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Research ArticleNew Research, Development

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

Milo R. Smith, Poromendro Burman, Masato Sadahiro, Brian A. Kidd, Joel T. Dudley and Hirofumi Morishita
eNeuro 15 December 2016, 3 (6) ENEURO.0240-16.2016; DOI: https://doi.org/10.1523/ENEURO.0240-16.2016
Milo R. Smith
1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029
2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029
4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
6Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029
7Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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Poromendro Burman
1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029
4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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Masato Sadahiro
1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029
4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
6Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029
8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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Brian A. Kidd
2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029
7Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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Joel T. Dudley
2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029
7Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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Hirofumi Morishita
1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029
4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029
5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
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  • Figure 1.
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    Figure 1.

    Diseases that dysregulate the juvenile plasticity signature are associated with inflammatory processes. a, b, Juvenile plasticity signature of 176 genes (represented by green bars) generated by differential expression of P29 vs >P60 C57BL/6 male mice primary visual cortex was computationally matched to 436 disease signatures (represented by orange bars; a) using rank-based molecular matching where large scores indicate shared transcriptional phenotype (b). c, DLA systematically identified processes associated to diseases that dysregulate the plasticity signature. Seven of the 14 largest associations were inflammation-related gene sets, and 7 of 7 of inflammation-related gene sets were strongly associated with plasticity (all at pcorrected < 5 × 10−5: OR = 25.8, 95% CI = 1.4–491.2, p = 2.7 × 10−3, Fisher’s exact test). See Figure 1-1 for source DLA data.

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    Figure 1-1.

    DLA identifies biological processes common to diseases that perturb the juvenile plasticity signature. To identify shared pathophysiology across the diverse list of diseases predicted to dysregulate the juvenile plasticity signature, we applied DLA. This approach calculates the association between diseases that dysregulate the plasticity signature genes and 50 well defined and distinct biological pathways. To do so, it computes a regression between the molecular match score (a measure that indicates the strength of association between the disease and plasticity signatures; see Table 3 and Materials and Methods) and the pathology score (a measure of activity of the biological pathway in that disease; see Materials and Methods). Large regression coefficients indicate that the biological pathway may disrupt juvenile plasticity. Using a multiple test-corrected, empirical p < 5 × 10−5, seven of the 14 largest DLA associations were inflammation-related gene sets, and every inflammation-related gene set in the hallmark library was strongly associated with diseases that dysregulate plasticity genes (seven of seven inflammation gene sets at pcorrected < 5 × 10−5: OR = 25.8, 95% CI = 1.4–491.2, p = 2.7 × 10−3, Fisher’s exact test). A total of 20,000 permutations of the gene sets was used to estimate p values and to normalize the regression coefficients to allow comparison between effect sizes for different biological pathways. Inflammation-related gene sets: TNF-α signaling via NF-κB, IFN-γ response, inflammatory response, complement, IL-2–Stat5 signaling, IFN-α response, IL-6–Jak–Stat3 signaling.

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    Figure 2.

    Diseases that dysregulate the adult Lynx1−/− plasticity signature are associated with inflammatory processes. Using an adult Lynx1−/− plasticity signature of 98 genes (generated by differential expression of primary visual cortex from >P60 Lynx1−/− vs >P60 C57BL/6 male mice), DLA systematically identified biological processes associated with diseases that dysregulate the adult Lynx1−/− plasticity signature genes. Using adult Lynx1−/− animals controls for age, as these adult animals have elevated plasticity similar to that of juvenile animals. Seven of the 11 largest associations were inflammation-related gene sets, and every inflammation-related gene set was strongly associated with plasticity (7 of 7 inflammation gene sets at pcorrected < 5 × 10−5: OR = 63.0, 95% CI = 3.2–1229.8, p = 7.6 × 10−5, Fisher’s exact test). See Figure 2-1 for source DLA data.

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    Figure 2-1.

    DLA identifies biological processes common to diseases that perturb the Lynx1−/− plasticity signature. To identify shared pathophysiology across the diverse list of diseases predicted to dysregulate the Lynx1−/− plasticity signature, we applied DLA. Large regression coefficients indicate that the biological pathway may disrupt Lynx1−/− plasticity. As with the juvenile plasticity signature, using a multiple test-corrected, empirical p < 5 × 10−5, we found that every inflammation-related gene set in the hallmark library was strongly associated with diseases that dysregulate plasticity genes (7 of 7 inflammation gene sets at pcorrected < 5 × 10−5: OR = 63.0, 95% CI = 3.2–1229.8, p = 7.6 × 10−5 Fisher’s exact test). A total of 20,000 permutations of the gene sets were used to estimate p values and to normalize the regression coefficients to allow comparison between effect sizes for different biological pathways. Inflammation-related gene sets: TNF-α signaling via NF-κB, IFN-γ response, inflammatory response, complement, IL-2–Stat5 signaling, IFN-α response, IL-6–Jak–Stat3 signaling.

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    Figure 3.

    LPS reverses plasticity signature gene expression. a, LPS disease signature shares plasticity signature genes in silico (molecular match rank #14, p = 7.9 × 10−4; Table 3; disease signature is from GSE3253: adult mouse whole-brain homogenate harvested 4 h after peripheral LPS injected intraperitoneally; genes with absolute value of the standardized expression (z-score) ≥2 SDs from the mean were selected as the most differentially expressed by LPS). b, The expression of the 16 genes shared between juvenile plasticity and the LPS disease signatures is anticorrelated (Spearman’s ρ = −0.77, p = 7.4 × 10−4; LPS disease signature gene expression values fell in the range [−1,+1]; for plotting purposes, the plasticity gene expression fold change was linear transformed to [−1,+1]). c, Of the 13 genes of the 16 predicted to be reversed by LPS, the majority (8 of 13; 61.5%) showed a complete reversal in their differential expression pattern in V1 after LPS administration (300 μg/kg LPS, intraperitoneally, at P26 during the peak of juvenile plasticity) relative to saline. LPS downregulated Cldn5 and Slc40a1 and upregulated Alox12b, S100a9a, Ch25h, Lrg1, S100a8, and Lcn2 (n = 5 mice per group). ***p < 0.001, **p > 0.001 and ≤0.01, *p > 0.01 and ≤0.05 (two-sided t tests of ΔCTs). Log2 fold change is −ΔΔ CT. Error bars indicate the SEM.

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    Figure 4.

    Inflammation induced by LPS suppresses experience-dependent plasticity in juvenile cortex. a, Juvenile mice (P26) during the peak of ocular dominance plasticity were injected intraperitoneally with either LPS (300 μg/kg) or saline. b, c, Mice were either subjected to qPCR analysis of plasticity effectors from V1 4 h after the injection (b) or underwent 3 d of MD followed by in vivo extracellular recordings to assess ocular dominance plasticity (c). b, LPS increased known plasticity brakes PirB and H2K1/H2D1, and decreased the plasticity trigger BDNF. LPS had no effect on the plasticity effectors Nptx2, Lynx1, NogoR, or Ppp3ca. Log2 FC (fold change) is −ΔΔ CT (n = 5 mice per group). Error bar indicates the SEM. ***p < 0.001, **p > 0.001 and ≤0.01, *p > 0.01 and ≤0.05 (t test of Δ CTs). c, Neurons from peripheral LPS-treated mice (purple histogram: n = 7 mice, 129 cells) showed decreased cortical responsivity to light in the ipsilateral vs contralateral eye, as quantified by a reduced right shift in the ODS distribution after 3 d of MD compared with control saline-treated juvenile mice with MD (gray histogram: 6 mice, 135 cells; χ2 test of ODS distribution: p = 2.6 × 10−6). Animal-level quantification of ocular dominance plasticity by CBI reflects the extent of the ocular dominance shift after 3 d of MD (right-side plot; low CBI indicates higher plasticity). CBI was strongly increased in the LPS-treated group (purple discs: CBI = 0.64 ± 0.02, 7 mice) compared with saline-treated group (gray discs: CBI = 0.49 ± 0.04, 6 mice), indicating that proinflammatory LPS had suppressed developmental plasticity (LPS vs saline, **p = 6 × 10−3, one-sided t test). qPCR data are reported as the mean ± SEM. Horizontal bars for the CBI plot indicate the mean.

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    Table 1:

    Statistics

    SubscriptData structureType of testPower
    aHypergeometricFisher's exact95% CI = 1.4–491.2
    bHypergeometricFisher's exact95% CI = 23.8–58.0
    cHypergeometricFisher's exact95% CI = 3.2–1229.8
    dApproximately normalWelch t test95% CI = −3.3 to −1.6, alternative hypothesis: true difference in means is not equal to 0
    eNon-normalEmpirical p valueNA
    fNon-normalSpearman rank correlationNA
    gApproximately normalWelch t testNA; no specific p values reported, rather a group of genes under a specified p value threshold
    hApproximately normalWelch t test95% CI = −3.0 to −0.1, alternative hypothesis: true difference in means is not equal to 0
    iApproximately normalWelch t test95% CI = −1.3 to −0.1, alternative hypothesis: true difference in means is not equal to 0
    jApproximately normalWelch t test95% CI = 0.3–1.6, alternative hypothesis: true difference in means is not equal to 0
    kApproximately normalWelch t testNA; no specific p values reported, rather a group of genes above a specified p value threshold (e.g., not significant)
    lApproximately normalWelch t test, one-sided (due to specific prior hypothesis as to direction of effect; results still significant using a two-sided test at a threshold of α = 0.05)95% CI = 0.1 to ∞], alternative hypothesis: true difference in means is not equal to 0
    mNon-normalχ2 test of ODS countsNA
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    Table 2:

