PDF Output of CLIC (clustering by inferred co-expression)

Dataset: Num of genes in input gene set: 13 Total number of genes: 16493

CLIC PDF output has three sections:

1) Overview of Co-Expression Modules (CEMs) Heatmap shows pairwise correlations between all genes in the input query gene set.

Red lines shows the partition of input genes into CEMs, ordered by CEM strength.

Each row shows one gene, and the brightness of squares indicates its correlations with other genes.

Gene symbols are shown at left side and on the top of the heatmap.

2) Details of each CEM and its expansion CEM+ Top panel shows the posterior selection probability (dataset weights) for top GEO series datasets.

Bottom panel shows the CEM genes (blue rows) as well as expanded CEM+ genes (green rows).

Each column is one GEO series dataset, sorted by their posterior probability of being selected.

The brightness of squares indicates the gene's correlations with CEM genes in the corresponding dataset.

CEM+ includes genes that co-express with CEM genes in high-weight datasets, measured by LLR score.

3) Details of each GEO series dataset and its expression profile: Top panel shows the detailed information (e.g. title, summary) for the GEO series dataset.

Bottom panel shows the background distribution and the expression profile for CEM genes in this dataset. Mrps12 Gnb2l1 Rps18 Rps28 Rps29 Rps16 Rps24 Rps25 Mrps2 Mrps6 Num ofGenesinQueryGeneset:13.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Rps6 Dap3 Fau

Rps29 Rps28 Fau Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 Singletons CEM 1(813datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:3.Predicted33.SelectedDatasets:813.Strength:4.4 CEM 1,Geneset"[G]smallribosomalsubunit",Page1 Tmsb4x Cox6a1 Rps3a1 Atp5g3 Cox4i1 Eef1b2 Rpl10a Rpl13a Rpl37a Rpl18a Rps19 Rps11 Rps4x Uba52 Rps28 Rps29 Actg1 Rplp0 Rplp2 Nme2 Rpl27 Rpl7a Rpl26 Rpl38 Rps2 Rps7 Rps5 Naca Eif3f Rpl7 Rpl8 Rpl6 Rpl4 Eif3i Eef2 Fau 0.0 1.0

GSE46871 [6] GSE15610 [12]

GSE7219 [12] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE32615 [10] GSE6785 [9] GSE4749 [6] GSE33471 [12] GSE22903 [24] GSE36530 [6] GSE14308 [12] GSE20727 [15] GSE23833 [12] GSE21944 [6] GSE2019 [12] GSE19286 [6] GSE39621 [51] GSE39897 [36] GSE2527 [6] GSE4288 [36] GSE47065 [8] GSE21143 [6] GSE24465 [6] GSE35844 [9] GSE10071 [10] GSE39592 [8] GSE6676 [8] GSE5497 [6] GSE8555 [8] GSE15458 [8] GSE36384 [12] GSE26745 [24] GSE13874 [14] GSE39082 [6] GSE5921 [6] GSE36618 [6] GSE32529 [224] GSE54581 [21] GSE41942 [6] GSE42061 [12] GSE16364 [6] GSE49346 [6] GSE14478 [7] GSE10552 [6] GSE33121 [10] GSE43620 [8] GSE58262 [18] GSE8503 [6] GSE10871 [32] GSE19687 [9] GSE34761 [8] GSE35825 [9] GSE17728 [12] GSE23178 [6] GSE35734 [6] GSE18010 [29] GSE3861 [6] GSE53299 [6] GSE19181 [6] GSE35318 [12] GSE42008 [6] GSE24726 [8] GSE13547 [12] GSE24437 [6] GSE6030 [6] GSE11358 [8] GSE12467 [6] GSE6084 [12] GSE38304 [8] GSE9978 [8] GSE58484 [15] GSE24695 [9] GSE31776 [10] GSE11149 [8] GSE6134 [7] GSE52474 [154] GSE58296 [9] GSE28093 [6] GSE42135 [42] GSE21900 [12] GSE11420 [15] GSE11044 [6] GSE11148 [6] GSE34206 [8] GSE6674 [15] GSE18115 [8] GSE34618 [7] GSE27717 [11] GSE2161 [8] GSE31086 [6] GSE19793 [32] GSE47421 [24] GSE18281 [33] GSE24789 [9] GSE19076 [12] GSE32903 [12] GSE37029 [15] GSE56755 [13] GSE10210 [16] GSE13805 [7] GSE11628 [12] GSE16210 [14] GSE51365 [28] GSE14672 [12] GSE32199 [6] GSE17097 [20] GSE36569 [6] GSE11766 [48] GSE27302 [16] GSE48811 [20] GSE7781 [12] GSE24873 [48] GSE7705 [10] GSE36414 [8] GSE6675 [8] GSE7605 [18] GSE12430 [21] GSE10216 [6] GSE31359 [8] GSE46094 [10] GSE8683 [11] GSE14698 [12] GSE23398 [7] GSE46242 [12] GSE30767 [8] GSE7810 [9] GSE11120 [10] GSE39375 [10] GSE6998 [32] GSE27378 [8] GSE38283 [7] GSE7111 [6] GSE47798 [30] GSE1999 [15] GSE21841 [18] GSE31598 [12] GSE11918 [9] GSE32102 [49] GSE13963 [15] GSE6259 [21] GSE14929 [38] GSE13690 [38] GSE20726 [9] GSE34423 [40] GSE43242 [10] GSE27675 [14] GSE6065 [100] GSE7683 [12] GSE49351 [6] GSE25140 [16] GSE26695 [20] GSE50439 [15] GSE48935 [12] GSE7657 [12] GSE40296 [6] CEM+ CEM GSE4656 [7] GSE9760 [12] GSE56492 [12] GSE12993 [6] GSE8836 [56] GSE21606 [6] 0.0 GSE15794 [6] GSE10954 [8]

GSE54656 [27] Scale ofaveragePearsoncorrelations GSE42688 [8] GSE4043 [6] GSE18460 [16] GSE40412 [14] GSE34324 [12] GSE19272 [30] 0.2 GSE5035 [12] GSE26076 [12] GSE8682 [8] GSE51686 [9] GSE46185 [6] GSE56482 [8] GSE6591 [15] GSE35106 [9] GSE3822 [16] 0.4 GSE18587 [9] GSE6526 [16] GSE7487 [24] GSE35077 [26] GSE21033 [12] GSE13799 [18] GSE17553 [16] GSE10556 [6] GSE31646 [11] 0.6 GSE13259 [10] GSE9316 [12] GSE17102 [9] GSE11496 [16] GSE25828 [8] GSE6482 [9] GSE59319 [6] GSE35998 [20] GSE21711 [6] 0.8 GSE41895 [12] GSE26025 [12] GSE21272 [44] GSE4734 [61] Score 5.39 13.81 15.97 18.66 22.80 44.13 47.84 97.20 167.17 212.21 245.03 327.57 389.57 414.31 439.83 457.74 472.00 497.93 506.94 512.94 551.86 605.21 619.89 624.52 627.69 655.55 692.60 694.20 716.72 763.57 784.08 802.10 943.77 1.0 Notes GEO Series "GSE46871" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46871 Status: Public on May 14 2013 Title: Hippocampal gene expression profiling of a model of Alzheimer`s Disease upon treatment with the ACE inhibitor captopril Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23959119 Summary & Design: Summary: Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition.

Overall design: Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip.

Background corr dist: KL-Divergence = 0.0289, L1-Distance = 0.0256, L2-Distance = 0.0007, Normal std = 0.6941

0.592 Kernel fit Pairwise Correlations Normal fit

Density 0.296

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Hippocampus,Hippocampus, Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe mice, Hippocampus,Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe with18 mice, month-old, high with18 mice,Abeta month-old, high [ ACE12 plaque mice,Abetamin month-old, inhibitor-treated-rep1 ACE12 load-rep1plaque month-old,] inhibitor-treated-rep2 with load-rep2 (0.113485) low with Abeta[ (0.195533) (0.0875443)lowmedium plaque Abeta (0.134632) load-rep1plaque load-rep2] (0.218563) (0.250242)[ max ] CEM 1 Rps29 12375.2 14976.7 24076.8 P ( S | Z, I ) = 1.00 Rps28 14336.5 16979.3 26885.3 Mean Corr = 0.99357 Fau 8290.9 9621.0 14102.9 Rpl38 15675.6 19214.5 28807.4 Rpl26 15073.9 17873.6 27509.8 Rpl18a 8685.9 10628.9 16424.2 Rpl37a 9947.9 11659.9 19225.9 Rps5 7671.9 9027.7 12613.7 CEM 1 + Rplp2 12205.7 15310.3 21225.1 Top 10 Genes Uba52 10119.0 11828.0 19404.2 Rpl7a 10525.7 13079.1 17966.5 Rps4x 10410.2 12306.3 18641.7 Rps7 11194.3 12860.6 18807.4

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE15610" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15610 Status: Public on Dec 22 2009 Title: Knockout of the selenocysteine tRNA (Trsp) gene in mouse macrophage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19863805 Summary & Design: Summary: Comparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.

Selenium, a micronutrient whose deficiency in the diet causes immune dysfunction and inflammatory disorders, exerts its physiological effects partly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins, is mediated by Sec tRNA[Ser]Sec. To identify macrophage-specific selenoprotein function, we generated mice with the Sec tRNA[Ser]Sec gene specifically deleted in myeloid cells. These mutant mice were devoid of the selenoproteome in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix. Therefore, selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.

Overall design: We have generated mice in which we have selectively removed the selenocysteine tRNA gene (trsp) in macrophages under the control of LysM-Cre promoter. Microarray analysis was performed on RNA samples taken from bone marrow-derived macrophages in knockout and control mice. 1. Control unstimulated 2. Knockout unstimulated 3. Control lipopolysaccharide (LPS) stimulated (4h) 4. Knockout LPS stimulated (4h). Three replicates for each condition. Thus, a total of 12 samples.

Background corr dist: KL-Divergence = 0.0769, L1-Distance = 0.0376, L2-Distance = 0.0023, Normal std = 0.4963

0.823 Kernel fit Pairwise Correlations Normal fit

Density 0.411

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Control_untreated_replicateControl_untreated_replicateControl_untreated_replicateKnockout_untreated_replicate 1Knockout_untreated_replicate (0.0211412) 2Knockout_untreated_replicate (0.129097) 3Control_4h (0.0344519)Control_4h 1 (0.0456166) lipopolysaccharide_replicateControl_4h 2 (0.112734) lipopolysaccharide_replicateKnockout_4h 3 (0.0576672) lipopolysaccharide_replicateKnockout_4h lipopolysaccharide_replicateKnockout_4h 1 (0.0525523) lipopolysaccharide_replicate 2 (0.0601958) lipopolysaccharide_replicate 3 (0.0435655) 1 [(0.109904) min 2 (0.263563) ] 3 (0.0695118)[ medium ] [ max ] CEM 1 Rps29 10019.8 14567.6 40250.1 P ( S | Z, I ) = 1.00 Rps28 13163.5 17561.0 46208.6 Mean Corr = 0.99298 Fau 9570.8 12193.0 27180.7 Rpl38 13214.9 18277.4 43990.9 Rpl26 12766.9 18220.0 41741.0 Rpl18a 9238.0 12201.3 22978.6 Rpl37a 8511.2 12573.8 29742.6 Rps5 9783.4 12289.5 24752.6 CEM 1 + Rplp2 12768.8 18070.8 40651.2 Top 10 Genes Uba52 9964.3 13435.0 21962.8 Rpl7a 11950.8 16802.2 30721.2 Rps4x 11102.1 16257.8 37275.2 Rps7 10988.3 14456.3 30910.0

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE7219" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7219 Status: Public on Mar 05 2008 Title: NIK/NF-kappaB2 regulated gene products. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18566401 Summary & Design: Summary: This study aims at identifying genes that are NIK/NF-kappaB2 responsive in murine dendritic cells matured in vivo.

Keywords: NIK/NF-kappaB2 responsive genes in dendritic cells after TLR/CD40 signaling

Overall design: This study isolated dendritic cells from the spleens of Alymphoplasia or heterozygeous littlermates (wild type). Mice were eiter not treated as a reference or treated I.P. with 25 micrograms of LPS and 100 micrograms of agonistic anti-CD40 antibody. DCs were isolated 6 hours after treatment allowing in vivo maturation via both TLR and CD40 signals. DCs from 3 mice per group were pooled. Experiment was performed in triplicate.

Background corr dist: KL-Divergence = 0.0960, L1-Distance = 0.0692, L2-Distance = 0.0095, Normal std = 0.4840

0.855 Kernel fit Pairwise Correlations Normal fit

Density 0.428

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT DendriticWT Dendritic Cells_untreated_replicate1WT Dendritic Cells_untreated_replicate2Alymphoplasia Cells_untreated_replicate3AlymphoplasiaAlymphoplasia splenic (0.0642716)WT splenicDC (0.0658516)Dendritic ex-vivoWT splenicDC (0.08281)Dendritic ex-vivofrom Cells_LPS+anti-CD40_replicate1WT DC untreated Dendritic ex-vivofrom Cells_LPS+anti-CD40_replicate2Alymphoplasia untreated from replicateCells_LPS+anti-CD40_replicate3Alymphoplasia untreated replicate Alymphoplasia1 Dendritic (0.0302162) replicate 2 Dendritic (0.0251913)(0.0947464) Cells_LPS+anti-CD40_replicate1 3 Dendritic (0.0280956)(0.059915) Cells_LPS+anti-CD40_replicate2 (0.0601343) Cells_LPS+anti-CD40_replicate3[ min ] (0.352851) (0.0808818)[ medium(0.0550349) ] [ max ] CEM 1 Rps29 35462.5 44293.0 193106.4 P ( S | Z, I ) = 1.00 Rps28 32323.0 38430.0 189890.4 Mean Corr = 0.99095 Fau 16061.3 22159.9 237225.2 Rpl38 20664.2 37644.3 243890.8 Rpl26 28062.7 44997.9 131193.9 Rpl18a 35109.4 48650.9 149422.8 Rpl37a 2529.2 8946.3 38982.8 Rps5 22016.1 27851.4 54819.1 CEM 1 + Rplp2 28815.7 44899.6 252935.8 Top 10 Genes Uba52 12342.7 17237.4 30515.6 Rpl7a 18950.2 34919.7 52808.5 Rps4x 32348.3 45157.9 79420.7 Rps7 29317.2 42014.4 58235.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE32615" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32615 Status: Public on Jun 30 2014 Title: Expression data of mouse Ewing's sarcoma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Ewings sarcoma is highly malignant bone tumor that involves childhood and adolescent, and its nature has not been well understood. To clarify its cellular origin and the mechanisms of tumorigenesis, we used ex vivo approach to create a murine model for Ewings sarcoma. The osteochondrogenic progenitors derived from the facial zone (FZ) of murine long bones at late gestation were purified by microdissection, introduced with EWS-FLI1 or EWS-ERG retroviruses and transplanted into nude mice. Ewings sarcoma-like small round cell sarcoma developed at 100% penetrance, whereas tumor induction was less effective when growth place (GP)-derived cells were used. The different response of gene expression to EWS-FLI1 between FZ and GP cells suggests importance of the specific cellular context for EWS-FLI1 to induce Ewings sarcoma. The Wnt/˛†-catenin pathway was involved in close relationship to the cellular context, with Dkk2 and Wipf1 as important downstream modulators. Furthermore, gene expression profiling revealed similarity between our models and human Ewings sarcoma. These results indicate that Ewings sarcoma originates from the embryonic osteochondrogenic progenitor.

Overall design: For comparing with human Ewing's sarcoma, we used expression databases E-MEXP-533 (Henderson SR et al, Genome Biol 6:R76, 2005) and E-MEXP-1142 (Schaefer KL et al, Eur J Cancer 44:699, 2008). In addition, the data sets for other sarcomas that include GSE6481 (Nakayama R et al, Mod Pathol 20:749, 2007), GSE7529 (Albino D et al, Cancer 113:1412, 2008) and GSE21122 (Barretina J et al, Nat Genet 42:715, 2010) were used for clustering analysis.

Background corr dist: KL-Divergence = 0.0865, L1-Distance = 0.0325, L2-Distance = 0.0021, Normal std = 0.4642

0.859 Kernel fit Pairwise Correlations Normal fit

Density 0.430

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Ewing'sEwing's sarcomaEwing's sarcoma 4 (0.0167343)Ewing's sarcoma 8 (0.0421402)Ewing's sarcoma 12 (0.119347)Ewing's sarcoma 14 (0.0251936)Ewing's sarcoma 15 (0.0935604)Ewing's sarcoma 17 (0.249891)Ewing's sarcoma 28 (0.0843072)Ewing's sarcoma 7 (0.0588836) sarcoma 23 (0.183378) 16 (0.126565)[ min ] [ medium ] [ max ] CEM 1 Rps29 40262.9 67017.4 106202.5 P ( S | Z, I ) = 1.00 Rps28 48832.6 82074.1 133314.7 Mean Corr = 0.98982 Fau 35022.7 56162.2 83309.7 Rpl38 50732.9 87471.9 141379.4 Rpl26 50193.9 85599.2 122228.6 Rpl18a 35993.6 55734.2 82346.7 Rpl37a 34527.7 55753.5 94948.5 Rps5 34894.8 62082.1 103204.9 CEM 1 + Rplp2 47920.0 84986.6 138282.2 Top 10 Genes Uba52 34380.5 55192.9 73327.6 Rpl7a 43181.0 77628.2 120754.7 Rps4x 48060.0 70686.6 81492.2 Rps7 41147.3 70658.7 121858.7

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE6785" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6785 Status: Public on Dec 15 2010 Title: Activation and Function of Alternatively and Classically Activated MH-S Alveolar Macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Alveolar macrophages (AMs), the tissue dwelling monocytes of the lungs, are the first to encounter the menagerie of items that pass the mechanical barriers of the nose and throat. AMs must be able to mount an effective immune response against invading pathogens as well as maintain homeostasis in the lungs to avoid excessive inflammatory responses. In vivo data suggests that AMs can take on different phenotypes depending on the conditions of simulation. Limited progress has been made in defining the mechanisms responsible for these phenotypic issues largely due to logistical difficulties in isolating a sufficient number of cells from the lungs that have not been activated by the isolation protocol. To circumvent these logistical issues, an in vitro cell culture model was developed to study AM biology with specific emphasis on the generation of alternatively activated alveolar macrophages (AAAMs). Utilizing the BALB/c AM cell line MH-S it was determined that LPS could be used to generate classically activated AMs (CAAMs) and that IL-4 was effective in producing AAAMs. We examined the full transcriptome of AAAMs and CAAMs using microarray technology in an attempt to confirm previously described AAAM expression patterns and to identify new molecules associated with AM phenotypic change. AAAMs up-regulated an entirely distinct group of transcripts including genes encoding Arg1, Ym1 and a number of repair and remodeling genes whereas CAAMs up-regulated proinflammatory cytokines such as IL-1, IL-6 and IL-12. Additional novel markers are identified in this study to better characterize CAAMs and AAAMs in the lung.

