PDF Output of CLIC (Clustering by Inferred Co-Expression)

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

Dataset: Num of genes in input gene set: 6 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. Meaf6 Kat6a Brpf1 Brpf3 Num ofGenesinQueryGeneset:6.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Brd1 Ing5

Brpf3 Brpf1 Kat6a Brd1 Ing5 Meaf6 CEM 1(12datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 2410131K14Rik 1700020D05Rik Symbol Num ofCEMGenes:6.Predicted205.SelectedDatasets:12.Strength:0.0 CEM 1,Geneset"[G]MOZ/MORFhistoneacetyltransferasecomplex",Page1 Zkscan17 Fam193b Msantd2 Ankrd26 Klhdc10 Mvb12b Ccdc13 Ccdc61 Dazap1 Med13l Utp14b Ubqln4 Ythdc1 Kctd13 Zfp532 Slc6a5 Tmcc1 Arid1a Clasrp Kmt2b Dhx34 Cdk17 Fnbp4 Ewsr1 Taok2 Meaf6 Hirip3 S1pr4 Kat6b Smg7 Kat6a Tcf23 Lats1 Brpf1 Brpf3 Map7 Olig3 Scrib Aqp9 Clip2 Spen Phc1 Sox8 Brd1 Pfas Frs3 Ing5 Lbr 0.0 1.0

GSE32199 [6] GSE13227 [6]

GSE27451 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38044 [6] GSE21944 [6] GSE5425 [6] GSE24793 [8] GSE18660 [10] GSE27564 [8] GSE29929 [14] GSE32598 [11] GSE16874 [12] GSE27455 [12] GSE16751 [6] GSE25825 [8] GSE16925 [15] GSE33761 [9] GSE11382 [10] GSE20335 [8] GSE17794 [44] GSE23119 [9] GSE27932 [14] GSE44355 [10] GSE45430 [9] GSE21716 [28] GSE32386 [13] GSE17266 [59] GSE12454 [13] GSE27546 [51] GSE13223 [6] GSE16623 [6] GSE41997 [6] GSE12432 [15] GSE23782 [18] GSE45618 [6] GSE44175 [18] GSE13364 [6] GSE32529 [224] GSE3126 [6] GSE57425 [6] GSE9249 [28] GSE30868 [8] GSE35077 [26] GSE51385 [8] GSE56755 [13] GSE32311 [11] GSE26668 [6] GSE12986 [10] GSE40156 [42] GSE30176 [12] GSE16110 [16] GSE44339 [14] GSE43779 [6] GSE39449 [6] GSE21224 [16] GSE34629 [6] GSE19729 [14] GSE30192 [6] GSE54653 [6] GSE40513 [6] GSE20636 [35] GSE21041 [6] GSE17796 [39] GSE15121 [6] GSE11973 [6] GSE41342 [26] GSE7050 [18] GSE32287 [16] GSE2433 [10] GSE15303 [11] GSE17097 [20] GSE28031 [6] GSE33308 [10] GSE46500 [6] GSE40260 [6] GSE8555 [8] GSE44162 [6] GSE7809 [8] GSE5041 [8] GSE6689 [12] GSE56542 [8] GSE10813 [12] GSE20398 [30] GSE10285 [8] GSE43042 [6] GSE18587 [9] GSE31199 [12] GSE6275 [36] GSE28457 [24] GSE46606 [30] GSE5037 [18] GSE13259 [10] GSE13493 [6] GSE1566 [6] GSE23002 [8] GSE10478 [6] GSE19073 [6] GSE30865 [68] GSE25645 [17] GSE13693 [9] GSE27378 [8] GSE20645 [8] GSE40286 [10] GSE35091 [11] GSE14308 [12] GSE22251 [9] GSE23833 [12] GSE6846 [6] GSE28823 [12] GSE11443 [6] GSE11018 [6] GSE21491 [9] GSE14012 [24] GSE42103 [9] GSE33942 [12] GSE20235 [6] GSE49194 [14] GSE15724 [9] GSE34618 [7] GSE43825 [31] GSE17923 [6] GSE51365 [28] GSE37563 [6] GSE36618 [6] GSE35899 [15] GSE21379 [10] GSE9441 [36] GSE24437 [6] GSE16679 [8] GSE9044 [6] GSE34002 [9] GSE48203 [9] GSE48790 [8] GSE13635 [6] GSE46797 [6] GSE41095 [6] GSE13103 [8] GSE10776 [15] GSE41084 [6] GSE54349 [6] GSE55356 [6] GSE6881 [10] GSE20500 [6] GSE24210 [16] GSE12985 [14] GSE46942 [7] GSE23502 [8] GSE9892 [12] GSE48811 [20] GSE14478 [7] GSE52101 [17] GSE12950 [6] GSE37029 [15] GSE46871 [6] CEM+ CEM GSE39916 [6] GSE4749 [6] GSE26151 [20] GSE10587 [6] GSE30873 [6] GSE5038 [9] 0.0 GSE33121 [10] GSE52118 [9]

GSE50813 [24] Scale ofaveragePearsoncorrelations GSE9124 [6] GSE18042 [18] GSE19004 [9] GSE45941 [8] GSE16048 [6] GSE48884 [12] 0.2 GSE15452 [26] GSE13874 [14] GSE55622 [22] GSE1983 [6] GSE6875 [8] GSE24705 [33] GSE32615 [10] GSE27114 [6] GSE36415 [14] 0.4 GSE6485 [6] GSE55809 [8] GSE7302 [6] GSE15267 [8] GSE9717 [6] GSE42299 [8] GSE13129 [12] GSE51355 [16] GSE12993 [6] 0.6 GSE43059 [8] GSE40655 [6] GSE9763 [20] GSE13421 [8] GSE38538 [6] GSE13563 [6] GSE57543 [6] GSE19355 [6] GSE4043 [6] 0.8 GSE48932 [12] GSE15232 [6] GSE46242 [12] GSE40660 [6] Score 1.80 1.82 1.85 1.85 1.86 1.86 1.87 1.88 1.92 1.97 2.08 2.10 2.16 2.23 2.25 2.34 2.43 2.44 2.54 2.59 2.65 2.77 2.78 2.79 2.81 2.82 2.87 2.89 2.98 2.99 3.09 3.14 3.17 3.24 3.25 3.29 3.42 3.55 3.60 3.66 3.81 3.94 4.35 7.88 1.0 Notes D430041D05Rik LOC101055948 Symbol Num ofCEMGenes:6.Predicted205.SelectedDatasets:12.Strength:0.0 CEM 1,Geneset"[G]MOZ/MORFhistoneacetyltransferasecomplex",Page2 Trp53i11 Fam53b Slc34a3 Ubxn2b Nup210 Shank3 Mgat5b Zcchc8 Gmppa Btbd17 Dyrk1a Pnldc1 Lrrtm4 Chtf18 Kmt2a Papd5 Abca2 Ppfia1 Ep400 Naa40 Eif2s1 Cxxc1 Gabrq Gpr45 Fanca Gon4l Brsk2 Spin1 Phf12 Wipf2 Scaf4 Espl1 Prr12 Kifc2 Pim3 Pogz Tbx6 Rfx2 Zar1 Dvl2 Ulk1 Avl9 St13 Tpt1 Cad Cbs Zp2 Tll2 0.0 1.0

GSE32199 [6] GSE13227 [6]

GSE50813 [24] Scale ofaveragePearsoncorrelations GSE9124 [6] GSE18042 [18] GSE19004 [9] GSE45941 [8] GSE16048 [6] GSE48884 [12] 0.2 GSE15452 [26] GSE13874 [14] GSE55622 [22] GSE1983 [6] GSE6875 [8] GSE24705 [33] GSE32615 [10] GSE27114 [6] GSE36415 [14] 0.4 GSE6485 [6] GSE55809 [8] GSE7302 [6] GSE15267 [8] GSE9717 [6] GSE42299 [8] GSE13129 [12] GSE51355 [16] GSE12993 [6] 0.6 GSE43059 [8] GSE40655 [6] GSE9763 [20] GSE13421 [8] GSE38538 [6] GSE13563 [6] GSE57543 [6] GSE19355 [6] GSE4043 [6] 0.8 GSE48932 [12] GSE15232 [6] GSE46242 [12] GSE40660 [6] Score 1.04 1.04 1.05 1.05 1.13 1.14 1.15 1.18 1.18 1.24 1.25 1.27 1.27 1.33 1.35 1.35 1.35 1.36 1.37 1.38 1.38 1.40 1.41 1.41 1.45 1.47 1.48 1.48 1.48 1.49 1.51 1.52 1.55 1.55 1.57 1.58 1.59 1.62 1.62 1.64 1.64 1.65 1.66 1.67 1.68 1.71 1.72 1.79 1.80 1.80 1.0 Notes Symbol Num ofCEMGenes:6.Predicted205.SelectedDatasets:12.Strength:0.0 CEM 1,Geneset"[G]MOZ/MORFhistoneacetyltransferasecomplex",Page3 Slc25a28 Rmnd5a Sema4g Fbxo21 Gnptab Tada2a Cnnm3 Kdm3b Pou3f2 Kdm7a Smad7 Zfp568 Slc4a7 Prrc2a Rfpl4b N4bp2 Papd7 Nova2 Pgap1 Cep72 Ep300 Chrnd Tead4 Acrbp Nrsn1 Hipk2 Clcn2 Pold1 Safb2 Desi1 Mpp3 Strn4 Wdr5 Dot1l Fgfr4 Coa6 Cbx7 Lnx1 Ints7 Tsc2 Fzd5 Sufu Sbf1 Aatk Fbrs Nsl1 Fibp Mag Rif1 Dut 0.0 1.0

GSE32199 [6] GSE13227 [6]