    Juvenile plasticity signature

    RPFCpfpp valueProbe_idSymbolmm_Entrez_IDhs_Entrez_IDGene_name
    2.81873.731300ILMN_2641456Pcp218545126006Purkinje cell protein 2 (L7)
    3.29163.42200ILMN_2503052Tnnc1219247134Troponin C, cardiac/slow skeletal
    4.28193.151900ILMN_2794645Cyr61160073491Cysteine-rich protein 61
    13.6322.538900ILMN_1251414Npas4225872266743Neuronal PAS domain protein 4
    28.31812.37500ILMN_2597827Arc1183823237Activity-regulated cytoskeletal-associated protein
    15.74722.341500ILMN_1230397A630064P09RikNANANA
    15.73732.33100ILMN_2622983Dusp1192521843Dual-specificity phosphatase 1
    14.42922.304600ILMN_3160970Gpr175744022840G-protein-coupled receptor 17
    16.96582.212300ILMN_1250438Marcksl11735765108MARCKS-like 1
    21.672.160600ILMN_2710253Cyr61160073491Cysteine-rich protein 61
    20.94782.143900ILMN_12174588430403J19RikNANANA
    23.87382.11100ILMN_1220034Junb164773726jun B proto-oncogene
    27.13652.086400ILMN_2744890Gadd45g2388210912Growth arrest and DNA-damage-inducible 45 gamma
    25.95862.054900ILMN_1227299Mbp171964155Myelin basic protein
    29.31882.000100ILMN_1239557Ugt8a222397368UDP galactosyltransferase 8A
    27.05141.997200ILMN_2619767Pdlim221301964236PDZ and LIM domain 2
    32.16961.994800ILMN_2707616Col22a169700169044Collagen, type XXII, alpha 1
    32.39971.965600ILMN_1221178Pdlim221301964236PDZ and LIM domain 2
    38.59831.92675.00E-040ILMN_2463181Tnc219233371Tenascin C
    37.22061.92395.00E-040ILMN_2810882Ppic190385480Peptidylprolyl isomerase C
    41.02561.92175.00E-040ILMN_2615034Mog174414340Myelin oligodendrocyte glycoprotein
    37.29061.91175.00E-040ILMN_2653205Gp1bb147242812Glycoprotein Ib, beta polypeptide
    43.05841.90674.00E-040ILMN_1212702Hba-a1NANANA
    47.39081.88558.00E-040ILMN_1240973Slc29a4243328222962Solute carrier family 29 (nucleoside transporters), member 4
    145.44931.83390.01080ILMN_1253365Lypd1711112863G-protein-coupled receptor 39
    49.15461.8328.00E-040ILMN_2802263Cnp1279912672',3'-cyclic nucleotide 3' phosphodiesterase
    89.43211.82120.00370ILMN_2491182A130010C12RikNANANA
    85.04351.82060.00240ILMN_2766894Enpp6320981133121Ectonucleotide pyrophosphatase/phosphodiesterase 6
    60.00871.79718.00E-040ILMN_1223244Hbb-b1NANANA
    71.27861.79080.00120ILMN_2906855Ky16716339855Kyphoscoliosis peptidase
    63.3271.78287.00E-040ILMN_2880906Pdlim221301964236PDZ and LIM domain 2
    79.67641.77990.00240ILMN_1256343H1914955NAH19, imprinted maternally expressed transcript
    100.42211.77440.00480ILMN_1252953Cbln112404869Cerebellin 1 precursor protein
    62.10781.76867.00E-040ILMN_2617162Mlp1735765108MARCKS-like 1
    83.66831.76070.00250ILMN_2955919Mcam840044162Melanoma cell adhesion molecule
    70.62841.75660.0010ILMN_1259536Mog174414340Myelin oligodendrocyte glycoprotein
    68.39871.7530.0010ILMN_2754447Mkrn3226527681Makorin, ring finger protein, 3
    68.31511.74640.0010ILMN_2597606Gjc211845457165Gap junction protein, gamma 2
    95.70421.73450.00440ILMN_2544056Hbb-b11005036053043Hemoglobin, beta adult s chain
    76.78261.72390.00240ILMN_1242456Kank110735123189KN motif and ankyrin repeat domains 1
    82.14121.71970.00260ILMN_1237021Mag171364099Myelin-associated glycoprotein
    107.56581.70770.00490ILMN_2675874Alas211656212Aminolevulinic acid synthase 2, erythroid
    105.28581.69610.00490ILMN_3161282Dpysl56525456896Dihydropyrimidinase-like 5
    104.96671.68010.0050ILMN_1216452Hbb-b1NANANA
    101.74411.6770.00480ILMN_2735184Col18a11282280781Collagen, type XVIII, alpha 1
    165.75671.67190.01371.00E-04ILMN_1241293Cldn5127417122Claudin 5
    104.2341.670.00510ILMN_2991389Ly6g6e70274NALymphocyte antigen 6 complex, locus G6E
    109.90561.66290.0060ILMN_3105563Dmkn7371293099Dermokine
    100.52251.66110.00460ILMN_1259039Sox8NANANA
    119.81521.65620.00820ILMN_1236718Hbb-b1NANANA
    107.44911.65430.0050ILMN_1234698Tspan27074710100Tetraspanin 2
    114.21911.6510.00710ILMN_2457585Trp53inp26872858476Transformation-related protein 53-inducible nuclear protein 2
    127.6721.64970.00910ILMN_2977558Dapk21314323604Death-associated protein kinase 2
    115.49081.64840.00780ILMN_2777359Serpinh112406871Serine (or cysteine) peptidase inhibitor, clade H, member 1
    133.21061.64680.0090ILMN_2757125Prc12334069055Protein regulator of cytokinesis 1
    168.13911.6450.01381.00E-04ILMN_24401945330423I11RikNANANA
    133.34241.63260.00880ILMN_2903945Gadd45g2388210912Growth arrest and DNA-damage-inducible 45 gamma
    237.45371.63070.02862.00E-04ILMN_3159435Mid117318NAMidline 1
    121.18581.62640.00830ILMN_2598103Emp2137312013Epithelial membrane protein 2
    129.30511.62580.00910ILMN_1215632Marcksl11735765108MARCKS-like 1
    132.44961.62570.00910ILMN_3144289Traf3220317187TNF receptor-associated factor 3
    139.36311.62190.00920ILMN_26750004930511J11Rik74720283953Claudin 26
    125.91.62170.00910ILMN_2439638Traf3220317187TNF receptor-associated factor 3
    264.96561.61460.03792.00E-04ILMN_2623983Egr2136541959Early growth response 2
    167.92581.61170.01411.00E-04ILMN_2506428Ky16716339855Kyphoscoliosis peptidase
    149.1691.60670.01090ILMN_2545963Hbb-b1NANANA
    147.56371.60530.01080ILMN_27694905430435G22Rik226421338382RIKEN cDNA 5430435G22 gene
    216.65051.60370.02341.00E-04ILMN_2443330Ttr221397276Transthyretin
    147.95211.60230.01110ILMN_2467151Cyp11a1NANANA
    177.20451.60050.01551.00E-04ILMN_12455496330404C01Rik8098257214Cell migration inducing protein, hyaluronan binding
    156.43861.59870.01160ILMN_1235571Cyr61160073491Cysteine-rich protein 61
    151.04461.59660.01080ILMN_2784078Mmp15173884324Matrix metallopeptidase 15
    128.56921.5920.00910ILMN_1234099Fermt124163955612Fermitin family homolog 1 (Drosophila)
    153.07221.5910.01090ILMN_2701891Marcksl11735765108MARCKS-like 1
    169.0691.58880.01381.00E-04ILMN_1255462Hbb-b1NANANA
    238.19181.57740.02832.00E-04ILMN_2750515Fos142812353FBJ osteosarcoma oncogene
    179.42861.57670.01571.00E-04ILMN_1258028Gal3st1538979514Galactose-3-O-sulfotransferase 1
    168.01941.57540.01391.00E-04ILMN_26215442700060E02Rik1807422795Nidogen 2
    179.19351.57060.01591.00E-04ILMN_2711163Ctsk130381513Cathepsin K
    203.95221.57020.0211.00E-04ILMN_2965660Apcdd1494504147495Adenomatosis polyposis coli downregulated 1
    186.07941.56610.01621.00E-04ILMN_2778722Ppapdc1a381925196051Phosphatidic acid phosphatase type 2 domain containing 1A
    183.69421.55650.01581.00E-04ILMN_1246139Cldn11184175010Claudin 11
    183.67361.55510.01611.00E-04ILMN_2838308Fmo1142612326Flavin-containing monooxygenase 1
    209.52651.55510.02191.00E-04ILMN_2769777Msc176819242Musculin
    256.12121.54960.03462.00E-04ILMN_2703138Tmem125230678128218Transmembrane protein 125
    204.05021.54650.02071.00E-04ILMN_2623184Nkiras27196628511NF-κB inhibitor interacting Ras-like protein 2
    202.99921.54540.02071.00E-04ILMN_2650447Col23a123775991522Collagen, type XXIII, alpha 1
    215.87331.5450.02311.00E-04ILMN_1239117Hbb-b1NANANA
    221.90561.54320.02511.00E-04ILMN_26384731190003M12Rik68888NAGastrokine 3
    202.51971.54250.02081.00E-04ILMN_2753342Hapln1129501404Hyaluronan and proteoglycan link protein 1
    210.59651.54090.0221.00E-04ILMN_2759371Fgfbp1141819982Fibroblast growth factor binding protein 1
    235.94541.53310.02842.00E-04ILMN_3097381Mobp174334336Myelin-associated oligodendrocytic basic protein
    217.93081.53050.02361.00E-04ILMN_2909782Rras26692222800Related RAS viral (r-ras) oncogene homolog 2
    229.13991.52990.02631.00E-04ILMN_2472451Traf4220329618TNF receptor-associated factor 4
    271.87321.52860.03982.00E-04ILMN_3162060EG574403574403100131897Family with sequence similarity 196, member B
    233.60471.52210.02772.00E-04ILMN_2747923Slc40a15394530061Solute carrier family 40 (iron-regulated transporter), member 1
    227.32951.51750.02631.00E-04ILMN_2517041Uhrf11814029128Ubiquitin-like, containing PHD and RING finger domains, 1
    280.34681.50860.04293.00E-04ILMN_1241168Dok411425555715Docking protein 4
    254.00571.50790.03412.00E-04ILMN_26258542310016C16Rik69590493869Glutathione peroxidase 8 (putative)
    256.23491.50770.03422.00E-04ILMN_1229726Fibcd19897084929Fibrinogen C domain containing 1
    304.07631.50740.04973.00E-04ILMN_25228849930105H17RikNANANA
    270.27531.50450.03932.00E-04ILMN_2815506Gamt144312593Guanidinoacetate methyltransferase
    262.31321.50160.03692.00E-04ILMN_2778111Etv4186122118ets variant 4
    288.4251.49790.04493.00E-04ILMN_2604224Sema5a203569037Sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A
    268.72631.49660.0392.00E-04ILMN_2688236Atp2a353313489ATPase, Ca++ transporting, ubiquitous
    284.24551.49580.0443.00E-04ILMN_1236788Igfbp2160083485Insulin-like growth factor-binding protein 2
    287.34251.4920.04513.00E-04ILMN_2737479Slc12a98370456996Solute carrier family 12 (potassium/chloride transporters), member 9
    274.56511.49050.0413.00E-04ILMN_1257097Cnp1279912672',3'-cyclic nucleotide 3' phosphodiesterase
    288.75931.48970.04463.00E-04ILMN_12190259030409G11Rik7152923254Kazrin, periplakin interacting protein
    297.69941.48910.04813.00E-04ILMN_1251524Them475778117145Thioesterase superfamily member 4
    303.85641.48770.05013.00E-04ILMN_1226329Cd931706422918CD93 antigen
    305.58891.48210.04923.00E-04ILMN_3126277Palmd11430154873Palmdelphin
    299.2261.48010.04863.00E-04ILMN_2655204Apc11789324Adenomatosis polyposis coli
    303.60341.47880.05053.00E-04ILMN_2726030AB023957NANANA
    304.18511.4760.04933.00E-04ILMN_2772155LOC100045780114928728A disintegrin and metallopeptidase domain 19 (meltrin beta)
    326.2746−1.54730.04924.00E-04ILMN_2939681Lyzs171104069Lysozyme 1
    324.3234−1.55130.04854.00E-04ILMN_2718266Fkbp5142292289FK506 binding protein 5
    300.7726−1.57550.03983.00E-04ILMN_2775885Calm212314NACalmodulin 2
    278.2959−1.58680.03432.00E-04ILMN_1224363Slc12a55713857468Solute carrier family 12, member 5
    281.5906−1.61130.03473.00E-04ILMN_1251998Gm765330390NAPredicted gene 765
    226.9486−1.61450.02491.00E-04ILMN_2488510Ppm1k243382152926Protein phosphatase 1K (PP2C domain containing)
    308.258−1.61680.04313.00E-04ILMN_1248368Mat2a2320874144Methionine adenosyltransferase II, alpha
    275.8602−1.61840.03432.00E-04ILMN_26690884930461P20Rik78244134218DNAJ (Hsp40) homolog, subfamily C, member 21
    253.8942−1.620.02982.00E-04ILMN_2435835Evpl140272125Envoplakin
    197.6328−1.62970.02111.00E-04ILMN_2602387Nr1d23531879975Nuclear receptor subfamily 1, group D, member 2
    311.5841−1.63290.04283.00E-04ILMN_2734000Elavl4155721996ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4 (Hu antigen D)
    311.1495−1.64040.0433.00E-04ILMN_2859032Gfod132823254438Glucose-fructose oxidoreductase domain containing 1
    253.0893−1.64550.02992.00E-04ILMN_2445958Tssc863830NAKCNQ1 overlapping transcript 1
    258.1943−1.65040.02992.00E-04ILMN_2419660mtDNA_ND4LNANANA
    215.9199−1.65230.02371.00E-04ILMN_1221817Cd7416149972CD74 antigen (invariant polypeptide of MHC, class II antigen-associated)
    308.2304−1.65950.04343.00E-04ILMN_2545149Nos1ap70729NANitric oxide synthase 1 (neuronal) adaptor protein
