Table 4.
The most variable hydroxymethylated loci in prefrontal cortex and cerebellum are enriched in distinct genomic regions
| Loci with detectable 5hmC in brain (%) | Top 1,000 most variable loci in prefrontal cortex | Top 1,000 most variable loci in cerebellum | |||||
|---|---|---|---|---|---|---|---|
| Sites with detectable 5hmC (%) | Enrichment (95 % CI) | P value | Sites with detectable 5hmC (%) | Enrichment (95 % CI) | P value | ||
| All probes (N = 79,263) | 1,000 | - | - | 1,000 | - | - | |
| CpG island feature | |||||||
| Island | 7,837 (9.9 %) | 159 (15.9 %) | 1.72 (1.44–2.05) | 4.037E-09 | 301 (30.1 %) | 3.92 (3.41–4.51) | 2.41E-69 |
| Shore | 22,593 (28.5 %) | 270 (27.0 %) | 0.93 (0.80–1.07) | 0.307 | 171 (17.1 %) | 0.52 (0.44–0.61) | 9.25E-17 |
| Shelf | 11,674 (14.7 %) | 107 (10.7 %) | 0.69 (0.56–0.85) | 2.23E-04 | 134 (13.4 %) | 0.90 (0.74–1.08) | 0.261 |
| Outside | 36,342 (45.8 %) | 376 (37.6 %) | 0.71 (0.62–0.81) | 1.82E-07 | 281 (28.1 %) | 0.46 (0.40–0.53) | 3.04E-30 |
| Unannotated | 817 (1.0 %) | 88 (8.8 %) | 9.26 (7.28–11.67) | 4.97E-50 | 113 (11.3 %) | 12.23 (9.85–15.09) | 1.10E-74 |
| Gene feature | |||||||
| Intergenic | 9,604 (12.1 %) | 99 (9.9 %) | 0.80 (0.64–0.98) | 0.032 | 80 (8.0 %) | 0.63 (0.49–0.79) | 3.86E-05 |
| Distal promoter | 3,703 (4.7 %) | 36 (3.6 %) | 0.76 (0.53–1.06) | 0.113 | 30 (3.0 %) | 0.63 (0.42–0.91) | 0.010 |
| Proximal promoter | 16,979 (21.4 %) | 172 (17.2 %) | 0.76 (0.64–0.90) | 1.10E-03 | 113 (11.3 %) | 0.47 (0.38–0.57) | 1.03E-16 |
| Gene body | 46,238 (58.3 %) | 583 (58.3 %) | 1.00 (0.88–1.14) | 1.000 | 642 (64.2 %) | 1.28 (1.12–1.46) | 1.78E-04 |
| Downstream | 1,922 (2.4 %) | 22 (2.2 %) | 0.91 (0.56–1.38) | 0.756 | 22 (22.0 %) | 0.91 (0.56–1.38) | 0.756 |
| Unannotated | 817 (1.0 %) | 88 (8.8 %) | 9.26 (7.28–11.67) | 4.97E-50 | 113 (11.3 %) | 12.23 (9.85–15.09) | 1.10E-74 |
| Transcription factor binding site | 25,482 (32.1 %) | 298 (29.8 %) | 0.90 (0.78–1.03) | 0.117 | 242 (24.2 %) | 0.67 (0.58–0.78) | 4.57E-08 |
| Dnase 1 hypersensitivity site | 8,155 (10.3 %) | 77 (7.7 %) | 0.73 (0.57–0.92) | 6.33E-03 | 61 (6.1 %) | 0.57 (0.43–0.74) | 4.56E-06 |
| Alternative transcription events (N = 30,659) | 385 | - | - | 418 | - | - | |
| A3SS | 798 (2.6 %) | 15 (3.9 %) | 1.52 (0.84–2.55) | 0.144 | 15 (3.6 %) | 1.39 (0.77–2.34) | 0.214 |
| A5SS | 827 (2.7 %) | 10 (2.6 %) | 0.96 (0.46–1.80) | 1.000 | 17 (4.1 %) | 1.53 (0.88–2.49) | 0.094 |
| AFE | 9,159 (29.9 %) | 103 (26.8 %) | 0.86 (0.68–1.08) | 0.197 | 82 (19.6 %) | 0.57 (0.44–0.73) | 2.55E-06 |
| ALE | 3,017 (9.8 %) | 36 (9.4 %) | 0.95 (0.65–1.34) | 0.863 | 38 (9.1 %) | 0.92 (0.64–1.28) | 0.679 |
| CE | 16,604 (54.2 %) | 200 (51.9 %) | 0.92 (0.74–1.13) | 0.410 | 187 (44.7 %) | 0.69 (0.56–0.84) | 1.38E-04 |
| CNE | 3,755 (12.2 %) | 60 (15.6 %) | 1.32 (0.98–1.75) | 0.051 | 86 (20.6 %) | 1.86 (1.44–2.37) | 1.95E-06 |
| EI | 50 (0.2 %) | 1 (0.3 %) | 1.59 (0.04–9.35) | 0.471 | 2 (0.5 %) | 2.94 (0.35–11.27 | 0.155 |
| II | 6,003 (19.6 %) | 74 (19.2 %) | 0.98 (0.75–1.27) | 0.897 | 69 (16.5 %) | 0.81 (0.62–1.06) | 0.121 |
| IR | 3,529 (11.5 %) | 41 (10.6 %) | 0.92 (0.64–1.27) | 0.688 | 68 (16.3 %) | 1.49 (1.13–1.95) | 4.24E-03 |
| MXE | 3,814 (12.4 %) | 40 (10.4 %) | 0.82 (0.57–1.14) | 0.244 | 31 (7.4 %) | 0.56 (0.38–0.82) | 1.26E-03 |
The level of enrichment of the top 1,000 loci in each brain region was determined by Fisher’s exact test. 5hmC, 5-hydroxymethylcytosine; CI, confidence interval; A3SS, alternative 3’ splice site; A5SS, alternative 5’ splice site; AFE, alternative first exon; ALE, alternative last exon; CE, cassette exon; CNE, constitutive exon; EI, exon isoforms; II, intron isoforms; IR, intron retention; MXE, mutually exclusive exon