title: White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
abstract: Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) ≤ 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data***.
authors.affiliation: NCE CECR PROOF Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Casey P
authors.initials: CP
authors.lastname: Shannon
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.forename: Janet
authors.initials: J
authors.lastname: Wilson-McManus
authors.forename: Robert
authors.initials: R
authors.lastname: Balshaw
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Ng
authors.forename: Robert
authors.initials: R
authors.lastname: McMaster
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keown
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Tebbutt