    256.5251−1.66310.02942.00E-04ILMN_1219573C130072A16Rik10572781539Solute carrier family 38, member 1
    292.3656−1.66640.03673.00E-04ILMN_2475376BC044804NANANA
    229.2861−1.66830.02511.00E-04ILMN_12535442900060B14Rik68204NARIKEN cDNA 2900060B14 gene
    318.4001−1.66940.04544.00E-04ILMN_1246494LOC3814452642226960Neurobeachin
    282.6027−1.67170.03453.00E-04ILMN_2666980BDNF12064627BDNF
    219.961−1.67220.02361.00E-04ILMN_1231445Inmt2174311185Indolethylamine N-methyltransferase
    240.372−1.67620.02692.00E-04ILMN_1240202Fnip121674296459Folliculin-interacting protein 1
    269.2034−1.67640.0332.00E-04ILMN_2987863Per2186278864Period circadian clock 2
    201.3209−1.6770.02121.00E-04ILMN_3157692Ankrd35213121148741Ankyrin repeat domain 35
    310.3109−1.6790.04323.00E-04ILMN_12184713-Sep2405055964Septin 3
    229.1441−1.67980.02541.00E-04ILMN_1229216Zbtb162353207704Zinc finger and BTB domain containing 16
    264.7303−1.68410.03162.00E-04ILMN_1253985A330021D07RikNANANA
    171.7223−1.68610.01631.00E-04ILMN_1235966Alox12b11686242Arachidonate 12-lipoxygenase, 12R type
    253.9144−1.68610.02952.00E-04ILMN_1245687Ash1l19219555870ash1 (absent, small, or homeotic)-like (Drosophila)
    294.7856−1.68750.03753.00E-04ILMN_2674890Tbl1x213726907Transducin (beta)-like 1 X-linked
    267.8862−1.68890.03282.00E-04ILMN_2828916Frmd6319710122786FERM domain containing 6
    254.4102−1.69320.02932.00E-04ILMN_12280776330437B22Rik78283256714MAP7 domain containing 2
    282.4957−1.69350.03473.00E-04ILMN_2589525Cpeb320892222849Cytoplasmic polyadenylation element binding protein 3
    277.0563−1.69550.03452.00E-04ILMN_2466121Twistnb28071221830TWIST neighbor
    250.5161−1.69780.0292.00E-04ILMN_2514631scl0002315.1_122178691983Eukaryotic translation initiation factor 5
    186.3783−1.70070.01951.00E-04ILMN_24930302310043N10Rik66961NANuclear paraspeckle assembly transcript 1 (non-protein coding)
    263.9285−1.70330.03152.00E-04ILMN_2677270Peg3186165178Paternally expressed 3
    239.6678−1.70390.02712.00E-04ILMN_1214405Cnksr224568422866Connector enhancer of kinase suppressor of Ras 2
    253.7716−1.70420.032.00E-04ILMN_2763404Nrxn318191NANeurexin III
    182.2435−1.70790.01861.00E-04ILMN_1246861Ctss130401520Cathepsin S
    278.7674−1.70820.03412.00E-04ILMN_1239608Arid4a2382475926AT-rich interactive domain 4A (RBP1-like)
    242.1379−1.70880.02692.00E-04ILMN_2745614Fam134b6627054463Family with sequence similarity 134, member B
    273.3035−1.70940.03362.00E-04ILMN_2762701Scn1a202656323Sodium channel, voltage-gated, type I, alpha
    235.4555−1.70970.02632.00E-04ILMN_1243910Zfp2923004623036Zinc finger protein 292
    182.6041−1.710.01841.00E-04ILMN_2690603Spp1207506696Secreted phosphoprotein 1
    262.6651−1.71670.03132.00E-04ILMN_2733314Rgs7bp52882401190Regulator of G-protein signaling 7 binding protein
    218.5161−1.71730.02371.00E-04ILMN_2593368Mat2a2320874144Methionine adenosyltransferase II, alpha
    248.3251−1.72180.02842.00E-04ILMN_2525034Cc1124219821RB1-inducible coiled-coil 1
    244.6249−1.72320.02732.00E-04ILMN_2713008C030011O14Rik215708374986Family with sequence similarity 73, member A
    244.4499−1.72440.02762.00E-04ILMN_12280201500010G04RikNANANA
    214.8649−1.72470.02421.00E-04ILMN_2664706Chic11221253344Cysteine-rich hydrophobic domain 1
    224.3588−1.72560.02521.00E-04ILMN_1251488A430041B07Rik32810823116Family with sequence similarity 179, member B
    167.7266−1.72830.01581.00E-04ILMN_2651054LOC10004717326958984958Synaptotagmin-like 1
    233.1724−1.73130.02622.00E-04ILMN_2713004C030011O14Rik215708374986Family with sequence similarity 73, member A
    224.4289−1.73460.02491.00E-04ILMN_1233554Pbrm16692355193Polybromo 1
    215.0498−1.73550.02391.00E-04ILMN_2669461Bbx7050856987Bobby sox homolog (Drosophila)
    220.6021−1.73820.02381.00E-04ILMN_1218712Jph4NANANA
    229.662−1.73940.02481.00E-04ILMN_1231596Mtap7NANANA
    217.0292−1.73970.02371.00E-04ILMN_24923952900064A13RikNANANA
    194.6882−1.74160.02131.00E-04ILMN_1218051Iqgap254496310788IQ motif containing GTPase activating protein 2
    224.9623−1.74220.02491.00E-04ILMN_12206262010007K12RikNANANA
    193.5535−1.74370.02131.00E-04ILMN_2689307Spnb2207426711Spectrin β, non-erythrocytic 1
    211.5491−1.74460.02351.00E-04ILMN_2594593Mpp55621764398Membrane protein, palmitoylated 5 (MAGUK p55 subfamily member 5)
    196.6783−1.74610.02141.00E-04ILMN_2541675LOC38212831967585459RIKEN cDNA 5830418K08 gene
    225.9716−1.74730.02511.00E-04ILMN_1230605Gm336212285116984ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2
    172.8921−1.75870.01621.00E-04ILMN_2803674S100a9202026280S100 calcium binding protein A9 (calgranulin B)
    192.6629−1.7590.02131.00E-04ILMN_3072536Eif52178691983Eukaryotic translation initiation factor 5
    138.7531−1.76060.01120ILMN_1255416Ly6a110454NALymphocyte antigen 6 complex, locus A
    206.7346−1.76240.02171.00E-04ILMN_25960772810474O19Rik6724655196RIKEN cDNA 2810474O19 gene
    190.8274−1.76270.02111.00E-04ILMN_1237335A730028C12RikNANANA
    197.1239−1.76620.02141.00E-04ILMN_2593230Mllt4173564301Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4
    200.8213−1.7690.02121.00E-04ILMN_25952822600005C20Rik7246223076Ribosomal RNA processing 1 homolog B (S. cerevisiae)
    200.7106−1.77020.02151.00E-04ILMN_2481389Zfp32654367284695Zinc finger protein 326
    164.0235−1.7740.01551.00E-04ILMN_12208282900075B16Rik78506286097Mitochondrial calcium uptake family, member 3
    155.2155−1.77560.01420ILMN_2571934D030034I04Rik10572781539Solute carrier family 38, member 1
    176.004−1.77810.01661.00E-04ILMN_1229727Gpr1235238984435G-protein-coupled receptor 123
    175.0744−1.78350.01641.00E-04ILMN_1237059Kcna1164853736Potassium voltage-gated channel, shaker-related subfamily, member 1
    152.5807−1.78670.0140ILMN_2512204mt-Nd4lNANANA
    191.3641−1.79150.0211.00E-04ILMN_1236941Csnk2a1-rs3129951457Casein kinase 2, alpha 1 polypeptide
    117.9399−1.7960.00950ILMN_2629112Asah3l230379340485Alkaline ceramidase 2
    154.7781−1.79760.01440ILMN_24232492010321I05Rik23383327327Trinucleotide repeat containing 6a
    169.376−1.79790.01571.00E-04ILMN_1260446Ttc3221297267Tetratricopeptide repeat domain 3
    159.9385−1.80050.01480ILMN_3151492Ankrd1210658523253ankyrin repeat domain 12
    159.7083−1.80080.01490ILMN_2747381Ddx242722557062DEAD (Asp-Glu-Ala-Asp) box polypeptide 24
    117.7708−1.8060.00940ILMN_2746797Hsf4263863299Heat shock transcription factor 4
    154.9416−1.81130.01410ILMN_1227149Meg317263NAMaternally expressed 3
    154.4618−1.81880.01410ILMN_25446032610015J01Rik67039NARNA binding motif protein 25
    149.6626−1.82180.01370ILMN_1234357A230057E24RikNANANA
    160.7228−1.82350.01450ILMN_2737867Mtap1b177554131Microtubule-associated protein 1B
    146.4398−1.82850.01320ILMN_2657911Cnot4536214850CCR4-NOT transcription complex, subunit 4
    137.4716−1.83120.01150ILMN_2654932Pdap123188711333PDGFA-associated protein 1
    149.0718−1.83420.01330ILMN_2542231LOC3821572280059360Peptidyl-prolyl isomerase G (cyclophilin G)
    136.8161−1.83720.01180ILMN_12567012900016B01Rik749019920Kelch repeat and BTB (POZ) domain containing 11
    140.2596−1.84060.01120ILMN_1217776Mll56918855904Lysine (K)-specific methyltransferase 2E
    123.3913−1.86320.00970ILMN_2466797scl0001284.1_18NANANA
    120.66−1.86570.00920ILMN_2495555Mapk8ip2NANANA
    110.3349−1.87160.0080ILMN_2720479Lpgat12268569926Lysophosphatidylglycerol acyltransferase 1
    107.1799−1.88150.00840ILMN_3031781Arid5b7137184159AT-rich interactive domain 5B (MRF1-like)
    108.2637−1.88220.00820ILMN_2968123Slc7a1424191957709Solute carrier family 7 (cationic amino acid transporter, y+ system), member 14
    102.8964−1.88960.00820ILMN_2524100Zswim66726357688Zinc finger SWIM-type containing 6
    106.148−1.89430.0080ILMN_1243996Ash1l19219555870ash1 (absent, small, or homeotic)-like (Drosophila)
    108.9677−1.89860.00820ILMN_1226085Syt1NANANA
    99.6837−1.89930.00810ILMN_2844963Nos1ap70729NANitric oxide synthase 1 (neuronal) adaptor protein
    80.4955−1.90040.00430ILMN_3107059Espn5622683715Espin
    150.8775−1.90260.01360ILMN_1245389LOC236604236604NAPhosphatidylserine decarboxylase, pseudogene 1
    99.2247−1.90290.00850ILMN_2715848Slitrk4245446139065SLIT and NTRK-like family, member 4
    104.8752−1.90330.00830ILMN_2771709Ppargc1b170826133522Peroxisome proliferative-activated receptor, γ, coactivator 1 β
    93.2724−1.9220.00760ILMN_3028837Pcdh92117125101Protocadherin 9
    70.0507−1.92340.00430ILMN_2752883Hsp90aa1155193320Heat shock protein 90, alpha (cytosolic), class A member 1
    68.4948−1.92490.00450ILMN_2702303Ch25h126429023Cholesterol 25-hydroxylase
    78.6377−1.93350.00450ILMN_3144164Irs23847838660Insulin receptor substrate 2
    83.4984−1.95390.0050ILMN_1255854Mtap921358279884Microtubule-associated protein 9
    62.4352−1.99160.00390ILMN_2639442Rock2198789475Rho-associated coiled-coil containing protein kinase 2
    65.2953−2.0060.00470ILMN_2703913Mtf21776522823Metal response element binding transcription factor 2
    57.2834−2.01450.00180ILMN_1236844A830094I09RikNANANA
    55.3183−2.02390.00210ILMN_12368209430047F21RikNANANA
    55.866−2.03920.00190ILMN_2432200Epb4.1NANANA
    49.8425−2.03960.00230ILMN_2642426Agmat7598679814agmatine ureohydrolase (agmatinase)
    45.5522−2.07430.00170ILMN_12375485830407P18RikNANANA
    44.5367−2.07560.00180ILMN_1259747Il337712590865Interleukin-33
    40.11−2.09420.0010ILMN_3124885Pdpk11860751703-Phosphoinositide dependent protein kinase 1
    35.7678−2.110600ILMN_2601176Meg317263NAMaternally expressed 3
    38.3554−2.12490.00110ILMN_1225423Mslnl328783NAMesothelin-like
    55.718−2.12950.0020ILMN_2668333Prg496875NAProteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)
    27.1219−2.171600ILMN_1216085B230387C07Rik10658523253Ankyrin repeat domain 12
    25.1926−2.211900ILMN_1238436Cplx21289010814Complexin 2
    107.5742−2.22020.00810ILMN_2965669Xlr4aNANANA
    28.7047−2.262400ILMN_2661820Agxt2l17176064850Ethanolamine phosphate phospholyase
    23.2317−2.400400ILMN_2652500Lrg176905116844Leucine-rich alpha-2-glycoprotein 1
    11.5889−2.510700ILMN_1229990Agxt2l17176064850Ethanolamine phosphate phospholyase
    14.3442−2.782400ILMN_2710905S100a8202016279S100 calcium binding protein A8 (calgranulin A)
    3.6486−3.741100ILMN_2712075Lcn2168193934Lipocalin 2
    • V1 transcriptomes were profiled with microarray from juvenile mice with naturally elevated experience-dependent plasticity to generate the juvenile plasticity differential expression signature. Using RankProd differential expression (DE) analysis, V1 of juvenile male mice C57BL/6 at P29 was compared to adult C57BL/6 mice (>P60; n = 3 each group) to identify 248 DE probes, which mapped to 193 unique mouse Entrez IDs. For downstream analysis, mouse Entrez IDs were mapped to human orthologs using the Mouse Genome Informatics homology reference to yield a 176 gene juvenile plasticity signature. FC, fold change. RP, rank product. pfp, percent false positive (i.e. false discovery rate).