Keywords: Characterization of Cell Type Based on Activation Stimulus

Overall design: MH-S Cells (ATCC CRL-2019) were stimulated with either 50 ng/ml IL-4 or 1´g/ml LPS and analyzed 12 hours later by whole genome DNA microarray analysis.

Background corr dist: KL-Divergence = 0.0806, L1-Distance = 0.0211, L2-Distance = 0.0007, Normal std = 0.4772

0.836 Kernel fit Pairwise Correlations Normal fit

Density 0.418

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

MH-S_CON_rep01MH-S_CON_rep02MH-S_CON_rep03 (0.0624428)MH-S_IL-4_rep01 (0.0787281)MH-S_IL-4_rep02 (0.0847543)MH-S_IL-4_rep03 (0.0989888)MH-S_LPS_rep01 (0.0807932)MH-S_LPS_rep02 (0.337662)MH-S_LPS_rep03 (0.103939) (0.0861344) (0.0665583) [ min ] [ medium ] [ max ] CEM 1 Rps29 10768.7 14332.9 35601.2 P ( S | Z, I ) = 1.00 Rps28 9344.1 10833.2 20542.3 Mean Corr = 0.98933 Fau 9583.8 12279.0 26498.6 Rpl38 11385.6 13743.9 34680.0 Rpl26 10423.6 11191.9 19210.3 Rpl18a 10345.7 11556.8 26815.2 Rpl37a 7958.9 9653.1 20242.9 Rps5 9397.8 10994.2 24614.8 CEM 1 + Rplp2 9537.1 11018.9 21978.0 Top 10 Genes Uba52 8829.5 11881.4 26406.5 Rpl7a 11513.2 14406.7 30524.2 Rps4x 8696.7 10066.1 17173.5 Rps7 9777.2 11768.4 24797.2

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE4749" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4749 Status: Public on Feb 20 2008 Title: Microarray based comparison of gene expression in stria vascularis of 129S6 mice lacking slc26a4 and wildtype controls Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17187680 Summary & Design: Summary: To see for differential expression of genes in the stria vascularis of wild type and pendrin knockout mice

Keywords: Knockout vs Control

Overall design: Six samples in total of stria vascularis RNA were analyzed. Triplicates from wild type and pendrin knockout mice were run and analyzed.

Background corr dist: KL-Divergence = 0.0292, L1-Distance = 0.0187, L2-Distance = 0.0004, Normal std = 0.6723

0.595 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Stria VascularisStria VascularisStria Control VascularisStria Control (Pendrin)-1 VascularisStria Control (Pendrin)-2 Vascularis (0.128034)Stria Knockout (Pendrin)-3 Vascularis (0.152208) Knockout (Pendrin)-1 (0.365599) Knockout (Pendrin)-2 (0.100542) (Pendrin)-3[ (0.112898) min (0.140718) ] [ medium ] [ max ] CEM 1 Rps29 13218.9 15099.2 28599.6 P ( S | Z, I ) = 1.00 Rps28 13143.2 13593.7 22068.4 Mean Corr = 0.98894 Fau 3568.8 4300.2 7952.2 Rpl38 9246.8 10657.0 15322.9 Rpl26 9768.7 12490.1 19697.6 Rpl18a 9511.4 10696.4 17612.6 Rpl37a 1802.7 2560.1 4152.4 Rps5 7376.9 8526.9 9842.7 CEM 1 + Rplp2 8556.1 10654.7 13571.6 Top 10 Genes Uba52 7171.1 8973.1 11249.3 Rpl7a 8617.9 10034.1 12522.8 Rps4x 8886.7 10257.4 10994.1 Rps7 10292.8 10737.0 12945.6

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE33471" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33471 Status: Public on Jan 04 2012 Title: Paracrine TGFˆ Signaling Counterbalances BMP-Mediated Repression in Hair Follicle Stem Cell Activation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22226356 Summary & Design: Summary: Hair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. We uncovered a hitherto unrecognized DP transmitter, TGFβ2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration.

We used microarrays to detect the genes specifically affected by TGFˆ receptor II-deficient mice upon HFSC activation.

Overall design: Hair follicle stem cells (HFSCs) of hair gem (HG) and bulge, and total skin keratinocytes were FACS-purified from the mouse back skin at 2nd telogen-to-anagen transition stages.

Background corr dist: KL-Divergence = 0.1215, L1-Distance = 0.0369, L2-Distance = 0.0028, Normal std = 0.4111

0.970 Kernel fit Pairwise Correlations Normal fit

Density 0.485

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

TˆRII-HetTˆRII-Het Hair GermTˆRII-Het Bugle setTˆRII-cKO set #1Total (0.0921129)#1TˆRII-cKO (0.0362575)skin Hair keratinocytesTˆRII-cKO Germ Bugle setTˆRII-Het set #1Total set (0.0376472)#1TˆRII-Het #1 (0.187124)skin Hair (0.0999657) keratinocytes GermTˆRII-Het Bugle setTˆRII-cKO set #2Total (0.114292) #2setTˆRII-cKO (0.0556051)skin #1 Hair (0.0390068) keratinocytesTˆRII-cKO Germ Bugle set set #2Total set (0.0877708)#2 #2 (0.0688549)skin (0.07093) keratinocytes[ min set #2 ](0.110433) [ medium ] [ max ] CEM 1 Rps29 36488.7 67363.2 111654.4 P ( S | Z, I ) = 1.00 Rps28 45057.1 78704.8 114308.0 Mean Corr = 0.98815 Fau 29286.9 49800.6 81775.4 Rpl38 44485.8 78061.4 123485.0 Rpl26 46672.5 81293.4 111441.2 Rpl18a 30340.3 55754.7 88728.8 Rpl37a 30156.6 51829.2 79505.2 Rps5 32307.4 56370.8 85587.4 CEM 1 + Rplp2 43694.8 70983.4 107283.1 Top 10 Genes Uba52 33034.6 53791.5 82118.8 Rpl7a 36631.6 59901.6 81730.1 Rps4x 45942.9 81941.3 125200.2 Rps7 38990.8 65204.8 98140.5

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE22903" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22903 Status: Public on Nov 14 2011 Title: Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22058113 Summary & Design: Summary: Diamond Blackfan Anemia (DBA) is associated with developmental defects and

profound anemia. Mutations in genes encoding a ribosomal protein of the

small (e.g. Rps19) or large (e.g. Rpl11) ribosomal subunit are found in over

half of these patients. The mutations cause ribosomal haploinsufficiency,

which reduces overall translation efficiency of cellular mRNAs. We reduced

expression of *Rps19* or *Rpl11* in mouse erythroblasts and investigated

mRNA polyribosome association, which revealed deregulated translation

initiation of specific transcripts. Among these were *Bag1*, encoding a

Hsp70 co-chaperone, and *Csde1*, encoding an RNA binding protein, both

expressed at increased levels in erythroblasts. Their translation initiation

is cap-independent and starts from an internal ribosomal entry site (IRES),

which appeared sensitive to knock down of Rps19 or Rpl11. Mouse embryos

lacking Bag1 die at embryonic day E13.5 with reduced erythroid colony

forming cells in the fetal liver, and low Bag1 expression impairs erythroid

differentiation in vitro. Reduced expression of Csde1 impairs proliferation

and differentiation of erythroid blasts. Protein but not mRNA expression of

*BAG1* and *CSDE1* was reduced in erythroblasts cultured from DBA patients.

Our data suggest that impaired IRES-mediated translation of mRNAs expressed

at increased levels in erythroblasts contributes to the erythroid phenotype

of DBA.

Overall design: 3 biological replicates of erythroblasts treated with different shRNA were used for polyribosomal sucrose gradients; RNA was extracted from gradients in 2 samples - mRNA associated with polyribosomes (poly) and the rest (sub).

Background corr dist: KL-Divergence = 0.1768, L1-Distance = 0.0435, L2-Distance = 0.0041, Normal std = 0.3482

1.146 Kernel fit Pairwise Correlations Normal fit

Density 0.573

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

wt_polysomalwt_subpolysomal sample_biologicalwt_polysomalwt_subpolysomal sample_biological sample_biologicalwt_polysomal replicatewt_subpolysomal sample_biological 1 sample_biological(0.0316392)replicateev_polysomal replicateev_subpolysomal 1 sample_biological(0.112726) 2 sample_bilogical(0.0283755)replicateev_polysomal replicateev_subpolysomal 2 sample_bilogical(0.0871691) 3 sample_bilogical(0.0352473)replicateev_polysomal replicateev_subpolysomal 3 sample_bilogical(0.0468309) 1 (0.0354025)replicate sample_bilogicalRps19_polysomal replicate Rps19_subpolysomal1 (0.0607712) sample_bilogical 2 (0.0227689)replicateRps19_polysomal replicate sample_bilogical Rps19_subpolysomal2 (0.0403198) 3 (0.0171279)replicate sample_bilogicalRps19_polysomal sample_bilogical replicate Rps19_subpolysomal3 (0.0571688) sample_bilogicalRpl11_polysomal 1 (0.0547609)replicate sample_bilogical replicateRpl11_subpolysomal 1 (0.0144982) sample_bilogicalRpl11_polysomal 2 (0.0167866) replicatesample_bilogical replicateRpl11_subpolysomal 2 (0.019393) sample_bilogicalRpl11_polysomal 3 (0.0200086) replicatesample_bilogical replicateRpl11_subpolysomal 3 (0.0138021) sample_bilogical 1 (0.0898991)replicate sample_bilogical replicate 1 (0.054582) sample_bilogical 2 (0.0500761)replicate replicate[ min 2 (0.0186851) 3 (0.0374488)replicate ] 3 (0.0345121)[ medium ] [ max ] CEM 1 Rps29 22060.3 43087.4 105616.3 P ( S | Z, I ) = 1.00 Rps28 25137.3 54037.2 112309.8 Mean Corr = 0.98786 Fau 17258.6 36473.4 84809.1 Rpl38 27193.3 51992.8 119704.8 Rpl26 26839.9 54348.6 137344.4 Rpl18a 20712.9 43671.7 98206.1 Rpl37a 18519.3 39347.2 80035.6 Rps5 19204.4 34928.2 87841.9 CEM 1 + Rplp2 26812.7 53838.2 118037.8 Top 10 Genes Uba52 20156.5 39317.3 86948.2 Rpl7a 24205.6 48199.3 108345.4 Rps4x 24784.7 49746.8 111026.6 Rps7 19840.5 43118.9 98921.6

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE36530" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36530 Status: Public on Mar 13 2013 Title: Expression data for program activation by IR-induced DNA breaks in G1 phase Murine PreB cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23496831 Summary & Design: Summary: The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.

Overall design: Murine v-abl-transformed pre-B cells were treated with 3 uM STI571 for 48 hours. The cell type is Wild type (3 biological replicates). For each wild type cell line, cells were treated with 1 Gy ionizing radiation or no ionizing radiation. Each sample was hybridized once using Affymetrix Mouse Genome 2.0 GeneChip arrays (Mouse 430 v2, Affymetrix, Santa Clara, CA). Data were analyzed using the unirradiated samples as the controls.

Background corr dist: KL-Divergence = 0.0424, L1-Distance = 0.0291, L2-Distance = 0.0011, Normal std = 0.6141

0.662 Kernel fit Pairwise Correlations Normal fit

Density 0.331

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT_STI_0Gy_Rep_1WT_STI_1Gy_Rep_1WT_STI_0Gy_Rep_2 (0.100868)WT_STI_1Gy_Rep_2 (0.279081)WT_STI_0Gy_Rep_3 (0.132924)WT_STI_1Gy_Rep_3 (0.127395) (0.251244) (0.108489)[ min ] [ medium ] [ max ] CEM 1 Rps29 26397.6 35722.1 40600.6 P ( S | Z, I ) = 1.00 Rps28 33991.3 42817.6 46676.3 Mean Corr = 0.98763 Fau 24354.9 29643.0 34509.3 Rpl38 34348.4 43804.5 49317.6 Rpl26 33815.5 43712.2 44853.2 Rpl18a 22877.0 31892.5 33761.1 Rpl37a 23805.4 29965.1 34664.7 Rps5 20767.1 25661.5 28896.5 CEM 1 + Rplp2 29814.7 38704.5 43550.9 Top 10 Genes Uba52 24519.9 31855.1 33804.4 Rpl7a 25525.5 31683.1 36890.7 Rps4x 25902.9 34578.3 38460.1 Rps7 28104.9 35580.8 40695.8

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE14308" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14308 Status: Public on Jan 08 2009 Title: Epigenetic Mechanisms Underlie T Cell Plasticity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19144320 Summary & Design: Summary: Multipotential naïve CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naïve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation.

Overall design: Different T helper subsets are profiled for mRNA expression.

Background corr dist: KL-Divergence = 0.0943, L1-Distance = 0.0377, L2-Distance = 0.0025, Normal std = 0.4622

0.876 Kernel fit Pairwise Correlations Normal fit

Density 0.438

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Th2-1 (0.0349725)Th2-2 (0.0354445)Th1-2 (0.052249)Th17-1 (0.0216683)Th1-1 (0.0426277)Th17-2 (0.0216345)Naive-1Naive-2 (0.266307)iTreg-1 (0.129309) iTreg-2(0.146521) nTreg-1(0.126293)nTreg-2 (0.0725811) (0.0503914) [ min ] [ medium ] [ max ] CEM 1 Rps29 32949.4 40511.5 93087.8 P ( S | Z, I ) = 1.00 Rps28 36307.5 42852.4 100277.2 Mean Corr = 0.98726 Fau 32234.1 37657.0 71706.3 Rpl38 42160.2 49490.5 97267.5 Rpl26 40559.2 49186.9 88505.1 Rpl18a 29994.7 36076.2 67661.9 Rpl37a 31545.6 33360.9 68766.7 Rps5 25631.8 33441.0 58814.6 CEM 1 + Rplp2 41629.9 49165.4 104146.7 Top 10 Genes Uba52 27634.3 34721.0 72718.4 Rpl7a 33759.5 41340.7 71471.8 Rps4x 34262.0 42491.7 77822.9 Rps7 32590.0 38493.3 78290.2

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE20727" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20727 Status: Public on Mar 10 2011 Title: Reactive oxygen species induced gene expression changes on dendritic cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22974541 Summary & Design: Summary: Identification of ROS induced genes on dendritic cells

Dendritic cells were incubated for 15 min with or without a ROS inhibitor (DPI), washed extensively and incubated for 30 min with a chemical allergen (DNFB), hydrogen peroxide, and vehicle alone in HBSS containing DPI or vehicle. After washed extensively, the samples were post-incubated for 5.5 h with DNFB, hydrogen peroxide, or vehicle in complete culture medium containing DPI or vehicle.

Overall design: Total RNA was extracted from cells treated with a chemical allergen, hydrogen peroxide, and vehicle alone in the presence or absence of a ROS inhibitor.

