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Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects

Xingpeng Li, Wen He, Ying Zhang, Karen Page, Craig Hyde, Mateusz Maciejewski
doi: https://doi.org/10.1101/2022.05.24.493180
Xingpeng Li
1Pfizer Inc., Cambridge, MA, USA
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  • For correspondence: matt@mattmaciejewski.com xingpeng.li@pfizer.com
Wen He
1Pfizer Inc., Cambridge, MA, USA
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Ying Zhang
1Pfizer Inc., Cambridge, MA, USA
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Karen Page
1Pfizer Inc., Cambridge, MA, USA
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Craig Hyde
1Pfizer Inc., Cambridge, MA, USA
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Mateusz Maciejewski
1Pfizer Inc., Cambridge, MA, USA
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  • For correspondence: matt@mattmaciejewski.com xingpeng.li@pfizer.com
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Abstract

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 Statement

Drs. Li, He, Zhang, Page, Hyde, and Maciejewski are full-time employees of Pfizer and own stock or stock options in Pfizer.

  • List of acronyms or abbreviations

    MAADT
    Meta-Analyzed Atopic Dermatitis Transcriptome
    AD
    Atopic Dermatitis
    LS
    Lesional
    NL
    Non-Lesional
    M-A
    Meta-Analysis
    OMA
    Omics Meta-Analysis
    SCORAD
    SCORing Atopic Dermatitis
    FC
    Fold-change
    GSI
    Gene Signature Improvement
    EASI
    Eczema Area and Severity Index
  • Copyright 
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    Posted May 27, 2022.
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    Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects
    Xingpeng Li, Wen He, Ying Zhang, Karen Page, Craig Hyde, Mateusz Maciejewski
    bioRxiv 2022.05.24.493180; doi: https://doi.org/10.1101/2022.05.24.493180
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    Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects
    Xingpeng Li, Wen He, Ying Zhang, Karen Page, Craig Hyde, Mateusz Maciejewski
    bioRxiv 2022.05.24.493180; doi: https://doi.org/10.1101/2022.05.24.493180

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