bioRxiv Science⌕ Search

Biology subjects

Kokoli, M.

Publications and source records attributed to Kokoli, M..

3 recordsLinked to original sources

Arena3D 3.0: a web server for exploring, analyzing, annotating and sharing multilayered networks in 3D

Multilayer networks describe biological entities linked by several kinds of relation or measured under several conditions. Arena3D 3.0, a complete reimplementation of Arena3Dweb, gives each layer its own place in an interactive 3D scene. Networks are uploaded or imported from STRING, IntAct, OmniPath, NDEx, Reactome and the Gene Ontology. Twelve layouts, seven in 3D, are available, and node copies can be aligned across layers. Layers are drawn as floors or 3D containers in thirteen arrangements, including 3D hive plots. Communities and annotated groups can be laid out apart and outlined as hulls or fog clouds, and edges can be bundled. Analyses cover node and multilayer metrics, distributions and perturbation, with chord, Sankey, heatmap, UpSet and UMAP views. Networks go to Cytoscape, Gephi Lite, NORMA and JBrowse 2, gene lists to Flame, and a REST API gives programmatic access. Arena3D 3.0 is free at www.arena3d.org without login.

bioinformatics↗

Familial Alzheimer disease mutation identifies novel role of SORLA in release of neurotrophic exosomes

Sortilin-related receptor with A-type repeats (SORLA) is an intracellular sorting receptor that directs target proteins between endocytic and secretory compartments of cells. Mutations in SORL1, encoding SORLA, are common in individuals suffering from Alzheimer disease (AD) of unknown etiology. Conceptually, characterization of inheritable SORL1 variants associated with AD can provide important new information about functions of this receptor relevant for aging brain health. Here, we focused on elucidation of the AD-associated variant SORLA N1358S, carrying a mutation in the main ligand binding domain of the receptor. Using unbiased quantitative proteome screens, we identified major alterations in the mutant receptor interactome linked to biogenesis and secretion of exosomes. Using advanced biophysical, cell biological, as well as functional studies in stem cell-derived human cell models we corroborated impaired release and loss of neurotrophic action of exosomes from neurons and microglia expressing SORLAN1358S. An impaired neurotrophic potential was attributed to an altered exosomal content of RNA binding proteins and associated microRNAs, known to control neuronal growth and maturation. Our studies identified a so far unknown function for SORLA in controlling the quantity and trophic quality of extracellular vesicles secreted by cells, and they argue for impaired cellular cross talk through exosomes as a pathological trail contributing to the risk of AD seen with carriers of SORL1 variants.

neuroscience↗

Arena3Dweb: Interactive 3D visualization of multilayered networks supporting multiple directional information channels, clustering analysis and application integration

Arena3Dweb is an interactive web tool that visualizes multi-layered networks in 3D space. In this update, Arena3Dweb supports directed networks as well as up to nine different types of connections between pairs of nodes with the use of Bezier curves. It comes with different color schemes (light/gray/dark mode), custom channel coloring, four node clustering algorithms which one can run on-the-fly, visualization in VR mode and predefined layer layouts (zig-zag, star and cube). This update also includes enhanced navigation controls (mouse orbit controls, layer dragging and layer/node selection), while its newly developed API allows integration with external applications as well as saving and loading of sessions in JSON format. Finally, a dedicated Cytoscape app has been developed, through which users can automatically send their 2D networks from Cytoscape to Arena3Dweb for 3D multi-layer visualization. Arena3Dweb is accessible at http://arena3d.pavlopouloslab.info or http://arena3d.org

bioinformatics↗