen, Wessel N. & Kun, David & Hampel, Regina & Boulesteix, Anne-Laure, 2009. "Survival prediction using gene expression data: A review and comparison," Computational Statistics & Data Analysis, Elsevier, vol. 53(5), pages 1590-1603, March.
    2. Binder Harald & Schumacher Martin, 2008. "Adapting Prediction Error Estimates for Biased Complexity Selection in High-Dimensional Bootstrap Samples," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 7(1), pages 1-28, March.
    3. W. Sauerbrei & P. Royston, 1999. "Building multivariable prognostic and diagnostic models: transformation of the predictors by using fractional polynomials," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 162(1), pages 71-94.
    4. Binder Harald & Müller Tina & Schwender Holger & Golka Klaus & Steffens Michael & Hengstler Jan G. & Ickstadt Katja & Schumacher Martin, 2012. "Cluster-Localized Sparse Logistic Regression for SNP Data," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 11(4), pages 1-31, August.
    5. Buhlmann P. & Yu B., 2003. "Boosting With the L2 Loss: Regression and Classification," Journal of the American Statistical Association, American Statistical Association, vol. 98, pages 324-339, January.
    6. Patrick Royston & Gareth Ambler, 1999. "Multivariable fractional polynomials," Stata Technical Bulletin, StataCorp LP, vol. 8(43).
    7. Gerhard Tutz & Harald Binder, 2006. "Generalized Additive Modeling with Implicit Variable Selection by Likelihood-Based Boosting," Biometrics, The International Biometric Society, vol. 62(4), pages 961-971, December.
    8. Hui Zou & Trevor Hastie, 2005. "Addendum: Regularization and variable selection via the elastic net," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 67(5), pages 768-768, November.
    9. Tutz, Gerhard & Binder, Harald, 2007. "Boosting ridge regression," Computational Statistics & Data Analysis, Elsevier, vol. 51(12), pages 6044-6059, August.
    10. Hui Zou & Trevor Hastie, 2005. "Regularization and variable selection via the elastic net," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 67(2), pages 301-320, April.
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