Fig. 4

Enrichment analysis of PLS1 − genes related to disease progression. A Enrichment network using merged PLS1 − genes across all stages. B The same enrichment network as in A with nodes as pie charts. Each pie sector is proportional to the number of hits originating from a gene list. The color code for the pie sector represents the gene list of a certain stage. As shown in the blue dotted box, the enriched term “dopaminergic synapse” originates from the gene list of stage 1, whereas the green dotted box indicates the enriched term “cGMP-PKG signaling pathway,” which mainly originated from genes from stages 2 and 3. The pink dotted box shows that “pathways of neurodegeneration-multiple diseases” was enriched from the gene lists of stages 3, 4, and 5. C Protein–protein interaction network using the PLS1 − genes of stage 1, including six MCODE networks. Each color represents an MCODE network. Gene Ontology enrichment analysis was applied to each MCODE network to extract “biological meanings” from the network component, and the top three terms (with the smallest p-values) were retained: “dopaminergic synapse,” “morphine addiction,” and “glutamatergic synapse.” D Protein–protein interaction network enriched with the merged PLS1 − gene lists of all stages, including nine MCODE networks. The terms “morphine addiction,” “GABAerigic synapse,” and “thermogenesis” (the three terms with the smallest p-values) were extracted using Gene Ontology enrichment analysis for each MCODE. Each color represents an MCODE network