Analysis of factorial time-course microarrays with application to a clinical study of burn injury

Baiyu Zhou, Weihong Xu, David Herndon, Ronald Tompkins, Ronald Davis, Wenzhong Xiao, Wing Hung Wong

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and non-normality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

Original languageEnglish (US)
Pages (from-to)9923-9928
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number22
DOIs
StatePublished - Jun 1 2010

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Wounds and Injuries
Genes
Immunoglobulin Genes
Transcriptome
Clinical Studies
Mitochondria
Age Groups
Pediatrics
Therapeutics

Keywords

  • Analysis of variance
  • Factorial design
  • Longitudinal data

ASJC Scopus subject areas

  • General

Cite this

Analysis of factorial time-course microarrays with application to a clinical study of burn injury. / Zhou, Baiyu; Xu, Weihong; Herndon, David; Tompkins, Ronald; Davis, Ronald; Xiao, Wenzhong; Wong, Wing Hung.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 22, 01.06.2010, p. 9923-9928.

Research output: Contribution to journalArticle

Zhou, Baiyu ; Xu, Weihong ; Herndon, David ; Tompkins, Ronald ; Davis, Ronald ; Xiao, Wenzhong ; Wong, Wing Hung. / Analysis of factorial time-course microarrays with application to a clinical study of burn injury. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 22. pp. 9923-9928.
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