GSE50813 [24] Scale ofaveragePearsoncorrelations GSE9124 [6] GSE18042 [18] GSE19004 [9] GSE45941 [8] GSE16048 [6] GSE48884 [12] 0.2 GSE15452 [26] GSE13874 [14] GSE55622 [22] GSE1983 [6] GSE6875 [8] GSE24705 [33] GSE32615 [10] GSE27114 [6] GSE36415 [14] 0.4 GSE6485 [6] GSE55809 [8] GSE7302 [6] GSE15267 [8] GSE9717 [6] GSE42299 [8] GSE13129 [12] GSE51355 [16] GSE12993 [6] 0.6 GSE43059 [8] GSE40655 [6] GSE9763 [20] GSE13421 [8] GSE38538 [6] GSE13563 [6] GSE57543 [6] GSE19355 [6] GSE4043 [6] 0.8 GSE48932 [12] GSE15232 [6] GSE46242 [12] GSE40660 [6] Score 0.51 0.51 0.51 0.52 0.53 0.59 0.60 0.60 0.60 0.61 0.62 0.63 0.65 0.67 0.67 0.68 0.68 0.68 0.69 0.71 0.71 0.72 0.72 0.73 0.75 0.78 0.79 0.79 0.81 0.82 0.82 0.83 0.84 0.84 0.85 0.86 0.89 0.90 0.92 0.92 0.92 0.95 0.98 0.98 0.99 0.99 1.00 1.00 1.01 1.04 1.0 Notes 2300002M23Rik 3110021N24Rik Symbol Num ofCEMGenes:6.Predicted205.SelectedDatasets:12.Strength:0.0 CEM 1,Geneset"[G]MOZ/MORFhistoneacetyltransferasecomplex",Page4 BC068157 Tbc1d22b Fam228a Tbc1d31 Arhgef1 Slc27a5 Fam98c Capn15 Elmod3 Cep192 Akap14 Hnrnpu Avpr1b Acvr2b Mthfd2 Shisa6 Zfp692 Zfp142 Zfp687 Zfp239 Zfp276 Slc7a1 Amer2 Pram1 Kcnh3 Reps1 Alms1 Nacc1 Thap1 Oxgr1 Srrm4 Zc3h3 Dgcr8 Btbd9 Chst3 Acin1 Padi2 Stac3 Actr5 Thpo Ybx2 Fosb Gdf3 Gpt2 Rtn4 Nxf7 Klk6 Cit 0.0 1.0

GSE32199 [6] GSE13227 [6]

GSE50813 [24] Scale ofaveragePearsoncorrelations GSE9124 [6] GSE18042 [18] GSE19004 [9] GSE45941 [8] GSE16048 [6] GSE48884 [12] 0.2 GSE15452 [26] GSE13874 [14] GSE55622 [22] GSE1983 [6] GSE6875 [8] GSE24705 [33] GSE32615 [10] GSE27114 [6] GSE36415 [14] 0.4 GSE6485 [6] GSE55809 [8] GSE7302 [6] GSE15267 [8] GSE9717 [6] GSE42299 [8] GSE13129 [12] GSE51355 [16] GSE12993 [6] 0.6 GSE43059 [8] GSE40655 [6] GSE9763 [20] GSE13421 [8] GSE38538 [6] GSE13563 [6] GSE57543 [6] GSE19355 [6] GSE4043 [6] 0.8 GSE48932 [12] GSE15232 [6] GSE46242 [12] GSE40660 [6] Score 0.09 0.09 0.09 0.09 0.11 0.13 0.13 0.14 0.14 0.15 0.15 0.16 0.18 0.19 0.20 0.22 0.22 0.22 0.22 0.22 0.24 0.24 0.25 0.26 0.26 0.27 0.27 0.29 0.30 0.30 0.30 0.30 0.31 0.31 0.32 0.32 0.34 0.37 0.39 0.44 0.44 0.45 0.45 0.47 0.48 0.48 0.50 0.50 0.50 0.51 1.0 Notes 8430419L09Rik Symbol Num ofCEMGenes:6.Predicted205.SelectedDatasets:12.Strength:0.0 CEM 1,Geneset"[G]MOZ/MORFhistoneacetyltransferasecomplex",Page5 Slc25a25 Pramel6 Map2k7 Zfp473 Pde1b Pum1 Fgf17 Ttll9 Npff Sp2 0.0 1.0

GSE32199 [6] GSE13227 [6]

GSE27451 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE38044 [6] GSE21944 [6] GSE5425 [6] GSE24793 [8] GSE18660 [10] GSE27564 [8] GSE29929 [14] GSE32598 [11] GSE16874 [12] GSE27455 [12] GSE16751 [6] GSE25825 [8] GSE16925 [15] GSE33761 [9] GSE11382 [10] GSE20335 [8] GSE17794 [44] GSE23119 [9] GSE27932 [14] GSE44355 [10] GSE45430 [9] GSE21716 [28] GSE32386 [13] GSE17266 [59] GSE12454 [13] GSE27546 [51] GSE13223 [6] GSE16623 [6] GSE41997 [6] GSE12432 [15] GSE23782 [18] GSE45618 [6] GSE44175 [18] GSE13364 [6] GSE32529 [224] GSE3126 [6] GSE57425 [6] GSE9249 [28] GSE30868 [8] GSE35077 [26] GSE51385 [8] GSE56755 [13] GSE32311 [11] GSE26668 [6] GSE12986 [10] GSE40156 [42] GSE30176 [12] GSE16110 [16] GSE44339 [14] GSE43779 [6] GSE39449 [6] GSE21224 [16] GSE34629 [6] GSE19729 [14] GSE30192 [6] GSE54653 [6] GSE40513 [6] GSE20636 [35] GSE21041 [6] GSE17796 [39] GSE15121 [6] GSE11973 [6] GSE41342 [26] GSE7050 [18] GSE32287 [16] GSE2433 [10] GSE15303 [11] GSE17097 [20] GSE28031 [6] GSE33308 [10] GSE46500 [6] GSE40260 [6] GSE8555 [8] GSE44162 [6] GSE7809 [8] GSE5041 [8] GSE6689 [12] GSE56542 [8] GSE10813 [12] GSE20398 [30] GSE10285 [8] GSE43042 [6] GSE18587 [9] GSE31199 [12] GSE6275 [36] GSE28457 [24] GSE46606 [30] GSE5037 [18] GSE13259 [10] GSE13493 [6] GSE1566 [6] GSE23002 [8] GSE10478 [6] GSE19073 [6] GSE30865 [68] GSE25645 [17] GSE13693 [9] GSE27378 [8] GSE20645 [8] GSE40286 [10] GSE35091 [11] GSE14308 [12] GSE22251 [9] GSE23833 [12] GSE6846 [6] GSE28823 [12] GSE11443 [6] GSE11018 [6] GSE21491 [9] GSE14012 [24] GSE42103 [9] GSE33942 [12] GSE20235 [6] GSE49194 [14] GSE15724 [9] GSE34618 [7] GSE43825 [31] GSE17923 [6] GSE51365 [28] GSE37563 [6] GSE36618 [6] GSE35899 [15] GSE21379 [10] GSE9441 [36] GSE24437 [6] GSE16679 [8] GSE9044 [6] GSE34002 [9] GSE48203 [9] GSE48790 [8] GSE13635 [6] GSE46797 [6] GSE41095 [6] GSE13103 [8] GSE10776 [15] GSE41084 [6] GSE54349 [6] GSE55356 [6] GSE6881 [10] GSE20500 [6] GSE24210 [16] GSE12985 [14] GSE46942 [7] GSE23502 [8] GSE9892 [12] GSE48811 [20] GSE14478 [7] GSE52101 [17] GSE12950 [6] GSE37029 [15] GSE46871 [6] CEM+ CEM GSE39916 [6] GSE4749 [6] GSE26151 [20] GSE10587 [6] GSE30873 [6] GSE5038 [9] 0.0 GSE33121 [10] GSE52118 [9]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32199 Status: Public on Nov 10 2011 Title: BMP and Activin treatment of mouse extraembryonic endoderm (XEN) cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22027433 Summary & Design: Summary: XEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm.

The experiment was performed to gain insight into genes regulated by BMP and activin in XEN cells, and also to more precisely define the VE subtypes formed in culture.

Overall design: IM8A1 XEN cells were treated for 6 days with BMP2 (20 ng/ml, R&D Systems), activin A (30 ng/ml, Peprotech), both, or neither in GMEM + 10% fetal bovine serum.

Background corr dist: KL-Divergence = 0.0437, L1-Distance = 0.0276, L2-Distance = 0.0009, Normal std = 0.6099

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

UntreatedActivin-treated XEN BMP2-treatedcells rep1 Activin+BMP2-treatedXEN (0.0946238) cells XENUntreated (0.0904508) cellsBMP2-treated rep1 XEN (0.165971) XENcells cells rep2 XEN (0.0576074)(0.400938) cells rep2 (0.190409)[ min ] [ medium ] [ max ] CEM 1 Brpf3 118.6 147.3 184.5 P ( S | Z, I ) = 1.00 Brpf1 788.1 936.0 1408.4 Mean Corr = 0.54617 Kat6a 900.9 1003.0 1129.5 Brd1 647.4 728.0 908.1 Ing5 125.7 212.8 342.1 Meaf6 53.8 87.6 99.1 Kmt2b 929.7 1037.1 1092.0 Spen 85.8 219.6 254.9 2410131K14Rik 63.7 121.9 152.2 Zkscan17 1686.4 1992.4 2266.3 Ankrd26 424.4 491.1 599.8 CEM 1 + Smg7 534.6 573.5 654.1 Top 10 Genes Kat6b 413.3 509.4 541.0 Tmcc1 155.7 210.4 265.5 Ubqln4 619.2 861.3 949.0 Lbr 4880.2 5204.7 6400.8

Null module GEO Series "GSE13227" 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=GSE13227 Status: Public on Nov 30 2008 Title: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 Thymus expression data Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19118016 Summary & Design: Summary: F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues

Keywords: Basal transcription profiles

Overall design: Thymus from adult F1 animals from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses was collected and arrayed on Affymetrics chip to identify basal differences in gene expression between the different genotypes

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0141, L2-Distance = 0.0002, Normal std = 0.7131

0.559 Kernel fit Pairwise Correlations Normal fit

Density 0.280

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

thymusthymus akr1 (0.108675)thymus akr2 (0.258652)thymus akr3 (0.0697119)thymus dba1 (0.222893)thymus dba2 (0.137475) dba3 (0.202593) [ min ] [ medium ] [ max ] CEM 1 Brpf3 353.4 420.4 453.2 P ( S | Z, I ) = 1.00 Brpf1 1023.8 1708.5 1883.8 Mean Corr = 0.46893 Kat6a 2555.1 2882.6 2972.5 Brd1 1087.0 1142.3 1208.0 Ing5 101.8 165.2 175.3 Meaf6 134.0 155.4 188.0 Kmt2b 1347.7 1820.9 1878.5 Spen 351.0 917.5 930.9 2410131K14Rik 64.7 84.4 114.7 Zkscan17 880.5 1037.3 1117.5 Ankrd26 261.8 311.7 336.3 CEM 1 + Smg7 459.1 667.7 697.9 Top 10 Genes Kat6b 887.6 1073.8 1375.9 Tmcc1 344.9 496.8 514.3 Ubqln4 567.6 692.3 814.7 Lbr 9693.8 12158.6 12410.4

Null module GEO Series "GSE27451" 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=GSE27451 Status: Public on Feb 25 2011 Title: Functions of HDAC1 and HDAC2 in Schwann cells during postnatal Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21423190 Summary & Design: Summary: The aim of our study is to determine the functions of histone deacetylases (HDACs) 1 and 2 in Schwann cells during postnatal development of the peripheral nervous system (PNS). Schwann cells are the myelinating glial cells of the PNS. At birth, mouse sciatic nerves mature in 2 subsequent phases: 1/ big caliber axons get sorted into a 1 to 1 relationship with Schwann cells, 2/ Schwann cells build a myelin sheath around sorted axons. In mice where both HDAC1 & HDAC2 have been specifically knocked out in Schwann cells, both phases are impaired. HDACs are chromatin remodeling enzymes, they can thus alter gene expression directly. We want to identify which genes controlled by HDAC1 and HDAC2 in Schwann cells are necessary for the maturation of sciatic nerves. Because HDAC1 and HDAC2 can compensate for each other loss to some extend, we will first analyze changes of gene expression in HDAC1/HDAC2 double KO animals. We expect to gain critical insights into the molecular mechanisms controlling Schwann cell differentiation and myelination. This knowledge is of key importance for the success of regenerative medicine in peripheral neuropathies, nerve tumors, and transplantation paradigms in non-regenerative CNS lesions and in large PNS injuries.