Background corr dist: KL-Divergence = 0.1500, L1-Distance = 0.0334, L2-Distance = 0.0023, Normal std = 0.3745

1.065 Kernel fit Pairwise Correlations Normal fit

Density 0.533

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

non-treatednon-treated rep1non-treated (0.0677885) rep2DNFB (0.0626464) rep3 rep1DNFB (0.0820891) (0.030008) rep2DNFB (0.0490481) rep3H2O2 (0.0469142) rep1H2O2 (0.0529681) rep2H2O2 (0.0274973) rep3DPI (0.0704782)rep1DPI (0.0792868) rep2DPI (0.036586) rep3DPI (0.0535349) + DNFBDPI + rep1 DNFBDPI (0.128326) + rep2 DNFB (0.0436358) rep3 (0.169193) [ min ] [ medium ] [ max ] CEM 1 Rps29 30988.8 41156.3 88371.2 P ( S | Z, I ) = 1.00 Rps28 39541.2 52271.6 108557.2 Mean Corr = 0.98693 Fau 26941.6 35404.1 73141.0 Rpl38 39237.4 53784.7 118095.7 Rpl26 34961.2 46079.7 99489.8 Rpl18a 28723.4 37367.2 80127.1 Rpl37a 26333.0 36337.2 68412.6 Rps5 28077.6 34387.5 67054.2 CEM 1 + Rplp2 36818.4 50212.6 92902.3 Top 10 Genes Uba52 32271.9 41982.2 90075.9 Rpl7a 30440.9 41041.2 71739.6 Rps4x 34816.4 48326.3 80619.8 Rps7 37683.1 45939.0 84006.8

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE23833" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23833 Status: Public on Sep 01 2010 Title: The Forkhead factor FoxQ1 influences epithelial differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20717954 Summary & Design: Summary: The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration and differentiation.In this study we identified the Forkhead factor FoxQ1 as increased in expression during TGF-beta1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity.The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts and an increased expression of several junction proteins (e.g. E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression.Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells.Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-beta1 induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, e.g. Ets-1, Zeb1 and Zeb2.In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation

Overall design:

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0772, L2-Distance = 0.0080, Normal std = 0.6930

0.668 Kernel fit Pairwise Correlations Normal fit

Density 0.334

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

2h_co._enriched12h_co._enriched22h_co._enriched3 (0.0593122)2h_co._total1 (0.0949823)2h_co._total2 (0.0915061) (0.0618767)2h_co._total3 (0.052812)2h_TGFbeta_enriched1 (0.135326)2h_TGFbeta_enriched22h_TGFbeta_enriched32h_TGFbeta_total1 (0.10138)2h_TGFbeta_total2 (0.0697737)2h_TGFbeta_total3 (0.103387) (0.0718904) (0.042963) (0.114791)[ min ] [ medium ] [ max ] CEM 1 Rps29 7341.0 19076.5 28524.7 P ( S | Z, I ) = 1.00 Rps28 12149.7 26282.1 34965.7 Mean Corr = 0.98656 Fau 2576.6 9953.7 17147.9 Rpl38 5561.2 16767.6 24002.2 Rpl26 6597.6 23628.2 34985.4 Rpl18a 6052.0 24429.1 35080.8 Rpl37a 912.6 4543.3 10855.3 Rps5 7399.0 21272.7 30296.7 CEM 1 + Rplp2 8319.7 22224.8 29673.3 Top 10 Genes Uba52 2011.3 9317.1 12552.4 Rpl7a 5187.7 25729.2 37453.6 Rps4x 14710.1 29622.3 38356.0 Rps7 10800.5 22563.7 26772.2

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE21944" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21944 Status: Public on Jul 02 2010 Title: The orphan nuclear hormone receptor ERRβ controls rod photoreceptor survival. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20534447 Summary & Design: Summary: Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERRβ as selectively expressed in rod photoreceptors. Overexpression of ERRβ induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRβ results in dysfunction and degeneration of rods, while inverse agonists of ERRβ trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRβ. ERRβ coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRβ activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRβ is a critical regulator of rod photoreceptor function and survival, and suggest that ERRβ agonists may be useful in the treatment of certain retinal dystrophies.

Overall design: Affymetrix MOE430 microarrays were used to analyze the expression patterns of P21 mouse retinal tissues. The results were compared across the variable of Genotype, specifically ERRβ knockout versus wildtype.

Background corr dist: KL-Divergence = 0.0113, L1-Distance = 0.0143, L2-Distance = 0.0002, Normal std = 0.8473

0.475 Kernel fit Pairwise Correlations Normal fit

Density 0.238

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

C57Bl/6C57Bl/6 P21, wildtypeC57Bl/6 P21, wildtype retina,C57Bl/6 x Sv129 1retina,C57Bl/6 x(0.119633) P21, Sv129 ERRβ2C57Bl/6 x(0.089574) P21, Sv129 -/-ERRβ P21, knockoutP21, wildtype -/-ERRβ knockout retina, -/- retina, knockout 1retina, (0.105454) 3[ (0.320083) min 2retina, (0.129002) 3 ](0.236254) [ medium ] [ max ] CEM 1 Rps29 8767.9 23849.8 24815.4 P ( S | Z, I ) = 1.00 Rps28 8805.8 23472.2 24348.7 Mean Corr = 0.98860 Fau 2788.1 10697.9 11731.0 Rpl38 6424.1 19396.8 20100.4 Rpl26 6822.5 26450.5 29712.1 Rpl18a 4320.8 11676.9 12410.2 Rpl37a 4221.0 17702.8 19795.9 Rps5 3313.9 10202.9 10839.3 CEM 1 + Rplp2 4056.4 14465.2 15840.4 Top 10 Genes Uba52 5361.2 12770.6 14925.8 Rpl7a 6103.0 14828.6 17034.5 Rps4x 6697.8 18030.1 19534.4 Rps7 8824.6 17453.7 18806.6

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE2019" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2019 Status: Public on Dec 21 2004 Title: Microarray Based Comparison of three Amplification Methods For Nanogram Amounts of Total RNA Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 15613496 Summary & Design: Summary: Two T7 based methods One round of Amplification (Affymetrix) and Two round of Amplification were compared to two Ribo-SPIA based systems, RiboSPIA and pico Ribo SPIA systems. Data for Pico-RiboSPIA are listed here.

All Hybridisation were performed using Affymetrix Mouse 430-2 gene chips. Data were all scaled to 500.

For 12 chips performed with pico Ribo SPIA the scaling factor average was 2.0 +/- 0.3, background intensities 74.4 +/- 12.7 , noise 3.9 +/- 0.6, rawQ 2.5 +/- 0.3

Keywords: ordered

Overall design:

Background corr dist: KL-Divergence = 0.0933, L1-Distance = 0.0666, L2-Distance = 0.0072, Normal std = 0.5386

0.832 Kernel fit Pairwise Correlations Normal fit

Density 0.416

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

mouse Kidneymouse KidneymousepRS 10 KidneymousepRSng -1 10 (0.141881) referencemousepRSng -2 10 (0.153236) referencemouseng pRS -3 (0.175789) 10referencemouse pRSng -1 10referencemouse (0.0302386) pRSng -2 10referencemouse (0.0207558) pRSng -3 3referencemouse (0.0265822) ng pRS -1 (0.020742)3referencemouse ng pRS -2 (0.0198658)3referencemouse ng pRS -3 (0.0602335)0.3reference pRS ng -1 0.3 (0.125555) pRS ng -2 0.3 (0.0846229) ng -3[ (0.140499) min ] [ medium ] [ max ] CEM 1 Rps29 10567.5 15419.8 21362.4 P ( S | Z, I ) = 1.00 Rps28 12246.3 16793.0 21375.0 Mean Corr = 0.98564 Fau 9548.4 14526.4 20236.7 Rpl38 14046.9 18166.1 25487.4 Rpl26 10263.6 15107.9 20039.1 Rpl18a 7829.3 13131.5 19677.6 Rpl37a 8844.6 14243.9 19635.6 Rps5 10410.1 14950.1 20388.1 CEM 1 + Rplp2 10953.8 15705.1 23104.5 Top 10 Genes Uba52 11650.9 15354.7 20761.8 Rpl7a 12026.5 17009.3 23170.0 Rps4x 10502.5 15555.9 19150.4 Rps7 9534.5 15899.5 22241.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE19286" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19286 Status: Public on Dec 03 2009 Title: Microarray gene expression profiling of aorta genes of APOE-deficient mice receiving the ACE inhibitor captopril Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20504763 Summary & Design: Summary: Microarray gene expression profiling of aorta genes of APOE-deficient mice receiving atherosclerosis treatment with the ACE inhibitor captopril.

Hypercholesterolemic APOE-deficient mice were used as a standard model of atherosclerosis to study gene expression changes during atherosclerosis treatment with the ACE inhibitor captopril. Microarray analysis was performed of whole aortas isolated from captopril-treated APOE-deficient mice relative to untreated APOE-deficient mice with overt atherosclerosis, and nontransgenic control mice. Microarray gene expression profiling revealed that captopril-mediated atherosclerosis prevention involved inhibition of aorta-infiltrating immune cells such as pro-atherogenic T lymphocytes and macrophages.

Overall design: Microarray gene expression profiling was performed of whole aortas isolated from APOE-deficient mice with atherosclerosis relative to captopril-treated APOE-deficient mice, and nontransgenic control mice. Three study groups were analyzed, i.e. 8-months-old untreated APOE-deficient mice with overt atherosclerosis, age-matched APOE-deficient mice treated for 7 months with the angiotensin-converting enzyme (ACE) inhibitor, captopril (20 mg/kg in drinking water), and nontransgenic control C57BL/6J mice. Two biological replicates were made of each group, and total RNA of three aortas was pooled for one gene chip.

Background corr dist: KL-Divergence = 0.0254, L1-Distance = 0.0174, L2-Distance = 0.0003, Normal std = 0.7080

0.572 Kernel fit Pairwise Correlations Normal fit

Density 0.286

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Aorta_APOE-deficientAorta_APOE-deficientAorta_APOE-deficient Aorta_APOE-deficientwith atherosclerosis_1 Aorta_non-transgenicwith atherosclerosis_2 Aorta_non-transgenicand captopril and (0.121552) captopril treated_1 C57BL/6J (0.154238) treated_2 C57BL/6J (0.226044) control_1[ (0.286709) control_2min (0.0785656) ] (0.132891) [ medium ] [ max ] CEM 1 Rps29 25414.7 31865.5 48649.3 P ( S | Z, I ) = 1.00 Rps28 26700.1 34765.1 52609.5 Mean Corr = 0.98430 Fau 17519.0 19183.2 26315.7 Rpl38 28292.9 33382.6 48076.4 Rpl26 29525.1 35104.0 52948.6 Rpl18a 18726.3 21186.4 34153.9 Rpl37a 19492.4 24881.2 35263.7 Rps5 15856.3 17616.7 26418.5 CEM 1 + Rplp2 31127.4 33490.4 53862.5 Top 10 Genes Uba52 19848.1 24811.7 35195.4 Rpl7a 20906.2 22805.1 31687.6 Rps4x 23062.3 25887.0 40117.3 Rps7 21264.0 22974.7 34507.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE39621" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39621 Status: Public on Dec 27 2012 Title: Expression data from brain, liver and spleen of Npc1-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23094108 Summary & Design: Summary: Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional neurological, lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1-/- mice (Npc1nih)relative to Npc1+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates for the neurological disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gauchers disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1-/- as well as Balb/c Npc1nmf164 mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry.

We used microarrays on the diseased organs, brain, liver and spleen of the Npc1-/- mice to unserstand the molecular changes occur during the progression of NPC diseases. From the data, we have identified 12 potential genes which can be potentially developed as blood-based biomarker. We have also discovered up regulation of innate iimunity genes in all three organs of Npc1-/- mice and functionally validated them in liver and spleen.

Overall design: Brain from 11 female Npc1/ and 16 control female mice (Npc1+/+ and Npc1+/) from 6 age groups (20-25, 37-40, 54-55, 59-62, 67-71 and 81-84 days) were surgically harvested. Liver and spleen from 6 Npc1-/- and 6 Npc1+/- female mice from three age group ( 20-25, 54-55 and 67-71 days) were surgically harvested. Organs were kept in RNA later and stored at -20 ´C until used. RNA was isolated and Affymetrix mouse 430 2.0 array hybridizations were performed by UCLA Clinical Microarray Core, UCLA, Los Angeles, CA, USA. Subsequent raw data were analyzed using DNA-Chip Analyzer (D-Chip) with the .CEL files obtained from AGCC. Data from Npc1-/- mice from all age groups were compared to control mice (Npc1+/- and/or Npc1-/- mice) from all age groups separately for brain, liver and spleen. 'Matrix Table1' corrsponds for brain, 'Matrix Table2' corresponds for liver and 'Matrix Table3' corresponds for spleen. Thresholds for selecting significant genes were set at a relative difference ³1.5-fold, absolute difference ³100 signal intensity units and p<0.05. Genes that met all three criteria simultaneously were considered as significant change.

Background corr dist: KL-Divergence = 0.0594, L1-Distance = 0.0598, L2-Distance = 0.0057, Normal std = 0.5712

0.698 Kernel fit Pairwise Correlations Normal fit

Density 0.349

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT BrainWT 20d Brain Mouse1HET 25d Brain Mouse1 HET(0.0126278) 20d Brain NPCMouse1(0.00979124) 25d Brain NPCMouse1 (0.0115782) 20d Brain HETMouse1 (0.00728756) 25d Brain HETMouse1 (0.00755476) 37d Brain NPCMouse1 (0.0109087) 40d Brain NPCMouse1 (0.00961141) 37d Brain HETMouse1 (0.0101827) 40d Brain HETMOuse1 (0.0120726) 54d Brain NPCMouse1 (0.00928923) 55d Brain NPCMouse1 (0.0109577) 54d Brain WTMOuse1 (0.00744) 55dBrain WTMouse1 (0.0110751) 60d Brain Mouse1HET (0.00812256) 60d Brain Mouse2 HET(0.0100278) 59d Brain NPCMouse1(0.0089843) 62d Brain NPCMouse1 (0.0117946) 59d Brain WTMouse1 (0.00558189) 62dBrain HETMouse1 (0.0185391) 67d Brain Mouse1NPC (0.00840014) 67d Brain HETMouse1(0.00823391) 67d Brain HETMouse1 (0.0102595) 81d Brain NPCMouse1 (0.0151654) 82d Brain NPCMouse1 (0.00864732) 82d Brain HETMouse1 (0.0088278) 84d Liver HETMouse1 (0.0103287) 20d Liver Mouse1NPC (0.0127964) 25d Liver Mouse1NPC (0.00882551) 20d Liver Mouse1HET (0.0126776) 25d Liver Mouse1HET (0.00802469) 54 Liver Mouse1NPC (0.00730791) 55d Liver (0.00604598)Mouse1NPC 54d Liver Mouse1HET (0.0102099) 55d Liver Mouse1HET (0.00562197) 67d Liver Mouse1NPC (0.00906381) 67d Liver Mouse2NPC (0.0100751) 67 Liver Mouse1HET (0.00936882) 71d Spleen (0.00607269)Mouse1HET Spleen20dNPC (0.00822238) Mouse1 25dSpleenNPC Mouse1 (0.0819045) Spleen20dHET Mouse1 (0.0567667) Spleen25dHET Mouse1 (0.059913) Spleen54dNPC Mouse1 (0.0524768) 55dSpleenNPC Mouse1 (0.0606114) Spleen54dHET Mouse1 (0.0619578) Spleen55dHET Mouse1 (0.0271943) Spleen67dNPC Mouse1 (0.040503) 67dSpleenNPC Mouse2 (0.0238055) Spleen67 Mouse1 (0.0374417) 71d (0.064926)Mouse1 (0.0548966)[ min ] [ medium ] [ max ] CEM 1 Rps29 15196.5 18025.2 50185.9 P ( S | Z, I ) = 1.00 Rps28 12599.6 16439.9 48007.9 Mean Corr = 0.98419 Fau 8547.8 10853.5 35763.1 Rpl38 15120.6 18886.1 47284.0 Rpl26 9341.7 11662.7 35968.1 Rpl18a 6962.1 10054.9 32773.5 Rpl37a 7414.5 10391.7 32212.6 Rps5 7106.1 9248.2 33079.0 CEM 1 + Rplp2 8971.0 11624.8 41527.8 Top 10 Genes Uba52 10709.3 13489.3 35081.6 Rpl7a 7950.3 9910.4 34729.6 Rps4x 7581.4 10106.0 36626.7 Rps7 9169.4 12111.8 35166.8

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE39897" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39897 Status: Public on Sep 11 2013 Title: Expression data for mouse embryogenesis from oocyte to newborn Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23961710 Summary & Design: Summary: Studies in mouse have led to enormous progress in our understanding of early human development. The identification of genes and the signaling pathways involved in mouse embryogenesis have helped us to better understand fertilization, morulation, gastrulation, organogenesis and embryonic development in mammals.

We report a detailed analysis of the global gene expression profiles from oocyte to the end of organogenesis in mouse. Our studies revealed distinct temporal regulation patterns for genes belonging to different functional categories, supporting their roles during organogenesis.

Overall design: Mouse embryos were selected at successive stage for for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of embryos at each developmental stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected embryos according to morphological criteria at 12 time-points from embryos to newborn

Background corr dist: KL-Divergence = 0.0939, L1-Distance = 0.0418, L2-Distance = 0.0040, Normal std = 0.4636

0.878 Kernel fit Pairwise Correlations Normal fit

Density 0.439

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

embryoembryo at Egg,embryo atbiological Egg,embryo atbiological Egg, rep1embryo at biological(0.0498027) TS01, rep2embryo at (0.0325661)biological TS01, rep3embryo at (0.0396105)biological TS01, rep1embryo at biological(0.0662346) TS09, rep2embryo at biological(0.0557298) TS09, rep3embryo at biological(0.0443955) TS09, rep1embryo at biological(0.030772) TS11, rep2embryo at biological(0.0303062) TS11, rep3embryo at biological(0.0304593) TS11, rep1embryo at biological(0.0326231) TS13, rep2embryo at biological(0.0470471) TS13, rep3embryo at biological(0.0400988) TS13, rep1embryo at biological(0.035396) TS16, rep2embryo at biological(0.0264413) TS16, rep3embryo at biological(0.0151035) TS16, rep1embryo at biological(0.0323746) TS19, rep2embryo at biological(0.0404865) TS19, rep3embryo at biological(0.0462863) TS19, rep1embryo at biological(0.0139685) TS21, rep2embryo at biological(0.0136) TS21, rep3embryo at biological(0.00929006) TS21, rep1embryo at biological(0.0248516) TS22, rep2embryo at biological(0.0177426) TS22, rep3embryo at biological(0.0050337) TS22, rep1embryo at biological(0.01599) TS23, rep2embryo at biological(0.0138065) TS23, rep3embryo at biological(0.0123453) TS23, rep1embryo at biological(0.0130076) TS25, rep2embryo at biological(0.0168988) TS25, rep3embryo at biological(0.0117846) TS25, rep1embryo at biological(0.0208999) TS27, rep2embryo at biological(0.0203672) TS27, rep3 at biological(0.0200214) TS27, rep1 biological(0.0177203) rep2 (0.0310681) rep3[ (0.0258698)min ] [ medium ] [ max ] CEM 1 Rps29 17504.9 23323.9 35763.7 P ( S | Z, I ) = 1.00 Rps28 19132.3 26089.3 40654.7 Mean Corr = 0.98283 Fau 10969.6 15548.7 30086.1 Rpl38 20578.7 28451.9 44147.8 Rpl26 18743.1 26431.0 44298.3 Rpl18a 12333.8 18322.5 30407.5 Rpl37a 14875.9 18558.5 27977.1 Rps5 14753.7 19562.6 27639.2 CEM 1 + Rplp2 17677.1 25822.0 41473.9 Top 10 Genes Uba52 15656.7 19318.8 28842.3 Rpl7a 18598.9 25756.0 34819.8 Rps4x 19447.9 24793.8 37393.6 Rps7 18107.8 23528.3 32221.4

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE2527" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2527 Status: Public on May 06 2005 Title: Gata-1 Knock Down - Wild Type Megakaryocyte Gene Expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 15860665 Summary & Design: Summary: Hematopoietic progenitor cells were isolated from 13.5 day mouse fetal livers by lineage depletion and expanded for three days. Fetal livers were isolated from both wild type and Gata-1 knock embryos. Gata-1 knock embryos contain a deletion of the Gata-1 promoter sequence that results in undetectable levels of Gata-1 protein specifically in the megakaryocyte lineage. Following progenitor outgrowth megakaryocytes were enriched in a differentiation media for three days and isolated on a discontinuous BSA gradient. The resulting megakaryocytes were >90% pure as determined by acetylcholinesterase staining. These cells were lysed in Trizol and the resulting RNA was used for hybridization.

