Assessing Facioscapulohumeral Muscular Dystrophy through Comparative Analysis of Bulk and Single-Cell Transcriptomes

Abstract

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by progressive weakening of the muscles. While the two types of FSHD (FSHD1 and FSHD2) have distinct genetic causes, they share similarities in their clinical presentations. Both result in muscle weakness, particularly in the face, shoulders, and upper arms. Genetic testing is essential for accurately diagnosing the specific type of FSHD and guiding treatment and management. MethodWe acquired bulk and single-cell gene expression data for FSHD2 from the NIH portal website. Our analysis involved an extensive array of differentially expressed genes, and pathway and gene ontology analysis. Using statistical tests, we identified the top up- and down-regulated genes, and the pathways and gene ontology terms characterizing those genes that exhibited substantial changes across both bulk and single-cell transcriptomes. ResultsThe top 10 up-regulated genes identified in the bulk gene expression analysis represent a diverse range of biological functions, but all are associated with FSHD. In contrast to the bulk down-regulated genes, the single-cell top 10 down-regulated genes are primarily linked to muscle-related functions. These genes, such as ACTC1, ACTA1, MYL11, MYH3, MYL6B, MYBPH, TPM2, MYL2, MYL1, and TNNI1 are integral to muscle contraction and skeletal muscle function. Moreover, all the top 10 single-cell down-regulated pathways are implicated in the pathogenesis of muscle dystrophy. Finally, the top 10 down-regulated gene ontology terms are all relevant to the pathogenesis of muscular dystrophy. ConclusionsThis study unequivocally demonstrates that single-cell transcriptomics surpasses bulk transcriptomics in elucidating the genes, pathways, biological processes, molecular functions, and cellular components associated with FSHD2. While bulk transcriptomics offers a broader perspective on gene expression, single-cell transcriptomics shines in its capacity to unveil cell-specific gene regulation, especially in the realm of muscle-related functions.