title: Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis.
abstract: Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.
authors.affiliation: Systems Biology / Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology Hans-Knöll-Institute Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dix
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Czakai
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Springer
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Fliesser
authors.affiliation: IMGM Laboratories Martinsried, Germany (Formerly Department of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany).
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.affiliation: Systems Biology / Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology Hans-Knöll-Institute Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Schmitt
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Systems Biology / Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology Hans-Knöll-Institute Jena, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Linde
authors.affiliation: University Hospital Würzburg, Medical Hospital II Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
keywords: allogeneic stem cell transplantation; fungal infection; gene expression data; human biomarker; invasive aspergillosis