Keywords = Gata-1

Keywords = Megakaryocytes

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0240, L1-Distance = 0.0329, L2-Distance = 0.0011, Normal std = 0.7666

0.546 Kernel fit Pairwise Correlations Normal fit

Density 0.273

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Gata-1 KnockGata-1 DownKnockGata-1 A Down KnockGata-1(0.146383) B Down WildGata-1(0.25283) Type C WildGata-1(0.155758) A Type(0.143063) Wild B Type(0.151629) C (0.150335)[ min ] [ medium ] [ max ] CEM 1 Rps29 18418.6 19818.4 28093.3 P ( S | Z, I ) = 1.00 Rps28 17418.0 18401.5 22228.7 Mean Corr = 0.98434 Fau 12229.1 14372.4 19712.5 Rpl38 18319.4 20613.6 24995.7 Rpl26 19626.7 22757.9 26975.3 Rpl18a 14637.3 18131.7 24609.6 Rpl37a 14989.0 17027.1 23611.3 Rps5 13541.3 15629.0 23010.5 CEM 1 + Rplp2 18522.7 20808.9 24242.8 Top 10 Genes Uba52 16123.1 18123.2 22746.4 Rpl7a 16562.0 19237.6 23800.6 Rps4x 16107.3 17360.5 22057.9 Rps7 17557.0 20240.1 23711.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE4288" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4288 Status: Public on Feb 05 2008 Title: Polysomal, free mRNP, and total cellular mRNA of J774.1 before and after LPS stimulation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18230670 Summary & Design: Summary: Bacterial lipopolysaccharide(LPS) dramatically activates macrophages. So far, dozen of papers indicated that many proinflammatory molecules are transcriptionaly regulated during response. Despite of this,translational regulation is not fully elucidated especially in a comprehensive fashion. In this series, we investigated expression profiles of translation active (polysome) inactive (free mRNP) mRNAs of a typical mouse macrophage cell line, J774.1. Moreover, we also measured total cellular RNA level as a reference.

Keywords: time-course

Overall design: Triplicates for each time points are included.

Background corr dist: KL-Divergence = 0.1306, L1-Distance = 0.0311, L2-Distance = 0.0019, Normal std = 0.3960

1.007 Kernel fit Pairwise Correlations Normal fit

Density 0.504

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

PolysomePolysome of J774-intact-rep1Polysome of J774-intact-rep2Polysome of J774-intact-rep3 Polysome(0.0245048) of J774-LPS Polysome(0.0180752) of J774-LPS Polysome(0.0165392) 1hr-rep1 of J774-LPSPolysome 1hr-rep2 (0.0186267) of J774-LPSPolysome 1hr-rep3 (0.0202025) of J774-LPSPolysome 2hr-rep1 (0.0148841) of J774-LPSPolysome 2hr-rep2 (0.014389) of J774-LPSPolysome 2hr-rep3 (0.0122107) of J774-LPSFree 4hr-rep1 (0.0138814) of mRNP J774-LPSFree 4hr-rep2 (0.017483) ofmRNP J774-intact-rep1Free 4hr-rep3 (0.0129422) ofmRNP J774-intact-rep2Free (0.0163789) ofmRNP J774-intact-rep3Free (0.0203795) ofmRNP J774-LPSFree (0.105976) ofmRNP J774-LPSFree (0.0573296) 1hr-rep1 ofmRNP J774-LPSFree 1hr-rep2 (0.019772) ofmRNP J774-LPSFree 1hr-rep3 (0.0154086) ofmRNP J774-LPSFree 2hr-rep1 (0.0362565) ofmRNP J774-LPSFree 2hr-rep2 (0.0250728) ofmRNP J774-LPSFree 2hr-rep3 (0.0722285) ofmRNP J774-LPSTotal 4hr-rep1 (0.103454) of cellular J774-LPSTotal 4hr-rep2 (0.0107572) cellularmRNATotal 4hr-rep3 (0.0357303) cellularofmRNATotal J774-intact-rep1 (0.0754942) cellularofmRNATotal J774-intact-rep2 cellularofmRNATotal J774-intact-rep3 (0.0145275) cellularofmRNATotal J774-LPS (0.00931047) cellularofmRNATotal J774-LPS (0.0205493) 1hr-rep1 cellularofmRNATotal J774-LPS 1hr-rep2 (0.011472) cellularofmRNATotal J774-LPS 1hr-rep3 (0.00983433) cellularofmRNATotal J774-LPS 2hr-rep1 (0.0212788) cellularofmRNATotal J774-LPS 2hr-rep2 (0.018191) cellularofmRNA J774-LPS 2hr-rep3 (0.0157329) ofmRNA J774-LPS 4hr-rep1 (0.0230598) of J774-LPS 4hr-rep2 (0.0215044)[ min4hr-rep3 (0.0179829) ](0.0385797) [ medium ] [ max ] CEM 1 Rps29 11799.0 27659.0 203282.3 P ( S | Z, I ) = 1.00 Rps28 15819.5 31056.6 122591.2 Mean Corr = 0.98266 Fau 17799.0 28386.8 161943.5 Rpl38 28142.4 41139.8 175189.0 Rpl26 26921.4 38345.6 190640.3 Rpl18a 21330.0 34753.7 187624.8 Rpl37a 20288.4 28799.5 174121.2 Rps5 18929.1 30591.1 160395.5 CEM 1 + Rplp2 27871.6 39223.6 177347.5 Top 10 Genes Uba52 18597.5 29875.8 161718.7 Rpl7a 24788.7 39739.4 161199.7 Rps4x 26341.9 34328.6 133275.1 Rps7 22225.9 31891.6 162762.5

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE47065" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47065 Status: Public on May 18 2013 Title: Gene expression profiling of IR-/-, IGF-1R-/- (dKO) newborn epidermis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23906066 Summary & Design: Summary: Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis.

Overall design: RNA was isolated from newborn mouse epidermis.Gene expression profiling was on on Affymetrix 430-2.0 platform.

Background corr dist: KL-Divergence = 0.0742, L1-Distance = 0.0224, L2-Distance = 0.0008, Normal std = 0.4920

0.811 Kernel fit Pairwise Correlations Normal fit

Density 0.405

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

NewbornNewborn epidermisNewborn epidermis of NewborndKO epidermis ofbiological NewborndKO epidermis ofbiological Newborn dKOreplicate epidermis ofbiological Newborn dKOreplicate epidermis1 (0.156226) ofbiological Newborn ctrlreplicate epidermis2 biological(0.0701297) of ctrlreplicate epidermis3 biological(0.13589) of replicate ctrl 4 biological(0.0753347) of replicate ctrl 1 (0.0399244) biological replicate[ 2 min(0.0629788) replicate 3 (0.324085) ] 4 (0.135431)[ medium ] [ max ] CEM 1 Rps29 27719.7 31347.2 44982.6 P ( S | Z, I ) = 1.00 Rps28 31793.5 35214.2 55393.1 Mean Corr = 0.98237 Fau 21671.0 23210.9 33342.7 Rpl38 32367.6 35905.5 49744.0 Rpl26 34839.8 36727.4 54734.3 Rpl18a 23608.7 26524.1 38066.1 Rpl37a 24971.0 28180.2 39483.2 Rps5 24550.0 26756.2 38091.6 CEM 1 + Rplp2 31345.5 35436.6 47370.4 Top 10 Genes Uba52 25070.1 28224.2 37369.3 Rpl7a 31203.9 34015.0 46222.0 Rps4x 31572.1 37487.4 54995.6 Rps7 27038.4 30470.8 42414.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE21143" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21143 Status: Public on Jun 14 2010 Title: PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and glioma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20478531 Summary & Design: Summary: A hallmark feature of glioblastoma (GBM) cells is its strong self-renewal potential and immature differentiation state -- stem cell-like properties which may contribute to the plasticity and intense therapeutic resistance of GBM. The molecular basis of the immature differentiation profile remains an area of active investigation. Here, integrated genomic and biological analyses identified PLAGL2 as a potent proto-oncogene targeted for amplification/gain in malignant gliomas as well as in colorectal cancers. High level of PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell (GIC) differentiation while promoting their proliferation and self-renewal capacity under differentiation induction conditions. On the mechanistic level, the PLAGL2 transcriptome analysis revealed that these differentiation suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling via up-regulation of Wnt6 ligand as well as Fzd9 and Fzd2 receptor expression. Correspondingly, inhibition of Wnt signaling in PLAGL2-expressing NSC partially restores their differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics on malignant cells.

Overall design: p53-null mouse NSCs are infected with retrovirus expressing either control vector or PlagL2. Total RNA were collected upon differentiation in 1% FBS for 24 hr. 3 replicates each.

Background corr dist: KL-Divergence = 0.0436, L1-Distance = 0.0242, L2-Distance = 0.0007, Normal std = 0.6035

0.674 Kernel fit Pairwise Correlations Normal fit

Density 0.337

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

NSC_FBS_V1NSC_FBS_L1 (0.13054)NSC_FBS_V2 (0.140299)NSC_FBS_L2 (0.206517)NSC_FBS_V3 (0.0726681)NSC_FBS_L3 (0.190982) (0.258994) [ min ] [ medium ] [ max ] CEM 1 Rps29 30241.9 47539.3 52494.3 P ( S | Z, I ) = 1.00 Rps28 28408.9 48579.8 50830.3 Mean Corr = 0.98229 Fau 12375.1 18194.1 21362.5 Rpl38 29044.8 38132.7 39803.1 Rpl26 23156.5 31559.4 33852.1 Rpl18a 16460.9 25303.1 33087.7 Rpl37a 16794.9 22721.2 24797.2 Rps5 14058.8 25965.5 33277.9 CEM 1 + Rplp2 18277.7 25877.1 29812.0 Top 10 Genes Uba52 20593.8 27814.8 29496.4 Rpl7a 26322.4 35246.1 42905.0 Rps4x 19056.4 26778.3 30104.0 Rps7 24984.0 37903.0 44503.5

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE24465" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24465 Status: Public on Sep 29 2011 Title: Mesenchymal Nuclear factor I B regulates cell proliferation and epithelial differentiation during lung maturation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We generated Nfibf/f mice and then cross with Dermo1-Cre mice to obtain Nfibf/f, Dermo1-Cre mice. In these Nfibf/f, Dermo1-Cre mice, there are defects in sacculation and epithelial cell differentiation. We performed micoarray analysis to find the genes which are possibley regulated by NFI-B and related to lung maturation during lung development.

Overall design: We used microarrays to performing transcriptional profiling of Nfibf/f, Dermo1-Cre and Nfibf/f lungs at E18.5

Background corr dist: KL-Divergence = 0.0391, L1-Distance = 0.0205, L2-Distance = 0.0004, Normal std = 0.6225

0.656 Kernel fit Pairwise Correlations Normal fit

Density 0.328

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

lung of lungNfibf/f of animal, lungNfibf/f of animal, biologicallungNfibf/f of animal, biologicallungNfibf/f, rep1 of biologicalDermo1-CrelungNfibf/f,(0.101971) rep2 of Dermo1-CreNfibf/f,(0.0760758) rep3 animal, Dermo1-Cre(0.260346) animal,biological animal,biological[ rep1 min biological(0.0765022) rep2 ] (0.21793) rep3 (0.267174)[ medium ] [ max ] CEM 1 Rps29 17217.4 22217.7 35424.0 P ( S | Z, I ) = 1.00 Rps28 20779.2 26358.0 37559.4 Mean Corr = 0.98083 Fau 16502.0 20097.3 31871.5 Rpl38 23490.0 29953.2 47453.3 Rpl26 21927.6 29139.8 46602.8 Rpl18a 16845.7 20747.9 32254.6 Rpl37a 14686.6 20346.7 30775.1 Rps5 16031.5 20162.9 30474.8 CEM 1 + Rplp2 15268.4 19136.7 22726.2 Top 10 Genes Uba52 16324.7 20507.8 29844.4 Rpl7a 18660.5 23547.6 35232.1 Rps4x 20342.2 26922.5 38423.7 Rps7 17547.6 22763.2 32218.8

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE35844" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35844 Status: Public on Jun 18 2012 Title: Dicer1 deletion in myeloid-committed progenitors causes neutrophil dysplasia and blocks macrophage/dendritic cell development in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22353998 Summary & Design: Summary: MiRNAs have the potential to regulate cellular differentiation programs. However, miRNA-deficiency in primary hematopoietic stem cells (HSCs) results in HSC depletion in mice, leaving the question of whether miRNAs play a role in early-lineage decisions unanswered. To address this issue, we deleted Dicer1, which encodes an essential RNaseIII enzyme for miRNA biogenesis, in murine CCAAT/enhancer-binding protein alpha (C/EBPA)-positive myeloid-committed progenitors in vivo. In contrast to the results in HSCs, we found that miRNA depletion affected neither the number of myeloid progenitors nor the percentage of C/EBPA-positive progenitor cells. Analysis of gene-expression profiles from wild type and Dicer1-deficient granulocyte-macrophage progenitors (GMPs) revealed that 20 miRNA families were active in GMPs. Of the derepressed miRNA targets in Dicer1-null GMPs, 27% are normally exclusively expressed in HSCs or are specific for multi-potent progenitors and erythropoiesis, indicating an altered gene-expression landscape. Dicer1-deficient GMPs were defective in myeloid development in vitro and exhibited an increased replating capacity, indicating a regained self-renewal potential of these cells. In mice, Dicer1 deletion blocked monocytic differentiation, depleted macrophages and caused myeloid dysplasia with morphological features of Pelger-Huët anomaly. These results provide evidence for a miRNA-controlled switch for a cellular program of self-renewal and expansion towards myeloid differentiation in GMPs.

Overall design: To generate Cebpa-Cre;R26-LSL-Eyfp;Dicer1wt/fl/Dicer1fl/fl mice, we crossed mice that contain floxed Dicer1 alleles (Dicer1fl) with Cebpa-Cre;R26-LSL-Eyfp reporter mice 2. Fetal livers were obtained on embryonic day (E) 13.5. Routine genotyping of Dicer1; Cebpa-Cre;R26-LSL-Eyfp mice was performed by PCR assays of DNA from tail or toe biopsies. For transplantation, 6 to 8-week-old recipient mice (C57Bl/6, Jackson Laboratories) were irradiated (8.5 Gy) and tail-vein injected with fetal liver single-cell suspensions. Typically, cells from each fetal liver were transplanted into two recipient mice. Hematopoietic tissues were analyzed 6-10 weeks post transplantation. EYFP positive GMPs from the bone marrow of Dicer wt control (n=3), Dicer -/wt (n=3 and Dicer fl/fl (n=3) were sorted and analyzed for gene expression profiles.

Background corr dist: KL-Divergence = 0.1010, L1-Distance = 0.0231, L2-Distance = 0.0009, Normal std = 0.4374

0.912 Kernel fit Pairwise Correlations Normal fit

Density 0.456

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

YFP-posYFP-pos GMP DicerYFP-pos GMP null DicerYFP-pos GMP rep1 null Dicer(0.085672)YFP-pos GMP rep2 null Dicer(0.0525263)YFP-pos GMP rep3 het Dicer(0.319032)YFP-pos GMPrep1 het (0.221453)DicerYFP-pos GMPrep2 het (0.051998)DicerYFP-pos GMPrep3 wt (0.0765922)Dicer rep1 GMP wt(0.0914511) Dicer rep2 wt(0.0554074) rep3 (0.0458689)[ min ] [ medium ] [ max ] CEM 1 Rps29 14205.1 20371.7 25893.2 P ( S | Z, I ) = 1.00 Rps28 27951.2 37118.6 44967.2 Mean Corr = 0.98055 Fau 6959.1 9408.8 11962.4 Rpl38 30304.4 40635.3 47420.2 Rpl26 33771.3 40821.0 47733.3 Rpl18a 25007.3 29678.4 35122.9 Rpl37a 7030.4 10350.7 13396.1 Rps5 23390.5 26379.1 31517.9 CEM 1 + Rplp2 17393.7 21600.9 25752.3 Top 10 Genes Uba52 13905.7 19029.1 22085.6 Rpl7a 26933.9 31547.9 36165.6 Rps4x 37194.0 44897.4 54547.8 Rps7 24179.8 30011.7 34307.0

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE10071" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10071 Status: Public on Jan 04 2008 Title: NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17589499 Summary & Design: Summary: Nuclear receptor-binding SET domain protein 1 (NSD1) prototype is a family of mammalian histone methyltransferases (NSD1, NSD2/MMSET/WHSC1, NSD3/WHSC1L1) that are essential in development and are mutated in human acute myeloid leukemia (AML), overgrowth syndromes, multiple myeloma and lung cancers. In AML, the recurring t(5;11)(q35;p15.5) translocation fuses NSD1 to nucleoporin-98 (NUP98). Here, we present the first characterization of the transforming properties and molecular mechanisms of NUP98-NSD1. We demonstrate that NUP98-NSD1 induces AML in vivo, sustains self-renewal of myeloid stem cells in vitro, and enforces expression of the HoxA7, HoxA9, HoxA10 and Meis1 proto-oncogenes. Mechanistically, NUP98-NSD1 binds genomic elements adjacent to HoxA7 and HoxA9, maintains histone H3 Lys 36 (H3K36) methylation and histone acetylation, and prevents EZH2-mediated transcriptional repression of the Hox-A locus during differentiation. Deletion of the NUP98 FG-repeat domain, or mutations in NSD1 that inactivate the H3K36 methyltransferase activity or that prevent binding of NUP98-NSD1 to the Hox-A locus precluded both Hox-A gene activation and myeloid progenitor immortalization. We propose that NUP98-NSD1 prevents EZH2-mediated repression of Hox-A locus genes by colocalizing H3K36 methylation and histone acetylation at regulatory DNA elements. This report is the first to link deregulated H3K36 methylation to tumorigenesis and to link NSD1 to transcriptional regulation of the Hox-A locus.

