%% 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;