Monogenic autoimmune/autoinflammatory (AIM/AIF) diseases highlight non-redundant regulators of immune homeostasis. To date, the discovery of these etiologies largely relies on individual case studies. Indeed, despite over 400 known genetic immune diseases, a unifying view of this important class of diseases is still lacking. The overarching ambition of this project was to develop a systems-level view of these diseases and showcase its utility for addressing a wide range of important biomedical questions. To achieve this, we developed a network-based framework for integrating all currently known monogenic immune defects and their molecular interactions. We identify the AutoCore, a markedly connected molecular subnetwork as the set of genes and their molecular interactions, that are essential for immune homeostasis. In our manuscript, titled: “AutoCore: network-based identification of a core module defining human autoimmunity and autoinflammation” we show that the AutoCore serves as a regulatory framework that can be queried to distill the molecular landscape of AIM/AIF. With the AutoCore, we quantify the separation of AIM/AIF, elucidate the links between polygenic and monogenic diseases, and define 19 distinct, molecularly, phenotypically and therapeutically cohesive disease subclusters of monogenic AIM/AIF.
Explore AIM/AIF disease data, the AutoCore, and the functional clusters here: Autocore