Multi-Omics Approaches to Brain Function and Disease: Single-Cell, Spatial, and Integrative Perspectives

The brain’s molecular complexity of the brain, with its enormous cellular diversity, intricate connectivity, and dynamic plasticity, has long challengedlimitedchallenged our ability to derive actionable insight for therapeutic development with conventional bulk-tissue approachesmethods. Over the past decade, the rapid maturation of single-cell and single-nucleus technologies (scRNA-seq, snRNA-seq, scATAC-seq, CITE-seq) and the emergence ofalongside spatial transcriptomics and spatial multi-omics platforms (Visium, MERFISH, Xenium, Stereo-seq, GeoMx, Slide-seq) have transformed our ability to dissect the brain at unprecedented molecular and cellular resolution. These technologies, combinedCombined with proteomics, epigenomics, metabolomics, and connectomics, and metabolomics, these approaches are reshaping our understanding of processes from neurodevelopment, and neuroplasticity, to glial and , vascular, and neurodegenerative biology, neurodegeneration, and and neuropsychiatric disorders.Despite this progress, key challenges remain. While the integration of multi-omic datasets across modalities and scales is still computationally and biologically demanding, overcoming these bottlenecks is critical to bridge the gap between molecular signatures and mechanistic or therapeutic insight. Currently, this translation is often hindered byThe sheer volume of data generated by these approaches has far outpaced our ability to extract meaningfulactionable insight from it, a shortfall compounded by methodological heterogeneity, limited reproducibility across cohorts, and the difficulty of linking molecular states to functional outcomes in vivo. Actively bridging cellular identity, spatial context, and integrative interpretation, especially inAdvancing the field will demand both more sophisticated computational methods and a clearer understanding of the data those methods most need to bridge the gap between molecular signatures and mechanistic or therapeutic insight. Meeting this challenge, particularly in human samples and disease models where the brain’s complexity is greatest, stands as a central goal for the next generation of neuroscience research.This Research Topic aims to bring together original research articles, reviews, methods, and perspectives that leverage single-cell, spatial, and integrative multi-omics approaches to advance our understanding of brain function in health and disease. We particularly welcome work that combines multiple omic layers, develops novel computational frameworks or open-source tools for data integration, or translates molecular discoveries into mechanistic or clinical insight builds predictive models of cellular state and function, or generates datasets designed to be maximally informative for these approaches. We welcome contributions on, but not limited to:o Single-cell and single-nucleus atlases of the developing, adult, and aging braino Spatial transcriptomic and spatial multi-omic profiling of brain regions, circuits, and disease nicheso Multi-omic dissection of neurodevelopmental and neuropsychiatric disorders (autism, schizophrenia, depression, bipolar disorder)o Multi-omic signatures of neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s, ALS, frontotemporal dementia)o Cell-type-specific epigenomic and proteomic landscapes of neurons, glia, and vascular cellso Spatial multi-omics of neuro-immune, neuro-endocrine and neuro-vascular interactionso Multi-omic approaches in brain organoids, iPSC-derived models, and humanized systemso Computational, statistical, and machine learning frameworks for multi-modal data integration, interpretation, trajectory inference and predictive modeling, including foundation and virtual cell models, and the data-generation strategies needed to train themo Translation of multi-omic discoveries into biomarkers, therapeutic targets, and precision neuroscienceo High-throughput single-cell perturbation screening (Perturb-seq) to functionally validate multi-omic discoveries in the brain.Topic Editor Carlos Alberto Galicia holds shares in and a position at Permanence Bio. All other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Andre Souza Mecawi, João Victor Nani, Carlos Alberto Galicia, Kizito-Tshitoko TSHILENGE PAYEYE Source: https://www.frontiersin.org/research-topics/82719/multi-omics-approaches-to-brain-function-and-disease-single-cell-spatial-and-integrative-perspectives