Table 3.
Gene enrichment analysis of the striatum
| MPTP mouse | Human PD | Overlap | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rank | 5 h | p value | # | 24 h | p value | # | 72 h | p value | # | p value | # | p value | # | Overlapping genes | ||
| Category: diseases and disorders | ||||||||||||||||
| 1 | Epileptic seizure | 2.55E-21 | 21 | Psoriasis | 6.98E-14 | 39 | Movement disorders | 1.05E-09 | 40 | Neurological signs | 5.52E-28 | 64 | Seizures | 4.14E-03 | 5 | CHGB, ENC1, KCNQ5, NPTX2, TGM2 |
| 2 | Seizures | 3.94E-18 | 25 | Glucose metabolism disorder | 3.37E-11 | 50 | Schizophrenia | 2.52E-08 | 25 | Dyskinesia | 5.52E-28 | 63 | Abnormal secretion by adrenal gland | 5.71E-03 | 2 | CHGB, ITSN1 |
| 3 | Epilepsy | 7.14E-18 | 22 | Inflammation of organ | 3.98E-11 | 51 | Amyloidosis | 7.20E-08 | 25 | Disorder of basal ganglia | 8.34E-28 | 69 | Epilepsy | 9.93E-03 | 4 | CHGB, ENC1, KCNQ5, NPTX2 |
| 4 | Dyskinesia | 1.07E-06 | 18 | Vascular disease | 7.16E-11 | 45 | Dementia | 2.41E-07 | 24 | Chorea | 7.07E-27 | 60 | Dyskinesia | 1.34E-02 | 5 | CHGB, DIRAS2, FABP7, S100A10, TGM2 |
| 5 | Endometriosis | 2.70E-06 | 14 | Inflammatory response | 3.45E-10 | 37 | Quantity of phagocytes | 6.73E-07 | 20 | Movement disorders | 8.28E-27 | 79 | Movement disorders | 1.34E-02 | 6 | CHGB, DIRAS2, FABP7, S100A10, TGM2, TMEM176B |
| Category: molecular and cellular functions | ||||||||||||||||
| 1 | Apoptosis | 5.80E-08 | 39 | Proliferation of cells | 3.23E-17 | 115 | Morphology of cells | 6.61E-11 | 59 | Neurotransmission | 1.44E-13 | 35 | Proliferation of endothelial cell lines | 2.37E-02 | 2 | ADAMTS1, ITSN1 |
| 2 | Differentiation of cells | 1.07E-06 | 31 | Morphology of cells | 7.55E-08 | 79 | Organization of cytoskeleton | 6.61E-11 | 45 | Synaptic transmission | 2.90E-11 | 29 | Apoptosis of neuroblastoma cell lines | 3.02E-02 | 2 | ITSN1, TGM2 |
| 3 | Proliferation of cells | 1.89E-06 | 43 | Necrosis | 3.61E-15 | 91 | Organization of cytoplasm | 1.93E-10 | 46 | Transport of molecule | 3.95E-09 | 63 | Cell death of cortical neurons | 4.08E-02 | 2 | ITSN1, TGM2 |
| 4 | Cell death | 2.58E-06 | 41 | Apoptosis | 2.05E-14 | 91 | Formation of cellular protrusions | 8.34E-10 | 33 | Transport of metal ion | 1.02E-08 | 24 | Neuritogenesis | 4.08E-02 | 3 | DCLK1, ENC1, ITSN1 |
| 5 | Cell cycle progression | 4.27E-06 | 21 | Cell movement | 2.81E-14 | 77 | Apoptosis | 8.34E-10 | 67 | Morphology of neurites | 2.10E-08 | 17 | Apoptosis of endothelial cells | 4.34E-02 | 2 | ADAMTS2, ITSN1 |
Ingenuity annotations of genes dysregulated by MPTP in the mouse striatum, after 5, 24, and 72 h between treatment and analyses (430 genes for time points combined), annotations of all dysregulated genes in the striatum of PD patients (259 genes), and those that are dysregulated in both the MPTP mouse model and human PD (i.e., 14 “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