Table 1.
Druggable genes of high interest retained by WENA analysis of the dynamics of genetic cooperativity in the brain of Hdh mice
| Gene name | WENA node | WENA edge | Brain area | Critical phase (age) | Rewiring to Class-II nodes (1) | Intra-node in BGM paths of interest (2) | LFC (3) |
|---|---|---|---|---|---|---|---|
| Cdkn2a | Class-II | Class-II | Striatum | Yes (10 months) | NA | No | 1.018 |
| Kcng4 | Class-III | NA | Striatum | No | Yes | No | 0.473 |
| Nr2f2 | Class-III | NA | Striatum | No | Yes | No | 0.414 |
| Cyp39a1 | NA | Class-I | Cortex | Yes (2 months) | NA | Yes | 0.364 |
| Kcns3 | Class-III | NA | Striatum | No | Yes | No | 0.353 |
| Kcnc2 | Class-III | NA | Striatum | No | Yes | No | 0.331 |
| Hcn3 | NA | Class-II | Striatum | Yes (10 months) | NA | Yes | 0.228 |
| Sirt2 | Class-III | NA | Striatum | No | Yes | No | 0.094 |
| Chrna4 | Class-III | NA | Striatum | No | Yes | No | 0.091 |
| Ptp4a2 | Class-II | Class-II | Striatum | Yes (10 months) | NA | No | −0.102 |
| Car4 | Class-III | NA | Striatum | No | Yes | No | −0.107 |
| Car8 | NA | Class-I | Cortex | Yes (2 months) | NA | Yes | −0.126 |
| Cpa6 | Class-I | Class-I | Cortex | Yes (2 months) | NA | No | −0.402 |
| Pde2a | NA | Class-II | Striatum | Yes (10 months) | NA | Yes | −0.605 |
| Ptpro | Class-I | Class-I | Cortex | Yes (2 months) | NA | No | −1.285 |
| Hipk4 | Class2 | Class-II | Striatum | Yes (10 months) | NA | No | −1.485 |
| Ptpn7 | NA | Class-I | Cortex | Yes (2 months) | NA | Yes | −1.493 |
Note: (1) Striatum only. (2) i.e. most deregulated and part of a highly dynamic WENA edge: see node content in Supplementary Table S14/BGM network data. (3) Log-fold-change (Q175; 10 months/Q20; 2 months). These 17 genes match either one of the following criteria: (i) recruited into the most dynamic (product-P ≥ 0.25) Class-I and Class-II edges in the cortex, (ii) recruited into the most dynamic (product-P ≥ 0.3) Class-I and Class-II edges in the striatum, (iii) Class-III genes that interact with neighbor genes in the Class-I or Class-II meta-network for the striatum (see Fig. 5) and (iv) BGM nodes involved in the meta-networks that define critical phases (for weighted edges with a product-P value ≥ 0.25) and that are part of the most deregulated BGM path that link two WENA nodes. Profiles of gene deregulation across CAG repeat lengths and age points in Hdh mice can be visualized in the BioGemix-3D database (see https://www.hdinhd.org/; see also http://www.broca.inserm.fr/webportal/Biogemix_3D.php). The full list of genes of interest retained by WENA contains 100 genes (see Supplementary Table S14).
NA, not applicable.