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Multicenter Study
. 2009 Sep 30;28(22):2817-32.
doi: 10.1002/sim.3665.

Analysis of the relationship between longitudinal gene expressions and ordered categorical event data

Natasa Rajicic  1 , Dianne M Finkelstein, David A Schoenfeld; Inflammation and Host Response to Injury Research Program Investigators
Collaborators, Affiliations
Multicenter Study

Analysis of the relationship between longitudinal gene expressions and ordered categorical event data

Natasa Rajicic et al. Stat Med. .

Abstract

The NIH project 'Inflammatory and Host Response to Injury' (Glue) is being conducted to study the changes in the body over time in response to trauma and burn. Patients are monitored for changes in their clinical status, such as the onset of and recovery from organ failure. Blood samples are drawn over the first days and weeks after the injury to obtain gene expression levels over time. Our goal was to develop a method of selecting genes that differentially expressed in patients who either improved or experienced organ failure. For this, we needed a test for the association between longitudinal gene expressions and the time to the occurrence of ordered categorical outcomes indicating recovery, stable disease, and organ failure. We propose a test for which the relationship between the gene expression and the events is modeled using the cumulative proportional odds model that is a generalization of the pooling repeated observation method. Given the high-dimensionality of the microarray data, it was necessary to control for the multiplicity of the testing. To control for the false discovery rate (FDR), we applied both a permutational approach as well as Efron's empirical estimation method. We explore our method through simulations and provide the analysis of the multi-center, longitudinal study of immune response to inflammation and trauma (http://www.gluegrant.org).

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Figures

Figure 1
Figure 1
Observed events over time
Figure 2
Figure 2
Null hypothesis distribution for different multiple testing procedures
See this image and copyright information in PMC

References

    1. National Institute of General Medical Sciences (NIGMS) [02 February 2008];Inflammation and Host Response to Injury: a multi-disciplinary research project. http://www.gluegrant.org.
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