title: Analysis of significance patterns identifies ubiquitous and disease-specific gene-expression signatures in patient peripheral blood leukocytes.
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.
authors.affiliation: The Baylor NIAID Cooperative Center for Translational Research on Human Immunology and Biodefense and Baylor Institute for Immunology Research, 3434 Live Oak Street, Suite 205, Dallas, TX 75204, USA. damienc@baylorhealth.edu
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.forename: Windy
authors.initials: W
authors.lastname: Allman
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
authors.forename: Wendy
authors.initials: W
authors.lastname: Chung
authors.forename: Lynda
authors.initials: L
authors.lastname: Bennett
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
mesh_terms: D000328:Adult; D002648:Child; D004927:Escherichia coli Infections / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007251:Influenza, Human / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D015201:Meta-Analysis as Topic; D020411:Oligonucleotide Array Sequence Analysis; D011008:Pneumococcal Infections / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000235:genetics / Q000276:immunology