Characterization of the Cellular Expression Profile of Genes Associated with Childhood Apraxia of Speech

• Grant number: 25/18385-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Maria Rita dos Santos e Passos Bueno
• Grantee: Francisco do Rego
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/21989-5 - Autism Spectrum Disorder: Genetic Architecture, Pathophysiological Mechanisms, and Diagnostic and Prognostic Tools., AP.TEM

Abstract

Childhood Apraxia of Speech (CAS) is a motor speech planning disorder that affects approximately one to two children per thousand. Although CAS broadly impacts language domains such as phonology, grammar, and literacy, studies investigating its genetic underpinnings remain incipient. This project proposes an in silico approach to characterize the expression profile of genes associated with CAS in neural tissues from neurotypical individuals. To this end, a systematic literature curation will be conducted for the selection and prioritization of candidate genes, followed by the analysis of single-nucleus transcriptomic (snRNA-seq) data from the human cortex. These data will undergo processing, annotation, and functional integration steps. Gene expression will be quantified by cell type and statistically assessed to identify significant enrichment in neuronal and glial subpopulations. Additionally, a graph neural network-based approach for single-cell analysis (scGNN) will be employed to integrate gene expression profiles with topological connectivity, thereby reconstructing latent representations of cellular profiles. This strategy is expected to identify neural cell types with enriched expression of risk genes, infer cell clusters with shared regulatory signatures, and map molecular pathways potentially implicated in the etiology of CAS. The findings may provide a functional reference for prioritizing genes and cell types in future experimental models, as well as supporting investigations into shared molecular mechanisms across neurodevelopmental disorders. (AU)