Single-cell sequencing combined with machine learning reveals the mechanism of interaction between epilepsy and stress cardiomyopathy

Abstract

Background: Epilepsy is a disorder that can manifest as abnormalities in neurological or physical function. Stress cardiomyopathy is closely associated with neurological stimulation. However, the mechanisms underlying the interrelationship between epilepsy and stress cardiomyopathy are unclear. This paper aims to explore the genetic features and potential molecular mechanisms shared in epilepsy and stress cardiomyopathy.

Methods: By analyzing the epilepsy dataset and stress cardiomyopathy dataset separately, the intersection of the two disease co-expressed differential genes is obtained, the co-expressed differential genes reveal the biological functions, the network is constructed, and the core modules are identified to reveal the interaction mechanism, the co-expressed genes with diagnostic validity are screened by machine learning algorithms, and the co-expressed genes are validated in parallel on the epilepsy single-cell data and the stress cardiomyopathy rat model.

Results: Epilepsy causes stress cardiomyopathy, and its key pathways are Complement and coagulation cascades, HIF-1 signaling pathway, its key co-expressed genes include SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3. The key immune cell subpopulations localized by single-cell data are the T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup.

Conclusion: We believe epilepsy causing stress cardiomyopathy results from a multi-gene, multi-pathway combination. We identified the core co-expressed genes (SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3) and the pathways that function in them (Complement and coagulation cascades, HIF-1 signaling pathway, JAK-STAT signaling pathway), and finally localized their key cellular subgroups (T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup). Also, combining cell subpopulations with hypercoagulability as well as sympathetic excitation further narrowed the cell subpopulations of related functions.

Keywords: epilepsy; immuno analysis; machine learning; metabolic analysis; single-cell sequencing; stress cardiomyopathy; stress cardiomyopathy rat model.