Biology subjects

Dominic, D.

Publications and source records attributed to Dominic, D..

5 recordsLinked to original sources

bioRxiv2026

A Brainwide Atlas of Synaptic Nanoarchitecture Across the Mouse Lifespan

How biological complexity emerges from the ordered assembly of molecular building blocks into supramolecular systems remains a central question, particularly in the mammalian brain with its vast synaptic diversity. We introduce NanoSYNMAP, a genetic, optical, and computational platform that integrates FRET with synaptome mapping to quantify nanoscale proximity of proteins in individual synapses brain-wide. We generate the first brain atlas of synaptic nanoarchitecture, based on the proximity of postsynaptic MAGUK supercomplexes. This reveals a molecular logic in which spacing of supramolecular assemblies specifies nanoscale architecture that organizes the global synaptome architecture. Nanoarchitecture varies across brain regions, differentiates during postnatal development, and remodels with aging. Supercomplex proximity reflects scaffold abundance, nanodomain organization, and competitive interactions among MAGUK assemblies. Deletion of a neuropsychiatric risk gene triggers widespread reorganization of nanoscale architecture. These findings establish molecular proximity as a fundamental scalable dimension of synapse diversity in health and disease.

neuroscience↗

bioRxiv2025

The Overlap Area as a Novel Measure of Effect Size in Neuroscience Research

In experimental biomedical research, a common concern is whether a manipulation produces a biologically meaningful effect. Another concern is whether effect sizes are reliable, statistically significant, and generalizable. Traditional effect size measures, such as Cohens d, quantify mean differences but ignore variance heterogeneity between groups. This can result in biased effect size estimates and a lack of thresholds for statistical significance testing. Motivated by this, we introduce a novel effect size measure, termed overlap area (OA), which quantifies the difference between the population distributions of the experimental and control groups. A robust Bayesian method estimated OA, and random resampling determined OA thresholds for statistical significance in single and replicated experiments. Simulations confirmed the approachs sensitivity and robustness. Applied to a real-world dataset, OA revealed that environmental enrichment affects the mouse brain synaptome. Moreover, we developed an open-source toolbox supporting OA as a powerful new measurement for conducting robust, reliable, and reproducible analyses of manipulation effects in neuroscience and related fields.

neuroscience↗

bioRxiv2025

Experiences are encoded by brainwide reprogramming of synaptome architecture

Synaptome architecture describes the spatiotemporal distribution of highly diverse excitatory synapses throughout the brain. Whether and how this architecture is impacted by experience is key to understanding its role in learning and memory. We found that environmental enrichment and monocular visual deprivation drive large-scale, type-and subtype-specific reorganisation of excitatory synapses in more than one hundred brain regions. Each experience modifies distinct subsets of synapses, with patterns aligned with protein turnover rates and connectome architecture. These reorganisations occur during development and adulthood, revealing a conserved mechanism of synaptome plasticity across the lifespan. Our findings support a population-selection model in which experience drives adaptation by selectively modifying synapse varieties, generating a distributed trace of past experiences. Our results also point to synaptome architecture as a shared framework integrating experience, lifespan changes, sleep, genetic variation and disease.

neuroscience↗

bioRxiv2025

PRMix: Primary Region Mix Augmentation and Benchmark Dataset for Precise Whole Mouse Brain Anatomical Delineation

The architecture of the mouse brain shares remarkable similarities with the human brain, making it an essential model for studying brain pathologies, synaptic diversity, and regional specialization. A key step in such studies involves registering molecular images to reference brain atlases, a process hindered by the difficulty of accurately delineating brain regions. Toward this, we have curated a collection of high-resolution, dual-fluorescence microscopy images, termed as dual-fluorescence mouse brain microscopy (DMBM) dataset, complemented by expert annotations of 118 subregions. This dataset provides unprecedented insights into the molecular and structural complexity of the mouse brain. However, its full potential for detailed whole-brain analysis is compromised by challenges such as boundary ambiguity and sample scarcity in existing automated segmentation methods, prompting the development of the primary region mix (PRMix) augmentation method. PRMix is specifically designed to expand these datasets, enhance the realism of synthetic data and minimize overlap between adjacent regions. Our approach, together with the curated dataset, achieves superior segmentation performance across the mouse brain compared with existing methods, setting a new benchmark in brain imaging research. Code and data are available at https://git-pages.ecdf.ed.ac.uk/dmbm-datasets-5c13cd/.

neuroscience↗

bioRxiv2025

SynaptopathyDB: a resource for studying the genetic and synaptic basis of nervous system disorders

Synaptic dysfunction resulting from pathogenic variants in genes encoding synaptic proteins is a major contributor to brain and behavioural disorders, collectively termed synaptopathies. To facilitate research into the genetic basis and clinical manifestations of synaptopathy we have created SynaptopathyDB, an online resource that integrates data from 64 mammalian synapse proteomic studies and multiple genetic and phenotypic resources. We identified a consensus set of 3,437 mammalian synapse proteins from presynaptic and postsynaptic compartments, which have wide application in genetic and omic studies. Mutations in 954 genes encoding 28% of the consensus synapse proteome were associated with 1,266 OMIM diseases of the central and peripheral nervous system. We present findings that underscore the pervasive role of synaptic gene variants in the phenotypes of neurological, psychiatric, developmental, and systemic disorders highlighting the significant burden they impose on individuals and healthcare systems. SynaptopathyDB is a versatile platform and discovery tool for understanding the role of synapse proteins and genetic variants in human disease phenotypes.

neuroscience↗