InTiCAR: Network-based identification of significant inter-tissue communicators for autoimmune diseases

Inter-tissue communicators (ITCs) are intricate and essential aspects of our body, as they are the keepers of homeostatic equilibrium. It is no surprise that the dysregulation of the exchange between tissues are at the core of various disorders. Among such conditions, autoimmune diseases (AIDs) refer to a collection of pathological conditions where the miscommunication drives the immune system to mistakenly attack one's own body. Due to their myriad and diverse pathophysiologies, AIDs cannot be easily diagnosed or treated, and continuous efforts are required to seek for potential diagnostic markers or therapeutic targets. The identification of ITCs with significant involvement in the disease states is therefore crucial. Here, we present InTiCAR, Inter-Tissue Communicators for Autoimmune diseases by Random walk with restart, which is a network exploration-based analysis method that suggests disease-specific ITCs based on prior knowledge of disease genes, without the need for the external expression data. We first show that distinct ITC profile s can be acquired for various diseases by InTiCAR. We further illustrate that, for autoimmune diseases (AIDs) specifically, the disease-specific ITCs outperform disease genes in diagnosing patients using the UK Biobank plasma proteome dataset. Also, through CMap LINCS dataset, we find that high perturbation on the AIDs genes can be observed by the disease-specific ITCs. Our results provide and highlight unique perspectives on biological network analysis by focusing on the entities of extracellular communications.