Overall design: 3 double knockout mutants for HDAC1 and HDAC2 and 3 control littermates were analyzed. Tissues analyzed: sciatic nerves of 2 day-old mouse pups

Background corr dist: KL-Divergence = 0.0264, L1-Distance = 0.0155, L2-Distance = 0.0002, Normal std = 0.6935

0.575 Kernel fit Pairwise Correlations Normal fit

Density 0.288

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 sciaticMouse nerve_P2sciaticMouse nerve_P2sciaticMouse Double nerve_P2sciaticMouse DoubleHDAC1-2 nerve_P2sciaticMouse DoubleHDAC1-2 KO_rep3 nerve_P2sciatic Control_rep3HDAC1-2 KO_rep2 (0.21065)nerve_P2 Control_rep2 KO_rep1 (0.0862165) (0.109936) Control_rep1 (0.0352527)[ (0.0994156) min (0.458529) ] [ medium ] [ max ] CEM 1 Brpf3 277.9 341.1 440.6 P ( S | Z, I ) = 0.99 Brpf1 269.2 337.5 380.7 Mean Corr = 0.51972 Kat6a 1464.8 1846.0 2282.5 Brd1 836.0 1105.7 1375.2 Ing5 95.2 124.3 134.7 Meaf6 86.1 126.8 289.3 Kmt2b 197.4 250.6 302.8 Spen 89.4 105.6 135.1 2410131K14Rik 31.9 45.7 71.0 Zkscan17 205.5 312.1 458.1 Ankrd26 80.1 111.9 173.0 CEM 1 + Smg7 2829.7 4142.1 4565.0 Top 10 Genes Kat6b 237.2 258.0 281.3 Tmcc1 66.2 86.4 100.7 Ubqln4 1926.6 2639.7 3341.0 Lbr 994.2 1768.2 2053.3

Null module GEO Series "GSE38044" 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=GSE38044 Status: Public on Mar 13 2013 Title: Gene activation by Rag-mediated DNA double-strand breaks in G1-phase murine pre-B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23496831 Summary & Design: Summary: The objective is to identify genes that are differentially expressed following the introduction of DNA double-strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired, and thus, will provide a continuous stimulus to the cell.

Overall design: Murine v-abl-transformed pre-B cells were treated with 3 uM STI571 for 48 hours. Cell types included RAG-2-deficient (3 biological replicates) and Artemis-deficient (3 biological replicates) G1-phase pre-B cells. 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 RAG-2-deficient samples as the controls.

Background corr dist: KL-Divergence = 0.0469, L1-Distance = 0.0246, L2-Distance = 0.0007, Normal std = 0.5897

0.684 Kernel fit Pairwise Correlations Normal fit

Density 0.342

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

Rag ReplicateRag Replicate 1Rag (0.10574) Replicate 2Art (0.115157) Replicate 3Art (0.435214) Replicate 1 Art(0.179587) Replicate 2 (0.0363758) 3 (0.127927) [ min ] [ medium ] [ max ] CEM 1 Brpf3 341.8 403.3 575.8 P ( S | Z, I ) = 0.98 Brpf1 1528.7 1776.2 1925.6 Mean Corr = 0.59847 Kat6a 1932.4 2430.0 2773.4 Brd1 1551.9 1779.8 2283.3 Ing5 90.1 105.1 139.6 Meaf6 106.4 129.2 155.5 Kmt2b 2193.4 2637.9 3374.1 Spen 557.3 797.2 959.4 2410131K14Rik 32.6 91.0 154.0 Zkscan17 2911.9 4008.9 4512.6 Ankrd26 316.4 453.5 525.9 CEM 1 + Smg7 828.0 977.5 1453.4 Top 10 Genes Kat6b 962.2 1129.8 1278.3 Tmcc1 811.3 953.7 1155.0 Ubqln4 503.7 846.7 1001.0 Lbr 9200.7 10422.8 11481.3

Null module 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 ERRÎ² 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 ERRÎ² as selectively expressed in rod photoreceptors. Overexpression of ERRÎ² induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRÎ² results in dysfunction and degeneration of rods, while inverse agonists of ERRÎ² trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRÎ². ERRÎ² coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRÎ² activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRÎ² is a critical regulator of rod photoreceptor function and survival, and suggest that ERRÎ² 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 ERRÎ² 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(0.0764766) P21, Sv129 ERRÎ²2C57Bl/6 x(0.181732) P21, Sv129 -/-ERRÎ² P21, knockoutP21, wildtype -/-ERRÎ² knockout retina, -/- retina, knockout 1retina, (0.136319) 3[ (0.353977) min 2retina, (0.0541641) 3 ](0.197331) [ medium ] [ max ] CEM 1 Brpf3 63.5 119.6 198.3 P ( S | Z, I ) = 0.96 Brpf1 663.8 800.9 1292.6 Mean Corr = 0.46089 Kat6a 1457.8 1814.6 3746.4 Brd1 618.5 736.3 1045.9 Ing5 106.0 152.7 246.5 Meaf6 66.3 83.0 111.7 Kmt2b 823.3 1169.0 2020.1 Spen 308.1 395.0 459.0 2410131K14Rik 196.9 241.3 269.1 Zkscan17 668.1 777.8 1098.8 Ankrd26 346.2 410.8 893.4 CEM 1 + Smg7 666.6 899.7 2044.2 Top 10 Genes Kat6b 1028.8 1254.3 2316.2 Tmcc1 68.8 139.2 295.5 Ubqln4 636.5 822.8 1265.0 Lbr 1139.7 1332.6 1906.7

Null module GEO Series "GSE5425" 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=GSE5425 Status: Public on Aug 02 2006 Title: Spinal cord and dorsal root ganglion gene expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16824496 Summary & Design: Summary: We used microarrays to test the fundamental quantitative differences between central and peripheral nervous system transcriptomes.

Keywords: repeat

Overall design: 3 independent SC and 3 independent DRG samples were analyzed. Each sample contained material from 4 age-matched male C57B/6 mice.

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0458, L2-Distance = 0.0024, Normal std = 0.8355

0.509 Kernel fit Pairwise Correlations Normal fit

Density 0.255

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

Dorsal RootDorsal Ganglion RootDorsal Ganglion RootDRG_REPSpinal Ganglion CordDRG_REPSpinal 1 SC_REP(0.148555) CordDRG_REPSpinal 2 SC_REP(0.278604) 1Cord (0.0714528) 3 SC_REP(0.129926) 2 (0.210433) 3 (0.161029)[ min ] [ medium ] [ max ] CEM 1 Brpf3 292.0 599.6 978.3 P ( S | Z, I ) = 0.86 Brpf1 441.0 515.7 594.0 Mean Corr = 0.68475 Kat6a 362.7 529.0 560.0 Brd1 463.5 498.5 503.2 Ing5 363.1 523.3 547.3 Meaf6 433.0 503.0 563.6 Kmt2b 430.9 501.4 509.6 Spen 451.2 483.6 552.2 2410131K14Rik 305.8 494.6 1379.5 Zkscan17 422.2 515.0 540.0 Ankrd26 416.0 507.7 569.6 CEM 1 + Smg7 416.7 491.7 513.2 Top 10 Genes Kat6b 360.9 506.3 520.6 Tmcc1 307.6 487.4 725.1 Ubqln4 412.6 505.4 551.2 Lbr 468.5 500.6 520.5

Null module GEO Series "GSE24793" 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=GSE24793 Status: Public on Mar 30 2012 Title: Target genes of thyroid hormone in cerebellum neurons Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22586439 Summary & Design: Summary: Cerebellar post-natal development is particularly sensitive to thyroid hormone and low levels of thyroid hormone (hypothyroidism) result in permanent defects in cerebellar architecture and function. All cell types of the cerebellum are affected, but the main sign of hypothyroidism in mice is the persistence of the external granular layer, composed of mitotic neuronal precursors at P21.

To make the genetic link between thyroid hormone and cerebellar development, we sought to identify new thyroid hormone target genes, in particular in granule cells which represent the vast majority of cerebellar cells.

Overall design: Primary cultures of cerebellar neurons were made by dissociation of cerebella from newborn wild-type mice. These cells were plated 48 hours in serum-free medium to avoid invasion of the culture by glial cells. In order to include a kinetic and a maximum number of target genes, several cultures were either treated or left untreated as controls for 6 hours (T1), 16 hours (T2), 24 hours (T3) or 48 hours (T4) and results were pairwise compared for each time point.