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    Table 3:

    Molecular matching among 436 disease signatures and the juvenile plasticity signature indicates diverse diseases may disrupt plasticity

    RankNormalized molecular match scoreEmp_pvalFDRSource_datSpeciesDiseaseTissue
    19.644.53E-081.22E-05GSE7958Mus musculusHuntington's diseaseCNS, brain, striatum (MMHCC)
    28.357.74E-081.22E-05GSE1623Mus musculusType 1 diabetes mellitusPancreas
    38.328.58E-073.40E-05GSE9857Mus musculusHuntington's diseaseCNS, brain, striatum (MMHCC)
    47.961.38E-071.22E-05GSE4648Mus musculusAcute myocardial infarctionMyocardial tissue
    57.591.40E-071.22E-05GSE4290Homo sapiensGlioblastomaCNS, brain (MMHCC)
    67.523.36E-072.44E-05GSE1481Homo sapiensAnterior horn cell diseaseCNS, spinal cord (MMHCC)
    76.819.04E-081.22E-05GSE2240Homo sapiensAtrial fibrillationMyocardial tissue
    86.731.47E-064.94E-05GSE5500Mus musculusCardiac hypertrophyMyocardial tissue
    96.478.10E-073.40E-05GSE5389Homo sapiensBipolar disorderfrontal cortex
    106.338.15E-073.40E-05GSE5078Mus musculusSenescenceHippocampus
    116.251.75E-065.46E-05GSE4764Mus musculusYersinia enterocolitica food poisoningPeyer's patch
    125.757.82E-073.40E-05GSE4290Homo sapiensAstrocytomaCNS, brain (MMHCC)
    135.71.73E-053.59E-04GSE1621Mus musculusCardiac hypertrophyMyocardial tissue
    145.676.55E-057.88E-04GSE3253Mus musculusBacterial infectionCNS, brain (MMHCC)
    155.611.16E-064.22E-05GSE10599Mus musculusSpinal muscular atrophyKidney
    165.552.49E-067.25E-05GSE3744Homo sapiensBreast cancerMammary gland tissue
    175.431.32E-053.04E-04GSE6731Homo sapiensCrohn's diseaseIntestine, large intestine, colon (MMHCC)
    185.382.24E-054.24E-04GSE6731Homo sapiensUlcerative colitisIntestine, large intestine, colon (MMHCC)
    195.351.29E-053.04E-04GSE11343Mus musculusDiabetic neuropathySciatic nerve
    205.357.33E-073.40E-05GSE4316Homo sapiensPrimary open angle glaucomaTrabecular meshwork
    215.282.67E-054.65E-04GSE5406Homo sapiensCardiomyopathyMyocardial tissue
    225.023.36E-055.29E-04GSE464Rattus norvegicusSpinal cord injuryCNS, spinal cord (MMHCC)
    234.981.87E-053.71E-04EXPE-MEXP-567Homo sapiensGlioblastomaBrain
    244.941.17E-041.13E-03GSE1025Mus musculusDMDMuscle, striated (skeletal) (MMHCC)
    254.95.26E-056.95E-04GSE1843Rattus norvegicusHepatic cirrhosisHepatic tissue
    264.861.54E-053.37E-04GSE1572Homo sapiensSenescencefrontal cortex
    274.816.87E-057.88E-04GSE1472Mus musculusDMDMuscle, striated (skeletal) (MMHCC)
    284.819.47E-062.43E-04GSE2510Homo sapiensObesityAdipocyte
    294.83.91E-055.49E-04GSE3383Mus musculusCardiac hypertrophyMyocardial tissue
    304.781.06E-041.05E-03GSE1629Homo sapiensDental cavity, complexDental pulp
    314.726.79E-057.88E-04GSE2629Mus musculusMuscular dystrophyMuscle, striated (skeletal) (MMHCC)
    324.673.90E-055.49E-04GSE4290Homo sapiensOligodendrogliomaCNS, brain (MMHCC)
    334.631.71E-041.49E-03GSE10760Homo sapiensMuscular dystrophyMusculus vastus lateralis
    344.629.53E-051.01E-03GSE1988Mus musculusCardiac failureMyocardial tissue
    354.614.84E-056.59E-04GSE3467Homo sapiensPapillary carcinoma of the thyroidThyroid gland (MMHCC)
    364.573.84E-055.49E-04GSE3621Mus musculusHuntington's diseaseBrain
    374.563.35E-055.29E-04GSE4107Homo sapiensCancer of colonIntestine, large intestine, colon (MMHCC)
    384.541.20E-041.14E-03GSE842Mus musculusMSCNS, spinal cord (MMHCC)
    394.538.18E-059.14E-04GSE14905Homo sapiensPsoriasis vulgarisSkin tissue
    404.513.40E-055.29E-04GSE7305Homo sapiensEndometriosisEndometrium
    414.488.91E-062.43E-04GSE16524Homo sapiensSetleis syndromeSkin fibroblast
    424.466.85E-057.88E-04GSE4183Homo sapiensCarcinoma in situ of large intestineColon
    434.432.37E-054.30E-04GSE12654Homo sapiensSchizophreniaCerebral cortex
    444.31.62E-041.44E-03GSE2866Mus musculusγ-Hydroxybutyric acidemiaCNS, brain, cerebellum (MMHCC)
    454.229.23E-051.01E-03GSE1859Mus musculusFDIUHepatic tissue
    464.195.52E-057.08E-04GSE4587Homo sapiensMalignant melanomaEpidermis
    474.162.13E-041.82E-03GSE63Mus musculusCerebral infarctionCNS, brain (MMHCC)
    484.162.26E-041.83E-03GSE6614Mus musculusGeneralized seizuresBrain
    494.081.58E-041.44E-03GSE6280Homo sapiensChronic kidney diseaseKidney
    504.013.19E-042.44E-03GSE5390Homo sapiensDown’s syndromeBrain
    514.012.66E-042.11E-03GSE2052Homo sapiensIdiopathic fibrosing alveolitisLung tissue
    5242.23E-041.83E-03GSE1873Mus musculusObstructive sleep apneaHepatic tissue
    533.974.39E-043.07E-03GSE4183Homo sapiensIBDColon
    543.961.01E-041.02E-03GSE3075Mus musculusSpinal muscular atrophy, infantileCNS, spinal cord (MMHCC)
    553.941.42E-041.32E-03GSE3167Homo sapiensUrothelial carcinoma in situUrothelium
    563.932.20E-041.83E-03GSE8514Homo sapiensAdenomaAdrenal gland
    573.934.01E-042.92E-03GSE6764Homo sapiensCarcinoma, hepatocellularLiver
    583.924.89E-043.18E-03GSE3585Homo sapiensCardiomyopathy, dilatedMyocardial tissue
    593.893.39E-042.55E-03GSE1420Homo sapiensBarrett esophagusEsophageal tissue
    603.889.89E-051.02E-03GSE1420Homo sapiensAdenocarcinoma of esophagusEsophageal tissue
    613.874.40E-043.07E-03GSE781Homo sapiensClear cell carcinoma of kidneyRenal tissue
    623.875.95E-043.51E-03GSE2528Mus musculusBreast cancerMammary gland
    633.849.37E-044.92E-03GSE1026Mus musculusDMDMuscle, striated (skeletal), diaphragm (MMHCC)
    643.795.25E-043.35E-03GSE3678Homo sapiensPapillary carcinoma of the thyroidThyroid gland (MMHCC)
    653.744.88E-043.18E-03GSE4619Homo sapiensMDSBone marrow stem cell
    663.735.92E-043.51E-03GSE3112Homo sapiensPolymyositisMuscle tissue
    673.723.51E-042.59E-03GSE3189Homo sapiensMultiple benign melanocytic neviEpidermis
    683.685.76E-043.49E-03GSE769Mus musculusCystic fibrosisPancreas
    693.665.76E-043.49E-03GSE10432Homo sapiensAcneSebocyte
    703.651.30E-036.16E-03GSE3252Mus musculusMuscular dystrophyMuscle, striated (skeletal), diaphragm (MMHCC)
    713.624.81E-043.18E-03GSE12649Homo sapiensSchizophreniaCerebral cortex
    723.67.41E-044.17E-03GSE2501Mus musculusThymic carcinomaThymus
    733.591.20E-035.87E-03GSE3268Homo sapiensSquamous cell carcinoma of lungLung tissue
    743.587.82E-044.32E-03GSE857Mus musculusHuntington's diseaseCNS, brain (MMHCC)
    753.582.96E-042.30E-03GSE1009Homo sapiensDiabetic nephropathyRenal tissue
    763.571.20E-035.87E-03GSE977Mus musculusAlexander diseaseCNS, brain, olfactory bulb (MMHCC)
    773.555.37E-043.35E-03GSE2826Mus musculusBruton's agammaglobulinemiaB-cell lymphocyte
    783.547.46E-044.17E-03GSE2640Mus musculusPulmonary fibrosisLung tissue
    793.535.37E-043.35E-03GSE2514Homo sapiensAdenocarcinoma of lungLung tissue
    803.538.90E-044.73E-03GSE1551Homo sapiensDermatomyositisMuscle, striated (skeletal) (MMHCC)
    813.524.50E-043.07E-03GSE2507Mus musculusMuscular dystrophyMuscle, striated (skeletal) (MMHCC)
    823.57.15E-044.10E-03GSE3189Homo sapiensMalignant melanomaEpidermis
    833.51.10E-035.58E-03GSE4764Mus musculusY. enterocolitica food poisoningLymph node
    843.458.68E-044.67E-03EXPE-MEXP-567Homo sapiensGlioblastomaBrain
    853.434.44E-043.07E-03GSE3408Homo sapiensAtypical mycobacterial infectionmacrophage
    863.431.10E-035.58E-03GSE6428Rattus norvegicusType 2 diabetes mellitusEndocrine pancreas, islet cell of Langerhans, β-cell (MMHCC)
    873.428.45E-044.61E-03GSE10575Homo sapiensArthropathyChondrocyte
    883.46.73E-043.91E-03GSE9375Mus musculusHuntington's diseaseCNS, brain, striatum (MMHCC)
    893.392.10E-039.16E-03GSE4390Mus musculusALSCNS, spinal cord (MMHCC)
    903.381.21E-035.87E-03GSE3644Mus musculusAcute pancreatitisPancreas
    913.381.30E-036.16E-03GSE3112Homo sapiensInclusion body myositidesMuscle tissue
    923.331.10E-035.58E-03GSE466Mus musculusDMDMuscle, striated (skeletal) (MMHCC)
    933.291.40E-036.36E-03GSE2144Homo sapiensGERDEsophageal tissue
    943.271.40E-036.36E-03EXPE-MEXP-1296Mus musculusCancer of prostateProstate
    953.241.70E-037.64E-03GSE2724Homo sapiensUterine leiomyomaUterus
    963.213.30E-031.30E-02GSE2825Rattus norvegicusIdiosyncratic drug effectHepatic tissue
    973.192.60E-031.08E-02GSE1007Homo sapiensDMDMuscle, striated (skeletal) (MMHCC)
    983.191.20E-035.87E-03GSE1781Rattus norvegicusSepsisHepatic tissue
    993.182.40E-031.03E-02GSE2899Mus musculusType 2 diabetes mellitusAdipose tissue
    1003.181.90E-038.37E-03GSE2557Mus musculusKidney disorder associated with type 2 diabetes mellitusMesangial cell
    1013.181.40E-036.36E-03GSE3524Homo sapiensSquamous cell carcinoma of mouthOropharynx epithelium
    1023.171.40E-036.36E-03GSE13355Homo sapiensPsoriasis vulgarisSkin tissue
    1033.152.20E-039.50E-03GSE2866Mus musculusγ-Hydroxybutyric acidemiaCerebral cortex
    1043.122.60E-031.08E-02GSE4911Mus musculusCleidocranial dysostosisHumerus
    1053.121.90E-038.37E-03GSE24807Homo sapiensNASHLiver
    1063.123.20E-031.28E-02GSE10631Homo sapiensLGLLPeripheral blood mononuclear cell
    1073.112.70E-031.11E-02GSE2052Homo sapiensSclerodermaLung tissue
    1083.072.90E-031.17E-02GSE4692Mus musculusObesityAdipose tissue
    1093.052.50E-031.06E-02GSE4824Homo sapiensNon-small cell lung cancerBronchial epithelium
    1103.033.80E-031.47E-02GSE1145Homo sapiensIschemic cardiomyopathyMyocardial tissue
    1113.014.90E-031.77E-02GSE6678Mus musculusInfantile neuronal ceroid lipofuscinosisBrain
    11233.30E-031.30E-02GSE3064Homo sapiensDystoniaBrain
    1132.994.70E-031.72E-02GSE2527Mus musculusThrombocytopeniaMegakaryocyte
