SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org).

Active actin gels.

The self-organization of actin filaments is a topic that links cell biology with condensed matter physics. In vitro assays allow precise manipulation of component mechanical and chemical properties, needed for rigorous tests of theoretical models. We review recent work on in vitro motility assays that documented emergence of ordered actin filament microdomains powered by myosin motor proteins at high filament densities. Motor and filament surface density and mechanochemical cycle kinetics are additional parameters under current investigation. Individual filament collisions have been studied in order to elucidate the emergent population behavior. Apolar, weak  interactions evidenced by local filament deformations during crossover events are attenuated at high motor densities. Theoretical analysis requires refinement of rigid rod filament models. In intact cells, accessory proteins modulate actin filament length, bundling or sliding and this gives rise to complex emergent structures and behaviors such as cell motility and chemotaxis. The development of generic, mechanical and biochemical frameworks with predictive power that link molecular properties with micro- and macroscopic phenomena seen in living cells requires dialogue between theoreticians and experimentalists.