Background corr dist: KL-Divergence = 0.0499, L1-Distance = 0.0304, L2-Distance = 0.0014, Normal std = 0.5750

0.720 Kernel fit Pairwise Correlations Normal fit

Density 0.360

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

NeuronsNeurons at 6h_T3Neurons at treatment 6h_untreatedNeurons at 16h_T3 (0.175271)Neurons at (0.281729) 16h_untreatedtreatmentNeurons at 24h_T3 (0.0309592)Neurons at 24h_untreated(0.0779162)treatmentNeurons at 48h_T3 (0.0811282) at 48h_untreated(0.072822)treatment (0.124502) (0.155672)[ min ] [ medium ] [ max ] CEM 1 Brpf3 38.2 91.3 102.4 P ( S | Z, I ) = 0.79 Brpf1 556.8 1068.2 2063.5 Mean Corr = 0.51656 Kat6a 1134.7 1860.4 2399.8 Brd1 781.7 1014.1 1521.9 Ing5 13.0 37.1 43.2 Meaf6 207.4 271.9 518.0 Kmt2b 608.6 811.8 1030.7 Spen 181.4 323.3 419.9 2410131K14Rik 42.2 76.3 123.6 Zkscan17 1401.0 1534.4 2165.9 Ankrd26 256.3 349.2 472.3 CEM 1 + Smg7 500.5 684.7 883.9 Top 10 Genes Kat6b 297.8 676.4 1201.7 Tmcc1 15.6 62.8 88.8 Ubqln4 1264.0 1972.8 2711.0 Lbr 1789.7 2606.2 4409.1

Null module GEO Series "GSE18660" 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=GSE18660 Status: Public on Jan 03 2011 Title: Modulation of calcium activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker- like cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20956206 Summary & Design: Summary: Background: Ion channels are key determinants for the function of excitable cells but little is known about their role and involvement during cardiac development. Earlier work identified Ca2+-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here, we have investigated their impact on the differentiation of pluripotent cells towards the cardiac lineage. Methods and Results: We have applied the SKCa-activator EBIO on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa-activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation and diminished teratoma formation. Time-restricted SKCa-activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the EBIO-induced effects.

Conclusions: SKCa-activation drives the fate of pluripotent cells towards the cardiac lineage and preferentially into pacemaker-like cardiomyocytes. This provides a novel strategy for the enrichment of cardiomyocytes and in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification.

Overall design: - EBIO-treated differentiated ES cells sample 2 (EBIO_day5+10_2)

Background corr dist: KL-Divergence = 0.0149, L1-Distance = 0.0633, L2-Distance = 0.0051, Normal std = 0.9657

0.413 Kernel fit Pairwise Correlations Normal fit

Density 0.207

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

UntreatedUntreated controlUntreated controlES cellsEBIO-treated controlES sample cellsEBIO-treated ES sample1 ES (0.141849)cellsEBIO-treated cells sample2 ES (0.0442903) sampleUntreated cells 3 ES (0.119493) sampleUntreated1 (0.0375314)cells control sampleEBIO-treated2 (0.0428914) controldifferentiated EBIO-treated3 (0.0873914) differentiated differentiated ES cellsdifferentiatedES ES sample ES cells cells sample1 (0.238503) sample [cells min 2 (0.224205)sample 1 (0.0147455) ] 2 (0.0491002)[ medium ] [ max ] CEM 1 Brpf3 235.4 362.0 467.3 P ( S | Z, I ) = 0.72 Brpf1 880.6 1086.0 1375.7 Mean Corr = 0.73522 Kat6a 663.7 1118.1 1517.8 Brd1 634.1 1026.6 1223.7 Ing5 81.2 126.4 139.4 Meaf6 58.3 112.1 147.3 Kmt2b 567.3 888.9 1140.5 Spen 139.6 438.4 597.0 2410131K14Rik 58.7 95.6 114.0 Zkscan17 960.8 1618.1 2103.4 Ankrd26 173.6 251.3 390.4 CEM 1 + Smg7 646.7 809.0 1325.3 Top 10 Genes Kat6b 769.4 1462.2 4388.9 Tmcc1 53.8 82.4 96.0 Ubqln4 819.3 1232.6 2976.6 Lbr 2139.1 6929.9 9154.8

Null module GEO Series "GSE27564" 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=GSE27564 Status: Public on Feb 24 2012 Title: Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We isolated myofibroblasts from C57BL6/J mouse ileum or colon and analyzed gene expression profiles from the cultured cells. We also isolated human colon cancer cells from xenografts interacting with mouse intestinal subepithelial myofibroblasts (ISEMFs) and analyzed gene expression in sorted human cancer cells.

We used Affymetrix microarrays to detail the global gene expression prolfiles in mouse fibroblasts and human colon cancer cells and identified distinct biological processes of differentially expressed genes in mouse fibroblasts and interacting human colon cancer cells

Overall design: For mouse SEMFs, we isolated fresh fibroblasts from mouse ileum and colon, confirmed their predicted immunophenotype (alpha SMA positive, vimentin positive, desmin negative), and expanded cells in culture before expression array analysis. We examined gene expression in human cancer cells following their interaction with murine ileal or colonic SEMFs, using flow cytometry to isolate DsRed-expressing Caco2 or T84 cells after 5 weeks of growth in NOD/SCID mice in the presence of GFP-expressing ileal or colonic SEMFs.

Background corr dist: KL-Divergence = 0.0164, L1-Distance = 0.0331, L2-Distance = 0.0015, Normal std = 0.7837

0.509 Kernel fit Pairwise Correlations Normal fit

Density 0.255

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 ileum1mouse (0.0527532)ileum2mouse (0.256032)ileum3mouse (0.0850679)ileum4mouse (0.187547)colon1mouse (0.0586844)colon2mouse (0.163131)colon3mouse (0.0909045)colon4 (0.105881) [ min ] [ medium ] [ max ] CEM 1 Brpf3 330.5 462.0 506.8 P ( S | Z, I ) = 0.72 Brpf1 605.7 725.5 832.4 Mean Corr = 0.56525 Kat6a 751.9 1034.8 1183.4 Brd1 338.5 590.4 735.1 Ing5 94.1 130.1 146.2 Meaf6 127.7 180.3 201.4 Kmt2b 435.7 787.7 920.0 Spen 344.0 665.9 710.3 2410131K14Rik 167.8 235.4 292.2 Zkscan17 957.7 1142.6 1360.4 Ankrd26 305.2 377.1 395.3 CEM 1 + Smg7 330.0 479.1 599.0 Top 10 Genes Kat6b 338.0 535.0 598.0 Tmcc1 161.3 319.5 386.4 Ubqln4 939.4 1265.6 1382.8 Lbr 751.7 1003.4 1726.9

Null module GEO Series "GSE29929" 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=GSE29929 Status: Public on Jan 20 2012 Title: The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21917591 Summary & Design: Summary: Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors PERK, ATF6, and IRE1 implement the UPR. PERK phosphorylation of eIF2 during ER stress represses protein synthesis, which prevents further influx of ER client proteins, along with preferential translation of ATF4, a transcription activator of the integrated stress response. In this study we show that the PERK/eIF2Î±~P/ATF4 pathway is required not only for translational control, but also activation of ATF6 and its target genes. The PERK pathway facilitates both the synthesis of ATF6 and trafficking of ATF6 from the ER to the Golgi for intramembrane proteolysis and activation of ATF6. As a consequence, liver-specific depletion of PERK significantly reduces both the translational and transcriptional phases of the UPR, leading to reduced protein chaperone expression, disruptions of lipid metabolism, and enhanced apoptosis. These findings show that the regulatory networks of the UPR are fully integrated, and helps explain the diverse pathologies associated with loss of PERK.

Overall design: Comparison of gene expression profiles for treated vs control in wildtype and knock-out.

Background corr dist: KL-Divergence = 0.1228, L1-Distance = 0.0299, L2-Distance = 0.0013, Normal std = 0.4159

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_6hTUN-rep1WT_6hTUN-rep2WT_6hTUN-rep3 (0.186546)WT_6hTUN-rep4 (0.11024)WT_Control_DMSO-rep1 (0.10147)WT_Control_DMSO-rep2 (0.0783124)WT_Control_DMSO-rep3lsPERK_6hTUN-rep1 (0.0543413)lsPERK_6hTUN-rep2 (0.0518994)lsPERK_6hTUN-rep3 (0.0986606) (0.0317699)lsPERK_6hTUN-rep4 (0.0149173)lsPERK_Control_DMSO-rep1 (0.00968474)lsPERK_Control_DMSO-rep2 (0.0423219)lsPERK_Control_DMSO-rep3 (0.105516) (0.098967) (0.015353)[ min ] [ medium ] [ max ] CEM 1 Brpf3 85.2 135.9 220.5 P ( S | Z, I ) = 0.71 Brpf1 257.8 485.8 766.3 Mean Corr = 0.29381 Kat6a 541.7 809.8 1174.8 Brd1 325.4 438.0 521.1 Ing5 41.9 70.5 107.0 Meaf6 104.4 150.8 213.1 Kmt2b 411.6 550.9 845.4 Spen 110.5 181.0 273.8 2410131K14Rik 13.4 50.2 152.5 Zkscan17 547.4 912.4 1631.3 Ankrd26 105.9 230.7 290.1 CEM 1 + Smg7 177.5 400.1 685.9 Top 10 Genes Kat6b 291.1 469.3 1279.4 Tmcc1 54.6 95.1 227.3 Ubqln4 711.8 1103.2 1737.2 Lbr 1151.2 1330.6 1888.1

Null module GEO Series "GSE32598" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -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=GSE32598 Status: Public on Oct 05 2011 Title: Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22064699 Summary & Design: Summary: The generation of sufficient numbers of mature ventricular myocytes for effective cell-based therapy is a central barrier for cardiac regenerative medicine. Here we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes, and consistent with other reports of iPSCs derived from various somatic cell types, ventricular myocyte derived iPSCs (ViPSCs) exhibit a markedly higher propensity to differentiate into beating cardiomyocytes as compared to genetically-matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, ViPSC-derived cardiomyocytes form up to 99% ventricular myocytes suggesting that ventricular myocyte-derived iPSCs may be a viable strategy to generate specific cardiomyocyte subtypes for cell-based therapies. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the ventricular myocyte fate in pluripotent stem cells.

Overall design: Total RNA was extracted from mouse ES cells, tail tip fibroblasts (TTFs), ventricular myocytes (VMs), TTF-derived induced pluripotent stem cells (TiPSCs) and VM-derived induced pluripotent stem cells (ViPSCs). Global gene expression profiling was performed using affymetrix mouse 430 2.0 gene arrays.

