A study on psoriasis linked comorbidities and integrative gene expression analysis to identify potential drug targets

Abstract

ABSTRACT newlinevii | P a g e newlineABSTRACT newlinePsoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- newline11.4%. Despite the rare mortality, the severity of the disease could be understood by the newlineaccompanying comorbidities that has even led to physical as well physiological newlinedifficulties amid psoriasis patients. The etiology and the pathogenesis of the disease newlineremains elusive. The contemporary study is an effort to understand the predominance of newlinecomorbid condition among psoriasis patients, the shared genes, biological processes, newlinemolecular function and pathways between them. The study also intends to explore the newlinepathways involved in psoriasis and identify the potential biomarkers that could act as newlinepotential therapeutics. newlineThe prevalence of psoriasis associated comorbidities was assessed using meta-analysis newlineapproach. Odds ratio was calculated to determine the association of psoriasis with newlineidentified comorbidities. Further, network medicine approach was used to identify the newlineshared dysregulated genes and pathways between psoriasis and its associated comorbid newlinecondition. The chosen GEO profile of individual comorbid condition including obesity newline(GSE48964), myocardial ischemia (GSE22255), dyslipidemia (GSE6054), newlineatherosclerosis (GSE6088) and type II diabetes (GSE23343) based upon inclusion and newlineexclusion criteria was pre-processed and normalized using RMA method and DEGs were newlineidentified using GEOquery and limma package. The shared genes were visualized in a newlinenetwork using Cytoscape v3.7.1. Interactome map between psoriasis and associated newlinecomorbidities was determined using database BIOGRID, 3.5. Molecular Comorbidity newlineIndex (MCI) was calculated to determine the strength of association between psoriasis newlineand its individual comorbidities. Additionally, to identify the potential therapeutic target newlinefor psoriasis different gene expression profile from NCBI-GEO were retrieved and newlineclassified into Lesional-Non lesional [LS-NL] (GSE30999, GEO34248, GSE41662, newlineGSE50790, GSE6710), Lesional- Non lesional and