| %% Convergent PD pathways: toxin evidence + enrichment |
| flowchart LR |
| n0[["Parkinson disease"]] |
| n1["Detoxification of Reactive Oxygen Species"] |
| n2(["CAT"]) |
| n3(["GPX1"]) |
| n4(["GPX2"]) |
| n5(["GPX3"]) |
| n6(["SOD1"]) |
| n7(["SOD2"]) |
| n8(["SOD3"]) |
| n9{{"chlorpyrifos"}} |
| n10{{"lead"}} |
| n11{{"manganese"}} |
| n12{{"mercury"}} |
| n13{{"paraquat"}} |
| n14{{"rotenone"}} |
| n15["Transcriptional activation of mitochondrial biogenesis"] |
| n16(["GABPA"]) |
| n17(["PPARGC1B"]) |
| n18{{"tetrachloroethylene"}} |
| n19["FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes"] |
| n20["Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation"] |
| n21["Interleukin-4 and Interleukin-13 signaling"] |
| n22(["AKT1"]) |
| n23(["BCL2"]) |
| n24(["IL6"]) |
| n25(["MAOA"]) |
| n26(["TNF"]) |
| n27{{"mptp"}} |
| n28{{"trichloroethylene"}} |
| n29["Catecholamine biosynthesis"] |
| n30(["TH"]) |
| n31["Biosynthesis of maresin-like SPMs"] |
| n32(["CYP2E1"]) |
| n33["CYP2E1 reactions"] |
| n34["Synthesis of 5-eicosatetraenoic acids"] |
| n35(["GPX4"]) |
| n36["Glutathione conjugation"] |
| n37(["HPGDS"]) |
| n38{{"dieldrin"}} |
| n39["Biogenic amines are oxidatively deaminated to aldehydes by MAOA and MAOB"] |
| n40(["MAOB"]) |
| n1 -->|q=0.015| n0 |
| n2 -->|in pathway| n1 |
| n3 -->|in pathway| n1 |
| n4 -->|in pathway| n1 |
| n5 -->|in pathway| n1 |
| n6 -->|in pathway| n1 |
| n7 -->|in pathway| n1 |
| n8 -->|in pathway| n1 |
| n9 -->|implicates| n1 |
| n10 -->|implicates| n1 |
| n11 -->|implicates| n1 |
| n12 -->|implicates| n1 |
| n13 -->|implicates| n1 |
| n14 -->|implicates| n1 |
| n15 -->|q=0.024| n0 |
| n16 -->|in pathway| n15 |
| n17 -->|in pathway| n15 |
| n7 -->|in pathway| n15 |
| n9 -->|implicates| n15 |
| n10 -->|implicates| n15 |
| n11 -->|implicates| n15 |
| n12 -->|implicates| n15 |
| n13 -->|implicates| n15 |
| n14 -->|implicates| n15 |
| n18 -->|implicates| n15 |
| n19 -->|q=0.033| n0 |
| n2 -->|in pathway| n19 |
| n7 -->|in pathway| n19 |
| n9 -->|implicates| n19 |
| n10 -->|implicates| n19 |
| n11 -->|implicates| n19 |
| n12 -->|implicates| n19 |
| n13 -->|implicates| n19 |
| n14 -->|implicates| n19 |
| n20 -->|q=0.015| n0 |
| n6 -->|in pathway| n20 |
| n7 -->|in pathway| n20 |
| n9 -->|implicates| n20 |
| n10 -->|implicates| n20 |
| n11 -->|implicates| n20 |
| n12 -->|implicates| n20 |
| n13 -->|implicates| n20 |
| n14 -->|implicates| n20 |
| n21 -->|q=0.0064| n0 |
| n22 -->|in pathway| n21 |
| n23 -->|in pathway| n21 |
| n24 -->|in pathway| n21 |
| n25 -->|in pathway| n21 |
| n26 -->|in pathway| n21 |
| n27 -->|implicates| n21 |
| n13 -->|implicates| n21 |
| n14 -->|implicates| n21 |
| n28 -->|implicates| n21 |
| n29 -->|q=0.016| n0 |
| n30 -->|in pathway| n29 |
| n27 -->|implicates| n29 |
| n14 -->|implicates| n29 |
| n31 -->|q=0.022| n0 |
| n32 -->|in pathway| n31 |
| n28 -->|implicates| n31 |
| n33 -->|q=0.048| n0 |
| n32 -->|in pathway| n33 |
| n28 -->|implicates| n33 |
| n34 -->|q=0.035| n0 |
| n3 -->|in pathway| n34 |
| n4 -->|in pathway| n34 |
| n35 -->|in pathway| n34 |
| n12 -->|implicates| n34 |
| n13 -->|implicates| n34 |
| n36 -->|q=0.022| n0 |
| n37 -->|in pathway| n36 |
| n9 -->|implicates| n36 |
| n38 -->|implicates| n36 |
| n39 -->|q=0.0064| n0 |
| n25 -->|in pathway| n39 |
| n40 -->|in pathway| n39 |
| n27 -->|implicates| n39 |
| classDef drug fill:#ddf4ff,stroke:#0969da,color:#0a3069; |
| classDef anchor fill:#eeeeee,stroke:#6e7781,color:#24292f,stroke-dasharray:4 3; |
| classDef target fill:#fff8c5,stroke:#9a6700,color:#4d2d00; |
| classDef toxin fill:#ffebe9,stroke:#cf222e,color:#5a0f14; |
| classDef pathway fill:#dafbe1,stroke:#1a7f37,color:#0a3622; |
| classDef disease fill:#fbefff,stroke:#8250df,color:#3b1a5c; |
| classDef readout fill:#f6f8fa,stroke:#6e7781,color:#24292f; |
| class n2,n3,n4,n5,n6,n7,n8,n16,n17,n22,n23,n24,n25,n26,n30,n32,n35,n37,n40 target; |
| class n9,n10,n11,n12,n13,n14,n18,n27,n28,n38 toxin; |
| class n1,n15,n19,n20,n21,n29,n31,n33,n34,n36,n39 pathway; |
| class n0 disease; |
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