Background corr dist: KL-Divergence = 0.0622, L1-Distance = 0.0594, L2-Distance = 0.0055, Normal std = 0.6305

0.704 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

ViPSCs,ViPSCs, rep1 (0.0740383)ViPSCs, rep2 (0.0838991)TiPSCs, rep3 (0.0625848)TiPSCs, rep1 (0.035676)TiPSCs, rep2 (0.0354305)mESCs, rep3 (0.0898097)mESCs, rep1 (0.0178455)mESCs, rep2 (0.0319416)Tail rep3 tip (0.00974122) fibroblastsVentricular (0.349038)cardiomyocytes (0.209995)[ min ] [ medium ] [ max ] CEM 1 Brpf3 264.5 510.9 614.2 P ( S | Z, I ) = 0.69 Brpf1 604.0 1339.5 1490.6 Mean Corr = 0.49370 Kat6a 571.0 871.2 1370.9 Brd1 624.2 1353.7 1678.5 Ing5 60.7 97.4 118.4 Meaf6 81.8 210.9 262.7 Kmt2b 820.0 1768.3 1980.8 Spen 187.1 524.0 745.9 2410131K14Rik 43.1 59.3 85.6 Zkscan17 1076.4 1912.7 3079.0 Ankrd26 72.5 199.6 343.0 CEM 1 + Smg7 415.8 1977.2 2378.5 Top 10 Genes Kat6b 396.9 2351.7 4174.9 Tmcc1 28.1 36.8 93.7 Ubqln4 432.6 2469.6 2634.9 Lbr 1807.8 8862.8 10486.8

Null module GEO Series "GSE16874" 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=GSE16874 Status: Public on Dec 07 2010 Title: Expression in wild type and TgDREAM mouse B cells unstimulated or 2 days after LPS+IL4 stimulation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21059893 Summary & Design: Summary: DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two proteins related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.

Overall design: We used Affymetrix microarrays (GeneChip Mouse Genome 430 2.0) to compare global gene expression in wild type (WT) versus transgenic B cells (Tg), unstimulated and 2 days after LPS + IL4 stimulation. For ech type of sample three hybridizations were carried-out (independent biological replicates).

Background corr dist: KL-Divergence = 0.0300, L1-Distance = 0.0974, L2-Distance = 0.0115, Normal std = 0.9421

0.423 Kernel fit Pairwise Correlations Normal fit

Density 0.212

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

BCells_WildType_day0_REP1BCells_WildType_day0_REP2BCells_WildType_day0_REP3BCells_Transgenic_day0_REP1 BCells_Transgenic_day0_REP2(0.0964647) BCells_Transgenic_day0_REP3(0.150999) BCells_WildType_day2_REP1(0.110573)BCells_WildType_day2_REP2 (0.0595542)BCells_WildType_day2_REP3 (0.0803994)BCells_Transgenic_day2_REP1 (0.0325868) BCells_Transgenic_day2_REP2(0.0823316) BCells_Transgenic_day2_REP3(0.0532163) (0.092208) (0.0680384) (0.0892871)[ (0.0843414)min ] [ medium ] [ max ] CEM 1 Brpf3 470.0 806.3 1062.5 P ( S | Z, I ) = 0.53 Brpf1 1265.4 1725.4 2066.9 Mean Corr = 0.47424 Kat6a 1495.5 2293.5 2928.3 Brd1 683.6 1256.5 1678.9 Ing5 88.4 150.7 197.5 Meaf6 254.7 289.3 382.9 Kmt2b 1356.2 1941.2 2158.6 Spen 415.0 568.5 727.0 2410131K14Rik 106.6 131.2 160.1 Zkscan17 796.2 946.4 1365.5 Ankrd26 185.5 218.8 363.4 CEM 1 + Smg7 877.4 1149.7 1433.6 Top 10 Genes Kat6b 281.2 817.9 1019.2 Tmcc1 135.8 224.8 423.3 Ubqln4 516.5 875.0 1050.2 Lbr 8000.4 11556.2 13153.4

Null module GEO Series "GSE27455" 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=GSE27455 Status: Public on Feb 24 2011 Title: Wnt and Tcf3-mediated regulation of gene expression in mouse embryonic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21685894 Summary & Design: Summary: The observation that Tcf3 (MGI name: Tcf7l1) bound the same genes as core stem cell transcription factors, Oct4 (MGI name:Pou5f1), Sox2 and Nanog, revealed a potentially important aspect of the poorly understood mechanism whereby Wnts stimulate self renewal of pluripotent mouse embryonic stem (ES) cells. Although the conventional view of Tcf proteins as the Î²-catenin-binding effectors of Wnt signaling suggested Tcf3 should activate target genes in response to Wnts, here we show that Wnt3a and Tcf3 effectively antagonize each others effects on gene expression. Genetic ablation of Tcf3 caused similar effects as treating cells with recombinant Wnt3a.

Moreover, Tcf3 was not necessary for Wnt3a-stimulation of gene expression as the majority of Wnt3a-stimulated genes exhibited a greater increase in Tcf3-/- ES cells than in Tcf3+/+ ES cells. These expression data, together with genetic experiments, show that Wnt3a stimulates ES cell self renewal by inhibiting Tcf3.

Overall design: Tcf3+/+ and Tcf3-/- mouse embryonic stem cells were cultured in self renewal conditions containing recombinant Wnt3a for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0555, L1-Distance = 0.0185, L2-Distance = 0.0004, Normal std = 0.5419

0.736 Kernel fit Pairwise Correlations Normal fit

Density 0.368

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

MouseESC_Tcf3WT_ControlMedia_replicate01MouseESC_Tcf3WT_ControlMedia_replicate02MouseESC_Tcf3WT_ControlMedia_replicate03MouseESC_Tcf3KO_ControlMedia_replicate01MouseESC_Tcf3KO_ControlMedia_replicate02MouseESC_Tcf3KO_ControlMedia_replicate03MouseESC_Tcf3WT_WntMedia_replicate01 (0.0213491)MouseESC_Tcf3WT_WntMedia_replicate02 (0.0790744)MouseESC_Tcf3WT_WntMedia_replicate03 (0.0391738)MouseESC_Tcf3KO_WntMedia_replicate01 (0.15768)MouseESC_Tcf3KO_WntMedia_replicate02 (0.0785604)MouseESC_Tcf3KO_WntMedia_replicate03 (0.112034) (0.0674263) (0.0549385) (0.0908188) (0.0772792)[ min (0.0701366) ] (0.151529) [ medium ] [ max ] CEM 1 Brpf3 335.1 403.4 528.5 P ( S | Z, I ) = 0.47 Brpf1 1235.4 1473.4 1721.7 Mean Corr = 0.35003 Kat6a 795.1 1306.4 1395.1 Brd1 810.0 844.1 936.1 Ing5 163.3 214.4 279.0 Meaf6 120.8 216.3 297.5 Kmt2b 818.1 1049.0 1197.6 Spen 353.6 439.3 547.5 2410131K14Rik 88.2 119.6 162.6 Zkscan17 1244.1 1540.2 1721.7 Ankrd26 255.4 302.6 371.9 CEM 1 + Smg7 658.6 760.0 1057.0 Top 10 Genes Kat6b 1385.8 2905.5 3126.9 Tmcc1 26.0 30.4 38.7 Ubqln4 2059.4 2212.3 2521.3 Lbr 6146.2 8749.8 9331.3

Null module GEO Series "GSE16751" 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=GSE16751 Status: Public on Jun 24 2009 Title: Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven acute lymphoblastic leukemia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Activation-Induced Cytidine Deaminase (AID) is required for somatic hypermutation and immunoglobulin (Ig) class switch recombination in germinal center B lymphocytes. Occasionally, AID targets non-Ig genes, thereby contributing to B cell lymphomagenesis. We recently reported aberrant expression of AID in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). To elucidate the biological significance of aberrant AID expression, we studied loss of AID function in a murine model of BCR-ABL1 ALL. Mice transplanted with BCR-ABL1-transduced AID-/- bone marrow had prolonged survival as compared to mice transplanted with leukemia cells generated from AID+/+ bone marrow. Consistent with a causative role of AID in genetic instability, AID-/- leukemia had a decreased frequency of amplifications, deletions and a lower frequency of mutations in non-Ig genes including Pax5 and Rhoh as compared to AID+/+ leukemias. AID-/- and AID+/+ ALL cells showed a markedly distinct gene expression pattern as determined by principle component analysis, with 2,365 genes differentially expressed. In contrast to AID+/+ leukemia, AID-/- ALL cells failed to downregulate a number of tumor suppressor genes such as Rhoh, Cdkn1a (p21), and Blnk (SLP65). We conclude that AID accelerates clonal evolution in BCR-ABL1 ALL by enhancing genetic instability, aberrant somatic hypermutation, and by transcriptional inactivation of tumor suppressor genes.

Overall design: We used microarrays to detect differences in gene expression profiles between AID expressing leukemia and AID deficient leukemia

Background corr dist: KL-Divergence = 0.0295, L1-Distance = 0.0170, L2-Distance = 0.0003, Normal std = 0.6752

0.599 Kernel fit Pairwise Correlations Normal fit

Density 0.300

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

AID-/- leukemiaAID-/- leukemiaAID-/- biological leukemiaAID+/+ biological replicate leukemiaAID+/+ biological replicate 1 leukemia(0.224481)AID+/+ biological replicate 2 leukemia(0.188137) biological replicate 3 (0.0485755) biological replicate 1 (0.41831) replicate 2[ (0.0497669) min 3 (0.0707292) ] [ medium ] [ max ] CEM 1 Brpf3 312.8 328.0 348.4 P ( S | Z, I ) = 0.17 Brpf1 1230.7 1542.3 1962.0 Mean Corr = 0.26893 Kat6a 1512.1 1757.9 1953.5 Brd1 772.8 1119.5 1144.5 Ing5 59.4 73.9 85.6 Meaf6 205.7 228.5 252.9 Kmt2b 850.3 1035.7 1628.7 Spen 227.3 308.4 379.0 2410131K14Rik 73.1 86.5 88.9 Zkscan17 3462.1 3816.7 4567.5 Ankrd26 217.9 361.6 367.8 CEM 1 + Smg7 876.5 1133.2 1297.8 Top 10 Genes Kat6b 495.9 547.9 748.6 Tmcc1 51.3 58.3 65.6 Ubqln4 1163.9 1297.8 2006.6 Lbr 13537.7 14162.3 14970.5

Null module GEO Series "GSE25825" 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=GSE25825 Status: Public on Dec 03 2010 Title: Expression data from MxCre;E2F1-/-2-/-3f/f Cd11B myeloid cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21115501 Summary & Design: Summary: To understand the underlying cause for the observed apoptosis in E2f1-3 deficient myeloid cells. We compared gene expression profiles of Cd11b+ sorted myeloid cells isolated from bone marrow of control (E2F1-/- ) and experimental (Mxcre;E2F1-/-2-/-3f/f ) mice.

Overall design: RNA was extracted from Cd11b cells from bone marrow of eight-week-old mice after FACS sorting with FITC- cojugated Cd11b antibody.

