Discovery of the gene signature for acute lung injury in patients with sepsis

Judie A. Howrylak, Tamas Dolinay, Lorrie Lucht, Zhaoxi Wang, David C. Christiani, Jigme M. Sethi, Eric P. Xing, Michael P. Donahoe, Augustine M.K. Choi

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsis alone (n = 1). An eight-gene expression profile was found to be associated with ALI. Internal validation found that the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. In the independently obtained external validation set, the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 88.9% accuracy. The use of classification models to develop a gene signature from gene expression profiles provides a novel and accurate approach for classifying patients with ALI.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalPhysiological genomics
Volume37
Issue number2
DOIs
StatePublished - Apr 1 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

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    Howrylak, J. A., Dolinay, T., Lucht, L., Wang, Z., Christiani, D. C., Sethi, J. M., Xing, E. P., Donahoe, M. P., & Choi, A. M. K. (2009). Discovery of the gene signature for acute lung injury in patients with sepsis. Physiological genomics, 37(2), 133-139. https://doi.org/10.1152/physiolgenomics.90275.2008