Deepening the knowledge of rare diseases dependent on angiogenesis through semantic similarity clustering and network analysis.

BACKGROUND: Angiogenesis is regulated by multiple genes whose variants can lead to different disorders. Among them, rare diseases are a heterogeneous group of pathologies, most of them genetic, whose information may be of interest to determine the still unknown genetic and molecular causes of other diseases. In this work, we use the information on rare diseases dependent on angiogenesis to investigate the genes that are associated with this biological process and to determine if there are interactions between the genes involved in its deregulation. RESULTS: We propose a systemic approach supported by the use of pathological phenotypes to group diseases by semantic similarity. We grouped 158 angiogenesis-related rare diseases in 18 clusters based on their phenotypes. Of them, 16 clusters had traceable gene connections in a high-quality interaction network. These disease clusters are associated with 130 different genes. We searched for genes associated with angiogenesis througth ClinVar pathogenic variants. Of the seven retrieved genes, our system confirms six of them. Furthermore, it allowed us to identify common affected functions among these disease clusters. AVAILABILITY: https://github.com/ElenaRojano/angio_cluster. CONTACT: seoanezonjic@uma.es and elenarojano@uma.es.

A modified chorioallantoic membrane assay allows for specific detection of endothelial apoptosis induced by antiangiogenic substances.

Current in vivo angiogenesis assays allow for the assessment of vascular growth inhibition induced by a test substance, but they usually do not provide information about the mechanisms underlying such an inhibition. A potential antiangiogenic mechanism is the triggering of endothelial apoptosis in the growing vessels. Apoptogenic substances can be of interest for antiangiogenic therapy specially if they specifically perform their action on the angiogenic endothelium. We have developed a modification of the chorioallantoic membrane (CAM) assay using embryos of quail ( Coturnix coturnix japonica ). This novel assay allows to elucidate whether an antiangiogenic substance is specifically triggering an apoptotic response in endothelial cells. We have used a quail-specific monoclonal endothelial marker (QH1), a standard TUNEL technique of apoptotic cell labelling together with a general nuclear counterstaining with propidium iodide. Through laser confocal microscopy, paraffin sections of chorioallantoic membranes treated with test substances are stained in three colours: red for normal cell nuclei, yellow-green for apoptotic nuclei and blue for endothelial cells and endothelial progenitors. In a test experience, our assay showed significant differences in the apoptogenic properties of two antiangiogenic substances, camptothecin and aeroplysinin-1.