Penalized Cumulative Probability Model for a Continuous Outcome Subject to Detection Limits

Vollständiger Abstract

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ABSTRACT Mixed‐type outcome data occur when the outcome variable's distribution is a mixture of both continuous and discrete ordinal variables. Such mixed‐type outcomes are common in biomedical, psychological, and the health sciences, particularly for variables having either a detection or quantitation limit. When interest lies in identifying a combination of genomic features associated with a mixed‐type outcome, any method used would require a variable selection strategy for high‐dimensional data. Unfortunately, few variable selection methods exist for modeling a mixed‐type outcome when the covariate space is high dimensional. This study develops a high‐dimensional penalized cumulative probability model (CPM), to allow for the identification of genomic features associated with mixed‐type outcome of interest. We demonstrated how such model may be estimated using the iterative penalization procedure—the generalized monotone incremental forward stagewise (GMIFS) algorithm. The Model‐X knockoffs procedure was combined with the estimation algorithm to control the false discovery rates (FDR) when performing variable selection. Through extensive simulation studies, our penalized CPM was shown to outperform alternative methods in terms of controlled variable selection performance by achieving high statistical power with the FDR being controlled at the target level. We demonstrate the utility of our method by applying it to predict estimated glomeruli filtration rate (eGFR) in kidney transplant recipients at 24 months post‐transplant using baseline gene expression data as predictors. Our CPM model identified five genes associated with this mixed‐type outcome which have important links to renal disease, which may provide prognostic guidance for kidney transplantation recipients.