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

Area of Science:

• Neuroscience
• Genetics
• Bioinformatics

Background:

• Synapses are crucial for brain function, and their dysfunction underlies many neurological disorders.
• A lack of systematic gene annotation and process ontology hinders synapse research.
• Existing resources do not comprehensively cover synaptic gene functions and locations.

Purpose of the Study:

• To establish SynGO, a comprehensive, interactive knowledge base for synapse biology.
• To annotate synaptic genes and processes using novel Gene Ontology (GO) terms.
• To provide a resource for understanding the genetic basis of brain disorders.

Main Methods:

• Developed novel Gene Ontology (GO) terms for 87 synaptic locations and 179 synaptic processes.
• Curated 2,922 annotations for 1,112 synaptic genes based on published, expert-reviewed evidence.
• Integrated SynGO into interactive online platforms for public access and data analysis.

Main Results:

• Synaptic genes are exceptionally conserved and less tolerant to mutations compared to other genes.
• SynGO terms are significantly enriched in gene variations associated with intelligence, educational attainment, ADHD, autism, bipolar disorder, and schizophrenia.
• Identified overrepresentation of SynGO terms in de novo variants linked to neurodevelopmental disorders.

Conclusions:

• SynGO provides a universal reference for synapse research, enhancing our understanding of synaptic gene function.
• The knowledge base facilitates the interpretation of large-scale omics data in the context of synaptic biology.
• SynGO highlights the critical role of synaptic genes in neurodevelopmental and psychiatric conditions.