IDENTIFICATION OF SYNAPTIC GENE SETS FOR CNS SYNAPSE TAXONOMY AND ANTIBODIES FOR THEIR ENGAGEMENT- SUPPLEMENT REQUEST 2018 The BRAIN Initiative Cell Census Network (BICCN) is providing a multimodal classification of cell types and a platform for understanding the role of cell types in brain function in health and disease. While synaptic connectivity and function are key parts of brain function, the present BICCN experimental design does not provide, as yet, systematic information about synaptic connectivity and function. With this supplement, the SynGO consortium, who are domain experts on synapses, and the Universal Protein Resource KnowledgeBase (UniProtKB) aim to enhance the knowledge of synaptic proteins and their expression in specific populations of neurons in the brain, based on BICCN single cell expression data. We propose to enhance this knowledge using two main activities:
Aim 1 : The SynGO consortium has annotated synaptic proteins to (new) Gene Ontology terms, implementing new approaches to synaptic ontology, expert annotation, systematic evidence tracking, community participation and visualization tools.
We aim to cross-section (filter) BICCN single cell expression data of mouse brain using SynGO synaptic protein sets to obtain cell type-specific synaptic protein sets. From these (larger) protein sets, we aim to select a small set of marker proteins (aiming at 4-6 proteins) that together are specific for specific synapse populations in the brain, ?synapse signatures?. Using new antibody resources described below, these synapse signatures can be used for the identification of specific synapses in intact tissue in the future and for synaptic changes in mouse models for disease.
Aim 2 : To further enhance the knowledge of synaptic proteins expressed in specific neuron populations, we aim to generate a catalogue of available antibodies/nanobodies and their specifications, e.g. applicability for different assays, proofs of principles, and reference data. We will cross section (filter) available antibody resources, such as Antibodypedia, and make the information available to the research community via the SynGO portal. Together with the synapse signatures described above, this resource can be used by the community to find appropriate tools for the engagement of specific synaptic proteins and synapse populations in the mouse brain and identify changes in mouse models for disease. This work enables complex querying of the UniProtKB database, for example to find proteins which interact with synaptic proteins but are not themselves in the synapse, or to find metabolites synthesised/bound by synaptic proteins.
IDENTIFICATION OF SYNAPTIC GENE SETS FOR CNS SYNAPSE TAXONOMY AND ANTIBODIES FOR THEIR ENGAGEMENT- SUPPLEMENT REQUEST 2018 With this supplement, we aim to combine SynGO and UniProtKB capacities to support enhanced and integrative analyses of synaptic proteins and enhance the BICCN?s knowledge at the level of synaptic connectivity in the brain. By characterizing synaptic protein sets expressed in different neuron types and identifying selective tools to delineate specific synapse populations in mouse brain, we open new avenues for building synaptic connectivity maps of the brain.
| Watkins, Xavier; Garcia, Leyla J; Pundir, Sangya et al. (2017) ProtVista: visualization of protein sequence annotations. Bioinformatics 33:2040-2041 |
