Transcriptomics of Autoimmune and Inflammatory Diseases
Open AccessWhile many diseases have a clear cause, such as infections or genetic mutations, others are heterogeneous, involving complex interactions between multiple genetic and environmental contributors. In these cases, transcriptomic analysis is a powerful tool that allows researchers to investigate how genes are regulated and expressed during disease. The identification of dysregulated genes, human endogenous retroviruses (HERVs), or long non-coding RNAs (lncRNAs) can help in the development of targeted therapies and improve treatments for complex diseases. We analyzed the transcriptomes of several diseases to identify genetic elements which are dysregulated or associated with dysregulated genes that may impact pathophysiology.Systemic lupus erythematosus is a chronic autoimmune disease that is extremely heterogeneous. One potential contributor to disease heterogeneity is the expression of HERVs. We analyzed RNA-Seq data from two independent whole blood studies using Telescope. We identified 481 HERVs that are differentially expressed between case and control individuals with 14% overlap of differentially expressed HERVs between these two datasets. Differentially expressed HERVs were significantly more physically proximal to differentially expressed genes than non-differentially expressed HERVs. Finally, we identified key molecular pathways which could be impacted by differential HERV expression in SLE. Bronchiolitis is an illness characterized by inflammation of the airways due to viral infection. The endotyping of bronchiolitis is of interest to researchers but the incorporation of gene expression in endotype definitions is only a recent occurrence. Long non-coding RNAs have been shown to modulate gene expression in a variety of diseases, including bronchiolitis. We examined the expression of genes and lncRNAs, as well as biological pathway differences, between defined endotypes in a dataset obtained from infants with bronchiolitis. The differential expression of lncRNAs between endotypes was comparatively small compared to differentially expressed genes. However, the pathway analysis indicated differences in inflammatory and immune related pathways, as well as a large difference in HIF1α that may be relevant to viral replication. Multiple sclerosis (MS) is a disease in which the immune system attacks the myelin sheaths around nerve fibers. We quantified HERV and gene expression as well as bacterial abundance in a set of epileptic and MS samples to find genetic elements associated with dysregulated gene expression in MS. While there were minimal significant differences in bacterial composition, we were able to find significant differences in HERV and gene expression as well as immune system pathways in MS. Moreover, many immune-related genes had significant associations with HERVs despite a lack of genetic proximity including several different cathepsin genes linked to antigen presentation in MS. In each of the analyses, we looked at the role different genetic elements play in the dysregulation of gene expression that could contribute to disease or otherwise be affected because of disease. Through bioinformatics methods we were able to characterize many genetic elements which may have an effect on gene expression and, by extension, disease progression.
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Stearrett_gwu_0075A_16352.pdf | 2023-11-14 | Open Access |
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