Background corr dist: KL-Divergence = 0.0635, L1-Distance = 0.0189, L2-Distance = 0.0006, Normal std = 0.5182

0.770 Kernel fit Pairwise Correlations Normal fit

Density 0.385

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

E2F1-/-2+/+3f/fE2F1-/-2+/+3f/f E2F1-/-2+/+3f/f(control), E2F1-/-2+/+3f/f(control), rep1 (0.0633147)Mxcre;E2F1-/-2-/-3f/f(control), rep2 (0.0591974)Mxcre;E2F1-/-2-/-3f/f(control), rep3 (0.175331)Mxcre;E2F1-/-2-/-3f/f rep4 (experimental), (0.175652)Mxcre;E2F1-/-2-/-3f/f (experimental), (experimental), rep1 (0.186244) (experimental), rep2 (0.299435) rep3[ min (0.0201363) rep4 (0.0206903)] [ medium ] [ max ] CEM 1 Brpf3 422.8 521.3 666.7 P ( S | Z, I ) = 0.15 Brpf1 2736.2 2932.2 3415.1 Mean Corr = 0.00785 Kat6a 1439.6 1916.5 2262.7 Brd1 676.3 843.9 971.5 Ing5 172.0 179.4 224.8 Meaf6 106.5 138.8 186.1 Kmt2b 703.6 873.9 1041.3 Spen 585.7 884.7 1031.5 2410131K14Rik 121.1 186.3 225.9 Zkscan17 282.8 497.7 591.7 Ankrd26 113.3 187.1 205.9 CEM 1 + Smg7 235.1 273.0 310.4 Top 10 Genes Kat6b 273.5 343.6 493.2 Tmcc1 975.0 1638.2 2773.5 Ubqln4 280.2 436.6 657.1 Lbr 10624.9 15781.8 17933.7

Null module GEO Series "GSE16925" 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=GSE16925 Status: Public on Aug 03 2009 Title: Expression data from mouse ES and iPS cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19672241 Summary & Design: Summary: Induced pluripotent stem (iPS) cells were produced from reprogramming of somatic cells, and they are shown to possess pluripotent properties similar to embryonic stem (ES) cells. Here we used microarrays to detail the global expression pattern among the ES cells and iPS cells, as well as the original mouse embryo fibroblast (MEF), to identify important players involved in the reprogramming process.

Overall design: Mouse ES cell cultures, as well as selected iPS cell lines and the original MEF cells they were derived from, were used for RNA extraction and hybridization on Affymetrix microarrays. Three biological replicates for each sample were processed. GeneChips were processed and data were analyzed as previously described (Zeng et al., Dev Biol 20004).

Background corr dist: KL-Divergence = 0.0695, L1-Distance = 0.0886, L2-Distance = 0.0130, Normal std = 0.6146

0.785 Kernel fit Pairwise Correlations Normal fit

Density 0.393

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

CL11-rep1CL11-rep2 (0.0239687)CL11-rep3 (0.0211387)MEF-rep1 (0.0342918)MEF-rep2 (0.135408)MEF-rep3 (0.197238)IP14D-1-rep1 (0.169976)IP14D-1-rep2 (0.0138534)IP14D-1-rep3 (0.0344952)IP14D-101-rep1 (0.0118926)IP14D-101-rep2IP14D-101-rep3 (0.0309358)IP20D-3-rep1 (0.0287884)IP20D-3-rep2 (0.0537815) (0.0908787)IP20D-3-rep3 (0.0646469) (0.0887058) [ min ] [ medium ] [ max ] CEM 1 Brpf3 152.7 338.2 588.9 P ( S | Z, I ) = 0.09 Brpf1 473.4 1018.3 1295.4 Mean Corr = 0.62014 Kat6a 723.1 1043.6 1170.6 Brd1 785.1 1063.3 1341.3 Ing5 76.9 170.1 195.1 Meaf6 61.8 168.3 234.2 Kmt2b 760.9 2330.1 2898.4 Spen 274.8 777.1 1669.0 2410131K14Rik 63.5 108.7 225.9 Zkscan17 705.5 1241.9 1558.0 Ankrd26 137.9 302.3 438.5 CEM 1 + Smg7 679.9 1722.4 2094.7 Top 10 Genes Kat6b 812.7 3677.2 6224.2 Tmcc1 6.6 71.0 186.6 Ubqln4 971.8 3866.3 6380.3 Lbr 1732.0 7507.4 9690.8

Null module GEO Series "GSE33761" 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=GSE33761 Status: Public on Apr 25 2012 Title: Gene expression in adipose tissue of intrauterine growth restricted (IUGR) and Macrosomic animals that developed in a crowded uterine horn Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Animals that are growth restricted in utero may show rapid postnatal growth that ultimately results in adult obesity. Macrosomic animals at birth typically remain large and are also obese as adults. Our goal was to examine the differences between animals that reach obesity in different ways. We also aimed to examine gene expression in animals that start out lean and stay lean compared to those that start out lean and become fat.

We used microarrays to detail gene expression in adipose tissue.

Overall design: 3 samples each from IUGR animals with rapid postnatal growth (IH), IUGR animals with slower postnatal growth (IL), and macromsomic animals (M).

Background corr dist: KL-Divergence = 0.0966, L1-Distance = 0.0243, L2-Distance = 0.0010, Normal std = 0.4445

0.897 Kernel fit Pairwise Correlations Normal fit

Density 0.449

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

IUGR_lowIUGR_low postnatalIUGR_low postnatal growth,IUGR_high postnatal growth, repIUGR_high 1 postnatal(0.11686) growth, repIUGR_high 2 postnatal(0.15754) repgrowth,Macrosomic, 3 postnatal(0.147545) growth, repMacrosomic, 1 (0.072845) repgrowth, repMacrosomic, 1 2(0.127411) (0.07679)rep rep 2 3(0.143566) (0.0973357)rep 3 (0.0601071)[ min ] [ medium ] [ max ] CEM 1 Brpf3 252.9 326.0 455.6 P ( S | Z, I ) = 0.07 Brpf1 453.5 689.9 889.0 Mean Corr = 0.40554 Kat6a 983.2 1241.3 1739.9 Brd1 602.5 613.6 930.8 Ing5 35.5 55.8 91.5 Meaf6 52.6 91.8 131.8 Kmt2b 390.9 638.8 800.1 Spen 251.7 291.3 380.3 2410131K14Rik 3.2 46.6 74.9 Zkscan17 262.7 350.8 535.0 Ankrd26 131.5 233.9 307.1 CEM 1 + Smg7 504.7 645.6 834.0 Top 10 Genes Kat6b 614.3 807.5 947.3 Tmcc1 15.5 142.4 222.1 Ubqln4 601.9 904.6 1002.6 Lbr 1028.6 1271.9 2059.5

Null module GEO Series "GSE11382" 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=GSE11382 Status: Public on May 09 2008 Title: Liver and cecum from mice exposed to aflatoxin B1 (AFB1) and/or Helicobacter hepaticus Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19850960 Summary & Design: Summary: We evaluated aflatoxin B1-induced liver tumor promotion by H. hepaticus. Microarrays of liver and cecum from female mice were used to evaluate the individual and combined transcriptional effects of AFB1 and H. hepaticus

Keywords: Tumor co-promotion study

Overall design: C3H/HeN mice were inoculated with 7 ug/g BW AFB1 or vehicle IP at 10 days of age, and gavaged with H. hepaticus or broth at 3 weeks; necropsied at 40 weeks

Background corr dist: KL-Divergence = 0.0322, L1-Distance = 0.0613, L2-Distance = 0.0051, Normal std = 0.7235

0.624 Kernel fit Pairwise Correlations Normal fit

Density 0.312

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 liver, biologicalAFB1 liver, liver,biologicalAFB1 rep biological 1liver, (0.0819273)AFB1+H. rep biological 2 rep(0.0876184)AFB1+H. hepaticus 1 (0.068226) repControl hepaticus 2 liver,(0.0660686)Control cecum, biological liver,AFB1+H. cecum,biological biological repAFB1+H. biological hepaticus1 rep(0.100649) rep 1 hepaticus(0.157133)2 rep(0.0844484) cecum, 2 (0.0714071) cecum,biological biological[ rep min 1 (0.112662) rep ]2 (0.16986) [ medium ] [ max ] CEM 1 Brpf3 63.5 156.5 500.6 P ( S | Z, I ) = 0.07 Brpf1 253.5 477.8 712.1 Mean Corr = 0.43472 Kat6a 618.2 896.1 2001.6 Brd1 331.9 422.7 931.7 Ing5 52.8 83.0 95.4 Meaf6 117.8 164.3 213.8 Kmt2b 703.7 919.4 1294.5 Spen 218.3 283.3 497.7 2410131K14Rik 5.3 13.9 70.9 Zkscan17 319.0 725.4 1060.3 Ankrd26 153.7 214.8 257.5 CEM 1 + Smg7 654.6 848.3 1308.6 Top 10 Genes Kat6b 341.7 496.7 1008.9 Tmcc1 92.2 160.8 266.5 Ubqln4 674.3 1238.9 1554.7 Lbr 727.1 1230.0 4961.3

Null module GEO Series "GSE20335" 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=GSE20335 Status: Public on Apr 17 2010 Title: Expression analysis data from large T antigen-immortalized murine embryonic fibroblasts (MEFs) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20399150 Summary & Design: Summary: Microarrays were used to examine the genome-wide expression in FIH null, VHL null and VHL/FIH double null MEFs.

We used these data to analyze how deletion of FIH or VHL alone affects gene expression and if VHL and FIH have synergistic effects and differential selectivity on regulating gene expression.

Overall design: To assess how deletion of FIH, VHL or both VHL and FIH affect gene expression genome-wide, we generated FIH null, VHL null and VHL/FIH double null MEFs after adeno-cre virus infection on large T-immortalized FIHdf, VHLdf, and VHLdf/FIHdf MEFs. These MEFs were cultured under normoxia (21% O2) with complete culture medium before RNA extraction. Total RNA were isolated by using the Qiagen RNeasy kit and treated with on-column DNase digestion. Affymetrix GeneChip Mouse Genome 430 2.0 Array was used.

