PT  - JOURNAL ARTICLE
AU  - Xingpeng Li
AU  - Wen He
AU  - Ying Zhang
AU  - Karen Page
AU  - Craig Hyde
AU  - Mateusz Maciejewski
TI  - Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects
AID  - 10.1101/2022.05.24.493180
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.24.493180
4099  - http://biorxiv.org/content/early/2022/05/27/2022.05.24.493180.short
4100  - http://biorxiv.org/content/early/2022/05/27/2022.05.24.493180.full
AB  - Background Atopic Dermatitis (AD) is a persistent inflammatory disease of the skin to which a few novel treatment options have recently become available. Multiple published datasets, from RNA sequencing (RNA-seq) and microarray experiments performed on lesional (LS) and non-lesional (NL) skin biopsies collected from AD patients, provide a useful resource to better define an AD gene signature and evaluate therapeutic effects.Methods We evaluated 22 datasets using defined selection criteria and leave-one-out analysis and then carried out a meta-analysis (M-A) to combine 4 RNA-seq datasets and 5 microarray datasets to define a disease gene signature for AD skin tissue. We used this gene signature to evaluate its correlation to disease activity in published AD datasets, as well as the treatment effect of some of the existing and experimental therapies.Results We report the AD gene signatures developed separately from the RNA-seq or the microarray datasets, as well as a gene signature from datasets combined across these two technologies; all 3 gene signatures showed a strong correlation to the disease activity score (SCORAD) – microarray: Pearson’s ρ = 0.651, p-value < 0.01, RNA-seq: ρ = 0.640, p < 0.01, combined: ρ = 0.649, p < 0.01. The gene signature improvement (GSI) of two existing effective therapies, Dupilumab and Cyclosporine, as well as that of other experimental treatments, is consistent with their reported cohort level efficacy from the associated clinical trials.Conclusions The M-A derived AD gene signature provides an evolution of an important resource to correlate gene expression to disease activity and will be helpful for evaluating potential treatment effects for novel therapies.Competing Interest StatementDrs. Li, He, Zhang, Page, Hyde, and Maciejewski are full-time employees of Pfizer and own stock or stock options in Pfizer.MAADTMeta-Analyzed Atopic Dermatitis TranscriptomeADAtopic DermatitisLSLesionalNLNon-LesionalM-AMeta-AnalysisOMAOmics Meta-AnalysisSCORADSCORing Atopic DermatitisFCFold-changeGSIGene Signature ImprovementEASIEczema Area and Severity Index