Keywords: expression analysis

Overall design:

Background corr dist: KL-Divergence = 0.0759, L1-Distance = 0.0227, L2-Distance = 0.0009, Normal std = 0.4842

0.824 Kernel fit Pairwise Correlations Normal fit

Density 0.412

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Myeloid_HoxA9Myeloid_HoxA9Myeloid_HoxA9 immortalized_inMyeloid_HoxA9+Meis1 immortalized_inMyeloid_HoxA9+Meis1 immortalized_in SCF_cloneMyeloid_HoxA9+Meis1 SCF_clone 1Myeloid_NUP98NSD1 immortalized_in(0.0915053) SCF_clone 2Myeloid_NUP98NSD1 immortalized_in(0.0719302) 3Myeloid_NUP98NSD1 immortalized_in(0.0920618) SCF_clone immortalized_inMyeloid_MLL-ENL SCF_clone 1immortalized_in (0.0561696) SCF_clone 2immortalized_in (0.0464359)SCF_clone immortalized_in 3 (0.0594016)SCF_clone 1 (0.118435)[ SCF_clone min 2SCF (0.151666) (0.135134) ] 3 (0.17726) [ medium ] [ max ] CEM 1 Rps29 23795.8 29249.8 46375.9 P ( S | Z, I ) = 1.00 Rps28 22069.2 25714.9 38943.3 Mean Corr = 0.98012 Fau 17474.9 21620.4 31997.0 Rpl38 24686.6 28840.9 43610.8 Rpl26 22160.7 29181.4 46794.5 Rpl18a 21588.1 26815.9 38276.5 Rpl37a 21382.1 25344.5 36538.7 Rps5 19822.8 24247.5 36137.7 CEM 1 + Rplp2 25003.2 29530.7 49511.8 Top 10 Genes Uba52 21612.2 25593.8 34918.7 Rpl7a 22824.5 27909.7 42468.2 Rps4x 21197.0 25328.7 40789.8 Rps7 22133.0 26409.7 35074.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE39592" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39592 Status: Public on Jul 24 2012 Title: Expression data from cAMP-treated WT or IFN-gR1-deficient T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: cAMP inhibits TCR signaling, T cell proliferation, cytokine production and T cell function.

We used microarrays to detail the global programme of gene expression in TCR-activated WT or IFN-gR1-deficient CD4+ T cells by db-cAMP.

Overall design: CD4+ T cells were purified from spleens of WT or IFN-gR1-deficient mice by autoMACS, and activated with anti-CD3 plus anti-CD28 for 15 h. db-cAMP or vehicle control (med) was added into cultures for the last 3 h.

Background corr dist: KL-Divergence = 0.0621, L1-Distance = 0.0240, L2-Distance = 0.0007, Normal std = 0.5343

0.755 Kernel fit Pairwise Correlations Normal fit

Density 0.378

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT CD4WT T cells, CD4WT Tvehicle-treated, cells, CD4WT Tvehicle-treated, cells, CD4IFN-gR1-KO TcAMP-treated, biologicalcells,IFN-gR1-KO cAMP-treated, biological CD4rep1IFN-gR1-KO biological T (0.144552) cells, CD4rep2IFN-gR1-KO biological T vehicle-treated,(0.147471) cells,rep1 CD4 (0.145114) Tvehicle-treated, cells,rep2 CD4 (0.219613) TcAMP-treated, biologicalcells, cAMP-treated, biological rep1[ biologicalmin (0.0856694) rep2 biological (0.119311)] rep1 (0.0780046) rep2 [(0.060265) medium ] [ max ] CEM 1 Rps29 47257.1 70141.8 102490.4 P ( S | Z, I ) = 1.00 Rps28 53095.3 69854.2 100839.9 Mean Corr = 0.97963 Fau 39055.7 52107.9 64212.5 Rpl38 58672.9 82840.3 118304.0 Rpl26 56321.2 77850.3 117935.7 Rpl18a 38083.7 55906.2 77629.4 Rpl37a 40206.4 59197.4 88959.6 Rps5 38311.2 54470.6 74784.7 CEM 1 + Rplp2 57585.1 82756.2 129872.3 Top 10 Genes Uba52 41115.1 55670.2 85719.2 Rpl7a 52271.2 75721.8 108615.1 Rps4x 50238.0 64957.5 98241.4 Rps7 43513.3 59781.9 84553.4

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE6676" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6676 Status: Public on Jan 09 2007 Title: Comparison of corneas from wildtype mice to those from mice under the influence of high doses of TGF-beta russe-affy-mouse-372894 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Characteristic structural details of the cornea are transparency, the absence of blood vessels, and the presence of numerous sensory nerve endings. The corneal epithelium is one of the most densely innervated tissues of the body. The characteristics of the cornea are established during fetal development, and are lost in adult life when the cornea regenerates after injury. The common reaction of the cornea to injury is the formation of opaque scars, the ingrowth of blood vessels, and distinct changes in the innervation pattern. Scar formation of the cornea is critically modulated by the expression of transforming growth factor-beta (TGF-beta).

To identify genes that are important for corneal transparency, dense innervation and absence of blood vessels by comparing corneas from wildtype mice with those that are under the influence of high doses of TGF-beta.

Transparency, dense innervation, and absence of blood vessels in the cornea all depend on the expression of a critical set of genes that are not expressed when TGF-beta is present.

Mice were generated that overexpress TGF-beta under control of a strong lens-specific promoter. These mice developed opaque corneas that are vascularized and lack sensory nerves. In addition, these corneas were densely populated with cells expressing neural cell adhesion protein.

RNA was isolated from corneas of transgenic animals and wildtype littermates in order to analyze differentially expressed genes and to identify those that are only expressed in transparent, avascular, and densely innervated wildtype corneas.

Keywords: TGF-beta overexpression

Overall design:

Background corr dist: KL-Divergence = 0.0715, L1-Distance = 0.0250, L2-Distance = 0.0011, Normal std = 0.5009

0.797 Kernel fit Pairwise Correlations Normal fit

Density 0.398

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

eye, cornea:eye, cornea: TRizoleye, cornea: Extraction_le1TRizoleye, cornea: Extraction_le1TRizoleye, cornea: Extraction_le11TRizol (0.106045)eye, cornea: Extraction_le12TRizol (0.104045)eye, cornea: Extraction_le13TRizol (0.063309)eye, cornea: Extraction_le14TRizol (0.109016) Extraction_le15TRizol (0.19822) Extraction_le16 (0.0615871) 7 (0.0356242)[ min 8 (0.322154) ] [ medium ] [ max ] CEM 1 Rps29 20857.8 24703.0 41446.7 P ( S | Z, I ) = 1.00 Rps28 27526.0 31831.7 49829.9 Mean Corr = 0.97871 Fau 13352.2 16808.9 27307.8 Rpl38 24304.7 30852.6 53235.1 Rpl26 30330.2 37846.5 65704.4 Rpl18a 22942.4 28647.7 48742.9 Rpl37a 9558.0 11793.1 22387.0 Rps5 17475.1 21942.5 38664.7 CEM 1 + Rplp2 22493.8 27832.8 41639.8 Top 10 Genes Uba52 17519.7 20849.3 32801.9 Rpl7a 22709.6 27631.3 43342.0 Rps4x 25640.5 30011.0 45469.7 Rps7 23602.2 27257.3 43233.9

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE5497" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5497 Status: Public on Aug 12 2006 Title: Pyruvate induces mitochondrial biogenesis by a PGC-1alpha independent mechanism Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17182725 Summary & Design: Summary: The present study examines the impact of altering energy provision on mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically treated with supraphysiological levels of sodium pyruvate for 72 hr. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in PGC-1alpha and PGC-1alpha mRNA expression. To further assess whether PGC-1alpha expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1alpha prior to treatment with pyruvate. Despite a 70% reduction in PGC-1alpha mRNA the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1alpha null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1alpha, suggesting the existence of a novel energy-sensing pathway regulating oxidative capacity.

Keywords: basal state versus treatment at one time point

Overall design: C2C12 myoblasts were incubated with either basal media or basal media supplemented with 50 mM sodium pyruvate for 72 hr. Total RNA was extracted using TRIzol and GeneChip experiment was conducted using Gene Chip Mouse Genome 430 2.0 Expression Array. A Gene Chip analysis for each condition was performed in triplicate.

Background corr dist: KL-Divergence = 0.0354, L1-Distance = 0.0303, L2-Distance = 0.0010, Normal std = 0.6606

0.632 Kernel fit Pairwise Correlations Normal fit

Density 0.316

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

myoblast_untreated_rep1myoblast_untreated_rep2myoblast_untreated_rep3myoblast_treated_rep1 (0.116024)myoblast_treated_rep2 (0.180831)myoblast_treated_rep3 (0.132882) (0.0932296) (0.181002) (0.296031)[ min ] [ medium ] [ max ] CEM 1 Rps29 15207.7 20990.0 23945.1 P ( S | Z, I ) = 1.00 Rps28 16062.2 19220.6 23348.5 Mean Corr = 0.97866 Fau 11180.8 14598.9 17665.8 Rpl38 16106.7 19387.9 21732.7 Rpl26 15378.0 20009.6 22081.7 Rpl18a 14641.3 19990.9 23363.2 Rpl37a 13919.3 21346.1 25413.3 Rps5 12514.3 19467.1 22450.4 CEM 1 + Rplp2 16666.4 22083.4 24548.7 Top 10 Genes Uba52 14660.1 19650.7 22963.4 Rpl7a 17477.8 24949.1 28908.7 Rps4x 14691.2 20012.0 23507.8 Rps7 16729.2 23012.2 28358.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE8555" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8555 Status: Public on Jul 25 2007 Title: Genome-wide analysis of Phgdh inactivation in murine embryonic head Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18228065 Summary & Design: Summary: D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion.

Keywords: genetic modification

Overall design: RNA of 4 biological replicates was hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0165, L2-Distance = 0.0003, Normal std = 0.6997

0.570 Kernel fit Pairwise Correlations Normal fit

Density 0.285

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Gene expressionGene expressionGene profiling expressionGene profiling of expression PhgdhGene profiling of expression knockoutPhgdhGene profiling of expression knockoutPhgdhGene embryo profiling of expression knockoutPhgdhGene embryo wild1profiling of expression knockoutPhgdh (0.121645) embryo KO1profiling of knockout Phgdh(0.111762) embryo wild2profiling of knockoutPhgdh (0.195197) embryo KO2 of knockout Phgdh(0.11273)[ embryo wild3min knockout (0.0760607) embryo KO3 ] (0.128664) embryo wild4 (0.171875) KO4[ medium (0.0820669) ] [ max ] CEM 1 Rps29 23446.2 34903.3 40924.1 P ( S | Z, I ) = 1.00 Rps28 21018.7 38754.1 47533.5 Mean Corr = 0.97852 Fau 10257.8 25671.1 31640.7 Rpl38 20271.2 37955.5 43966.1 Rpl26 18576.6 47469.3 55902.9 Rpl18a 14364.0 30078.3 40464.7 Rpl37a 18932.5 32342.4 40432.8 Rps5 19400.4 30140.1 37064.2 CEM 1 + Rplp2 17772.6 36290.2 40553.5 Top 10 Genes Uba52 13846.8 29154.2 36705.9 Rpl7a 21380.7 38732.2 51798.7 Rps4x 20527.3 32401.2 40141.8 Rps7 24796.7 32738.8 37563.9

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE15458" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15458 Status: Public on Jun 30 2009 Title: Effect of v-erbA on T3-responsive genes in AML-12 hepatocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The v-erbA oncogene belongs to a superfamily of transcription factors called nuclear receptors, which includes the thyroid hormone receptors (TRs) responsible for mediating the effects of thyroid hormone (T3). Nuclear receptors bind to specific DNA sequences in the promoter region of target genes and v-erbA is known to exert a dominant negative effect on the activity of the TRs. The repressor activity of v-erbA has been linked to the development of hepatocellular carcinoma (HCC) in a mouse model. We have used microarray analysis to identify genes differentially expressed in hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to T3. We have found that v-erbA can negatively regulate expression of T3-responsive genes known to have a protective function against tumor development. We have also identified a number of v-erbA- (but not T3-) responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC.

Overall design: AML12 control cells and v-erbA-transfected AML12 cells were exposed to 10 nM T3 for 3h or 24h. Using microarray analysis, we compared gene expression in the presence and absence of v-erbA and identified T3-regulated genes differentially expressed in the presence of v-erbA.

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0167, L2-Distance = 0.0003, Normal std = 0.6313

0.632 Kernel fit Pairwise Correlations Normal fit

Density 0.316

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

AML12 AML12control v-erbA-transfectedcontrol(3h) (0.0989423) v-erbA-transfected(24h) (0.127167)AML12+T3 AML12AML12+T3 (3h) AML12controlT3-treated, (0.15692) (24h) control(3h)T3-treated, (0.0520712)(0.0871617) v-erbA-transfected (24h) (0.100914) v-erbA-transfected AML12[ AML12(3h) min (0.233447) (24h) ] (0.143377) [ medium ] [ max ] CEM 1 Rps29 15489.1 19908.5 23734.9 P ( S | Z, I ) = 1.00 Rps28 16548.9 23219.3 26011.5 Mean Corr = 0.97773 Fau 13572.6 18106.2 22815.3 Rpl38 17026.6 25936.6 29990.3 Rpl26 17139.5 24672.9 30799.4 Rpl18a 15425.9 18690.6 21487.2 Rpl37a 15586.4 21880.9 24121.4 Rps5 17230.0 20477.3 23715.8 CEM 1 + Rplp2 17116.1 25562.6 28818.5 Top 10 Genes Uba52 13710.1 18214.9 20424.7 Rpl7a 16962.2 24602.4 27132.1 Rps4x 16262.8 22926.9 27691.2 Rps7 14296.7 20414.8 22531.0

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE36384" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36384 Status: Public on Dec 31 2012 Title: ZNF335 regulates stem cell proliferation and neuronal differentiation via Trithorax complex and REST/NRSF [gene expression] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23178126 Summary & Design: Summary: The progression from stem cell to differentiated neuron is associated with extensive chromatin remodeling that controls gene expression, but the mechanisms that connect chromatin to gene expression are not well defined. Here we show that mutation of ZNF335 causes severe human microcephaly (""small brain""), small somatic size, and neonatal death. Germline Znf335 null mutations are embryonically lethal in mice, whereas RNA-interference studies and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 is a component of a vertebrate-specific, trithorax H3K4 methylation complex, while global ChIP-seq and mRNA expression studies show that Znf335 is a previously unsuspected, direct regulator of REST/NRSF, a master regulator of neural gene expression and neural cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct evidence that this pathway regulates human neurogenesis and neuronal differentiation.

Overall design: ShRNA knockdown cells were FACS sorted and analyzed for changes in gene expression

Background corr dist: KL-Divergence = 0.0259, L1-Distance = 0.0379, L2-Distance = 0.0021, Normal std = 0.6957

0.573 Kernel fit Pairwise Correlations Normal fit

Density 0.287

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

SiRNA knockdownSiRNA knockdownSiRNA 1 [CW2011082536] knockdowncontrol1 2 [CW2011082537]control2 [CW2011082539] 3 [CW2011082538]control3 (0.192374)[CW2011082540]control2 (0.066218)[CW2011082541] (0.179987)control3 (0.0456424)[CW2011060317] (0.0551554)SiRNA [CW2011060318] (0.0633849) knockdownSiRNA (0.0550887) knockdownSiRNA (0.0650524) 1 [CW2011060313] knockdowncontrol1 2 [CW2011060314] [CW2011060316] 3 [CW2011060315] (0.0470138) (0.130427) (0.0522187)[ (0.0474373) min ] [ medium ] [ max ] CEM 1 Rps29 4846.1 15283.6 23104.7 P ( S | Z, I ) = 1.00 Rps28 7729.5 24606.4 36432.3 Mean Corr = 0.97791 Fau 3136.6 11977.7 22291.6 Rpl38 7771.3 19251.4 28418.7 Rpl26 5636.7 15122.0 21780.6 Rpl18a 3319.0 14960.6 26481.9 Rpl37a 1940.8 7575.0 17875.6 Rps5 3257.9 12896.1 18991.3 CEM 1 + Rplp2 2667.3 12200.6 32250.9 Top 10 Genes Uba52 6134.3 21026.3 37406.8 Rpl7a 5878.3 21813.7 35925.3 Rps4x 6165.0 17600.5 24062.2 Rps7 5547.9 14209.2 17848.0

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE26745" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26745 Status: Public on Jul 21 2011 Title: Comparison of total and polyribosome-associated mRNA levels in male Fmr1 KO mice and male WT littermates Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21784246 Summary & Design: Summary: The Fragile X Mental Retardation Protein, FMRP, is thought to regulate the translation of a specific set of neuronal mRNAs on polyribosomes. Therefore, we prepared polyribosomes on sucrose gradients and purified mRNA specifically from these fractions, as well as the total mRNA levels, to determine whether a set of mRNAs might be changed in its % association with polyribosomes in the absence of FMRP in the KO mouse model.

