Table 1.
Association of 25(OH)D target gene sets with either 25(OH)D, IFNB-1b treatment or Gd-enhancing lesions in BENEFIT, as determined by GSEA
| Association with 25(OH)D | Association with IFNB-1b | Association with GELs | |||||
|---|---|---|---|---|---|---|---|
| Gene set name | Description | NES | p/FDR-q value1 | NES | p/FDR-q value1 | NES | p/FDR-q value1 |
| KnightUp [2010] | Genes that are bound and upregulated by the 25(OH)D receptor2 | 2.09 | 0.000/0.000 | 2.46 | 0.000/0.000 | −1.96 | 0.000/0.004 |
| MS_vitD_genes0.05 Munger et al. | BENEFIT gene expression profiles3 | 2.08 | 0.000/0.000 | 2.21 | 0.000/0.000 | −2.83 | 0.000/0.000 |
| STAMBOLSKY_RESPONSE_TO_VITAMIN_D3_UP [2010] | Genes induced in SKBR3 cells by 25-hydroxyvitamin D34 | 1.58 | 0.006/0.038 | 1.47 | 0.039/0.102 | 1.15 | 0.236/0.417 |
| CarlbergUp [2011] | Genes that are bound and upregulated by the 25(OH)D receptor5 | 1.54 | 0.004/0.040 | −1.06 | 0.357/0.710 | 0.64 | 0.974/0.961 |
| BIOCARTA_VDR_PATHWAY [2005] | Control of Gene Expression by Vitamin D Receptor6 | 1.44 | 0.088/0.087 | −0.93 | 0.557/0.804 | −0.84 | 0.654/0.983 |
| 25(OH)D_GO_associated_genes [2009] | Genes annotated for GO terms related to Vitamin D | 1.36 | 0.121/0.118 | 1.42 | 0.102/0.104 | 0.92 | 0.581/0.742 |
| V$DR3_Q4 [2005] | Genes with promoter regions containing the motif RRTGNMCYTNNTGAMCCNYNT7 | 1.01 | 0.435/0.720 | −0.77 | 0.947/0.844 | 1.16 | 0.207/0.527 |
| V$VDR_Q3 [2005] | Genes with promoter regions containing the motif GGGKNARNRRGGWSA8 | 0.99 | 0.500/0.672 | −1.07 | 0.267/1.000 | 1.44 | 0.002/0.205 |
| V$VDR_Q6 [2005] | Genes with promoter regions containing the motif CNSNNTGAACCN9 | 0.85 | 0.828/0.897 | 0.71 | 0.978/0.897 | 1.25 | 0.067/0.469 |
| STAMBOLSKY_RESPONSE_TO_VITAMIN_D3_DN [2010] | Genes repressed in SKBR3 cells (breast cancer) by 25-hydroxyvitamin D310 | 0.77 | 0.814/0.953 | 1.03 | 0.418/0.578 | 1.15 | 0.301/0.345 |
25(OH)D, 25-hydroxyvitamin D; IFNB-1b, interferon beta-1b; BENEFIT, Betaferon/Betaseron in Newly Emerging For Initial Treatment; GSEA, Gene Set Enrichment Analysis; FDR, false discovery rate; GELs, gadolinium-enhancing lesions; NES, normalized enrichment score.
FDR < 0.1 designated as statistically significant in GSEA analyses.36
Set derived from Ramagopalan et al.: 25(OH)D receptor ChIP-Seq and GEP in lymphoblastoid cell line after stimulation with calcitriol for 36 h → identification of genes that are bound and upregulated by the 25(OH)D receptor.
Set derived from BENEFIT gene expression profiles and 25(OH)D data from the model GeneExpression∼25(OH)D*IFNß+covariates. To enter the set, the particular gene had to have a nominal P-value of ≤0.05.
Genes induced in SKBR3 cells by 25-hydroxyvitamin D3. From Broad Institute MSigDB v3.1.
Set derived from Heikkinen et al. 25(OH)D receptor ChIP-Seq after 40-min stimulation with calcitriol and gene expression profiling after 4-h stimulation with calcitriol in THP-1 monocytic leukemia cells followed by the identification of genes that are bound and upregulated by the 25(OH)D receptor.
Control of Gene Expression by Vitamin D Receptor. From Broad Institute MSigDB v3.1, derived from Biocarta.
Genes with promoter regions [−2 kb, 2 kb] around transcription start site containing the motif RRTGNMCYTNNTGAMCCNYNT which matches annotation for VDR: vitamin D (1,25- dihydroxyvitamin D3) receptor. From Broad Institute MSigDB v3.1.
Genes with promoter regions [−2 kb, 2 kb] around transcription start site containing the motif GGGKNARNRRGGWSA which matches annotation for VDR: vitamin D (1,25- dihydroxyvitamin D3) receptor. From Broad Institute MSigDB v3.1.
Genes with promoter regions [−2 kb, 2 kb] around transcription start site containing the motif CNSNNTGAACCN which matches annotation for VDR: vitamin D (1,25- dihydroxyvitamin D3) receptor. From Broad Institute MSigDB v3.1.
Genes repressed in SKBR3 cells (breast cancer) by 25-hydroxyvitamin D3. From Broad Institute MSigDB v3.1.