    1142.994.30E-031.62E-02GSE2433Mus musculusLeukemia, acute megakaryocyticMegakaryocyte
    1152.934.60E-031.71E-02GSE1776Mus musculusNutritional deficiency, NECSkeletal myocyte
    1162.933.90E-031.49E-02GSE4587Homo sapiensIn situ melanoma of skinEpidermis
    1172.925.30E-031.88E-02GSE9579Homo sapiensAppendicitisAppendix
    1182.915.80E-032.01E-02GSE2411Mus musculusVentilator-associated lung injuryLung tissue
    1192.92.80E-031.14E-02GSE1037Homo sapiensSmall cell carcinoma of lungLung tissue
    1202.865.20E-031.86E-02GSE2401Rattus norvegicusHypotensive episodeRenal tissue
    1212.854.70E-031.72E-02GSE765Mus musculusCystic fibrosisIntestinal epithelium
    1222.833.60E-031.40E-02EXPE-MEXP-882Homo sapiensInvasive ductal breast cancerMammary epithelium
    1232.836.70E-032.28E-02GSE1869Homo sapiensIschemic cardiomyopathyMyocardial tissue
    1242.825.60E-031.95E-02GSE4183Homo sapiensAdenomaColon
    1252.825.40E-031.90E-02GSE1004Homo sapiensDMDMuscle, striated (skeletal) (MMHCC)
    1262.814.30E-031.62E-02GSE9944Homo sapiensGlaucomaAstrocyte
    1272.796.20E-032.13E-02EXPE-TABM-176Homo sapiensIrritable bowel syndrome variant of childhood with diarrheaSigmoid colon
    1282.728.40E-032.75E-02GSE2779Homo sapiensMDSBone marrow stem cell
    1292.727.20E-032.43E-02GSE1947Mus musculusPeripheral motor neuropathySciatic nerve
    1302.718.40E-032.75E-02GSE593Homo sapiensUterine leiomyomaUterus, myometrium (MMHCC)
    1312.717.50E-032.52E-02GSE2712Homo sapiensClear cell sarcoma of kidneyRenal tissue
    1322.698.50E-032.75E-02GSE1459Mus musculusBacterial InfectionMacrophage
    1332.678.50E-032.75E-02GSE1811Mus musculusOccupational lung diseaseLung Tissue
    1342.678.90E-032.85E-02GSE2508Homo sapiensObesityAdipocyte
    1352.668.10E-032.70E-02GSE1462Homo sapiensMELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)Muscle, striated (skeletal) (MMHCC)
    1362.659.00E-032.86E-02GSE4130Rattus norvegicusDehydrationCNS, brain, hypothalamus (MMHCC)
    1372.619.10E-032.88E-02GSE1378Homo sapiensBreast cancerMammary gland tissue
    1382.61.14E-023.45E-02GSE1375Mus musculusAlzheimer's diseaseCerebral cortex
    1392.599.80E-033.03E-02GSE2719Homo sapiensGastrointestinal stromal tumorConnective tissue
    1402.599.60E-033.01E-02GSE7036Homo sapiensBipolar disorderLymphocyte
    1412.571.00E-023.07E-02GSE1724Homo sapiensSclerodermaFibroblast
    1422.569.70E-033.02E-02GSE3790Homo sapiensHuntington's diseaseCaudate nucleus
    1432.551.25E-023.68E-02GSE6764Homo sapiensHepatic cirrhosisLiver
    1442.541.24E-023.68E-02GSE2457Rattus norvegicusErectile dysfunction associated with type 2 diabetes mellitusPenis, NOS
    1452.541.47E-024.14E-02GSE2457Rattus norvegicusErectile dysfunctionPenis erectile tissue
    1462.541.05E-023.20E-02GSE3110Rattus norvegicusDehydrationHypothalamus
    1472.531.22E-023.64E-02GSE2712Homo sapiensNephroblastomaRenal tissue
    1482.511.42E-024.05E-02GSE7999Rattus norvegicusTachycardiaMyocardial tissue
    1492.511.29E-023.77E-02GSE609Homo sapiensSCIDThymic lymphocyte
    1502.491.19E-023.58E-02GSE1869Homo sapiensCardiomyopathyMyocardial tissue
    1512.491.36E-023.93E-02GSE7621Homo sapiensParkinson's diseaseSubstantia nigra
    1522.481.35E-023.92E-02GSE10971Homo sapiensSerous carcinomaFallopian tube
    1532.481.40E-024.02E-02GSE3418Mus musculusLung transplant rejectionTrachea
    1542.471.45E-024.11E-02EXPE-MEXP-476Homo sapiensCancer of prostateEndothelial cell
    1552.471.54E-024.28E-02GSE3184Mus musculusAsthma, allergicLung tissue
    1562.461.49E-024.16E-02GSE4616Mus musculusType 1 diabetes mellitusMyocardial tissue
    1572.411.68E-024.64E-02GSE4612Mus musculusCarcinoma, hepatocellularHepatic tissue
    1582.41.77E-024.85E-02GSE2725Homo sapiensUterine leiomyomaUterus
    1592.391.81E-024.90E-02GSE3365Homo sapiensUlcerative colitisPeripheral blood mononuclear cell
    1602.371.80E-024.90E-02GSE1813Rattus norvegicusObesityAdipose tissue
    1612.361.87E-025.03E-02GSE4060Homo sapiensCushing syndromeAdrenal gland
    1622.352.07E-025.50E-02GSE1145Homo sapiensPrimary cardiomyopathyMyocardial tissue
    1632.311.88E-025.03E-02GSE6461Mus musculusSynovial sarcomaSynovial membrane
    1642.32.15E-025.68E-02GSE1037Homo sapiensNon-small cell lung cancerLung tissue
    1652.272.29E-026.01E-02GSE10921Homo sapiensIdiopathic fibrosing alveolitisFibroblast
    1662.262.41E-026.28E-02GSE3248Mus musculusHuntington's diseaseCNS, brain, cerebellum (MMHCC)
    1672.252.42E-026.28E-02GSE4788Mus musculusParkinson's diseaseSubstantia nigra
    1682.242.52E-026.46E-02GSE4710Mus musculusHeart injuryMyocardial tissue
    1692.212.52E-026.46E-02GSE6364Homo sapiensEndometriosisEndometrium
    1702.22.68E-026.83E-02GSE1462Homo sapiensCPEO (chronic progressive external ophthalmoplegia)Muscle, striated (skeletal) (MMHCC)
    1712.193.00E-027.56E-02GSE1724Homo sapiensIdiopathic fibrosing alveolitisFibroblast
    1722.182.87E-027.28E-02GSE6955Homo sapiensRett syndromefrontal cortex
    1732.133.24E-028.12E-02GSE1017Homo sapiensMyopathy NOSSkeletal muscle
    1742.133.39E-028.45E-02GSE2429Homo sapiensBreast cancerMammary gland tissue
    1752.123.57E-028.79E-02GSE6764Homo sapiensHepatocellular dysplasiaLiver
    1762.113.64E-028.92E-02GSE4516Rattus norvegicusSmoke inhalationLung tissue
    1772.13.41E-028.45E-02GSE567Homo sapiensEssential thrombocythemiaMegakaryocyte
    1782.093.92E-029.39E-02EXPE-TABM-176Homo sapiensIrritable bowel syndrome variant of childhood with constipationSigmoid colon
    1792.083.69E-028.99E-02GSE4130Rattus norvegicusDehydrationPituitary gland
    1802.073.72E-029.01E-02GSE9006Homo sapiensType 2 diabetes mellitusPeripheral blood mononuclear cell
    1812.064.00E-029.40E-02GSE2899Mus musculusType 2 diabetes mellitusSoleus muscle
    1822.064.01E-029.40E-02GSE3125Rattus norvegicusDehydrationHypothalamus
    1832.063.99E-029.40E-02GSE3407Homo sapiensCockayne syndromeFibroblast
    1842.063.79E-029.13E-02GSE2866Mus musculusγ-Hydroxybutyric acidemiaHippocampus
    1852.054.07E-029.49E-02GSE2077Homo sapiensProtozoan InfectionIntestinal epithelium
    1862.054.14E-029.60E-02GSE9006Homo sapiensType 1 diabetes mellitusPeripheral blood mononuclear cell
    1872.034.01E-029.40E-02GSE10123Homo sapiensPremature agingSkin fibroblast
    1882.014.45E-021.01E-01GSE3365Homo sapiensCrohn's diseasePeripheral blood mononuclear cell
    1892.014.33E-029.99E-02GSE1297Homo sapiensAlzheimer's diseaseHippocampus
    19024.40E-021.01E-01GSE2254Mus musculusType 1 diabetes mellituspancreatic islet
    19124.57E-021.03E-01GSE3489Homo sapiensHIV encephalitisfrontal cortex
    19224.44E-021.01E-01GSE3203Mus musculusInfluenzaB-cell lymphocyte
    1931.994.67E-021.05E-01GSE2559Homo sapiensPulmonary hypertension, primaryPulmonary artery
    1941.984.76E-021.06E-01GSE3807Homo sapiensAplastic anemiaBone marrow
    1951.984.85E-021.07E-01GSE4105Rattus norvegicusMyocardial infarctionMyocardial tissue
    1961.964.72E-021.06E-01GSE4479Mus musculusSepsisSplenocyte
    1971.955.26E-021.15E-01GSE3676Mus musculusInfertility due to azoospermiaTesticular tissue
    1981.945.21E-021.15E-01GSE10064Homo sapiensMSB-cell lymphocyte
    1991.935.48E-021.17E-01GSE5090Homo sapiensPolycystic ovary syndromeAdipose tissue
    2001.935.43E-021.17E-01GSE11Mus musculusType 1 diabetes mellitusThymic epithelial cell
    2011.925.28E-021.15E-01GSE582Mus musculusTransplanted heart complicationMyocardial tissue
    2021.925.44E-021.17E-01GSE10586Homo sapiensType 1 diabetes mellitusT lymphocyte
    2031.925.77E-021.21E-01GSE2049Homo sapiensAMLHaematopoietic stem cell
    2041.915.56E-021.18E-01GSE11208Homo sapiensNicotine addictionGanglioneuroblastoma
    2051.915.61E-021.18E-01GSE5538Mus musculusHepatic lipidosisHepatic Tissue
    2061.95.37E-021.16E-01EXPE-MEXP-692Homo sapiensBarrett esophagusEsophagus
    2071.95.60E-021.18E-01GSE1659Mus musculusType 1 diabetes mellitusMuscle, striated (skeletal) (MMHCC)
    2081.896.00E-021.25E-01GSE4170Homo sapiensCMLHaematopoietic stem cell
    2091.886.33E-021.31E-01EXPE-MEXP-692Homo sapiensAdenocarcinoma of esophagusEsophagus
    2101.866.21E-021.29E-01GSE422Mus musculusCarcinoma in situ of small intestineIntestinal epithelium
    2111.826.93E-021.41E-01GSE1822Homo sapiensEwing's sarcomaRenal tissue
    2121.816.69E-021.37E-01GSE755Homo sapiensOsteolysisLeukocyte, lymphocyte, B lymphocyte, plasma cell (MMHCC)
    2131.816.60E-021.36E-01GSE3004Homo sapiensAsthma, allergicBronchial epithelium
    2141.787.26E-021.47E-01GSE4060Homo sapiensACTH-dependent Cushing syndromeAdrenal gland
    2151.767.71E-021.54E-01GSE4120Mus musculusArrhythmogenic right ventricular cardiomyopathyMyocardial tissue
    2161.768.01E-021.59E-01GSE3790Homo sapiensHuntington's diseasefrontal cortex
    2171.767.70E-021.54E-01GSE9800Homo sapiensCardiomyopathy, dilatedMyocardial tissue
    2181.718.68E-021.70E-01GSE3915Mus musculusCancer of the intestineSmall bowel
    2191.699.30E-021.80E-01GSE5581Mus musculusRetinoschisisRetina
    2201.688.96E-021.75E-01GSE868Mus musculusFamilial hypophosphatemic ricketsRenal tissue
    2211.688.99E-021.75E-01EXPE-TABM-176Homo sapiensIBSSigmoid colon
    2221.669.61E-021.85E-01GSE6965Homo sapiensInfection by Aspergillus fumigatusDendritic cell
    2231.669.71E-021.87E-01GSE6012Homo sapiensEczemaIntegument
    2241.659.80E-021.87E-01GSE3554Mus musculusGlaucomaRetina
    2251.651.00E-011.90E-01GSE2223Homo sapiensGlioblastomaCNS, brain (MMHCC)
    2261.639.98E-021.90E-01EXPE-TABM-26Homo sapiensCancer of prostateProstate