No significant differences were found, other than the Fmr1 transcript itself, in total mRNA levels or % polyribosome association that withstood multiple test correction, in P7 Fmr1 KO mouse cerebral cortex compared with WT littermates..

Overall design: We prepared polyribosomes on sucrose gradients from 6 littermate pairs of Fmr1 KO and WT littermates (FVB background, P7 males, cerebral cortex) and purified RNA from both polyribosomal fractions and input to the gradient, reflecting total mRNA levels for comparison.

Background corr dist: KL-Divergence = 0.1111, L1-Distance = 0.0459, L2-Distance = 0.0033, Normal std = 0.4392

0.968 Kernel fit Pairwise Correlations Normal fit

Density 0.484

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT P7 mouseWT P7 cerebralmouseWT P7 cerebralmouseWT cortex, P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseFmr1 cortex,polyribosomalRNA, KO biologicalcerebralFmr1 cortex,polyribosomalRNA, P7 mouseKO biologicalFmr1 cortex,polyribosomalRNA, P7replicate cerebral mouseKO biologicalFmr1 polyribosomalRNA, P7replicate 1 cerebral mouseKO(0.0646638) cortex,biologicalFmr1 RNA, P7replicate 2 cerebral mouseKO(0.0516712) cortex,polyribosomalbiologicalFmr1 RNA, P7replicate 3 cerebral mouseKO(0.0419552) cortex,polyribosomalbiologicalWT P7replicate P74 cerebralmouse (0.0621124) cortex,polyribosomalRNA,mouseWT replicate P75 biologicalcerebral (0.0446649) cortex,polyribosomalRNA,cerebralmouseWT P76 biological (0.0326343) cortex,polyribosomalRNA,cerebralmouse WT replicatecortex, P7 biological polyribosomalRNA,cerebralmouse WT replicatecortex,total 1 P7(0.0452717) biological cortical RNA,cerebralmouse WT replicatecortex,total 2 P7(0.049599) biological cortical lysateRNA,cerebralmouse Fmr1 replicatecortex,total 3 (0.0331274) biological RNA,KOcortical lysatecerebral Fmr1 replicatecortex,total P74 biological(0.0253037) mouseRNA,KOcortical lysate Fmr1 replicatecortex,total P75 biological(0.0792129) cerebralmouseRNA,KOcortical lysatereplicateFmr1 total P76 biological(0.0360955) cerebralmouseRNA,KO cortical cortex,lysatereplicateFmr1 1 P7 (0.0285094) biological cerebralmouseRNA,KO cortex,totallysatereplicateFmr1 2 P7 (0.0386138) biologicalcortical cerebralmouseRNA,KO cortex,totalreplicate 3 P7 (0.0378719) biologicalcortical lysatecerebralmouse cortex,totalreplicate 4 (0.0223179) RNA,cortical lysatecerebral cortex,totalreplicate 5 biological (0.0336629) RNA,cortical lysate cortex,total[ 6 biological min(0.0317963) RNA,cortical lysatereplicate total biological RNA,cortical ]lysatereplicate 1 (0.0324898) biological RNA, lysatereplicate 2 (0.0321398) biological[ RNA, replicatemedium 3 (0.0576115) biological replicate 4 (0.0188321) replicate 5 (0.0586949)] 6 (0.0411475)[ max ] CEM 1 Rps29 3772.2 20377.1 23446.8 P ( S | Z, I ) = 1.00 Rps28 14990.1 43169.9 51600.3 Mean Corr = 0.97720 Fau 3990.6 12761.8 15325.0 Rpl38 6073.9 20767.3 24410.7 Rpl26 11994.6 20349.6 23175.9 Rpl18a 7860.8 15932.1 20512.6 Rpl37a 6118.6 23918.0 26539.1 Rps5 16250.3 26186.4 30744.7 CEM 1 + Rplp2 7869.8 27121.7 32159.1 Top 10 Genes Uba52 7905.3 22859.0 26420.4 Rpl7a 17975.0 19915.8 24374.6 Rps4x 15856.6 22220.8 26532.7 Rps7 15319.9 18936.4 24030.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE13874" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13874 Status: Public on Mar 05 2009 Title: microRNA-1 negatively regulates expression of the hypertrophy-associated genes calmodulin and Mef2a Organism: Mus musculus Experiment type: Non-coding RNA profiling by array Platform: GPL1261 Pubmed ID: 19188439 Summary & Design: Summary: Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, precise regulation of calmodulin expression may be an important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3-untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through the calcineurin to NFAT. miR-1 also negatively regulated expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, Mef2a, and Gata4.

Overall design: We show that miR-1 is downregulated in a murine heart failure model. miRNAs expression changes were measured in calcineurin transgenic model of heart failure and control mice using a Luminex platform. Reduced miR-1 expression was associated with broad alteration in expression of predicted target genes. To test this, we measured miRs including miR-1 and genome wide transcriptome changes in vivo and in vitro system. Calcineurin transgenic heart was compared to nontransgenic heart (NTg vs. CNTg). We also investigated the gene expression changes during the course of cardiomyocytes differentiation using DMSO treated P19CL6 cell lines. Two time points (day 6 and day 10) were compared to identified the gene expression changes of predicted miR-1 targets (Day 6 vs. Day 10).

Background corr dist: KL-Divergence = 0.0212, L1-Distance = 0.0629, L2-Distance = 0.0054, Normal std = 0.8282

0.482 Kernel fit Pairwise Correlations Normal fit

Density 0.241

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

NTg, biologicalNTg, biologicalNTg, replicate biologicalNTg, replicate 1 (Affymetrix) biologicalCalcineurin replicate 2 (Affymetrix)Calcineurin replicate (0.0604107) 3 (Affymetrix)Tg,Calcineurin biological (0.0459814) 4 (Affymetrix)Tg,Calcineurin biological (0.0278872) replicate Tg,Differentiating biological (0.0621117) replicate Tg, 1 (Affymetrix)Differentiating biological replicate 2 P19CL6(Affymetrix)Differentiating replicate (0.0566681) 3 P19CL6(Affymetrix)Differentiating cells (0.0419513) 4at P19CL6(Affymetrix)Differentiating cellsday (0.0370626)6 at afterP19CL6Differentiating cellsday DMSO(0.038499)6 at afterP19CL6 cellsday treatment, DMSO6 at afterP19CL6 cellsday treatment, DMSO10 at replicate aftercellsday treatment, 10 DMSOat replicate[ afterday 1min (Affymetrix) 10 treatment,DMSO replicate after 2 (Affymetrix)] treatment,DMSO (0.0851149)replicate 3 (Affymetrix) treatment, (0.114278)replicate [1 (Affymetrix)medium (0.193294)replicate 2 (Affymetrix) (0.104774) 3 (Affymetrix) ] (0.0950386) (0.0369297)[ max ] CEM 1 Rps29 14975.8 19329.7 36720.8 P ( S | Z, I ) = 1.00 Rps28 11853.7 14487.5 32328.7 Mean Corr = 0.98470 Fau 7315.6 8788.8 33893.1 Rpl38 13650.3 15486.8 38358.2 Rpl26 11275.9 14269.4 40144.8 Rpl18a 11302.1 12584.2 35073.7 Rpl37a 11720.4 14126.5 32101.1 Rps5 11185.1 12822.8 34392.7 CEM 1 + Rplp2 13171.1 14661.1 33856.9 Top 10 Genes Uba52 13562.0 17711.0 29920.0 Rpl7a 13440.3 15267.5 35498.4 Rps4x 11096.3 12583.4 31923.0 Rps7 11402.2 12830.5 30465.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE39082" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39082 Status: Public on Jul 04 2012 Title: Expression data from cultured c-Kit+Sca-1+Lin- (KSL)cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The Notch signaling pathway plays a critical role in regulating the proliferation and differentiation of stem and progenitor cells including hematopoietic stem and progenitor cells (HSPCs). Notch receptors and ligands are expressed in BM stromal and hematopoietic cells. A large body of evidence has demonstrated that activating Notch signaling enhances HSCs self-renewal and facilitates its expansion ex vivo. We report that an endothelium-targeted soluble Notch ligand, the DSL domain of mouse Delta-like 1 fused with a RGD motif (mD1R), efficiently promotes the expansion ex vivo of mouse bone marrow HSPCs in a Notch signaling and endocytosis dependent manner. HSPCs expanded in the presence of mD1R kept long-term HSPC repopulation capacity.

We used microarrays to compare the gene expression profiles of HSPCs expanded in the presence of PBS and mD1R.

Overall design: KSL cells were plated on Human umbilical vein endothelial cells (HUVECs) and cultured in a serum-free medium supplemented with a cocktail containing 5 types of mouse cytokines (m5GF) in the presence of PBS or mD1R for 7 days. Then KSL cells were sorted from these cultured hematopoietic cells for RNA extraction and hybridization on Affymetrix microarrays. The experiments were repeated 3 times.

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0284, L2-Distance = 0.0010, Normal std = 0.6605

0.620 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

PBS-expandedPBS-expanded PBS-expandedKSL cells, mD1R-expandedKSL biological cells, mD1R-expandedKSL biological cells, rep1mD1R-expanded KSL biological(0.128593) rep2cells, KSL (0.113549) biological rep3cells, KSL (0.148182) biological cells, rep1 biological(0.30528)[ rep2 min (0.151587) rep3 ] (0.152809) [ medium ] [ max ] CEM 1 Rps29 23131.2 35131.2 35912.3 P ( S | Z, I ) = 1.00 Rps28 26825.4 40243.5 43665.0 Mean Corr = 0.97578 Fau 16988.8 28339.8 33152.1 Rpl38 25311.2 39281.8 44786.2 Rpl26 25023.6 37449.7 46360.0 Rpl18a 15367.3 25627.8 28146.1 Rpl37a 16949.4 26562.1 29928.5 Rps5 17141.3 24543.6 28634.8 CEM 1 + Rplp2 26078.1 42194.9 43852.8 Top 10 Genes Uba52 16275.4 27504.5 28515.4 Rpl7a 20761.6 30889.4 34144.3 Rps4x 18914.3 27412.5 29569.1 Rps7 19172.8 28915.0 30590.7

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE5921" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5921 Status: Public on Sep 26 2007 Title: Differential expression of BMP4-regulated genes associated with commitment of C3H10T1/2 cells into adipocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17204246 Summary & Design: Summary: C3H10T1/2 stem cells are committed to the adipocyte lineage by treatment with BMP-4 and grown to postconfluence. When subjected to our standard differentiation protocol, the committed cells differentiate into adipocytes in a manner indistinguishable from that of 3T3-L1 preadipocytes. In contrast, C3H10T1/2 cells not committed with BMP-4 remain undifferentiated despite treatment with differentiation inducers. The molecular basis of the commitment process, however, has not been elucidated. Since postconfluent uncommitted and committed C3H10T1/2 cells respond differently to the differentiation inducers, it was reasoned that the two cell types differed at the gene expression level. Therefore, we undertook microarray gene expression profiling to detect changes between the two cell populations at postconfluence to identify expressed genes that may be responsible for the dramatic change in phenotype.

Keywords: control vs treated

Overall design: C3H10T1/2 cells were plated and treated with 50 ng/ml BMP4 and grown to postconfluence. Control samples were treated in the same manner were not given BMP4. Total RNA was collected at postconfluence. There were 3 replicates each for control and treated cells.

Background corr dist: KL-Divergence = 0.0414, L1-Distance = 0.0193, L2-Distance = 0.0004, Normal std = 0.6115

0.661 Kernel fit Pairwise Correlations Normal fit

Density 0.331

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

10T1/2 cells_treated_BMP4_rep110T1/2 cells_treated_BMP4_rep210T1/2 cells_treated_BMP4_rep310T1/2 cells_control_rep110T1/2 (0.193317) cells_control_rep210T1/2 (0.241627) cells_control_rep3 (0.0833795)(0.345622) (0.069317) (0.0667375)[ min ] [ medium ] [ max ] CEM 1 Rps29 21847.1 28716.6 31575.1 P ( S | Z, I ) = 1.00 Rps28 22508.9 28446.6 31680.5 Mean Corr = 0.97465 Fau 14155.8 19181.4 19927.6 Rpl38 22825.9 29199.3 31465.4 Rpl26 19502.4 23336.8 24286.3 Rpl18a 16890.5 23354.7 24887.9 Rpl37a 17358.3 23014.5 24556.6 Rps5 16299.2 21758.4 22040.1 CEM 1 + Rplp2 18333.9 21632.5 23970.2 Top 10 Genes Uba52 17489.1 21762.3 23670.8 Rpl7a 22013.6 27665.8 30997.0 Rps4x 19091.7 23872.5 25575.1 Rps7 22251.4 27712.7 31217.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE36618" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36618 Status: Public on Mar 20 2012 Title: Mechanisms of terminal erythroid differentiation defect in EKLF-deficient mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18852285 Summary & Design: Summary: EKLF is a Krüppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf -/-) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differention in Eklf -/- embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild type and Eklf -/- early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf -/- early erythroid progenitor cells, which showed a delay in the G1-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding-sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation.

Overall design: RNA was isolated from flow-sorted early erythroid progenitors in 13.5 day old fetal livers from EKLF knock out mice (n=3 fetal livers) and wild-type control mice (n=3 fetal livers) for gene expression analysis

Background corr dist: KL-Divergence = 0.0121, L1-Distance = 0.0188, L2-Distance = 0.0005, Normal std = 0.8297

0.481 Kernel fit Pairwise Correlations Normal fit

Density 0.240

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Wild type,Wild replicate type,Wild replicate 1type, (0.118887)EKLF, replicate 2 (0.14849)replicateEKLF, 3 (0.194542)replicateEKLF, 1 (0.17139) replicate 2 (0.162104) 3 (0.204587) [ min ] [ medium ] [ max ] CEM 1 Rps29 20939.3 25785.7 50515.0 P ( S | Z, I ) = 1.00 Rps28 19594.0 26354.6 48959.9 Mean Corr = 0.98229 Fau 12187.6 17908.4 30552.3 Rpl38 21164.8 26180.6 48190.7 Rpl26 22138.5 27309.2 48612.1 Rpl18a 18217.5 22351.5 36442.7 Rpl37a 16575.7 21916.7 33199.9 Rps5 17568.6 23472.4 42866.7 CEM 1 + Rplp2 18606.5 25802.3 41917.0 Top 10 Genes Uba52 17058.6 21857.0 36746.8 Rpl7a 20635.5 28807.0 47024.4 Rps4x 18741.6 22829.6 38149.1 Rps7 20231.1 23682.0 43357.7

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE32529" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 224 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

Details of this dataset are not shown due to large number of samples and the page size limit. Find details in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32529

Background corr dist: KL-Divergence = 0.0225, L1-Distance = 0.0447, L2-Distance = 0.0023, Normal std = 0.7763 GEO Series "GSE54581" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 21 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54581 Status: Public on Jun 02 2014 Title: Selective mRNA translation during eIF2 phosphorylation induces expression of IBTKalpha Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24648495 Summary & Design: Summary: Disruption of protein folding in the endoplasmic reticulum triggers the Unfolded Protein Response (UPR), a transcriptional and translational control network designed to restore protein homeostasis. Central to the UPR is PERK phosphorylation of the alpha subunit of eIF2 (eIF2~P), which represses global translation coincident with preferential translation of mRNAs, such as ATF4 and CHOP, that serve to implement the UPR transcriptional regulation. In this study, we used sucrose gradient ultracentrifugation and a genome-wide microarray approach to measure changes in mRNA translation during ER stress. Our analysis suggests that translational efficiencies vary across a broad range during ER stress, with the majority of transcripts being either repressed or resistant to eIF2~P, while a notable cohort of key regulators are subject to preferential translation. From this latter group, we identify IBTKa as being subject to both translation and transcriptional induction during eIF2~P in both cell lines and a mouse model of ER stress. Translational regulation of IBTKalpha mRNA involves the stress-induced relief of two inhibitory uORFs in the 5'-leader of the transcript. Depletion of IBTKalpha by shRNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKalpha is a key regulator in determining cell fate during the UPR.

We used a genome-wide microarray approach to determine how individual mRNAs were differentially translated during endoplasmic reticulum stress.

Overall design: Please note that the treatment plus fractionation based on association with different numbers of ribosomes did yield different populations of mRNAs, which resulted in considerable variation in normalized data across the samples.

Background corr dist: KL-Divergence = 0.1148, L1-Distance = 0.0307, L2-Distance = 0.0019, Normal std = 0.4200

0.950 Kernel fit Pairwise Correlations Normal fit

Density 0.475

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

ControlControl MEFs, biologicalControl MEFs, biologicalControl MEFs, rep 1 biologicalControl MEFs,(0.0161848) rep 1, biologicalControl MEFs, frac rep 1-4 1, biologicalControl MEFs, frac (0.114831) rep 5-8 1, biologicalControl MEFs, frac (0.0247945) rep 9-14 2 biologicalControl MEFs,(0.0235431) rep(0.0338853) 2, biologicalControl MEFs, frac rep 1-4 2, biologicalControl MEFs, frac (0.155506) rep 5-8 2, biologicalControl MEFs, frac (0.0240027) rep 9-14 3 biologicalStressed MEFs,(0.0193278) rep(0.0265682) 3, biologicalStressed fracMEFs, rep 1-4 3,Stressed biological fracMEFs,(0.082843) rep 5-8 3,Stressed biological fracMEFs,(0.0379152) rep 9-14Stressed 1 biological MEFs,(0.0172397) (0.027449) repStressed 2 biological MEFs,(0.0323111) replStressed 2,biological MEFs, frac replStressed 1-4 2,biological MEFs, frac (0.0756751)replStressed 5-8 2,biological MEFs, frac (0.0230226)rep 9-143 biological MEFs,(0.0138377) repl (0.0405415) 3,biological frac repl 1-4 3, frac (0.144675)repl [5-8 3, min frac (0.0338341) 9-14 ] (0.0320125) [ medium ] [ max ] CEM 1 Rps29 12396.7 24549.7 65496.6 P ( S | Z, I ) = 1.00 Rps28 17226.5 27011.7 71670.2 Mean Corr = 0.97319 Fau 10332.4 19661.0 42332.0 Rpl38 18080.6 30146.0 68558.4 Rpl26 18001.3 31072.8 81610.8 Rpl18a 13964.7 21210.4 59633.9 Rpl37a 11019.3 21294.9 51215.9 Rps5 13334.7 20078.5 50525.2 CEM 1 + Rplp2 19720.0 28492.2 75126.9 Top 10 Genes Uba52 12479.1 21228.2 54694.0 Rpl7a 19107.5 27011.5 68107.2 Rps4x 18712.7 25789.7 70397.7 Rps7 18013.7 25609.5 63945.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE41942" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41942 Status: Public on Nov 01 2012 Title: Overexpression of miR-9 and miR-9* in 32D cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Overexpression of miR-9 and miR-9* in 32D cells, cells grown under IL-3 conditions and miR-9 and miR-9* were introduced with retroviral vectors containing about ~150 bp up and downstream of mmu-mir-9-2.

