Figure 10

Deconvolution of brain infectome by disease correlation. The 3rd deconvolution approach of the total brain infectome predicts correlation between T. gondii infection and common neurological diseases using IPA disease and function tool (see Supplement B: Table S10A,B). (a) Grouping of disease annotations included p-value and group size. The 4 disease groups are detected for all Type I, II and III infections. (b) Alzheimer group included Alzheimer’s disease, tauopathy and amyloidosis annotations. IPA Canonical analysis indicates this disease gene network is mediated by signaling pathways of adaptor protein 14-3-3 (7 genes), retinoic acid receptor LXR/RXR (7 genes), tumor suppressor protein p53 (7 genes), cytokine IL-17A (5 genes) and glucocorticoid receptor (13 genes). (c) Movement disorders. This entails predictions for movement disorders, disorder of basal ganglia, neuromuscular disease, dyskinesia and Huntington’s Disease. IPA canonical analysis of this gene network indicates signaling pathways mediated by G-Protein coupled receptor (13 genes), by cAMP (10 genes), transcriptional regulator 14-3-3 (7 genes), cytokine Endothelin-1 (8 genes), polypeptide hormone relaxin (9 genes) and corticotropin releasing hormone (8 genes). (d) Epileptic disorders pathways for seizures, seizure disorder and epileptic seizure. IPA canonical analysis of the 81-gene network indentifies top-ranking signaling pathways that are associated with retinoic acid receptor (6 genes), endothelin-1 (6 genes), Gaq protein (5 genes) and corticotropin releasing hormone (5 genes). (e) Cancer group. This illustrated mechanisms of cancer, malignant solid tumor, abdominal neoplasm, abdominal cancer, urogenital cancer and genital tumor that are potentially activated in the infected brain. The top 10 canonical pathways (Supplement B: Tables S8,9) reveal important mechanisms that may potentiate cancer development in the T. gondii infected brain, such as Wnt/Ca + pathway (14 genes) and role of IL-17A in arthritis (14 genes). Wnt/Ca + pathway annotation contains 6 frizzled class receptors (FZD2, FZD3, FZD4, FZD5, FZD8, FZD9) and receptor tyrosine kinase-like ROR1. Not shown in diagram is the association with the schizophrenia 19-gene network: ABAT, ABCB1, ADRA1D, ANK3, APOL1, CHRNA5, CHRNA7, E2F1, EGR3, EGR4, GAP43, GRIN2A, HOMER1, IL6, PMP22, PTGS2, SCG2, SOD2, TMTC1.