    2271.621.03E-011.94E-01GSE4172Homo sapiensViral cardiomyopathyMyocardial tissue
    2281.61.08E-012.01E-01GSE2191Homo sapiensAMLMononuclear leukocyte
    2291.61.08E-012.01E-01GSE2155Homo sapiensBreast cancerEpithelial cell
    2301.561.18E-012.16E-01GSE1299Homo sapiensBreast cancerMammary epithelium
    2311.551.15E-012.13E-01GSE3320Homo sapiensCOPDBronchial epithelium
    2321.551.19E-012.17E-01GSE5774Homo sapiensNonspecific interstitial pneumoniaLung tissue
    2331.551.18E-012.16E-01GSE6710Homo sapiensPsoriasis vulgarisSkin tissue
    2341.531.29E-012.31E-01GSE4250Homo sapiensHereditary gingival fibromatosisGingiva
    2351.531.24E-012.25E-01GSE5364Homo sapiensCancer of thyroidThyroid
    2361.531.18E-012.16E-01GSE3583Mus musculusHuntington's diseaseCNS, brain, striatum (MMHCC)
    2371.521.30E-012.32E-01GSE12654Homo sapiensBipolar disorderCerebral cortex
    2381.521.29E-012.31E-01GSE973Homo sapiensFunisitisUmbilical blood
    2391.511.32E-012.34E-01GSE12649Homo sapiensBipolar disorderCerebral cortex
    2401.51.33E-012.35E-01GSE925Rattus norvegicusCardiac hypertrophyCardiomyocyte
    2411.481.38E-012.42E-01GSE3544Mus musculusMODYPancreatic islet
    2421.471.42E-012.46E-01GSE420Homo sapiensAtherosclerosisAorta smooth muscle tissue
    2431.471.37E-012.42E-01GSE422Mus musculusAdenoma of small intestineIntestinal epithelium
    2441.461.41E-012.46E-01EXPE-TABM-36Homo sapiensHepatocellular adenomaHepatocyte
    2451.451.38E-012.42E-01GSE4302Homo sapiensAsthmaEpithelial cell
    2461.451.44E-012.50E-01GSE5370Homo sapiensDermatomyositisMuscle, striated (skeletal) (MMHCC)
    2471.421.53E-012.61E-01GSE2172Mus musculusColitisIntestine, large intestine, colon (MMHCC)
    2481.411.55E-012.63E-01GSE11750Homo sapiensSenescenceMuscle, striated (skeletal) (MMHCC)
    2491.411.56E-012.63E-01GSE3Homo sapiensChromophobe cell carcinoma of kidneyRenal cell
    2501.411.52E-012.61E-01GSE2705Homo sapiensPrimary open angle glaucomaOptic disk
    2511.371.68E-012.80E-01GSE3860Homo sapiensProgeriaFibroblast
    2521.371.73E-012.86E-01GSE674Homo sapiensSenescenceMuscle, striated (skeletal) (MMHCC)
    2531.361.72E-012.84E-01GSE2549Homo sapiensMalignant mesothelioma of pleuraPleura
    2541.361.71E-012.84E-01GSE1466Homo sapiensLymphoblastic leukemiaT lymphocyte
    2551.331.82E-012.97E-01GSE1611Mus musculusDown syndromeCNS, brain, cerebellum (MMHCC)
    2561.331.79E-012.93E-01GSE997Homo sapiensEssential thrombocythemiaMegakaryocyte
    2571.321.91E-013.09E-01GSE6798Homo sapiensPolycystic ovary syndromeSkeletal muscle
    2581.321.83E-012.98E-01GSE3790Homo sapiensHuntington's diseaseCNS, brain, cerebellum (MMHCC)
    2591.311.87E-013.03E-01GSE2503Homo sapiensActinic keratosisSkin tissue
    2601.291.94E-013.12E-01GSE1010Homo sapiensFamilial combined hyperlipidemiaLymphoblast
    2611.272.00E-013.17E-01GSE1028Homo sapiensScott syndromeB-cell lymphocyte
    2621.271.98E-013.16E-01GSE5388Homo sapiensBipolar disorderFrontal cortex
    2631.272.00E-013.17E-01GSE2067Homo sapiensHepatitis C infectionHepatocyte
    2641.262.04E-013.22E-01GSE3280Homo sapiensAcute monocytic leukemiaBlood monocyte
    2651.262.07E-013.24E-01GSE642Mus musculusType 2 diabetes mellitusRenal tissue
    2661.262.07E-013.24E-01GSE5281Homo sapiensAlzheimer's diseaseSuperior frontal gyrus
    2671.212.28E-013.54E-01GSE11348Homo sapiensRhinovirus infectionNose
    2681.22.34E-013.61E-01GSE7486Homo sapiensEpilepsyLymphoblast
    2691.162.46E-013.74E-01GSE3384Mus musculusNemaline myopathyTibialis Muscle
    2701.162.45E-013.73E-01GSE473Homo sapiensAsthmaCD4-positive lymphocyte
    2711.162.45E-013.73E-01GSE474Homo sapiensObesityMuscle, striated (skeletal) (MMHCC)
    2721.142.50E-013.78E-01EXPE-MEXP-669NULLNeuroblastomaAdrenal cortex
    2731.122.62E-013.95E-01GSE3889Mus musculusHypercholesterolemiaHepatic tissue
    2741.112.66E-013.97E-01GSE2175Homo sapiensAdenoma of pituitary glandPituitary gland
    2751.12.71E-014.03E-01GSE3925Mus musculusHyperreactive airway diseaseLung tissue
    2761.092.79E-014.13E-01GSE10162Mus musculusNephrolithiasisKidney
    2771.092.62E-013.95E-01GSE2470Rattus norvegicusType 2 diabetes mellitusPancreas
    2781.082.77E-014.10E-01GSE362Homo sapiensSenescenceMuscle, striated (skeletal) (MMHCC)
    2791.062.87E-014.23E-01GSE2973Mus musculusInfection by Y. enterocoliticaMacrophage
    2801.042.98E-014.35E-01GSE4785Homo sapiensSimian acquired immune deficiency syndromeT lymphocyte
    2811.042.97E-014.35E-01GSE923Homo sapiensPseudomonas infectionLung tissue
    2821.023.07E-014.46E-01GSE12654Homo sapiensDepressionCerebral cortex
    2831.013.08E-014.47E-01GSE2053Homo sapiensRASynovial membrane
    2841.013.14E-014.54E-01GSE1037Homo sapiensAdenocarcinoma of lungLung tissue
    28513.18E-014.58E-01GSE4333Mus musculusLymphatic edemaSkin tissue
    2860.993.22E-014.62E-01GSE10964Mus musculusCOPDLung
    2870.993.28E-014.69E-01GSE2657Homo sapiensSarcoidosisT lymphocyte
    2880.963.41E-014.81E-01GSE1767Homo sapiensHuntington's diseaseBlood
    2890.963.35E-014.77E-01GSE7753Homo sapiensJRAPeripheral blood mononuclear cell
    2900.953.40E-014.81E-01GSE4125Homo sapiensAdenocarcinoma of kidneyKidney
    2910.943.46E-014.87E-01GSE8762Homo sapiensHuntington's diseaseLymphocyte
    2920.933.48E-014.88E-01GSE5788Homo sapiensLeukemia, chronic T cellT lymphocyte
    2930.923.56E-014.98E-01GSE483Mus musculusAsthma, allergicLung tissue
    2940.913.58E-014.99E-01GSE2566Rattus norvegicusNeurogenic muscular atrophyMuscle, striated (skeletal) (MMHCC)
    2950.913.60E-014.99E-01GSE2600Homo sapiensAnaplasmosisLeukemic cell
    2960.913.68E-015.06E-01GSE2127Mus musculusCarcinoma, hepatocellularHepatic tissue
    2970.913.59E-014.99E-01GSE2052Homo sapiensMCTDLung tissue
    2980.843.85E-015.26E-01GSE2276Mus musculusAsthma, allergicLung tissue
    2990.844.07E-015.52E-01GSE4707Homo sapiensPreeclampsiaPlacenta
    3000.814.22E-015.68E-01GSE3871Homo sapiensAndrogen insensitivity syndromeFibroblast
    3010.814.17E-015.63E-01GSE1606Mus musculusTurner syndromeCNS, brain (MMHCC)
    3020.84.27E-015.70E-01GSE1674Mus musculusHypertensionAdrenal gland
    3030.84.28E-015.70E-01GSE3195Mus musculusHypoxiaFibroblast
    3040.794.28E-015.70E-01GSE475Homo sapiensCOPDMuscle, striated (skeletal), diaphragm (MMHCC)
    3050.794.34E-015.75E-01GSE1872Rattus norvegicusBreast cancerMammary gland tissue
    3060.794.29E-015.70E-01GSE3868Homo sapiensCancer of prostateProstate
    3070.764.46E-015.87E-01EXPE-MEXP-669NULLNeuroblastomaAdrenal cortex
    3080.764.43E-015.85E-01GSE5109Homo sapiensObesityMuscle, striated (skeletal) (MMHCC)
    3090.734.64E-016.07E-01GSE1413Mus musculusCancer of prostateProstate
    3100.724.76E-016.18E-01GSE5281Homo sapiensAlzheimer's DiseaseMiddle temporal gyrus
    3110.724.71E-016.15E-01GSE3384Mus musculusNemaline myopathyExtensor digitorum longus muscle
    3120.694.89E-016.32E-01GSE2223Homo sapiensAstrocytomaCNS, brain (MMHCC)
    3130.684.97E-016.42E-01EXPE-MEXP-476Homo sapiensCancer of prostateEndothelial cell
    3140.684.99E-016.42E-01EXPE-MEXP-476Homo sapiensCancer of prostateEndothelial cell
    3150.665.10E-016.54E-01GSE9877Homo sapiensSickle cell anemiaEndothelial cell
    3160.655.18E-016.62E-01GSE3026Homo sapiensBacterial infectionPeripheral blood mononuclear cell
    3170.635.30E-016.76E-01GSE128Mus musculusRetinitis pigmentosaRetina
    3180.615.34E-016.77E-01GSE1379Homo sapiensBreast cancerMammary gland tissue
    3190.585.63E-017.02E-01GSE867Mus musculusHepatitis, autoimmuneHepatic tissue
    3200.585.63E-017.02E-01GSE465Homo sapiensDMDMuscle, striated (skeletal) (MMHCC)
    3210.585.61E-017.02E-01GSE1871Mus musculusAcute lung injuryLung tissue
    3220.575.65E-017.02E-01GSE5900Homo sapiensMGUSBone marrow
    3230.575.70E-017.02E-01GSE2223Homo sapiensOligodendrogliomaCNS, brain (MMHCC)
    3240.575.65E-017.02E-01GSE1055Rattus norvegicusCardiac hypertrophyCardiomyocyte
    3250.575.70E-017.02E-01GSE4748Homo sapiensBacterial infectionDendritic cell
    3260.575.73E-017.03E-01GSE3384Mus musculusNemaline myopathyMuscle, striated (skeletal), diaphragm (MMHCC)
    3270.575.70E-017.02E-01GSE2236Mus musculusCongestive heart diseaseMyocardial tissue
    3280.565.74E-017.03E-01GSE1008Mus musculusDMDExtraocular muscle
    3290.535.90E-017.15E-01GSE1472Mus musculusDMDExtraocular muscle
    3300.536.02E-017.20E-01GSE85Mus musculusAPECEDThymic epithelial cell
    3310.535.92E-017.15E-01GSE1849Homo sapiensSickle cell anemiaPulmonary artery
    3320.525.99E-017.19E-01GSE3311Rattus norvegicusAlcohol poisoningPancreas
    3330.516.03E-017.21E-01GSE2503Homo sapiensSquamous cell carcinomaSkin tissue
    3340.56.17E-017.35E-01GSE2899Mus musculusType 2 diabetes mellitusHepatic tissue
    3350.486.26E-017.42E-01GSE1739Homo sapiensSARSPeripheral blood mononuclear cell
    3360.466.46E-017.57E-01GSE5900Homo sapiensSmoldering multiple myelomaBone marrow
    3370.456.64E-017.74E-01GSE4678Mus musculusVentricular hypertrophyMyocardial tissue
    3380.436.63E-017.74E-01GSE4128Mus musculusAdenovirus infectionHepatic tissue
    3390.426.79E-017.81E-01GSE11889Homo sapiensCMLHematopoietic stem cell
    3400.426.72E-017.79E-01GSE2779Homo sapiensVitamin B 12 deficiencyBone marrow stem cell
    3410.46.89E-017.90E-01GSE3Homo sapiensClear cell carcinoma of kidneyRenal cell
    3420.387.02E-017.97E-01GSE9692Homo sapiensSeptic shockWhole blood
    3430.387.10E-018.01E-01GSE6740Homo sapiensHIVT lymphocyte
    3440.367.13E-018.03E-01GSE121Homo sapiensType 2 diabetes mellitusMuscle tissue
