Kellie Archer

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  Ordinal Response Models for Modeling Longitudinal High-Dimensional Genomic Feature Data
  Kellie Archer

  Ordinal scales are commonly used to measure health status and disease related outcomes. Notable examples include cancer staging, histopathological classification, adverse event rating, and severity of illness. In addition, repeated measurements are common in clinical practice for tracking and monitoring the progression of complex diseases. Classical likelihood-based ordinal modeling methods have contributed to the analysis of data in which the response categories are ordered and the number of covariates (p) is smaller than the sample size (n). With the emergence of genomic technologies being increasingly applied to identify molecular markers associated with complex disease phenotypes and outcomes, many research studies now include high dimensional feature data where p >> n, so that traditional methods cannot be applied. To fill this void we have developed an innovative penalized random coefficient ordinal response model for classifying and predicting disease progression along with time. Specifically our method extends the Generalized Monotone Incremental Forward Stagewise method (Hastie et al, 2007) to the ordinal response setting in combination with classical mixed effects modeling methods. We demonstrate our method using data from the Inflammation and the Host Response to Injury study in which Affymetrix gene expression profiles and Marshall Multiple Organ Dysfunction Score on six body systems were longitudinally collected at hospitalization day 1 up to day 30 in 169 patients.