Background corr dist: KL-Divergence = 0.0547, L1-Distance = 0.0269, L2-Distance = 0.0009, Normal std = 0.5587

0.729 Kernel fit Pairwise Correlations Normal fit

Density 0.365

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-typeWild-type MEFs,FIH biological MEFs, nullFIH MEFs, biological null rep1 VHLbiological MEFs, (0.0908019) nullrep2 VHLbiological MEFs, (0.0602389) rep1 nullVHL/FIH (0.160193)biological MEFs, rep2VHL/FIH (0.183779)biologicalnull rep1 MEFs, null(0.287511) rep2 biological MEFs, (0.0597088) biological rep1 (0.043478) [rep2 min (0.114289) ] [ medium ] [ max ] CEM 1 Brpf3 214.2 304.2 345.4 P ( S | Z, I ) = 0.07 Brpf1 827.5 914.6 975.0 Mean Corr = 0.26324 Kat6a 1080.2 1341.5 1467.8 Brd1 643.4 702.9 823.3 Ing5 148.5 218.9 300.8 Meaf6 125.6 151.5 167.3 Kmt2b 420.0 521.7 641.4 Spen 196.8 323.3 451.7 2410131K14Rik 72.1 181.5 231.0 Zkscan17 772.5 1173.8 1274.8 Ankrd26 421.9 542.6 737.2 CEM 1 + Smg7 610.2 878.4 971.0 Top 10 Genes Kat6b 464.6 598.0 652.6 Tmcc1 14.3 50.8 58.7 Ubqln4 1026.6 1786.6 1848.8 Lbr 5827.2 6174.9 6426.6

Null module GEO Series "GSE17794" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 44 -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=GSE17794 Status: Public on Jan 11 2010 Title: Expression data from B6C3F1 mice treated with 2-butoxyethanol Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.

Overall design: Mice were euthanased by cervical dislocation under ketamine / acepromazine (100 mg/kg / 5 mg/kg, I.P) anesthesia. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 44 arrays.

Background corr dist: KL-Divergence = 0.0249, L1-Distance = 0.0283, L2-Distance = 0.0013, Normal std = 0.6953

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

liver-vehicle-4hours-repliver-vehicle-4hours-repliver-vehicle-4hours-repliver-2BE-4hours-rep 1 (0.0295293)liver-2BE-4hours-rep 2 (0.0307577)liver-2BE-4hours-rep 3 (0.0344149) 1liver-2BE-4hours-rep (0.0245376) 2spleen-vehicle-4hours-rep (0.0251168) 3spleen-vehicle-4hours-rep (0.0272701) 4spleen-vehicle-4hours-rep (0.021914)spleen-vehicle-4hours-rep 1 (0.0166208)spleen-2BE-4hours-rep 2 (0.014355)spleen-2BE-4hours-rep 3 (0.0265385)spleen-2BE-4hours-rep 4 (0.030976)spleen-2BE-4hours-rep 1 (0.0126397)liver-vehicle-7days-rep 2 (0.0189811)liver-vehicle-7days-rep 3 (0.0126401)liver-vehicle-7days-rep 4 (0.0117997)liver-vehicle-7days-rep 1 (0.0404117)liver-2BE-7days-rep 2 (0.0332343)liver-2BE-7days-rep 3 (0.0263818)liver-2BE-7days-rep 4 (0.0279283) 1 (0.0393956)liver-2BE-7days-rep 2 (0.0300303)liver-2BE-7days-rep 3 (0.0358064)bone 4marrow-vehicle-7days-rep (0.0378629)bone 5marrow-vehicle-7days-rep (0.0209972)bone marrow-vehicle-7days-repbone marrow-vehicle-7days-repbone 1 (0.0120789) marrow-vehicle-7days-repbone 2 (0.0196737) marrow-2BE-7days-repbone 3 (0.0234619) marrow-2BE-7days-repbone 4 (0.00854941) marrow-2BE-7days-repbone 5 (0.0120235) marrow-2BE-7days-rep 1bone (0.02629) marrow-2BE-7days-rep 2spleen-vehicle-7days-rep (0.0134058) 3spleen-vehicle-7days-rep (0.0255969) 4spleen-vehicle-7days-rep (0.0179554) 5spleen-vehicle-7days-rep (0.00723278) 1 (0.0193146)spleen-vehicle-7days-rep 2 (0.00711621)spleen-2BE-7days-rep 3 (0.0124314)spleen-2BE-7days-rep 4 (0.0092585)spleen-2BE-7days-rep 5 (0.00813642) spleen-2BE-7days-rep1 (0.0372902) spleen-2BE-7days-rep2 (0.0383878) 3 (0.0333081) 4 (0.0276289) 5 (0.01072)[ min ] [ medium ] [ max ] CEM 1 Brpf3 415.0 657.9 1911.0 P ( S | Z, I ) = 0.06 Brpf1 525.7 930.2 1290.9 Mean Corr = 0.55452 Kat6a 448.1 1681.9 2119.4 Brd1 508.5 1179.0 1434.8 Ing5 71.2 111.0 221.9 Meaf6 104.5 158.1 198.3 Kmt2b 646.1 1282.6 1480.6 Spen 309.4 588.3 801.5 2410131K14Rik 71.5 85.3 112.3 Zkscan17 600.4 970.5 1232.1 Ankrd26 163.6 273.3 516.9 CEM 1 + Smg7 454.0 967.9 1278.2 Top 10 Genes Kat6b 264.7 408.0 616.0 Tmcc1 156.1 355.9 906.5 Ubqln4 565.0 740.0 990.4 Lbr 506.0 7548.5 17424.1

Null module GEO Series "GSE23119" 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=GSE23119 Status: Public on Aug 03 2010 Title: Effect of vitamin A deficiency (VAD) on mouse spermatogonial transcriptome profiles Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23253600 Summary & Design: Summary: The objective of this study was to understand the genetic mechanisms of Vitamin-A-Deficiency (VAD)-induced arrest of spermatogonial stem-cell differentiation. Vitamin A and its derivatives (the retinoids) participate in many physiological processes including vision, cellular differentiation and reproduction. VAD affects spermatogenesis, the subject of our present study. Spermatogenesis is a highly regulated process of differentiation and complex morphologic alterations that, in the postnatal testis, leads to the formation of sperm in the seminiferous epithelium. VAD causes early cessation of spermatogenesis, characterized by degeneration of meiotic germ cells, leading to seminiferous tubules containing mostly type A spermatogonia and Sertoli cells. In this study, we investigated the molecular basis of VAD on spermatogenesis in mice. We used adult Balb/C mice fed with a Control or VAD diet for an extended period of time (8-28 weeks) and selected two time points (18 and 25 weeks) for microarray analysis.

To understand the effect of VAD on the spermatogonial stem cell transcriptome, we studied isolated pure populations of spermatogonia from control and vitamin-A-deficient mice from two representative time points (18 and 25 weeks) using Affymetrix GeneChip microarrays. We identified target genes involved in the arrest of spermatogonial differentiation and spermatogenesis. Our results establish a better understanding of the chronology and magnitude of the consequences of VAD on mouse testes and add to the current knowledge of the molecular regulatory mechanisms of germ cell development.

Overall design: Spermatogonia were isolated by the STATPUT procedure with minor modifications. VAD mice were sacrificed at 18 and 25 weeks of VAD treatment for spermatogonia isolation. Decapsulated testes from 2 mice were suspended in RPMI medium containing collagenase (0.6 mg/ml), Hyaluronidase (0.12 mg/ml) and DNAse I (1.25 mg/ml) and incubated at 37ÂºC for 30 minutes in a shaking water bath. The tissues were then allowed to come down the tube and the supernatant (containing interstitial cells) was removed. The pellet was incubated with 3 ml of 0.25% Trypsin /EDTA (GIBCO, Invitrogen, USA), in the presence of DNAse I (0.2 mg/ml) at 37ÂºC for 15 minutes in a shaking water bath. The dispersed cells were washed twice with RPMI medium containing 10% heat inactivated FBS to neutralize the protease activity, and filtered through a sterile 0.22 nylon to remove any undigested fragments. Cells of the dissociated seminiferous epithelium were then plated overnight in a 34ÂºC 3% CO2 incubator. The following day, germ cells, in suspension, were separated by sedimentation with use of a 2-4% BSA gradient. The cells were allowed to sediment for a standard period of 2.5 h, and fractions of 2-ml volume were collected. The cells of each fraction were examined under a phase contrast microscope, and fractions containing cells of similar size and morphology were pooled and spun down by low-speed centrifugation. Purity of spermatogonia was estimated and was routinely higher than 90%. Total RNA was extracted from the isolated germ cells using TRIzol Â® Reagent, and cleaned with RNeasy minicolumns. RNA content was determined by measurement of optical density at 260 nm. Only the RNA samples showing an OD 260/280 ratio higher than 1.8 were used for microarray hybridization. Raw expression values in Affymetrix CEL file format were generated by GeneChip Operating Software.

Background corr dist: KL-Divergence = 0.0289, L1-Distance = 0.0374, L2-Distance = 0.0019, Normal std = 0.6920

0.576 Kernel fit Pairwise Correlations Normal fit

Density 0.288

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

Normal Normalspermatogonia Normalspermatogonia VADspermatogonia control, spermatogoniaVAD control, rep1 spermatogonia (0.0588785)VAD control, rep2 spermatogonia at (0.101093)VAD 18 rep3 weeks, spermatogonia at (0.264898)VAD 18 weeks,rep1 spermatogonia atVAD 18(0.0212056) weeks,rep2 spermatogonia at 25(0.0467003) weeks,rep3 at 25(0.0248842) weeks,rep1 at 25(0.0613633) weeks,rep2[ (0.0680524) min rep3 (0.352924) ] [ medium ] [ max ] CEM 1 Brpf3 267.0 413.3 759.8 P ( S | Z, I ) = 0.06 Brpf1 333.7 609.5 919.6 Mean Corr = 0.47003 Kat6a 137.2 393.8 1092.7 Brd1 1384.5 1768.2 6453.6 Ing5 10.3 65.2 215.8 Meaf6 233.9 298.9 424.5 Kmt2b 615.1 791.2 1086.3 Spen 513.4 774.9 1225.5 2410131K14Rik 4.4 19.4 72.1 Zkscan17 6391.5 9033.0 11778.8 Ankrd26 72.5 141.5 226.7 CEM 1 + Smg7 509.7 752.9 1138.6 Top 10 Genes Kat6b 196.5 336.7 396.3 Tmcc1 95.8 133.9 405.4 Ubqln4 291.1 512.3 1116.2 Lbr 917.2 1503.2 3042.2

Null module GEO Series "GSE27932" 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=GSE27932 Status: Public on Mar 16 2011 Title: FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17254969 Summary & Design: Summary: Activated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis.

Overall design: Mice were engineered with negative control (MxCre- Fk1 L/L Fk2 L/L Afx L/L) and experimental (MxCre+ Fk1 L/L Fk2 L/L Afx L/L) genotypes. RNAs were isolated from Lung endothelial cells (2 negative controls, 2 experimental), liver sinusoidal endothelial cells (3 negative controls, 3 experimental) and thymus cells (2 negative controls, 2 experimental), and profiled on Affymetrix Mouse Genome 430 2.0 Array.

