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1. Introduction

1.1 Statement of Problem

Atopic Dermatitis (AD), also known as eczema, is a chronic, inflammatory skin disease of a multifactorial nature1, but is predominantly caused by genetics2. Such dermatosis is characterised by complex pathogenesis, immune changes in the regulation of the functional activity of T-lymphocytes, consequently, affecting the barrier function. AD is distinguished by the activation of T-helper 2 cells (Th2)3 and their production of cytokines (Interleukins (IL)-4, -5 and -13)4, which leads to the excessive synthesis of Immunoglobulin E (IgE)5. The binding of allergens to IgE causes the release of inflammatory mediators6.

Psoriasis (PSO) is another chronic inflammatory skin disease which is based on the pathology of keratinocyte proliferation7 and polarised by Th17 and IL-238. Both PSO and AD are accompanied by itching, however, in AD the intensity is more severe. Furthermore, AD is more common among children and adolescents9, while PSO usually appears in older age groups10.

A growing body of literature has stressed PSO and AD as being highly heterogeneous diseases with a wide variety of phenotypes4,11. What is not yet clear is the progression of these diseases from the acute to the chronic stages, and the transcriptome alterations over their progression. This indicates a need to discover the genes that are associated with different stages of PSO and AD.

1.2 Research Aim and Objectives

The aim of this research stems from the need to identify AD- and PSO-related genes from high-dimensional RNA-sequencing (RNA-Seq) data, contributing towards a better understanding of the underlying pathogenesis of the disease.

Four Research Objectives were framed in order to meet the main research aim:

  1. To evaluate the relevant computational methods.

  2. To identify and apply algorithms that can help generate a better understanding of the transcriptome changes of PSO and AD progressions.

  3. To identify the signature genes for both AD and PSO.

  4. To interpret the results in a biological context.


  1. Yanoff M, Sassani JW. Skin and Lacrimal Drainage System. In: Ocular Pathology. Elsevier; 2020. p. 163-233.e10. ↩

  2. Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP, et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015 Dec 1;47(12):1449–56. ↩

  3. Vestergaard C, Deleuran M, Gesser B, Gronhoj Larsen C. Expression of the T-helper 2-specific chemokine receptor CCR4 on CCR10-positive lymphocytes in atopic dermatitis skin but not in PSOriasis skin. Br J Dermatol [Internet]. 2003 Sep 1 [cited 2020 Apr 21];149(3):457–63. Available from: http://doi.wiley.com/10.1046/j.1365-2133.2003.05505 ↩

  4. Tsoi LC, Rodriguez E, Degenhardt F, Baurecht H, Wehkamp U, Volks N, et al. Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to PSOriasis. J Invest Dermatol [Internet]. 2019 Jul 1 [cited 2020 Apr 21];139(7):1480–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30641038 ↩↩

  5. Juhlin L, Johansson SGO, Bennich H, Högman C, Thyresson N. Immunoglobulin E in Dermatoses: Levels in Atopic Dermatitis and Urticaria. Arch Dermatol. 1969 Jul 1;100(1):12–6. ↩

  6. Leung DYM, Schneeberger EE, Siraganian RP, Geha RS, Bhan AK. The presence of IgE on macrophages and dendritic cells infiltrating into the skin lesion of atopic dermatitis. Clin Immunol Immunopathol. 1987 Mar 1;42(3):328–37. ↩

  7. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in PSOriasis is amplified by keratinocyte responses. Vol. 34, Trends in Immunology. Elsevier Current Trends; 2013. p. 174–81. ↩

  8. Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015 Feb 1;135(2):324–36. ↩

  9. DaVeiga SP. Epidemiology of atopic dermatitis: A review. Vol. 33, Allergy and Asthma Proceedings. 2012.
    p. 227–34. ↩

  10. Swanbeck G, Inerot A, Martinsson T, Wahlstrom J. A population genetic study of PSOriasis. Br J Dermatol [Internet]. 1994 Jul 1 [cited 2020 Apr 21];131(1):32–9. Available
    from: http://doi.wiley.com/10.1111/j.1365-2133.1994.tb08454 ↩

  11. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. Vol. 139, Journal of Allergy and Clinical Immunology. Mosby Inc.; 2017. p. S65–76. ↩