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Sample size requirements for training high-dimensional risk predictors.

ABSTRACT: A common objective of biomarker studies is to develop a predictor of patient survival outcome. Determining the number of samples required to train a predictor from survival data is important for designing such studies. Existing sample size methods for training studies use parametric models for the high-dimensional data and cannot handle a right-censored dependent variable. We present a new training sample size method that is non-parametric with respect to the high-dimensional vectors, and is developed for a right-censored response. The method can be applied to any prediction algorithm that satisfies a set of conditions. The sample size is chosen so that the expected performance of the predictor is within a user-defined tolerance of optimal. The central method is based on a pilot dataset. To quantify uncertainty, a method to construct a confidence interval for the tolerance is developed. Adequacy of the size of the pilot dataset is discussed. An alternative model-based version of our method for estimating the tolerance when no adequate pilot dataset is available is presented. The model-based method requires a covariance matrix be specified, but we show that the identity covariance matrix provides adequate sample size when the user specifies three key quantities. Application of the sample size method to two microarray datasets is discussed.

SUBMITTER: Dobbin KK

PROVIDER: S-EPMC3770001 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Sample size requirements for training high-dimensional risk predictors.

Dobbin Kevin K KK Song Xiao X

Biostatistics (Oxford, England) 20130719 4

A common objective of biomarker studies is to develop a predictor of patient survival outcome. Determining the number of samples required to train a predictor from survival data is important for designing such studies. Existing sample size methods for training studies use parametric models for the high-dimensional data and cannot handle a right-censored dependent variable. We present a new training sample size method that is non-parametric with respect to the high-dimensional vectors, and is dev ...[more]

PMID: 23873895

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Project description:DNA methylations in critical regions are highly involved in cancer pathogenesis and drug response. However, to identify causal methylations out of a large number of potential polymorphic DNA methylation sites is challenging. This high-dimensional data brings two obstacles: first, many established statistical models are not scalable to so many features; second, multiple-test and overfitting become serious. To this end, a method to quickly filter candidate sites to narrow down targets for downstream analyses is urgently needed. BACkPAy is a pre-screening Bayesian approach to detect biological meaningful patterns of potential differential methylation levels with small sample size. BACkPAy prioritizes potentially important biomarkers by the Bayesian false discovery rate (FDR) approach. It filters non-informative sites (i.e., non-differential) with flat methylation pattern levels across experimental conditions. In this work, we applied BACkPAy to a genome-wide methylation dataset with three tissue types and each type contains three gastric cancer samples. We also applied LIMMA (Linear Models for Microarray and RNA-Seq Data) to compare its results with what we achieved by BACkPAy. Then, Cox proportional hazards regression models were utilized to visualize prognostics significant markers with The Cancer Genome Atlas (TCGA) data for survival analysis. Using BACkPAy, we identified eight biological meaningful patterns/groups of differential probes from the DNA methylation dataset. Using TCGA data, we also identified five prognostic genes (i.e., predictive to the progression of gastric cancer) that contain some differential methylation probes, whereas no significant results was identified using the Benjamin-Hochberg FDR in LIMMA. We showed the importance of using BACkPAy for the analysis of DNA methylation data with extremely small sample size in gastric cancer. We revealed that RDH13, CLDN11, TMTC1, UCHL1, and FOXP2 can serve as predictive biomarkers for gastric cancer treatment and the promoter methylation level of these five genes in serum could have prognostic and diagnostic functions in gastric cancer patients.

Dataset Information

Sample size requirements for training high-dimensional risk predictors.

Publications

Sample size requirements for training high-dimensional risk predictors.

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