Application of genome-wide expression analysis to human health and disease

J. Perren Cobb, Michael N. Mindrinos, Carol Miller-Graziano, Steve E. Calvano, Henry V. Baker, Wenzhong Xiao, Krzysztof Laudanski, Bernard H. Brownstein, Constance M. Elson, Douglas L. Hayden, David Herndon, Stephen F. Lowry, Ronald V. Maier, David A. Schoenfeld, Lyle L. Moldawer, Ronald W. Davis, Steven Wolf

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.

Original languageEnglish (US)
Pages (from-to)4801-4806
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number13
DOIs
StatePublished - Mar 29 2005

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Genome
Gene Expression
Leukocytes
Health
Healthy Volunteers
Wounds and Injuries
Oligonucleotide Array Sequence Analysis
Critical Illness
Noise

Keywords

  • Clinical studies
  • Gene expression
  • Inflammation
  • Microarray
  • Trauma

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Application of genome-wide expression analysis to human health and disease. / Cobb, J. Perren; Mindrinos, Michael N.; Miller-Graziano, Carol; Calvano, Steve E.; Baker, Henry V.; Xiao, Wenzhong; Laudanski, Krzysztof; Brownstein, Bernard H.; Elson, Constance M.; Hayden, Douglas L.; Herndon, David; Lowry, Stephen F.; Maier, Ronald V.; Schoenfeld, David A.; Moldawer, Lyle L.; Davis, Ronald W.; Wolf, Steven.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 13, 29.03.2005, p. 4801-4806.

Research output: Contribution to journalArticle

Cobb, JP, Mindrinos, MN, Miller-Graziano, C, Calvano, SE, Baker, HV, Xiao, W, Laudanski, K, Brownstein, BH, Elson, CM, Hayden, DL, Herndon, D, Lowry, SF, Maier, RV, Schoenfeld, DA, Moldawer, LL, Davis, RW & Wolf, S 2005, 'Application of genome-wide expression analysis to human health and disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 13, pp. 4801-4806. https://doi.org/10.1073/pnas.0409768102
Cobb, J. Perren ; Mindrinos, Michael N. ; Miller-Graziano, Carol ; Calvano, Steve E. ; Baker, Henry V. ; Xiao, Wenzhong ; Laudanski, Krzysztof ; Brownstein, Bernard H. ; Elson, Constance M. ; Hayden, Douglas L. ; Herndon, David ; Lowry, Stephen F. ; Maier, Ronald V. ; Schoenfeld, David A. ; Moldawer, Lyle L. ; Davis, Ronald W. ; Wolf, Steven. / Application of genome-wide expression analysis to human health and disease. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 13. pp. 4801-4806.
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