Expression regulation of gene cohorts in AT-EAE mouse spinal cord. A–B. Log₂ratios (negative for down-regulation) and standard deviation of expression ratios of gene cohorts sharing the same molecular function (A) or chromosomal location (B). Note that while the average fold change was less than 1.5 for all cohorts, the standard deviation of the fold change exceeded 1.5. Highest standard deviations were obtained for JAE genes and for those located on chromosome 17. (C) Heatmap of the regulated JAE-J genes. C1–C4 = logratios in the four controls, E1–E4 = logratios in the four AT-EAE mice. All logratios were computed with respect to the average expression level in control mice. Red/green/black color indicates up/down/no regulation in the respective set. Note both the reproducibility (green, red, or black color for all four sets of the same condition) and the variability (non-uniform nuance of the color) of the gene expression patterns among the animals of the same condition.

Regulation of the mean relative expression variability (REV) of gene cohorts sharing the same molecular function (A) or chromosomal location (B) in spinal cords of AT-EAE mice compared to control mice. (C) Average gene expression stability (GES) of functional gene cohorts. Note the uniformity of the two REV distributions both among functional classes: REV(C) = (42.9 ± 2.3)%, REV(E) = (50.2 ± 2.3)% and among chromosomes: REV(C) = (42.5 ± 2.1)%, REV(E) = (49.7 ± 2.3)% and that all functional and chromosomal cohorts became less stably expressed (higher REV) in AT-EAE mice, with the highest increments in the transport into cell (23.8%) and chromosome 13 (34.1%). Cytoskeleton genes were the most unstably expressed in both conditions. Observe the quasi-uniform distribution of GES values among functional categories for both control and AT-EAE specimens.

Transcription coordination. (A) The 95% confidence intervals of the percentages of synergistically (Syn), antagonistically (Ant), and independently (Ind) expressed gene pairs in spinal cord of control (C) and AT-EAE (E) mice. Note that the intervals remained practically unchanged in AT-EAE. (B) Histograms of the expression coordinations (SYN + ANT) in control and AT-EAE spinal cord. Note the two modal distributions in both conditions, with two distinct groups of genes: one group in which most genes are coordinately expressed with 4–8% of the other genes and the second group in which most genes are coordinately expressed with 40–44% of the other genes. (C) Examples in which percentages of statistically significant coordination partners of myelination genes differed between control and AT-EAE spinal cords. Chk, choline kinase; Fyn, Fyn proto-oncogene; Hmgcr, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Mal, myelin and lymphocyte protein T-cell differentiation protein; Mpz, myelin protein zero; Nsmaf, neutral sphingomyelinase activation-associated factor; Pdgfra, platelet derived growth factor receptor alpha polypeptide; Pdgfrb, platelet derived growth factor receptor beta polypeptide; Pdgfrl, platelet-derived growth factor receptor-like; Plp, proteolipid protein; Pmp22, peripheral myelin protein; Qk, quaking; Scd1, stearoyl-coenzyme A desaturase 1; Scd2, stearoyl-coenzyme A desaturase 2; Smpd1, sphingomyelin phosphodiesterase 1 acid lysosomal; Smpdl3a, sphingomyelin phosphodiesterase acid-like 3A.

Average percentages of synergistically (Syn), antagonistically (Ant), and independently (Ind) expressed gene pairs in functional categories (A and B), chromosomes (C and D) and GES percentiles for control (A, C, E) and AT-EAE (B, D, F) spinal cords. Note the quasi-uniform distributions of the percentages in functional categories and chromosomal locations in both conditions, the not-significant alteration of the percentages in AT-EAE mice and the inverse exponential relationship between synergistic and antagonistic coordination and expression stability (GES percentile).

See-saw partners of peripheral myelin protein (Pmp22) in control spinal cord and alteration by AT-EAE. (A and D) Immune response partners. (B and E) Platelet derived growth factors. (C and F) Calcium signaling genes. The correlation coefficients of the indicated genes with each other gene were plotted against those of Pmp22 with each other gene. In controls, red color indicates likeness, green neutrality, and blue opposition. The table presents the overlap (OVL) of the coordination profiles in both conditions. Note that the AT-EAE turned the significant similarity and opposition of the coordination profiles into neutrality. Cklfsf3, chemokine-like factor super family 3; Ifitm3, interferon-induced transmembrane protein 3; Ier3, immediate early response 3; Pdgfra, platelet derived growth factor receptor, alpha polypeptide; Pdfrl, platelet-derived growth factor, receptor-like; Pdgfc, platelet-derived growth factor, C polypeptide; Itpr1, inositol 1,4,5-triphosphate receptor 1; Grinl1a, glutamate receptor, ionotropic, N-methyl D-aspartate-like 1A; P2rx3, purinergic receptor P2X, ligand-gated ion channel, 3. The overlap scores (OVL) of the Pmp22 in the two conditions were: PartnerCklfsf3Ifitm3Ier3PdgfraPdfrlPdgfcItpr1Grinl1aP2rx3Control98.51−93.57−4.5693.23−81.123.9492.30−95.59−0.86AT-EAE15.5421.4416.34−12.172.72−15.15−6.0937.860.50