Profound effects of SD on transcriptome, metabolome, and phenome.

<p>EEG/behavioral phenotypes, metabolites, and transcripts are organized into 3 “columns” (from left to right). Top 3 panels show the SD response (recovery/baseline fold change). Bottom 3 panels depict examples of allelic effects on the SD responses, with color-coding indicating the presence of a C57BL/6J or DBA/2J haplotype under the mapped QTL peaks (B6: gray for BXD and black for parental; D2: light brown for BXD and dark brown for parental). White bars mark the F1s and hatched bars strain in which haplotype could not be unambiguously determined. (A) Phenotypic changes after SD. The top significantly changed phenotype was the increase in NREM sleep EEG delta power (1–4 Hz) after SD (far-left blue data point). The most up-regulated phenotype was time spent in REM sleep during the first 6 h of darkness (ZT12–18) after SD (highest green data point). (B) Metabolite changes after SD. Most amino acids (blue) were down-regulated and most sphingolipids (brown) up-regulated after SD. The acylcarnitines C18:1 and C18:2 (highest red dots) increased the most. Vertical red line: significant threshold (FDR-adjusted <i>p</i>-value = 0.05). (C) DE analysis (SD/Ctr) for cortex (left) and liver (right). Genes were sorted according to their ranked <i>p</i>-value along the x-axis. Significantly affected transcripts in red (FDR-adjusted <i>p</i>-value < 0.05), nonsignificant results in black. Blue dots indicate 78 genes considered core molecular components of the sleep homeostatic response in the cortex [<a href="" target="_blank">34</a>]. Note that no low fold change threshold was applied. (D-F) Examples of genetically driven EEG/behavioral, metabolic, and transcriptional responses to SD, respectively. See text for details. <i>Arc</i>, <i>activity-regulated cytoskeletal-associated protein</i>; Ctr, control; DE, differential gene expression; EEG, electroencephalography; <i>Egr2</i>, <i>early growth response 2</i>; <i>Fam107a</i>, <i>family with sequence similarity 107</i>, <i>A</i>; FDR, false discovery rate; LMA, locomotor activity; <i>Mlycd</i>, <i>malonyl-CoA decarboxylase</i>; NREM, non-REM; <i>Plin4</i>, <i>Perilipin 4; Pla2g4e</i>, <i>phospholipase A2</i>, <i>group IVE</i>; QTL, quantitative trait locus; SD, sleep deprivation; <i>Ttll8</i>, <i>tubulin tyrosine ligase-like family 8</i>; ZT, zeitgeber time.</p>