Motivation: The development of methods for linking gene expressions to various clinical and phenotypic characteristics is an active area of genomic research. Scientists hope that such analysis may, for example, describe relationships between gene function and clinical events such as death or recovery. Methods are available for relating gene expression to measurements that are categorized or continuous, but there is less work in relating expressions to an observed event time such as time to death, response, or relapse. When gene expressions are measured over time, there are methods for differentiating temporal patterns. However, no methods have yet been proposed for the survival analysis of longitudinally collected microarrays. Results: We describe an approach for the survival analysis of longitudinal gene expression data. We construct a measure of association between the time to an event and gene expressions collected over time. The issue of high dimensionality and dependence when assessing statistical significance is addressed using permutations and control of the false discovery rate. Our proposed method is illustrated on a data set from a multi-center research study of inflammation and response to injury that aims to uncover the biological reasons why patients can have dramatically different outcomes after suffering a traumatic injury (www.gluegrant.org).
Rajicic, Natasa; Finkelstein, Dianne M.; and Schoenfeld, David A., "Survival Analysis of Longitudinal Microarrays" (July 2006). COBRA Preprint Series. Working Paper 7.