## 3 Results and Discussion
### Gene Set Enrichment Analysis  
A final step was to study the biological processes, cellular components, and molecular functions in which the 286 genes making up the network module under investigation were involved, with a particular focus on mitochondrial functions. As shown in Figure 7, the genes in this module exploit different functions, the largest part of which regard regulatory and structural processes (light-yellow, ocher). However, five tiles, which are colored \"salmon\", significantly enrich mitochondrial-specific functions, thereby confirming the statistical over-representation of mitochondrial genes in this network module. Moreover, since mitochondria are responsible for energy production via oxidative phosphorylation, ion transport across mitochondrial membranes is essential for their proper function and plays a critical role in various cellular processes such as cytoplasmic homeostasis, energy generation, and the compartmentation of metabolism. Several ion transport-related functions were statistically enriched by this analysis and are represented in the figure below by the green tiles. Finally, mitochondria provide the energy required for muscle contraction, as they are responsible for producing ATP. Most ATP is produced in mitochondria through a series of reactions known as the Krebs cycle. During muscle contraction, calcium ions are released, which bind to proteins that enable the myosin and actin filaments to slide past each other, resulting in muscle contraction. In this regard, several muscle and locomotion  
Figure 6: Graphical representation of the “lightsalmon” cluster obtained using igraph. Each node is a gene. When two genes co-express, an edge connects them. The “lightsalmon” module contains five topologically highly ranked mitochondrial genes: UQCR-C1, ND-20, Pdhb, ND-B17.2, and ABCB7. Nuclear and mitochondrial genes are colored in red and green, respectively.  
related biological processes were statistically enriched and represented by \"darkorange\" tiles in Figure 7 (Supplementary Materials Figure S3). These are particularly important since mitochondrial dysfunction has also been linked to various muscle-related diseases, including mitochondrial myopathies [41].  
The analysis of the \"cellular component\" GO class of terms confirmed these results (Supplementary Materials Figure S4). The most statistically significant GO term was \"mitochondrial inner membrane;\" which indicates that a significantly high number of genes in our cluster lie in this cellular compartment. Other cellular components resulted from this analysis to be significantly over-represented by the genes of this cluster: the \"organelle inner membrane\", the \"mitochondrial protein-containing complex\", and the \"inner mitochondrial membrane protein complex\". These components are essential for maintaining cellular homeostasis, energy production, and metabolic regulation.  
The analysis of the GO \"molecular functions\" category (Supplementary Materials Figure S5) revealed that the genes in this cluster primarily exploit the transport of ions and cations as well as membrane functions associated with ATP synthesis.  
In addition, we performed a metabolic pathway enrichment analysis against the KEGG database (Figure 8). In accordance with the previous results, the most significant ones relate to mitochondrial processes that were strongly statistically enriched and significant, such as oxidative phosphorylation, carbon metabolism, and the citrate cycle (TCA cycle).  
Figure 7: TreeMap representing the GO terms statistically enriched by the genes composing the “lightsalmon” network cluster. The terms, i.e., the TreeMap tiles, are joined into ‘super tiles’ of loosely related GO terms, visualized with different colors. The size of each tile represents either the \(p\)-value, or the frequency of the GO term in the underlying GO database.