Tissue specific LRRK2 interactomes reveal a distinct striatal functional unit
Fig 3
Differential Expression Analysis (DEA) on the LRRK2int.
A) DEA was performed to compare the expression levels of each LRRK2 interactor across different tissues. Tissues were ranked based on the significant comparison results. The bar graph shows the distribution of the ranks of different tissues. Each bar in the graph represents a tissue, and segments in the bar represent ranks of that tissue at three levels: AVERAGE (≤ 4); MIDDLE (between 5 and 9); HIGH (≥ 10). Of note, an AVERAGE rank suggests that for interactor I, the expression level in a given tissue is lower/not significantly higher than in other tissues, or only higher than in ≤ 4 tissues (< 27% of all tissues), while a HIGH rank means the expression level of interactor I is significantly higher in a given tissue than in ≥ 10 other tissues (> 67% of all tissues). B) The network graph shows the LRRK2 interactors with significantly high expression in certain tissues (tissue ranks ≥ 12), suggesting that the expression levels of these interactors in a specific tissue are significantly higher than in ≥ 12 other tissues (86% of all tissues). Tissues are represented as rectangular nodes, while interactors are represented as round nodes. Different colour indicates different tissues. C) Heatmap_DEA was generated from normalised read counts (log2 transformed) of LRRK2 interactors in different tissues derived from DEA. Darker colour represents higher expression levels. The horizonal dendrogram of Heatmap_DEA was extracted as Den_DEA1. It shows the hierarchical clustering of tissues in which the LRRK2int exhibits similar expression patterns. The vertical dendrogram of Heatmap_DEA was extracted as Den_DEA2. It shows the hierarchical clustering of LRRK2 interactors based on the similarity of their expression figures across different tissues. Den_DEA2 was cut to generate 4 clusters of LRRK2 interactors (Cluster 1–4, marked in green, red, blue and yellow, respectively). The cluster containing LRRK2 (marked in red) is defined as DEA_ClusterLRRK2, in which the interactors presented similar overall expression distribution across tissues as LRRK2. Abbreviations: ACC: Anterior Cingulate Cortex; AMYG: Amygdala; CAU: caudate; CR: cerebellum; FC: frontal cortex; HP: hippocampus; HYPT: hypothalamus; NAc: nucleus accumbens; PUT: putamen; SN: substantia nigra; SPC: spinal cord c-1; Kidney_c: kidney cortex.