The Autoimmune Tautology: An In Silico Approach

Abstract

There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren's syndrome—systemic lupus erythematosus, and autoimmune thyroid disease—type1 diabetes—rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.

Autoimmune Disease Classification Based on PubMed Text Mining

“…Figure 1 shows the AIDs association matrix of systemic lupus erythematosus (SSE), Sjögren’s syndrome (SS), type 1 diabetes (T1D), autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic sclerosis (SSc). Figure 1 also shows the association matrix reported by Cifuentes et al [ 3 ] Remarkably, the correlation between these two matrices is high (R = 0.91) and corroborates our predicted association of AIDs [ 3 ].…”

“…To validate our technique, we calculated the association values of a limited dataset of 7 AIDs reported by Cifuentes et al [ 3 ]. The training dataset comprised systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), type 1 diabetes (T1D), autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic sclerosis.…”

“…These cells promote the secretion of high-affinity autoantibodies that target and react with the “self” molecules [ 2 ]. AIDs are sometimes comorbid, and a higher susceptibility to a second AID is regarded as an indication of potential common pathogenic mechanisms among autoimmune diseases [ 3 ]. AIDs are infrequent causes of death, yet they do contribute to mortality and to the quality of life, and their classification is an unmet need [ 4 ].…”

Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

“…To find out the genetic similarity of the “HLA-A” and “Alzheimer's disease” concepts, we used the Anni software [ 17 ] because it uses the concept profile methodology that has proven to be effective in finding information in the form of associations in the biological domain [ 18 ], as previously described [ 19 ]. Briefly, we first mapped those concepts in the thesaurus of the software and built the concept profile for each one.…”

“…For this purpose, the software, Genes2networks, was employed because it provides a reference network of experimentally known protein-protein interactions [ 20 ]. Then, in order to find tightly connected proteins, the settings that were used to build the network were (1) no filter for minimum number of references, (2) the maximum links per reference were four, (3) a maximum pathway length of two, and (4) a significant z -score of 2.5 of the intermediate nodes, which was calculated through a binomial proportions test, as previously described [ 19 ].…”