Analysis of significance patterns identifies ubiquitous and disease-specific gene-expression signatures in patient peripheral blood leukocytes.

Damien J. Chaussabel, Windy Allman, Asuncion Mejias, Wendy Chung, Lynda Bennett, Octavio Ramilo, Virginia Pascual, A. Karolina Palucka, Jacques Banchereau

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37 Citations (Scopus)

Abstract

The utilization of gene-expression microarrays in patient-based research creates new prospects for the discovery of diagnostic biomarkers and the identification of genes or pathways linked to pathogenesis. Gene-expression signatures in peripheral blood mononuclear cells isolated from over one hundred patients with conditions presenting a strong immunological component (patient with autoimmune, graft versus host and infectious diseases, as well as immunosuppressed transplant recipients) were generated. This dataset provides the opportunity to carry out comparative analyses and define disease signatures in a broader context. Transcriptional changes of 22,283 probe sets were evaluated through statistical group comparison performed systematically for seven diseases versus their respective healthy control group. Patterns of significance were generated by hierarchical clustering of P-values. This approach led to the identification of a SLE-specific "diagnostic signature," formed by genes that did not change compared to healthy subjects in the other six diseases. Conversely, a "sentinel signature" that was common to all seven diseases was characterized. These findings bring new perspectives for the application of blood leukocyte expression signatures for diagnosis and early disease detection.

Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1062
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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