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A data-driven framework linking the connectome to spatial gene expression gradients inspired by chemoaffinity theory
Jigen Koike1,2, Ken Nakae3,4, Riichiro Hira5
1Laboratory of Data-driven Biology, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashihiroshima 739-8526, Japan.
Summary
SPERRFY operationalizes Sperry
Area of Science:
- Neuroscience
- Genetics
- Computational Biology
Background:
- Understanding genetic mechanisms of brain-wide neural circuit wiring is crucial.
- Sperry's chemoaffinity theory explains axonal projections via molecular gradients, but is limited to sensory systems.
Purpose of the Study:
- To develop a data-driven framework, SPERRFY, for applying Sperry's theory to whole-brain connectivity.
- To infer latent positional gradients guiding axonal wiring across the entire brain.
Main Methods:
- Integrated connectomic data with spatial transcriptomic profiles from the Allen Mouse Brain Atlas.
- Employed canonical correlation analysis (CCA) to identify key positional gradients.
- Developed connectivity reconstruction models based on inferred gradients.
Main Results:
- SPERRFY successfully inferred latent positional gradients underlying axonal wiring.
- Connectivity reconstruction demonstrated strong predictive performance.
- Identified candidate genes potentially involved in positional wiring.
Conclusions:
- SPERRFY extends Sperry's chemoaffinity theory to the whole-brain scale.
- Provides a unified framework for understanding genetically encoded brain-wide circuitry.
- Offers molecular insights into neural development and connectivity.