    3450.367.25E-018.14E-01GSE1402Homo sapiensSpondyloarthropathyPeripheral blood mononuclear cell
    3460.347.34E-018.20E-01GSE2271Mus musculusHypoxiaHeart
    3470.347.40E-018.21E-01GSE2466Homo sapiensLymphocytic leukemia, chronic, B CellPBL
    3480.347.37E-018.21E-01GSE1751Homo sapiensHuntington's diseaseBlood
    3490.287.76E-018.48E-01GSE10211Mus musculusSendai virus infectionTracheal epithelium
    3500.277.86E-018.57E-01GSE2379Homo sapiensHypopharyngeal cancerPharynx
    3510.258.01E-018.70E-01GSE2884Rattus norvegicusNeurological pain disorderDorsal root ganglia
    3520.248.02E-018.70E-01GSE1560Mus musculusAtherosclerosisAorta smooth muscle tissue
    3530.198.51E-019.11E-01GSE18803Rattus norvegicusNeurological pain disorderCNS, spinal cord (MMHCC)
    3540.178.63E-019.18E-01GSE1124Homo sapiensMalariaBlood
    3550.178.69E-019.19E-01EXPE-MEXP-1050Homo sapiensIUGRDecidua basalis
    3560.158.82E-019.28E-01GSE4697Mus musculusObesityAdipose tissue
    3570.129.02E-019.43E-01GSE3249Mus musculusLeber congenital amaurosisRetina
    3580.129.02E-019.43E-01GSE1852Mus musculusMarfan’s syndromeMyocardial tissue
    3590.089.34E-019.66E-01GSE7654Rattus norvegicusHepatitisLiver
    3600.089.35E-019.66E-01GSE2504Homo sapiensHIVT lymphocyte
    3610.089.39E-019.66E-01GSE1710Homo sapiensUlcerative colitisSigmoid colon
    3620.089.40E-019.66E-01GSE3167Homo sapiensUrothelial carcinomaUrothelium
    3630.079.45E-019.66E-01GSE5281Homo sapiensAlzheimer's diseaseEntorhinal cortex
    3640.079.46E-019.66E-01GSE3586Homo sapiensCardiomyopathy, dilatedMyocardial tissue
    3650.049.70E-019.88E-01GSE10758Homo sapiensDown syndromeFetus
    3660.029.82E-019.89E-01GSE15966Homo sapiensGastrointestinal stromal tumorGastric tissue
    3670.019.94E-019.96E-01GSE11969Homo sapiensSmall cell carcinoma of lungLung tissue
    36809.98E-019.98E-01GSE4482Homo sapiensCancer of cervixCervix
    369−0.019.93E-019.96E-01GSE11393Homo sapiensFamilial combined hyperlipidemiaBlood monocyte
    370−0.029.81E-019.89E-01GSE10474Homo sapiensAcute lung injuryWhole blood
    371−0.029.81E-019.89E-01GSE574Homo sapiensPurpura, idiopathic thrombocytopenicT lymphocyte
    372−0.029.80E-019.89E-01GSE3827Homo sapiensCBCLSkin tissue
    373−0.039.76E-019.89E-01GSE8835Homo sapiensB-cell chronic lymphocytic leukemia/small lymphocytic lymphomaPeripheral blood mononuclear cell
    374−0.079.42E-019.66E-01GSE2779Homo sapiensFolic acid deficiencyBone marrow stem cell
    375−0.19.19E-019.54E-01GSE860Homo sapiensPTSDPeripheral blood mononuclear cell
    376−0.119.18E-019.54E-01GSE2935Mus musculusSendai virus infectionMacrophage
    377−0.119.15E-019.54E-01GSE4483Homo sapiensHypoxiaAstrocyte
    378−0.148.89E-019.34E-01GSE1650Homo sapiensCOPDLung tissue
    379−0.168.74E-019.23E-01EXPE-MEXP-1278Rattus norvegicusArteriotomyCarotid artery
    380−0.178.68E-019.19E-01GSE1541Homo sapiensLung injuryLung tissue
    381−0.188.52E-019.11E-01GSE2899Mus musculusType 2 diabetes mellituspancreatic islet
    382−0.198.55E-019.12E-01GSE935Homo sapiensGranulomatous disease, chronicBlood neutrophil
    383−0.198.42E-019.06E-01GSE2171Homo sapiensHIV infectionPeripheral blood mononuclear cell
    384−0.28.46E-019.08E-01GSE4036Homo sapiensSchizophreniaCNS, brain, cerebellum (MMHCC)
    385−0.228.27E-018.93E-01GSE14245Homo sapiensMalignant tumor of pancreasSaliva
    386−0.248.06E-018.72E-01GSE2459Mus musculusHypertrophy, left ventricularMyocardial tissue
    387−0.297.69E-018.44E-01GSE1818Homo sapiensCancer of the testisTestis
    388−0.297.71E-018.44E-01GSE10789Homo sapiensLeukemia, adult T cellBlood monocyte
    389−0.37.66E-018.43E-01GSE2368Mus musculusVentilator-associated lung injuryLung tissue
    390−0.327.59E-018.38E-01GSE11Mus musculusType 1 diabetes mellitusSplenic tissue
    391−0.327.44E-018.24E-01GSE2507Mus musculusMuscular dystrophyMyocardial tissue
    392−0.347.39E-018.21E-01GSE11969Homo sapiensAdenocarcinoma of lungLung tissue
    393−0.347.29E-018.17E-01GSE3Homo sapiensChromophil carcinoma of kidneyRenal cell
    394−0.377.05E-017.99E-01GSE1710Homo sapiensCrohn's diseaseSigmoid colon
    395−0.386.97E-017.93E-01GSE1987Homo sapiensSquamous cell carcinomaLung tissue
    396−0.46.96E-017.93E-01GSE1719Homo sapiensMacular degenerationFibroblast
    397−0.46.91E-017.90E-01GSE2737Homo sapiensPsoriasis vulgarisEpidermis
    398−0.416.78E-017.81E-01GSE2729Homo sapiensRotavirus infection of childrenPeripheral blood mononuclear cell
    399−0.416.78E-017.81E-01GSE14577Homo sapiensCFSPeripheral blood mononuclear cell
    400−0.436.66E-017.74E-01GSE363Mus musculusAtherosclerosisHepatic tissue
    401−0.466.46E-017.57E-01GSE1987Homo sapiensAdenocarcinoma of lungLung tissue
    402−0.476.42E-017.57E-01GSE1786Homo sapiensSenescenceMuscle, striated (skeletal) (MMHCC)
    403−0.476.33E-017.48E-01GSE2018Homo sapiensLung transplant rejectionLung tissue
    404−0.496.26E-017.42E-01GSE5113Mus musculusIntestinal flagellate infectionSmall intestinal lamina propria
    405−0.525.99E-017.19E-01GSE4646Homo sapiensMeningococcal infectionUmbilical vein
    406−0.545.89E-017.15E-01GSE3934Homo sapiensMeningococcal infectionBlood
    407−0.545.86E-017.13E-01GSE11969Homo sapiensSquamous cell carcinoma of lungLung tissue
    408−0.555.80E-017.08E-01GSE3606Homo sapiensOverexertionLeukocyte
    409−0.595.55E-016.99E-01GSE2378Homo sapiensGlaucomaAstrocyte
    410−0.615.43E-016.86E-01GSE11969Homo sapiensLarge cell carcinoma of lungLung tissue
    411−0.635.34E-016.77E-01GSE1907Homo sapiensSarcoidosisBlood corpuscle
    412−0.74.74E-016.17E-01GSE3100Mus musculusCystic fibrosisLung
    413−0.744.62E-016.07E-01GSE7277Mus musculusArthritisfrontal cortex
    414−0.853.97E-015.39E-01GSE3384Mus musculusNemaline myopathyGastrocnemius muscle
    415−0.853.95E-015.38E-01GSE1363Mus musculusPrimary pulmonary hypoplasiaLung tissue
    416−0.863.85E-015.26E-01GSE11886Homo sapiensAnkylosing spondylitismacrophage
    417−0.93.66E-015.05E-01GSE1542Homo sapiensDuct cell carcinomaPancreas
    418−0.943.40E-014.81E-01GSE3414Mus musculusSCIDLung tissue
    419−1.042.98E-014.35E-01GSE2223Homo sapiensAnaplastic oligoastrocytomaCNS, brain (MMHCC)
    420−1.112.66E-013.97E-01GSE1615Homo sapiensPolycystic ovary syndromeTheca cells
    421−1.172.41E-013.70E-01GSE1402Homo sapiensChronic polyarticular juvenile rheumatoid arthritisPeripheral blood mononuclear cell
    422−1.182.37E-013.65E-01GSE5786Mus musculusHuntington's diseaseCNS, brain, striatum (MMHCC)
    423−1.232.19E-013.42E-01GSE3284Homo sapiensBacterial infectionLeukocyte
    424−1.282.01E-013.18E-01GSE3512Rattus norvegicusHyperlipidemiaHepatic tissue
    425−1.291.97E-013.16E-01EXPE-MEXP-357Rattus norvegicusHypertensionLeft ventricle
    426−1.361.75E-012.88E-01GSE4630Homo sapiensHypoxiamacrophage
    427−1.381.68E-012.80E-01GSE1294Mus musculusDown’s syndromeCNS, brain (MMHCC)
    428−1.391.61E-012.70E-01GSE5112Mus musculusIntestinal flagellate infectionIntestinal epithelium
    429−1.421.53E-012.61E-01GSE2006Homo sapiensEssential thrombocythemiaThrombocyte
    430−1.441.46E-012.52E-01GSE1402Homo sapiensPauciarticular juvenile arthritisPeripheral blood mononuclear cell
    431−1.541.24E-012.25E-01EXPE-MEXP-1283Homo sapiensHodgkin’s lymphomaPeripheral blood mononuclear cell
    432−1.631.03E-011.94E-01GSE1919Homo sapiensRASynovial membrane
    433−1.738.56E-021.69E-01GSE2395Homo sapiensCystic fibrosisBronchial epithelium
    434−1.748.09E-021.60E-01GSE6435Mus musculusBacterial infectionLeukocyte, monocyte, macrophage (MMHCC)
    435−1.767.44E-021.50E-01GSE1919Homo sapiensOsteoarthritisSynovial membrane
    436−2.774.80E-031.74E-02GSE10121Homo sapiensSquamous cell carcinoma of buccal mucosaBuccal mucosa
    • We computationally matched the juvenile plasticity signature to 436 disease signatures derived from public microarray data. This systematic method applies a rank-based molecular matching algorithm to determine the molecular concordance between the plasticity signature and a given disease signature, where high scores indicate that plasticity genes are significantly dysregulated by the disease and low scores indicate that the disease has no impact on plasticity genes. Highly ranked diseases included not only brain disorders known to disrupt plasticity such as Huntington’s disease, but also non-neurologic disorders (e.g., bacterial infections, inflammatory bowel disease, metabolic diseases), suggesting that a broad range of disease states may impact molecular pathways involved in plasticity. ALS, Amyotrophic lateral sclerosis; AML, acute myeloid leukemia; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; CBCL, cutaneous B-cell lymphoma; CFS, chronic fatigue syndrome; CML, chronic myeloid leukemia; COPD, chronic obstructive pulmonary disease; DMD, Duchenne muscular dystrophy; FDIU, fetal death in utero; FDR, false discovery rate; GERD, gastroesophageal reflux disease; HIV, human immunodeficiency virus; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; IUGR, intrauterine growth retardation; JRA, juvenile rheumatoid arthritis; LGLL, large granular lymphocytic leukemia; MCTD, mixed connective tissue disease; MDS, myelodysplastic syndrome; MGUS, Monoclonal gammopathy of undetermined significance; MMHCC, Mouse Models of Human Cancers Consortium; MODY, maturity onset diabetes in youth type 1; MS, multiple sclerosis; PBL, peripheral blood lymphocyte; PTSD, post-traumatic stress disorder; RA, rheumatoid arthritis; SARS, severe acute respiratory syndrome; SCID, severe combined immunodeficiency.

