Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling David A. Ewald, MSc, Shinji.

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Presentation transcript:

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling David A. Ewald, MSc, Shinji Noda, MD, PhD, Margeaux Oliva, BA, Thomas Litman, PhD, Saeko Nakajima, MD, PhD, Xuan Li, MSc, Hui Xu, MSc, Christopher T. Workman, PhD, Peter Scheipers, PhD, Naila Svitacheva, PhD, Tord Labuda, PhD, James G. Krueger, MD, PhD, Mayte Suárez-Fariñas, PhD, Kenji Kabashima, MD, PhD, Emma Guttman-Yassky, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 2, Pages 562-571 (February 2017) DOI: 10.1016/j.jaci.2016.08.029 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Representative pictures of murine models. B, Venn diagram of overlapping unique HGNC symbol DEGs for 4 AD models. Flaky tail and Flg-mutated models are excluded because of their small numbers of DEGs. C, Proportion of MADAD DEGs represented in each model.9 IL-23–injected mice appear separated because these data are from our previous study (GSE50400).29 D, Overlap between the top upregulated (red) and downregulated (dark blue) genes in each model and the MADAD transcriptome was estimated for rank N = 1 … 5000.35 The light blue line outlines the overlap expected by chance, such that any line above it indicates significant overlap.36 HGNC, Human Genome Organization Gene Nomenclature Committee. Journal of Allergy and Clinical Immunology 2017 139, 562-571DOI: (10.1016/j.jaci.2016.08.029) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, Kyoto Encyclopedia of Genes and Genomes analysis in the respective MADAD and murine model transcriptomes. The black horizontal line indicates an FDR of 0.05. B, Heat map of the top 30 upregulated and downregulated MADAD DEGs with orthologs in murine models.9 Corresponding log2(FCH) values are shown. *P < .05, **P < .01, and ***P < .001. Coloring (blue, downregulated; red, upregulated) appears for an absolute log2(FCH) value of 1 or greater, with adjusted P values of less than .05. PPAR, Peroxisome proliferator-activated receptor. Journal of Allergy and Clinical Immunology 2017 139, 562-571DOI: (10.1016/j.jaci.2016.08.029) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Genome-wide neighboring analysis of the 8400 genes represented in human-murine orthologs. A, Dendrogram applying unsupervised clustering with the Pearson correlation distance and McQuitty agglomeration. Significant clusters have approximately unbiased (AU) P values of 95% or greater.55 B, Principal component analysis using log2(FCH) for the 8400 genes. PSO, Psoriasis. Journal of Allergy and Clinical Immunology 2017 139, 562-571DOI: (10.1016/j.jaci.2016.08.029) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Heat map of qRT-PCR–derived mRNA expression differences. CD data are shown separated because data from only 13 genes were available.33 Corresponding log2(FCH) values are shown. +P < .1, *P < .05, **P < .01, and ***P < .001. Dendrograms represent unsupervised clustering with Euclidean distance and McQuitty agglomeration. LS, Lesional; N/A, not available; NL, nonlesional; PSO, psoriasis. Journal of Allergy and Clinical Immunology 2017 139, 562-571DOI: (10.1016/j.jaci.2016.08.029) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions