Table 2.
Gene enrichment analysis of the substantia nigra
| MPTP mouse | Human PD | Overlap | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rank | Shorter interval | p value | # | Longer interval | p value | # | p value | # | p value | # | Overlapping genes | ||
| Category: diseases and disorders | |||||||||||||
| 1 | Movementdisorders | 1.54E-16 | 89 | Movement disorders | 3.41E-10 | 58 | Disorder of basal ganglia | 2.35E-22 | 203 | Dyskinesia | 1.91E-07 | 24 | ACHE, ATP5C1, BCL2, CDH2, CDK5, DDX1, FAM3C, GABRG2, GRIN1, MAP2K4, NDRG1, PFKM, RAB11A, RAB6A, RGS4, RTN2, SLC6A3, SNAP25, SOX2, ST8SIA3, TH, VAMP2, VSNL1, YWHAZ |
| 2 | Disorder of basal ganglia | 1.30E-12 | 66 | Neuromuscular disease | 2.48E-07 | 45 | Movement disorders | 4.33E-20 | 250 | Disorder of basal ganglia | 2.86E-07 | 26 | ACHE, ATP5C1, BCL2, CDH2, CDK5, DDX1, EIF4G1, FAM3C, GABRG2, GRIN1, MAP2K4, NDRG1, NR4A2, PFKM, RAB11A, RAB6A, RGS4, RTN2, SLC6A3, SNAP25, SOX2, ST8SIA3, TH, VAMP2, VSNL1, YWHAZ |
| 3 | Dyskinesia | 3.02E-12 | 57 | Neurological signs | 1.26E-06 | 36 | Neuromuscular disease | 6.42E-19 | 211 | Neuromuscular disease | 5.35E-07 | 27 | ACHE, ATP5C1, BCL2, CDH2, CDK5, DDX1, EIF4G1, FAM3C, GABRG2, GRIN1, MAP2K4, NDRG1, NR4A2, PFKM, RAB11A, RAB6A, RGS4, RPL5, RTN2, SLC6A3, SNAP25, SOX2, ST8SIA3, TH, VAMP2, VSNL1, YWHAZ |
| 4 | Neurological signs | 3.02E-12 | 58 | Disorder of basal ganglia | 1.63E-06 | 40 | Chorea | 1.24E-16 | 154 | Huntington’s disease | 5.78E-07 | 22 | ATP5C1, BCL2, CDH2, CDK5, DDX1, FAM3C, GABRG2, GRIN1, MAP2K4, NDRG1, PFKM, RAB11A, RAB6A, RGS4, RTN2, SLC6A3, SNAP25, SOX2, ST8SIA3, VAMP2, VSNL1, YWHAZ |
| 5 | Huntington’s disease | 1.11E-11 | 54 | Dyskinesia | 1.74E-06 | 35 | Neurological signs | 1.41E-16 | 163 | Movement disorders | 1.70E-06 | 28 | ACHE, ATP5C1, ATXN10, BCL2, CDH2, CDK5, DDX1, EIF4G1, FAM3C, GABRG2, GRIN1, MAP2K4, NAPB, NDRG1, NR4A2, PFKM, RAB11A, RAB6A, RGS4, RTN2, SLC6A3, SNAP25, SOX2, ST8SIA3, TH, UGT8, VAMP2, VSNL1, YWHAZ |
| Category: molecular and cellular functions | |||||||||||||
| 1 | Cell death | 1.11E-12 | 170 | Proliferation of cells | 2.28E-11 | 128 | Transport of vesicles | 9.27E-11 | 40 | Neuronal cell death | 5.01E-05 | 20 | ACHE, AKT1S1, BCL2, CDK5, FYN, GRIN1, KIFAP3, L1CAM, MAGED1, MAP2K4, MAPK8, NFKBIA, NR4A2, RET, SLC6A3,SNAP25, SOX11, SRPK2, STXBP1, YWHAZ |
| 2 | Microtubule dynamics | 1.30E-12 | 77 | Cell death | 3.41E-10 | 118 | Formation of plasma membrane projections | 6.45E-08 | 112 | Microtubule dynamics | 9.35E-05 | 25 | ACTG1, ATXN10, BCL2, CDH2, CDK5, CHP1, CRMP1, FYN, GRIN1, IFT20, KLC1, L1CAM, LPAR1, MAP2K4, MAP4, MAPK8, MARK2, NDRG1, NFIB, NFKBIA, RAB11A, RANBP9, RET, TNK2, UGT8 |
| 3 | Organization of cytoskeleton | 1.30E-12 | 85 | Proliferation of tumor cell lines | 8.64E-09 | 67 | Microtubule dynamics | 8.73E-08 | 195 | Synthesis of neurotransmitter | 9.67E-05 s | 6 | BCL2, NR4A2, SLC6A3, SNAP25, TH, YWHAZ |
| 4 | Organization of cytoplasm | 4.30E-12 | 88 | Apoptosis | 1.13E-08 | 97 | Organization of cytoplasm | 1.09E-07 | 237 | Exocytosis by cells | 1.05E-04 | 8 | CDK5, GNAI2, NAPB, NSF, RAB11A, SNAP25, STXBP1, VAMP2 |
| 5 | Proliferation of cells | 1.96E-11 | 173 | Degeneration of cells | 2.24E-08 | 24 | Formation of cellular protrusions | 1.47E-07 | 149 | Production of catecholamine | 1.54E-04 | 5 | BCL2, NR4A2, SLC6A3, TH, YWHAZ |
Ingenuity annotations of genes dysregulated by MPTP in the mouse substantia nigra, after short and longer intervals between treatment and analyses (608 genes for intervals combined), annotations of all dysregulated genes in the substantia nigra of PD patients (2027 genes), and those that are dysregulated in both the MPTP mouse model and human PD (i.e., 116 “overlapping” genes). Data are extracted from references in Table 1. The top 5 Ingenuity annotations of the categories “diseases and disorders” and “molecular and cellular functions” are displayed, as well as their respective p value and number of genes involved (#). All p values are corrected for multiple testing by the Benjamini-Hochberg false discovery rate. Categories with only one (target) gene were discarded. See text for further details