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    Table 4:

    Lynx1−/− plasticity signature

    RPFCpfpp valueProbe_idSymbolmm_Entrez_IDhs_Entrez_IDGene_name
    1.25996.110200ILMN_1213274Ydjc69101150223YdjC homolog (bacterial)
    26.13781.72200ILMN_2744660Igh-6NANANA
    87.04351.58960.03250ILMN_1259747Il337712590865Interleukin-33
    79.55781.5830.02330ILMN_1231445Inmt2174311185Indolethylamine N-methyltransferase
    99.16931.55840.01890ILMN_1252675D230019G01RikNANANA
    95.56041.55810.02670ILMN_2499166Tmem6574868157378Transmembrane protein 65
    98.1061.54810.02130ILMN_1251713Car1276459771Carbonic anyhydrase 12
    94.61781.54360.0320ILMN_1244887Gria4NANANA
    96.49061.53390.02290ILMN_2649671Ipas5341764344Hypoxia-inducible factor 3, α subunit
    122.01521.52760.0350ILMN_2680188Bai1107831575Brain-specific angiogenesis inhibitor 1
    137.26491.50130.040ILMN_2968369Kcnip17035730820Kv channel-interacting protein 1
    128.5591.49890.04180ILMN_2744657Igh-6NANANA
    135.65891.49110.04250ILMN_3049896Evi2bNANANA
    295.2115−1.48850.04643.00E-04ILMN_2847144Hist1h2ak319169221613Histone cluster 1, H2ak
    271.4427−1.50150.03892.00E-04ILMN_2619455Mcat22372227349Malonyl CoA:ACP acyltransferase (mitochondrial)
    309.8626−1.50830.04943.00E-04ILMN_2700265Pex11a186318800Peroxisomal biogenesis factor 11 alpha
    310.3477−1.51350.04873.00E-04ILMN_1254828A730014O07RikNANANA
    306.798−1.51450.0493.00E-04ILMN_2684693Dusp3723491845Dual-specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)
    307.0792−1.51790.04883.00E-04ILMN_2869715Nell2540034753NEL-like 2
    277.2855−1.51910.03932.00E-04ILMN_2491589Vgll42323349686Vestigial like 4 (Drosophila)
    311.6705−1.52180.04874.00E-04ILMN_2568488A530089A20Rik21891423063Wings apart-like homolog (Drosophila)
    300.5669−1.52210.04743.00E-04ILMN_2768841Rab22aNANANA
    312.3161−1.52210.04844.00E-04ILMN_3163448Cdh8125641006Cadherin 8
    261.4704−1.52370.03652.00E-04ILMN_1214071Ifitm168713NAInterferon-induced transmembrane protein 1
    273.6424−1.52790.03942.00E-04ILMN_2757232Aqp411829361aquaporin 4
    285.8745−1.53140.04223.00E-04ILMN_1241551Nell2540034753NEL-like 2
    240.2307−1.5340.03222.00E-04ILMN_2629112Asah3l230379340485Alkaline ceramidase 2
    295.481−1.53540.0463.00E-04ILMN_2688728Pcyt1a130265130Phosphate cytidylyltransferase 1, choline, α isoform
    249.2494−1.53660.03282.00E-04ILMN_3151149Cpne866871144402Copine VIII
    273.9191−1.53850.03912.00E-04ILMN_2657911Cnot4536214850CCR4-NOT transcription complex, subunit 4
    309.8885−1.53890.0493.00E-04ILMN_12571902900083I11Rik58212NASerine/arginine repetitive matrix 3
    269.2151−1.53920.03852.00E-04ILMN_2639849Cbln4228942140689Cerebellin 4 precursor protein
    290.2289−1.54040.04453.00E-04ILMN_1255457Crebbp129141387CREB binding protein
    256.2379−1.54080.03562.00E-04ILMN_3072536Eif52178691983Eukaryotic translation initiation factor 5
    242.1891−1.5420.03152.00E-04ILMN_12490001500015O10Rik7889684417RIKEN cDNA 1500015O10 gene
    306.5435−1.54320.04943.00E-04ILMN_1214405Cnksr224568422866Connector enhancer of kinase suppressor of Ras 2
    278.6573−1.55160.03932.00E-04ILMN_2751988Kitl173114254Kit ligand
    274.1734−1.55180.03912.00E-04ILMN_2673566Eif4ebp2136881979Eukaryotic translation initiation factor 4E binding protein 2
    274.7663−1.55380.03912.00E-04ILMN_1216085B230387C07Rik10658523253Ankyrin repeat domain 12
    267.3929−1.55470.03792.00E-04ILMN_2703913Mtf21776522823Metal response element binding transcription factor 2
    218.0454−1.55690.031.00E-04ILMN_2535881Macrod272899140733MACRO domain containing 2
    298.574−1.55710.04683.00E-04ILMN_1246494LOC3814452642226960Neurobeachin
    240.5714−1.55760.03182.00E-04ILMN_1225224Ttc1467120151613Tetratricopeptide repeat domain 14
    257.4399−1.56010.03642.00E-04ILMN_1259724Man1b1715610905Mannosidase, α, class 1A, member 2
    225.5851−1.56030.03051.00E-04ILMN_1227376BC042720329178285175unc-80 homolog (Caenorhabditis elegans)
    233.0899−1.56450.03061.00E-04ILMN_2741677Bach112013571BTB and CNC homology 1
    241.988−1.56450.03192.00E-04ILMN_1230312A830054O04RikNANANA
    309.3927−1.56840.04973.00E-04ILMN_2793638H2-Tw3NANANA
    275.3065−1.56960.03912.00E-04ILMN_2757889Zfp91-cntfNANANA
    225.8264−1.57060.03011.00E-04ILMN_2654822Chd41079321108Chromodomain helicase DNA binding protein 4
    247.466−1.57280.03242.00E-04ILMN_2731854Creg2263764200407Cellular repressor of E1A-stimulated genes 2
    218.4269−1.57550.02971.00E-04ILMN_12215989330133O14RikNANANA
    259.2859−1.5780.03632.00E-04ILMN_1227149Meg317263NAMaternally expressed 3
    245.0182−1.5790.0322.00E-04ILMN_2601176Meg317263NAMaternally expressed 3
    246.2646−1.57930.03232.00E-04ILMN_1230605Gm336212285116984ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2
    225.2295−1.58050.03091.00E-04ILMN_2638066Gria3536232892Glutamate receptor, ionotropic, AMPA3 (alpha 3)
    224.7568−1.58080.03111.00E-04ILMN_1253224Dhcr2474754171824-Dehydrocholesterol reductase
    204.3878−1.58250.02561.00E-04ILMN_25446032610015J01Rik67039NARNA binding motif protein 25
    190.3687−1.58530.02331.00E-04ILMN_2593230Mllt4173564301Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4
    190.5304−1.58530.02251.00E-04ILMN_2519673Vwf223717450Von Willebrand factor homolog
    194.1056−1.58680.02291.00E-04ILMN_1215713Egr4136561961Early growth response 4
    220.9951−1.58960.02931.00E-04ILMN_1239599Bat2d22656223215Proline-rich coiled-coil 2C
    218.0063−1.59110.03041.00E-04ILMN_2637413Dbpht2386753NADNA binding protein with his-thr domain
    185.7923−1.59570.0231.00E-04ILMN_1247295Hook17796351361Hook homolog 1 (Drosophila)
    225.437−1.59570.03091.00E-04ILMN_2520582Plxna424374391584Plexin A4
    204.4627−1.60080.02491.00E-04ILMN_2674890Tbl1x213726907Transducin (β)-like 1 X-linked
    198.2794−1.60180.02381.00E-04ILMN_2541675LOC38212831967585459RIKEN cDNA 5830418K08 gene
    202.278−1.60490.02511.00E-04ILMN_2690603Spp1207506696Secreted phosphoprotein 1
    204.4135−1.60640.02521.00E-04ILMN_1224992Gcap147297254462Coiled-coil serine rich 2
    236.1982−1.6090.03092.00E-04ILMN_1235124Thsd420759679875Thrombospondin, type I, domain containing 4
    193.5829−1.6160.02311.00E-04ILMN_2737867Mtap1b177554131Microtubule-associated protein 1B
    219.8212−1.6160.02961.00E-04ILMN_1254547Nr4a2182274929Nuclear receptor subfamily 4, group A, member 2
    174.6364−1.61680.02121.00E-04ILMN_1235652Usp3731965157695Ubiquitin-specific peptidase 37
    190.4584−1.62020.02291.00E-04ILMN_1255854Mtap921358279884Microtubule-associated protein 9
    183.2527−1.62150.02261.00E-04ILMN_3114632Ddx6132091656DEAD (Asp-Glu-Ala-Asp) box polypeptide 6
    168.6428−1.62210.02041.00E-04ILMN_2561533Vps13a27156423230Vacuolar protein sorting 13A (yeast)
    169.7224−1.62360.02041.00E-04ILMN_1241229Bat2d22656223215Proline-rich coiled-coil 2C
    161.0071−1.63160.01760ILMN_1231734Nsd11819364324Nuclear receptor-binding SET-domain protein 1
    228.5556−1.63270.03031.00E-04ILMN_1259781A430041B07Rik32810823116Family with sequence similarity 179, member B
    164.2141−1.63320.01931.00E-04ILMN_1250030Cdc42ep110444511135CDC42 effector protein (Rho GTPase binding) 1
    186.6603−1.63320.02291.00E-04ILMN_2795040Hist1h2adNANANA
    189.467−1.63640.02391.00E-04ILMN_1216322Hmgcs21536031583-Hydroxy-3-methylglutaryl-coenzyme A synthase 2
    189.7896−1.63670.02351.00E-04ILMN_2646070Mtap1a177544130Microtubule-associated protein 1 A
    173.3318−1.63910.02121.00E-04ILMN_1229727Gpr1235238984435G-protein-coupled receptor 123
    182.5954−1.6420.02271.00E-04ILMN_2715848Slitrk4245446139065SLIT and NTRK-like family, member 4
    154.7165−1.64450.01570ILMN_2481391Zfp32654367284695Zinc finger protein 326
    144.623−1.64610.01320ILMN_1224129Dennd310584122898DENN/MADD domain containing 3
    175.2067−1.64610.02081.00E-04ILMN_2445958Tssc863830NAKCNQ1 overlapping transcript 1
    201.9407−1.64960.02531.00E-04ILMN_3059326Sparc206926678Secreted acidic cysteine-rich glycoprotein
    153.5956−1.66360.01540ILMN_3031781Arid5b7137184159AT-rich interactive domain 5B (MRF1-like)
    140.1691−1.66940.01260ILMN_2481389Zfp32654367284695Zinc finger protein 326
    134.6324−1.670.01090ILMN_1257525Cpeb320892222849Cytoplasmic polyadenylation element binding protein 3
    135.784−1.67060.01080ILMN_12375485830407P18RikNANANA
    158.0665−1.67140.01610ILMN_1220048A330086O21Rik434089NAPredicted gene 10010
    131.7096−1.6720.01160ILMN_1254296Chd1126481105Chromodomain helicase DNA binding protein 1
    134.8336−1.68210.01060ILMN_2654932Pdap123188711333PDGFA-associated protein 1
    156.3313−1.68270.0160ILMN_2457731A930010C08RikNANANA
    124.0646−1.68460.01170ILMN_2747381Ddx242722557062DEAD (Asp-Glu-Ala-Asp) box polypeptide 24
    138.2192−1.68750.01140ILMN_1248181Zbtb7a1696951341Zinc finger and BTB domain containing 7a
    109.4147−1.72320.00890ILMN_24923952900064A13RikNANANA
    127.2584−1.73070.01160ILMN_1251488A430041B07Rik32810823116Family with sequence similarity 179, member B
    93.3629−1.73730.00640ILMN_12184713-Sep2405055964Septin 3
    93.4053−1.7470.00620ILMN_2675914R3hdm122641223518R3H domain containing 1
    124.2134−1.75870.01130ILMN_2680128Zc3h1367302NAZinc finger CCCH type containing 13
    80.5466−1.76520.00550ILMN_1239042Ankhd110885754882Ankyrin repeat and KH domain containing 1
    86.1003−1.77650.00540ILMN_3162820Odz42396626011Teneurin transmembrane protein 4
    82.5619−1.79310.00570ILMN_12368209430047F21RikNANANA
    134.4843−1.7940.01120ILMN_2750515Fos142812353FBJ osteosarcoma oncogene
    71.9896−1.80540.00550ILMN_1258834Chd1126481105Chromodomain helicase DNA binding protein 1
    141.8688−1.81090.01280ILMN_3035795Mllt3701224300Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3
    271.3241−1.81260.03922.00E-04ILMN_2965669Xlr4aNANANA
    58.7952−1.84770.00310ILMN_2589525Cpeb320892222849Cytoplasmic polyadenylation element binding protein 3
    108.4816−1.85460.00930ILMN_2803674S100a9202026280S100 calcium-binding protein A9 (calgranulin B)
    73.6082−1.86530.00570ILMN_2639442Rock2198789475Rho-associated coiled-coil containing protein kinase 2
    65.4886−1.87370.00320ILMN_26179201110017D15Rik7372184688RIKEN cDNA 1110017D15 gene
    48.1193−1.94360.00210ILMN_1217776Mll56918855904Lysine (K)-specific methyltransferase 2E
    53.5131−1.98140.00270ILMN_2702303Ch25h126429023Cholesterol 25-hydroxylase
    43.2714−2.00640.00150ILMN_2649773Slc38a520983792745Solute carrier family 38, member 5
    37.5276−2.00929.00E-040ILMN_1244343B230369L08Rik22369725777Sad1 and UNC84 domain containing 2
    41.0522−2.03250.00170ILMN_1226085Syt1NANANA
    30.3722−2.06610.00110ILMN_12567012900016B01Rik749019920Kelch repeat and BTB (POZ) domain containing 11
    33.181−2.06650.0010ILMN_27780762210021J22Rik72355150383Cysteine-rich, DPF motif domain containing 1
    61.2262−2.09420.00290ILMN_2668333Prg496875NAProteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)
    61.9241−2.10570.00330ILMN_2623983Egr2136541959Early growth response 2
    18.8649−2.48260.00140ILMN_2652500Lrg176905116844Leucine-rich alpha-2-glycoprotein 1
    13.3721−2.485100ILMN_2654906Mgat3173094248Mannoside acetylglucosaminyltransferase 3
    25.6626−2.62120.00120ILMN_2710905S100a8202016279S100 calcium binding protein A8 (calgranulin A)
    6.5864−3.755200ILMN_2712075Lcn2168193934Lipocalin 2
    4.4996−4.757400ILMN_1243615Gramd422375223151GRAM domain containing 4
    3.677−5.359100ILMN_1223734Atf411911468Activating transcription factor 4
    2.1886−7.331400ILMN_2507182Tomm2222369656993Translocase of outer mitochondrial membrane 22 homolog (yeast)
    1−13.927600ILMN_1256369Lynx12393666004Ly6/neurotoxin 1
    • V1 transcriptomes were profiled with microarray from Lynx1−/− mice (the plasticity brake Lynx1 is genetically deleted to allow experience-dependent plasticity even in adulthood) to generate the Lynx1−/− plasticity differential expression signature. Using RankProd differential expression (DE) analysis, V1 of adult Lynx1−/− male mice >P60 was compared with adult wild-type mice (> P60; n = 3 each group) to identify 132 DE probes, which mapped to 107 unique mouse Entrez IDs. For downstream analysis, mouse Entrez IDs were mapped to human orthologs using the Mouse Genome Informatics homology reference to yield a 98 gene Lynx1−/− plasticity signature. FC, fold change. RP, rank product. pfp, percent false positive (i.e. false discovery rate).

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Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity
Milo R. Smith, Poromendro Burman, Masato Sadahiro, Brian A. Kidd, Joel T. Dudley, Hirofumi Morishita
eNeuro 15 December 2016, 3 (6) ENEURO.0240-16.2016; DOI: 10.1523/ENEURO.0240-16.2016

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Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity
Milo R. Smith, Poromendro Burman, Masato Sadahiro, Brian A. Kidd, Joel T. Dudley, Hirofumi Morishita
eNeuro 15 December 2016, 3 (6) ENEURO.0240-16.2016; DOI: 10.1523/ENEURO.0240-16.2016
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Keywords

  • bioinformatics
  • critical period
  • inflammation
  • plasticity
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