Cross-study homogeneity of psoriasis gene expression in skin across a large expression range

• Published in: PloS one 2013-01, Vol.8 (1), p.e52242-e52242
• Main Authors: Bigler, Jeannette, Rand, Hugh A, Kerkof, Keith, Timour, Martin, Russell, Christopher B
• Format: Article
• Language: English
• Subjects: Adult; Arrays; Bioinformatics; Biology; Change detection; Datasets; Dendritic cells; Deoxyribonucleic acid; DNA; DNA microarrays; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic aspects; Genomics; Health aspects; Homogeneity; Humans; Hybridization; Interleukin 1; Interleukin 13; Lesions; Lists; Male; Medicine; Middle Aged; Oligonucleotide Array Sequence Analysis; Osteoprotegerin; Platforms; Psoriasis; Psoriasis - genetics; Psoriasis - pathology; Qualitative analysis; Real-Time Polymerase Chain Reaction; Reproducibility; Skin; Skin - metabolism; Skin - pathology; Statistics; Stem cells; Studies; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052242

In psoriasis, only limited overlap between sets of genes identified as differentially expressed (psoriatic lesional vs. psoriatic non-lesional) was found using statistical and fold-change cut-offs. To provide a framework for utilizing prior psoriasis data sets we sought to understand the consistency of those sets. Microarray expression profiling and qRT-PCR were used to characterize gene expression in PP and PN skin from psoriasis patients. cDNA (three new data sets) and cRNA hybridization (four existing data sets) data were compared using a common analysis pipeline. Agreement between data sets was assessed using varying qualitative and quantitative cut-offs to generate a DEG list in a source data set and then using other data sets to validate the list. Concordance increased from 67% across all probe sets to over 99% across more than 10,000 probe sets when statistical filters were employed. The fold-change behavior of individual genes tended to be consistent across the multiple data sets. We found that genes with 10-fold changes in either direction such as CHRM3, IL12B and IFNG. Gene expression changes in psoriatic lesions were consistent across different studies, despite differences in patient selection, sample handling, and microarray platforms but between-study comparisons showed stronger agreement within than between platforms. We could use cut-offs as low as log10(ratio) = 0.1 (fold-change = 1.26), generating larger gene lists that validate on independent data sets. The reproducibility of PP signatures across data sets suggests that different sample sets can be productively compared.