Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Abstract

Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

How Does Chronic Cigarette Smoke Exposure Affect Human Skin? A Global Proteomics Study in Primary Human Keratinocytes

“…High-throughput investigations of skin diseases such as eczema and psoriasis have aided in a greater understanding of the underlying genetic and/or molecular basis of disease pathologies (Cole et al, 2014;Jiang et al, 2015;Kang et al, 2016). In addition, computational systems biology approaches that integrate data from large ''omics'' datasets can aid in gaining mechanistic insights into disease pathology (Sevimoglu and Arga, 2015). In this study, we investigated the molecular alterations in skin keratinocytes on exposure to cigarette smoke by using quantitative proteomics.…”

The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

“…Psoriasis is a disease with a very complex pathogenesis involving genetic factors, skin cells, innate and adaptive immune cells and a network of signaling molecules including autoantigens, cytokines and chemokines. The results that have been reported include in vitro assays, ex vivo assays, in vivo assays using animal models, in vivo assays in humans, clinical trials, cell biology, molecular biology and, more recently, genome-wide assays at the level of transcriptomics [131], proteomics [132], metabolomics [133], as well as their multi-omics integration and in silico predictions via modeling approaches [134]. This systems biology approach has been applied to help unravel the pathological mechanisms in human diseases, such as Alzheimer's [135], coronary artery disease [136], cardiovascular disease, type 2 diabetes [137] and cancer [138], among others.…”

<p>Omics-Driven Biomarkers of Psoriasis: Recent Insights, Current Challenges, and Future Prospects</p>

“…Although limited in number, meta-analyses of transcriptome datasets were also performed and resulted in proposals for a core transcriptome 30 and a disease pathway. 31 The core transcriptome, which was enriched mostly in IL-17A pathway, atherosclerosis signaling, and fatty acid metabolism, proposed several biomarker candidates for molecular diagnosis of psoriasis, and also molecular signatures to associate psoriasis and its systemic manifestations such as metabolic syndrome and cardiovascular diseases. 30 From a comprehensive perspective on the molecular basis of psoriasis, a total of twelve transcriptome datasets were analyzed in an integrative framework and several candidate biomarkers and therapeutic targets and a JAK/STAT signaling pathway involving cytokines, interferon-stimulated genes, and antimicrobial peptides were proposed.…”

“…30 From a comprehensive perspective on the molecular basis of psoriasis, a total of twelve transcriptome datasets were analyzed in an integrative framework and several candidate biomarkers and therapeutic targets and a JAK/STAT signaling pathway involving cytokines, interferon-stimulated genes, and antimicrobial peptides were proposed. 31 More recently, a set of biomarker candidates was also proposed through a transcriptome based meta-analysis considering also the sex differences of patients. 32 They suggested IRF9 and NMI in women, and SUB1 in men as potential biomarkers, and verified the biomarker potential of PI3, WIF1 , and PC4 both at transcriptome level using qRT-PCR and protein level via ELISA.…”