Cross-Species Transcriptomic Integration Identifies a Conserved Molecular Core and Regulatory ceRNA Network in...

Duchenne muscular dystrophy (DMD) is a monogenic disorder caused by dystrophin deficiency, but its downstream molecular consequences involve complex and interconnected regulatory networks.

In this study, we performed a cross-species integrative transcriptomic analysis of skeletal muscle RNA-seq datasets from humans, mice, and rats to identify conserved molecular signatures of DMD.

Differential expression analysis identified 1367 shared differentially expressed genes (DEGs) across the three datasets, of which 62 showed concordant directionality in all species. After ortholog filtering, which excluded five genes lacking confirmed one-to-one orthologs across all three species, 57 conserved genes were retained as the conserved DMD-associated gene (DAG) set. Functional enrichment (GO/KEGG) was performed on the cross-species shared DEG set, and the 57 conserved genes were subsequently mapped onto these enrichment outputs. The DAG-containing categories included focal adhesion, apoptosis, and calcium signaling, which remained significant after Benjamini-Hochberg correction, together with nominally enriched Rap1 signaling. Integration of circRNA, miRNA, and mRNA data further identified a candidate, computationally inferred hub-dominated ceRNA network involving DMD, RYR3, KLF4, ID1, TIMP4, and CASP7.

Together, these findings support a model in which conserved core molecular programs are superimposed on species- and context-dependent transcriptional responses, prioritizing the conserved genes and candidate circRNA-related network components for future mechanistic and translational studies.