Expression was determined to find out the effect of miR-9/9*overexpression on the transcriptome level compared to introduction of empty vector control.

Overall design: Transcriptome levels were determined for 32D cells expressing miR-9 and miR-9* and empty vector control. Experiment performed in three independent replicates.

Background corr dist: KL-Divergence = 0.0444, L1-Distance = 0.0310, L2-Distance = 0.0014, Normal std = 0.6092

0.699 Kernel fit Pairwise Correlations Normal fit

Density 0.349

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

32D-EV 32D-EVIL-3 #1 32D-EV(0.108058)IL-3 #2 32D-miR-9/9*(0.225106)IL-3 #3 32D-miR-9/9*(0.339797) IL-332D-miR-9/9* #1 (0.0735484)IL-3 #2 (0.111491)IL-3 #3 (0.142) [ min ] [ medium ] [ max ] CEM 1 Rps29 26985.4 31127.8 39322.1 P ( S | Z, I ) = 1.00 Rps28 29162.7 32989.7 38573.1 Mean Corr = 0.97307 Fau 23855.8 26342.4 29612.4 Rpl38 31864.9 37379.2 43377.7 Rpl26 32847.8 36162.6 42989.5 Rpl18a 22763.8 24720.7 30796.7 Rpl37a 21059.3 24126.5 28882.0 Rps5 21534.0 24972.2 30162.1 CEM 1 + Rplp2 31001.8 37876.2 44363.6 Top 10 Genes Uba52 23011.3 24851.6 32468.2 Rpl7a 27411.9 32708.0 40561.5 Rps4x 30159.7 34060.3 42373.7 Rps7 28211.0 32454.2 37961.7

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE42061" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42061 Status: Public on Nov 07 2012 Title: hyperlipidemia impaired innate response Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To explore the effect of hyperlipidemia on macrophages' innate immune response to Porphyromonas gingivalis invasion

Overall design: 12 samples, 3 replicates in 4 groups, with cells from hyperlipidemic ApoE deficient mice and nonhyperlipidemic C57BL/6 mice stimulate with or without P.gingivalis(Pg)

Background corr dist: KL-Divergence = 0.0969, L1-Distance = 0.0429, L2-Distance = 0.0028, Normal std = 0.4676

0.895 Kernel fit Pairwise Correlations Normal fit

Density 0.448

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Macrophages_hyperlipid_blank_rep1Macrophages_hyperlipid_blank_rep2Macrophages_hyperlipid_blank_rep3Macrophages_hyperlipid_Pg_rep1Macrophages_hyperlipid_Pg_rep2 Macrophages_hyperlipid_Pg_rep3(0.14232) Macrophages_normallipid_blank_rep1(0.0597489) Macrophages_normallipid_blank_rep2(0.0709917) (0.131834)Macrophages_normallipid_blank_rep3 (0.0641793)Macrophages_normallipid_Pg_rep1 (0.129424)Macrophages_normallipid_Pg_rep2Macrophages_normallipid_Pg_rep3 (0.0572005) (0.0733041) (0.0651927) (0.0601761) (0.064551)[ min (0.081077) ] [ medium ] [ max ] CEM 1 Rps29 27979.9 35283.8 36566.8 P ( S | Z, I ) = 1.00 Rps28 30916.7 39390.8 41698.4 Mean Corr = 0.97279 Fau 22196.4 28049.2 30048.7 Rpl38 30849.1 38242.4 40680.6 Rpl26 30846.6 38128.9 40728.8 Rpl18a 18399.0 20695.5 24651.6 Rpl37a 22439.6 25775.9 28602.6 Rps5 18828.0 21846.4 23656.6 CEM 1 + Rplp2 30932.3 35219.1 40744.5 Top 10 Genes Uba52 19952.0 20998.2 25809.2 Rpl7a 24113.6 27869.4 30782.2 Rps4x 21053.5 26400.5 28031.7 Rps7 22549.3 24414.3 28461.6

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE16364" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16364 Status: Public on Feb 05 2010 Title: Polycomb-like 2 associates with PRC2 and is required for mouse embryonic stem cell Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20144788 Summary & Design: Summary: Polycomb group (PcG) proteins are highly conserved epigenetic transcriptional repressors important for the control of numerous developmental gene expression programs and have recently been implicated in the modulation of embryonic stem cell (ESC) identity. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for novel regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a novel Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation and altered patterns of histone methylation. Through integration of global gene expression and promoter occupancy analyses of both PCL2 and PRC2 components EZH2 and SUZ12, we have predicted PCL2 target genes and formulated regulatory networks describing the role of PCL2 both in modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation.

Overall design: Cells were stably expressing Pcl2 shRNA or shRNA mismatch control sequences. Hybridizations of three biological replicates for both the control and Pcl2 shRNA clone were performed.

Background corr dist: KL-Divergence = 0.0389, L1-Distance = 0.0217, L2-Distance = 0.0005, Normal std = 0.6242

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Mouse_ESC_Pcl2_mismatch_control_sampleMouse_ESC_Pcl2_mismatch_control_sampleMouse_ESC_Pcl2_shRNA_sampleMouse_ESC_Pcl2_shRNA_sampleMouse_ESC_Pcl2_mismatch_control_sampleMouse_ESC_Pcl2_shRNA_sample 2 (0.0721675) 2 (0.149375) 3 (0.15944) 3 (0.202697)[ min 1 (0.100063) 1 (0.316257) ] [ medium ] [ max ] CEM 1 Rps29 18163.0 26017.7 33908.1 P ( S | Z, I ) = 1.00 Rps28 23405.0 31404.8 40616.9 Mean Corr = 0.97277 Fau 11192.6 15650.2 19950.4 Rpl38 19928.9 29433.5 35948.4 Rpl26 20522.0 28549.4 38963.9 Rpl18a 14399.4 20816.1 25026.8 Rpl37a 13472.0 18137.4 25055.0 Rps5 17026.1 23937.3 30237.8 CEM 1 + Rplp2 19485.3 26457.2 34788.9 Top 10 Genes Uba52 15240.7 17248.8 20838.6 Rpl7a 21500.6 30609.3 38416.9 Rps4x 21829.6 27110.0 32921.3 Rps7 19886.8 27193.1 34060.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE49346" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49346 Status: Public on Mar 07 2014 Title: Expression data from adult ATII and E18 Bipotent progenitor cells in the mouse lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24499815 Summary & Design: Summary: Alveoli are thin-walled sacs that serve as the gas exchange units of the lung. They are affected in devastating lung diseases including COPD, Idiopathic Pulmonary Fibrosis, and the major form (adenocarcinoma) of lung cancer, the leading cause of cancer deaths. The alveolar epithelium is composed of two morphologically distinct cell types: alveolar type (AT) 1 cells, exquisitely thin cells across which oxygen diffuses to reach the blood, and AT2 cells, specialized surfactant-secreting cells. Classical studies suggested that AT1 cells arise from AT2 cells during development and following injury, but more recent studies suggest other sources. Here we use histological and marker analysis, lineage tracing, and clonal analysis in mice to identify alveolar progenitor and stem cells and map their locations and potential in vivo. The results show that AT1 and AT2 cells arise independently during development from a bipotential progenitor. After birth, new AT1 cells derive from rare, long-lived, self-renewing AT2 cells, each producing a slowly expanding clonal focus of regenerated alveoli contiguous with the founder AT2 cell. This stem cell function of AT2 cells is broadly activated by diffuse AT1 cell injury, and AT2 self-renewal can be induced in vitro by EGF ligands and permanently activated in vivo by AT2 cell-specific targeting of the oncogenic KrasG12D allele, efficiently transforming AT2 cells into monoclonal adenomatous tumors that rapidly enlarge and prove fatal. Thus, there is a developmental switch in alveolar progenitor cells after birth, when mature AT2 cells function as facultative stem cells that contribute to local alveolar renewal, repair, and cancer. We propose that short-range signals from dying AT1 cells regulate AT2 stem cell activity: a signal transduced by EGFR-KRAS controls AT2 self-renewal and is hijacked during oncogenic transformation, and a separate signal controls reprogramming to AT1 cell fate.

Overall design: To compare expression between ATII and E18 BP populations, RNA was isolated from either population purified by FACS. Two populations are analyzed with 3 biological replicates per population.

Background corr dist: KL-Divergence = 0.0359, L1-Distance = 0.0425, L2-Distance = 0.0025, Normal std = 0.6765

0.609 Kernel fit Pairwise Correlations Normal fit

Density 0.304

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Muc1+_Pdpn+_E18-1Muc1+_Pdpn+_E18-2Muc1+_Pdpn+_E18-3 (0.145218)Lyz2+_EpCAM+_Adult-1 (0.0756078)Lyz2+_EpCAM+_Adult-2 (0.107907)Lyz2+_EpCAM+_Adult-3 (0.380434) (0.0798524) (0.210981)[ min ] [ medium ] [ max ] CEM 1 Rps29 12873.3 18858.9 37898.0 P ( S | Z, I ) = 1.00 Rps28 22232.0 27740.5 62023.7 Mean Corr = 0.97300 Fau 8882.2 16804.2 30561.0 Rpl38 18605.7 25337.0 57126.1 Rpl26 16559.9 27173.2 50321.1 Rpl18a 12935.4 20473.5 30427.5 Rpl37a 2769.2 8382.6 14086.2 Rps5 13092.1 18251.2 21534.4 CEM 1 + Rplp2 16880.5 27212.7 48942.2 Top 10 Genes Uba52 9340.3 16824.5 27178.1 Rpl7a 13893.6 19207.3 30282.9 Rps4x 19095.3 23940.2 31049.0 Rps7 19464.7 22603.4 41510.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE14478" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14478 Status: Public on Jan 31 2009 Title: SCL knockouts in mouse megakaryocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19211936 Summary & Design: Summary: The bHLH transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Sclfl/fl fetal liver progenitor cell lines. Analysis of Mef2C-/- embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre+Mef2Cfl/fl mice exhibited platelet defects similar to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.

Overall design: ˛/˛ cell line, and the Scl ˛/˛ cell line was transduced with Scl retrovirus to re-introduce Scl expression (Scl ˛/˛ +Scl cell line). Megakaryocyte differentiation was enhanced by adding Tpo for 5 days before harvesting the cells. RNA was extracted with Trizol (Gibco BRL) and RNEasy (Qiagen) kits. Differential gene expression between Sclfl/fl, Scl ˛/˛ and Scl ˛/˛ +Scl cell lines was analyzed by Affymetrix MOE430_2 microarray in the microarray core facility at the Dana-Farber Cancer Institute.

Background corr dist: KL-Divergence = 0.0243, L1-Distance = 0.0154, L2-Distance = 0.0003, Normal std = 0.6951

0.574 Kernel fit Pairwise Correlations Normal fit

Density 0.287

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

Exp 1 SCLExp fl/fl 1 SCL (0.12361)Exp fl/fl 1 SCL +CreExp fl/fl 2 (0.155433) SCL +CreExp fl/fl 2 +SCL SCL (0.10384)Exp fl/fl(0.146094) 2 SCL +CreExp fl/fl 2 a SCL (0.302582)+Cre fl/fl b (0.05575)+Cre +SCL (0.112692)[ min ] [ medium ] [ max ] CEM 1 Rps29 15263.8 22736.3 23402.4 P ( S | Z, I ) = 1.00 Rps28 13396.7 18985.2 20585.5 Mean Corr = 0.97305 Fau 9806.8 14381.1 17797.9 Rpl38 13864.8 17699.7 20011.0 Rpl26 14572.7 20253.7 22304.7 Rpl18a 12355.4 16328.3 19850.9 Rpl37a 12168.2 17296.5 19134.4 Rps5 13840.9 20163.7 21582.0 CEM 1 + Rplp2 13601.0 17609.8 20322.3 Top 10 Genes Uba52 12150.5 14405.6 18727.1 Rpl7a 13480.8 19270.3 21367.2 Rps4x 12973.3 18267.3 20214.4 Rps7 14068.2 20299.2 22538.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE10552" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10552 Status: Public on Dec 31 2008 Title: Genome wide expression analysis in AtT-20 cells following Dnmt1 knockdown Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18922972 Summary & Design: Summary: Efficient and sustained knockdown of DNMT1 transcript and protein was achieved using a consecutive transfection protocol in the mouse pituitary adenoma cell line, AtT-20. Genome wide microarray analysis identified 91 transcripts that were significantly differentially expressed relative to cells treated with a non-targeting control.

Keywords: Differential expression

Overall design: AtT-20 cells were repeatedly treated with 20 nM siRNA (siDNMT1 or siNT) over an eight day period. After eight days total RNA was extracted and prepared for microarray analysis. The procedure was repeated three times independently.

Background corr dist: KL-Divergence = 0.0482, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.5806

0.695 Kernel fit Pairwise Correlations Normal fit

Density 0.347

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

AtT-20_siDNMT1_Rpt1AtT-20_siNT_Rpt1AtT-20_siDNMT1_Rpt2AtT-20_siNT_Rpt2 (0.130957) (0.237728)AtT-20_siDNMT1_Rpt3AtT-20_siNT_Rpt3 (0.248919) (0.153192) (0.174494) (0.0547108)[ min ] [ medium ] [ max ] CEM 1 Rps29 24967.4 36930.8 45288.7 P ( S | Z, I ) = 1.00 Rps28 25428.2 38578.7 44337.6 Mean Corr = 0.97242 Fau 17807.7 27668.9 36342.0 Rpl38 30711.7 48138.1 56328.0 Rpl26 28649.7 43160.0 47871.6 Rpl18a 21193.5 33416.9 39964.0 Rpl37a 21485.8 32584.0 39213.0 Rps5 24416.9 37568.7 42411.6 CEM 1 + Rplp2 32572.3 47541.3 53072.5 Top 10 Genes Uba52 24086.3 38444.8 44733.0 Rpl7a 23295.6 34756.4 40271.1 Rps4x 14493.4 21211.5 22380.3 Rps7 23377.9 32469.0 35263.3

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE33121" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33121 Status: Public on Dec 15 2011 Title: Expression data from ESC and in vitro derived somatic cells and germ cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22194959 Summary & Design: Summary: We performed gene expression profiling on in vitro derived PGCs, undifferentiated ESCs, and somatic cells from the EB to examine germ cell expression in ESC-derived cells

Overall design: All cells were collected using fluorescence activated cell sorting to isolate SSEA1+/cKit+ ESCs, SSEA1+/cKitbright PGCs, Oct4-gfp+/cKitbright PGCs, and SSEA1-/cKit- somatic cells and Oct4-gfp-/cKit- somatic cells.

Background corr dist: KL-Divergence = 0.0409, L1-Distance = 0.0340, L2-Distance = 0.0016, Normal std = 0.6170

0.673 Kernel fit Pairwise Correlations Normal fit

Density 0.337

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

undifferentiatedundifferentiatedcKit+ cKit+ SSEA+ SSEA+cKit+ cKit+ SSEA+iPGC SSEA+cKit+ESC rep rep Oct4+iPGC cKit+ ESC1 1 (0.0176181) (0.143058) rep iPGCrep Oct4+cKit- 2 2 (0.0630465) rep(0.31102) iPGCSSEA- 1cKit- (0.0853836) rep somaticSSEA- 2cKit- (0.0427601) somaticOct4- repcKit- 1 somatic(0.0869396) Oct4- rep 2 somatic(0.119104) rep 1 (0.0713494) rep 2 (0.0597201)[ min ] [ medium ] [ max ] CEM 1 Rps29 5472.9 7076.7 11366.5 P ( S | Z, I ) = 1.00 Rps28 10336.6 12002.1 16974.2 Mean Corr = 0.97216 Fau 7958.9 8928.9 14122.2 Rpl38 10769.2 11798.7 18296.2 Rpl26 8299.5 9303.5 15087.0 Rpl18a 9537.0 10196.1 16153.3 Rpl37a 4848.3 5887.7 9192.8 Rps5 8662.2 9276.9 12990.7 CEM 1 + Rplp2 8872.5 9900.3 16162.6 Top 10 Genes Uba52 8613.0 9731.8 14599.9 Rpl7a 10947.6 11777.7 17003.3 Rps4x 10358.6 11203.8 15283.1 Rps7 8098.1 9281.4 14348.9

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE43620" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43620 Status: Public on Jan 19 2014 Title: Effects of sodium tungstate administration in Irs2 -/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24253047 Summary & Design: Summary: Relative beta cell deficit and increased beta cell apoptosis are hallmarks of type 2 diabetes (T2D). The Insulin/Insulin Growth Factor (Igf) signaling pathway is an established regulator of beta cell survival and is found downregulated in human T2D islets. The Insulin Receptor Substrate 2 (Irs2) plays a central role in the coordination of this pathway in beta cells. Thus, Irs2 knockout mice (Irs2 -/-) exhibit increased beta cell apoptosis that leads to a progressive decline of beta cell mass and hyperglycaemia. In this study, we sought to determine whether the anti-diabetic compound sodium tungstate could prevent the onset of diabetes in Irs2 -/- mice. Oral administration of tungstate resulted in an overall improvement in whole-body glucose tolerance in Irs2 -/- mice which correlated with increased beta cell mass. Enhanced beta cell mass was due to a dramatic reduction of beta cell apoptosis without changes in proliferation. Whole genome gene profiling analysis of islets isolated from treated Irs2 -/- mice confirmed a broad impact of tungstate on cell death pathways. Mechanistically, tungstate induced Erk1/2 phosphorylation in islets in vitro and, in agreement, treated Irs2 -/- islets exhibited increased basal Erk1/2 phosphorylation. Tungstate also downregulated expression of apoptosis-related genes in Irs2-/- islets in vitro, uncovering a direct effect of this compound in islets. All together, our data demonstrate that tungstate can restore beta cell mass and glucose homeostasis in a context of deficient Insulin/Igf signaling. This study underscores the importance of developing strategies specifically designed to arrest beta cell apoptosis as a means to prevent progressive beta cell failure in diabetes.

Overall design: 10-week old WT and Irs2 -/- mice were randomly divided into two treatment group, in a total of 4 experimental groups. For 21 days one group received distilled water as drinking water (untreated group) whilst the other received ad libitum a solution of 2mg/ml of sodium tungstate in distilled water (treated group). For each experimental group 2 independent samples were analysed, in a total of 8 samples.

Background corr dist: KL-Divergence = 0.0481, L1-Distance = 0.0167, L2-Distance = 0.0003, Normal std = 0.5662

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.352

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

WT Control-rep1WT Control-rep2WT (0.177424) treated-rep1WT (0.122835) treated-rep2Irs2-/- (0.0806799) Control-rep1Irs2-/- (0.0605726) Control-rep2Irs2-/- (0.183145) treated-rep1Irs2-/- (0.18075) treated-rep2 (0.117586) (0.0770072)[ min ] [ medium ] [ max ] CEM 1 Rps29 39315.2 43661.9 47124.3 P ( S | Z, I ) = 1.00 Rps28 29195.1 31501.1 36341.1 Mean Corr = 0.97205 Fau 14134.0 17187.8 21136.5 Rpl38 32728.1 35992.9 39590.7 Rpl26 31616.7 34817.3 39047.3 Rpl18a 12344.9 17758.4 23323.7 Rpl37a 34420.6 37950.0 39475.0 Rps5 18744.4 25335.3 27348.0 CEM 1 + Rplp2 20234.5 22249.4 26811.8 Top 10 Genes Uba52 14418.2 18152.0 21488.7 Rpl7a 22816.7 27197.6 28612.6 Rps4x 25816.2 28675.3 32361.7 Rps7 22732.6 25834.2 27366.2

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE58262" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58262 Status: Public on Jun 06 2014 Title: Impact of gamma chain cytokines on the differentiation of recently antigen-activated CD8 T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Analysis of how different gamma chain family cytokines influence CD8 T cell differentiation.

Overall design: Naïve CD8 T cells were isolated from the spleens OT-I Thy1.1 TCR Tg mice. Whole splenocytes from wild-type C57BL/6 mice were used as stimulator cells. Purified naˆflve wild-type OT-I (1ˆ106/well) were stimulated with OVA peptide (SIINFEKL) pulsed (5 ´g/ml) and irradiated (2,000 rads) syngeneic splenocytes (6ˆ106/well) in 24-well plates. Forty-eight hours later, activated OT-I T cells were harvested and viable cells were enriched over a Ficoll-paque gradient and washed with cRPMI prior to being reseeded in cRPMI (5ˆ105 cells/ml) and treated with the media supplemented with various γc cytokines (IL-2, IL-4, IL-7, IL-15 and IL-21). Experimental samples were treated with 100 ng/ml of their respective gamma chain cytokine and incubated at 37ºC for 24 hours. RNA was isolated using either the RNeasy Mini kit, or a combination of TRIzol reagent and the Direct-zol RNA miniprep kit, all following manufacturer protocols. Two biological replicates for mRNA analysis were prepped using the RNeasy kit. The third replicate was prepped using the Trizol/Direct-zol approach. The quality and quantity of RNA samples was further analyzed on the Bioanalyzer. Labeled target cDNA was prepared from total RNA samples using the Ambion MessageAmp Premier protocol (3IVT assay). Each sample target was hybridized to a Mouse 430 2.0 GeneChip array. Image processing and expression analysis were performed using Affymetrix GeneChip Command Console (AGCC) v. 3.1.1 and Affymetrix Expression Console v.1.1 software, respectively. Data from all biological replicates and conditions was imported into the Affymetrix Expression Console and normalized (RMA). RNA processing and microarray hybridization were performed by the Oregon Health & Science University Gene Microarray Shared Resource core facility in Portland, Oregon.

Background corr dist: KL-Divergence = 0.0628, L1-Distance = 0.0441, L2-Distance = 0.0034, Normal std = 0.5375

0.745 Kernel fit Pairwise Correlations Normal fit

Density 0.372

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

CD8 MediaCD8 Control MediaCD8 Control Rep#1MediaCD8 Control (0.0277999)Rep#2IL-2CD8 Rep#1 (0.0398704)Rep#3IL-2CD8 (0.0779282)Rep#2 (0.189522) IL-2CD8 (0.040921)Rep#3 IL-4CD8 (0.10983)Rep#1 IL-4CD8 (0.0520508)Rep#2 IL-4CD8 (0.0355152)Rep#3 IL-7CD8 (0.0626855)Rep#1 IL-7CD8 (0.0336268)Rep#2 IL-7CD8 (0.0605782)Rep#3 IL-15CD8 (0.0330041) Rep#1 IL-15CD8 (0.0155454)Rep#2 IL-15CD8 (0.0373517)Rep#3 IL-21CD8 (0.0921475)Rep#1 IL-21CD8 (0.0290399)Rep#2 IL-21 (0.0297271)Rep#3 (0.0328566) [ min ] [ medium ] [ max ] CEM 1 Rps29 41958.9 44646.1 102364.6 P ( S | Z, I ) = 1.00 Rps28 37325.9 39069.2 84928.3 Mean Corr = 0.97192 Fau 27425.7 31378.7 56695.9 Rpl38 37564.7 39671.4 78323.5 Rpl26 42228.7 43476.4 94672.5 Rpl18a 36256.2 39962.1 84898.9 Rpl37a 38364.7 42087.7 93933.9 Rps5 33534.1 35621.1 70130.7 CEM 1 + Rplp2 39347.8 45523.1 85329.6 Top 10 Genes Uba52 29400.3 31184.8 50920.5 Rpl7a 32036.7 34717.9 68407.1 Rps4x 37940.1 40046.6 80849.9 Rps7 36113.3 38780.6 89076.5

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE8503" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8503 Status: Public on Jan 01 2008 Title: mRNA expression analysis of undifferentiated Dicer -/- (27H10) embryonic stem cells after miRNA transfection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18311153 Summary & Design: Summary: We have analyzed the transcript expression levels in Dicer knock-out embryonic stem (ES) cells 24 hours after transfection with either control siRNA agains Renilla luciferase or miRNA Mimics (Dharmacon) of mmu-miR-290 cluster members in order to identify primary targets of miR-290 cluster miRNAs.

Keywords: Comparison of effect of two different transfections on transcriptome of Dicer-KO ES cells

Overall design: Cell were analysed 24h after transfections in an undifferentiated state. Triplicates of both transfections were analyzed.

Background corr dist: KL-Divergence = 0.0399, L1-Distance = 0.0219, L2-Distance = 0.0005, Normal std = 0.6216

0.653 Kernel fit Pairwise Correlations Normal fit

Density 0.327

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

UndifferentiatedUndifferentiatedUndifferentiated Dicer Undifferentiated-/- Dicer (27H) Undifferentiated-/- ES Dicer (27H) cell Undifferentiated-/- ES lineDicer (27H) cell transfected -/- ES lineDicer (27H) cell transfected -/- ES lineDicer with(27H) cell transfected siRL-/- ESline with(27H) cell replicate_1transfected siRL[ ESline withmin cell replicate_2transfected siRL line(0.252206) with ] replicate_3transfected miR-290 (0.129051) with miR-290 cluster(0.148517) with[ medium miR-290 clusterreplicate_1 clusterreplicate_2 (0.147493) replicate_3] (0.232068) (0.090666)[ max ] CEM 1 Rps29 30039.0 34342.5 35216.3 P ( S | Z, I ) = 1.00 Rps28 31976.9 35758.3 36450.0 Mean Corr = 0.97058 Fau 23237.7 26138.5 26454.0 Rpl38 36995.1 41394.1 42726.0 Rpl26 37905.1 43659.3 47001.7 Rpl18a 27071.4 30408.7 31682.5 Rpl37a 26449.3 29336.4 30686.2 Rps5 25410.1 28195.6 29180.7 CEM 1 + Rplp2 34980.5 39061.9 41388.4 Top 10 Genes Uba52 26356.3 28057.9 30711.0 Rpl7a 32250.5 36396.5 37530.0 Rps4x 29100.8 31506.3 32953.0 Rps7 29645.4 33038.6 33942.4

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE10871" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 32 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10871 Status: Public on May 28 2008 Title: Differentiated, partially- and fully-reprogrammed MEFs/B-cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18509334 Summary & Design: Summary: Expression profiles generated during dissection of the molecular mechanisms underlying direct reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells, iPS).

Keywords: Cell type comparison/Timecourse

Overall design: 2 technical replicates of B lymphocytes, partially reprogrammed (MCV8, MCV6, BIV1), MEF-iPS(Oct4) and B-iPS(Nanog) cell lines.

Background corr dist: KL-Divergence = 0.2296, L1-Distance = 0.0483, L2-Distance = 0.0064, Normal std = 0.3326

1.221 Kernel fit Pairwise Correlations Normal fit

Density 0.610

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

PartiallyPartially reprogrammedPartially reprogrammedPartially reprogrammedcell linePartially reprogrammedcell MCV8 linePartially reprogrammed(SSEA+)cell MCV8 linePartially reprogrammed(SSEA+)cell MCV8replicate linePartially reprogrammed(SSEA-)cell MCV8replicate 1 line (0.0123997)Partially reprogrammed(SSEA-)cell replicateMCV8 2 line (0.0169767)Partially reprogrammed(Lowcell replicateMCV8 1 line(0.0219987) MHC)Partially reprogrammed(lowcell MCV8 2 replicateline(0.0164674)MHC)Partially reprogrammed(mediumcell MCV8 replicate line Partially1 reprogrammed(Mediumcell(0.0359002) MCV8 MHC) line 2Partially (0.00564858)reprogrammed (Highcell replicateMCV8 MHC) line PartiallyMHC) reprogrammed (Highcell replicateBIV1 1 (0.0105408)linereplicate PartiallyMHC)(Dox+) reprogrammedcell BIV1 2 (0.00962204) linereplicate B-iPS replicate(Dox+)1 reprogrammed cell (0.00722202)BIV1 linereplicate B-iPS replicate(Dox-)2 cell1 (0.0090831)BIV1 (0.0149488) linereplicate replicate MEFs1(Dox-) cell2 (0.0582003)MCV6 (0.0181758) lineexpressing replicate MEFs2 1 replicate (0.0517932)MCV6 (0.0127491) expressingMEFs 2replicate Oct4,(0.0156078)1 (0.0209371) expressingMEFs Sox2, Oct4,2 (0.0162253) expressing MEFsKlf4, Sox2, Oct4, c-Myc expressing MEFsKlf4, Sox2, Oct4, (Day4, c-Myc expressing MEFsKlf4, Sox2, Oct4, replicate(Day4, c-Myc expressing MEFsKlf4, Sox2, Oct4, replicate(Day c-Myc 1)expressing Activated Klf4,(0.0069507) Sox2, 8, Oct4, (Dayreplicate c-Myc2) Activated Klf4,(0.00811307) Sox2, 8, BOct4, (Dayreplicatelymphocytes c-Myc 1) ActivatedKlf4, (0.00690857)Sox2, 12,B (Daylymphocytes c-Mycreplicate 2) ActivatedKlf4, (0.00989451) 12,B (replicate (Daylymphocytes c-Mycreplicate Oct4-iPS1) 16,(0.0210645)B (replicate (Daylymphocytes replicate1) Oct4-iPS2) (0.0716321) cell16,(0.0417001) expressing replicate2)line 1) (0.0879528) cell (0.00633839) MCV8.1expressing line 2)Oct4, (0.00445325)MCV8.1 (replicate Sox2, Oct4, (replicate Klf4, Sox2,1)[ (0.135046) c-Mycmin Klf4, 2) (0.152338)(replicate c-Myc ] (replicate 1) (0.0416642)[ 2) medium (0.0514466) ] [ max ] CEM 1 Rps29 10512.4 55265.7 94395.1 P ( S | Z, I ) = 1.00 Rps28 12775.9 48105.5 76178.5 Mean Corr = 0.97030 Fau 10071.6 44961.7 67888.1 Rpl38 13744.1 62330.3 93274.9 Rpl26 13203.7 64743.6 97166.8 Rpl18a 11105.8 45829.5 65850.2 Rpl37a 9124.6 47431.5 69773.1 Rps5 8962.3 42545.2 58417.8 CEM 1 + Rplp2 13373.4 51701.0 84340.6 Top 10 Genes Uba52 10358.0 34166.6 54982.4 Rpl7a 12179.6 54186.0 72549.9 Rps4x 12725.2 44760.3 67017.5 Rps7 12232.9 51903.5 84914.8

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE19687" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19687 Status: Public on Dec 30 2009 Title: shGFP- and shQk-transduced Ink4a/Arf-/- Pten-/- primary mouse astrocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Identify potential QK-regulated mRNAs and linked pathways by comparing the transcriptional profiles of shGFP- and shQK-transduced Ink4a/Arf-/- Pten-/- primary mouse astrocytes

Overall design: Ink4a/Arf-/- Pten-/- primary mouse astrocytes infected with shQk-1, shQk-2 and infected with shGFP as control

Background corr dist: KL-Divergence = 0.1127, L1-Distance = 0.0284, L2-Distance = 0.0014, Normal std = 0.4172

0.956 Kernel fit Pairwise Correlations Normal fit

Density 0.478

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

IP-1a (0.17892)IP-1b (0.117563)IP-1c (0.135376)IP-2a (0.087514)IP-2b (0.159151)IP-2c (0.0487465)IP-Ga (0.0759192)IP-Gb (0.102261)IP-Gc (0.0945497) [ min ] [ medium ] [ max ] CEM 1 Rps29 50533.1 54989.3 65672.1 P ( S | Z, I ) = 1.00 Rps28 53147.4 57197.4 70952.0 Mean Corr = 0.96875 Fau 32496.7 34000.2 41699.0 Rpl38 50354.7 57789.6 68267.8 Rpl26 51530.1 56993.8 67827.5 Rpl18a 34725.9 38222.1 46503.0 Rpl37a 28397.9 34817.9 42117.2 Rps5 35562.4 38194.3 45643.6 CEM 1 + Rplp2 35002.8 38655.4 46074.9 Top 10 Genes Uba52 30013.4 31947.8 40631.5 Rpl7a 51567.8 57147.6 69310.1 Rps4x 41058.1 45290.4 55545.6 Rps7 54061.3 58642.3 73279.1

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE34761" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34761 Status: Public on Feb 01 2012 Title: All-iPS cell mice generated from terminally differentiated B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22387999 Summary & Design: Summary: The generation of induced pluripotent stem cells (iPSCs) often results in aberrant silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises their ability to generate entirely iPSC-derived mice (all-iPSC mice). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration at its imprint control region that interferes with abnormal binding of the DNA methyltransferase Dnmt3a. This approach allowed us to generate adult all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal mice. Our data demonstrate that factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that the choice of culture conditions used for transcription factor-mediated reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs.

Overall design: iPS cells were generated from MEFs of the Col-OKSM reprogrammable mice. In the presence of doxycycline, the reprogramming transcription factors Oct4, Sox2, Klf4, and cMyc were induced in MEFs to derivate iPS cells. Total RNA was isolated from iPS cells derivated in the presence or absence of ascorbic acid in culture medium.

Background corr dist: KL-Divergence = 0.0891, L1-Distance = 0.0231, L2-Distance = 0.0007, Normal std = 0.4564

0.874 Kernel fit Pairwise Correlations Normal fit

Density 0.437

0.000 CEM 1

Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00

Pre-normalization Quantiles

iPS cloneiPS 1 clonederivatediPS 2 clonederivated iniPS the 3 clonederivated presence iniPS the 4 clonederivated presence in iPSof the 1ascorbic clonederivated presence in iPSof the 2ascorbic clone derivatedacid presence in iPSof the (0.240712) 3ascorbic clone derivatedacid absence in of the (0.0524964) 4ascorbic derivatedacid absence inof the(0.0895264)ascorbic acid absence inof the(0.162734)ascorbic acid absence of[ (0.107659) ascorbicmin acid of (0.0750905) ascorbic acid] (0.102473) acid (0.169309)[ medium ] [ max ] CEM 1 Rps29 16772.1 24916.0 27002.0 P ( S | Z, I ) = 1.00 Rps28 20461.9 28176.5 30546.1 Mean Corr = 0.96845 Fau 10606.1 15342.2 16333.6 Rpl38 20193.7 27423.3 29586.8 Rpl26 19056.6 27153.8 30819.2 Rpl18a 14457.5 19623.3 21837.8 Rpl37a 14743.2 20515.0 21771.4 Rps5 16081.4 23051.2 26254.8 CEM 1 + Rplp2 20058.0 24981.5 27884.4 Top 10 Genes Uba52 15541.2 19223.8 21280.4 Rpl7a 18424.8 25013.1 28632.6 Rps4x 16939.8 25042.0 27718.3 Rps7 18068.1 23690.3 27211.2

Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16