Background corr dist: KL-Divergence = 0.0486, L1-Distance = 0.0400, L2-Distance = 0.0023, Normal std = 0.5970

0.712 Kernel fit Pairwise Correlations Normal fit

Density 0.356

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 EC,Lung control, EC,Lung control, rep1 EC,Lung (0.101408) experimental, rep2 EC,Liver (0.0835306) experimental, sinusoidalLiver rep1 sinusoidal (0.0411991)Liver rep2EC, sinusoidalcontrol, (0.0736825)Liver EC, sinusoidalcontrol, rep1Liver EC, (0.0439567) sinusoidalcontrol, rep2Liver EC, (0.0142612) sinusoidalexperimental, rep3Thymus, EC, (0.0400427) experimental,Thymus, EC,control, rep1 experimental,Thymus, control, rep1(0.0275759) rep2 Thymus,(0.127538) experimental, rep2(0.0487881) rep3 (0.178537) experimental, (0.0130848) rep1 (0.11936) rep2 (0.0870352)[ min ] [ medium ] [ max ] CEM 1 Brpf3 260.9 319.6 484.0 P ( S | Z, I ) = 0.05 Brpf1 638.8 1008.0 1448.9 Mean Corr = 0.21872 Kat6a 1126.1 1554.0 2883.0 Brd1 720.8 841.9 1503.8 Ing5 49.3 102.7 174.6 Meaf6 93.2 130.3 156.8 Kmt2b 606.1 886.8 2437.6 Spen 573.0 803.5 2144.0 2410131K14Rik 126.4 170.2 254.6 Zkscan17 543.2 702.7 1114.2 Ankrd26 151.1 237.5 554.7 CEM 1 + Smg7 612.7 831.4 1617.3 Top 10 Genes Kat6b 446.5 599.9 931.3 Tmcc1 86.0 117.0 567.3 Ubqln4 454.2 892.0 1078.3 Lbr 1909.6 2206.2 9232.7

Null module GEO Series "GSE44355" 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=GSE44355 Status: Public on Jul 04 2013 Title: Expression data from Adriamycin-treated Emu-myc; Suv39h1-/- B-cell lymphoma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23945590 Summary & Design: Summary: Oncogene-induced senescence (OIS), a terminal cell cycle block countering (pre)neoplastic lesions, is characterised on the molecular level by trimethylated histone H3 lysine 9 (h3K9me3), a transcriptionally repressive chromatin mark linked to silencing of S-phase-promoting genes. Whether H3K9-governed chromatin remodelling influences anticancer treatment-induced senescence (TIS) and whether functional control of this mark impacts on treatment outcome is not known. We used global gene expression profiling by microarrays to gain insight into the molecular responses of Emu-myc; Suv39h1-/- B-cell lymphoma cells to senescence-inducing anticancer agent Adriamycin (ADR).

Overall design: Primary lymphoma cells isolated from lymph nodes of Emu-Myc; Suv39h1-/- mice were used. In this model, the c-Myc oncogene is constitutively expressed in the cells of the B-cell lineage, leading to spontaneous development of aggressive B-cell lymphomas. Adriamycin (ADR), a cytostatic drug used as a standard part of several lymphoma treatment regimens, is known to massively induce TIS in Suv39h1-proficient lymphomas, protected from apoptosis by Bcl-2 over expression (Myc;Bcl2). In order to discern the impact of Suv39h1 to TIS induction under these conditions, we analysed here transcriptional profiles of matched pairs of Emu-myc;Suv39h1-/-;Bcl2 lymphomas, untreated or treated for 5 days with ADR.

Background corr dist: KL-Divergence = 0.0962, L1-Distance = 0.0259, L2-Distance = 0.0011, Normal std = 0.4443

0.898 Kernel fit Pairwise Correlations Normal fit

Density 0.449

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

lymphoma_5783_ntlymphoma_5783_ADRlymphoma_7890_nt (0.0325792)lymphoma_7890_ADR lymphoma_9250_nt(0.0734315) (0.110757)lymphoma_9250_ADR lymphoma_1032_nt(0.0621685) (0.0371898)lymphoma_1032_ADR lymphoma_4936_nt(0.0797952) (0.141689)lymphoma_4936_ADR (0.307661) (0.0815863) (0.073142)[ min ] [ medium ] [ max ] CEM 1 Brpf3 347.0 557.2 624.3 P ( S | Z, I ) = 0.04 Brpf1 1013.4 1434.3 1664.8 Mean Corr = 0.54489 Kat6a 781.4 1246.8 1446.8 Brd1 608.6 952.2 1195.8 Ing5 86.6 112.0 130.8 Meaf6 68.2 94.9 121.3 Kmt2b 675.5 895.4 1276.1 Spen 229.0 421.4 532.4 2410131K14Rik 67.4 84.1 122.1 Zkscan17 533.1 884.1 1860.5 Ankrd26 87.5 264.7 403.1 CEM 1 + Smg7 600.6 983.7 1416.4 Top 10 Genes Kat6b 256.3 584.5 650.9 Tmcc1 37.2 60.6 76.4 Ubqln4 896.5 1363.2 1735.9 Lbr 3881.6 8062.4 11212.8

Null module GEO Series "GSE45430" 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=GSE45430 Status: Public on Mar 23 2013 Title: Sox4 is a key oncogenic target in C/EBPÎ± mutant Acute Myeloid Leukemia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24183681 Summary & Design: Summary: Mutation or epigenetic silencing of the transcription factor C/EBPÎ± is observed in ~10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but down-stream targets relevant for leukemogenesis are not known. Here we identify Sox4 as a direct target of C/EBPÎ± whereby its expression is inversely correlated with C/EBPÎ± activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia initiating cells (LICs) from both Sox4 overexpression and murine mutant C/EBPÎ± AML models clustered together, but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBPÎ± inactivation contributes to the development of leukemias with a distinct LIC phenotype.

Overall design: K/L (bi-allelic Cebpa mutations) leukemic mice and Sox4 overexprssing leukemic mice were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the C57/BL6 wild type mice.

Background corr dist: KL-Divergence = 0.0498, L1-Distance = 0.0448, L2-Distance = 0.0033, Normal std = 0.5848

0.766 Kernel fit Pairwise Correlations Normal fit

Density 0.383

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

FrII_Wildtype_BL6_mice_1FrII_Wildtype_BL6_mice_2FrII_Wildtype_BL6_mice_3FrII_Leukemic_Sox4_mice_1 (0.0898015)FrII_Leukemic_Sox4_mice_2 (0.0960408)FrII_Leukemic_Sox4_mice_3 (0.382467)FrII_Leukemic_K\L_mice_1 (0.192424)FrII_Leukemic_K\L_mice_2 (0.0387821)FrII_Leukemic_K\L_mice_3 (0.0446325) (0.0500056) (0.0530877) (0.052759)[ min ] [ medium ] [ max ] CEM 1 Brpf3 314.4 474.7 561.2 P ( S | Z, I ) = 0.03 Brpf1 233.9 531.5 760.9 Mean Corr = 0.56128 Kat6a 1608.8 2199.2 2297.4 Brd1 1411.2 2183.7 2304.7 Ing5 241.9 346.3 469.3 Meaf6 163.3 261.5 416.3 Kmt2b 122.7 494.4 604.9 Spen 127.2 421.5 483.2 2410131K14Rik 68.4 91.4 120.1 Zkscan17 410.4 522.0 609.7 Ankrd26 81.7 111.0 146.4 CEM 1 + Smg7 2979.9 3829.8 4337.6 Top 10 Genes Kat6b 144.2 192.7 240.0 Tmcc1 46.6 64.6 153.4 Ubqln4 1411.1 2609.1 3467.4 Lbr 4516.4 5125.0 6042.2

Null module GEO Series "GSE21716" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 28 -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=GSE21716 Status: Public on Oct 01 2010 Title: Hepatic xenobiotic metabolizing enzyme gene expression through the life stages of the mouse Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Using full-genome arrays, the expression of all XMEs was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver and compared to young adults. Fetal and neonatal life stages had a dramatic effect on XME expression compared to the relatively minor effects of old age. At all life stages except PND30 down-regulated genes outnumbered up-regulated genes. The altered XMEs included those in all of the major metabolic phases including phase I (alcohol and aldehyde dehydrogenase and Cyp genes), phase II (aldo-keto reductase, glutathione-S-transferases, sulfotransferases and UDP-glucuronosyl transferases) and phase III (transporters). We have generated a comprehensive catalog of XME hepatic gene changes through the life stages of the mouse that can be used to predict chemicals and chemical classes different life stages are more sensitive to. Some CEL files used in this study have been submitted through GSE21224.

Keywords: gene expression/microarray

Overall design: We characterized gene expression changes in the developing mouse liver at gestational days (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver using full-genome microarrays and compared these changes to that in the adult liver.. We also compared results to GD19, PND32, and PND67 C3H mice. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 28 samples, four mice in each of the age groups for C57BL/6 and C3H, were analyzed.

Background corr dist: KL-Divergence = 0.1189, L1-Distance = 0.0776, L2-Distance = 0.0143, Normal std = 0.4578

1.037 Kernel fit Pairwise Correlations Normal fit

Density 0.519

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 liver_6month_2Mouse liver_6month_11Mouse liver_6month_16Mouse (0.0129198) liver_6month_21Mouse (0.0149029) liver_12month_3Mouse (0.0115669) liver_12month_6Mouse (0.00663853) liver_12month_13Mouse (0.0082212) liver_12month_17Mouse (0.00895914) liver_18month_4Mouse (0.0188347) liver_18month_9Mouse (0.0138925) liver_18month_14Mouse (0.0134066) liver_18month_19Mouse (0.0034957) liver_24month_25Mouse (0.00861119) liver_24month_29Mouse (0.0051054) liver_24month_33Mouse (0.0199401) liver_24month_34Mouse (0.0187142) liver_C3H_GD19_1Mouse (0.0131509) liver_C3H_GD19_2Mouse (0.0182078) liver_C3H_GD19_3Mouse (0.15889) liver_C3H_GD19_4Mouse (0.0665555) liver_C3H_PD32_1Mouse (0.163845) liver_C3H_PD32_2Mouse (0.287571) liver_C3H_PD32_3Mouse (0.0221199) liver_C3H_PD32_4Mouse (0.00696856) liver_C3H_PD67_1Mouse (0.0149005) liver_C3H_PD67_2Mouse (0.0097143) liver_C3H_PD67_3Mouse (0.0233711) liver_C3H_PD67_4 (0.0134649) (0.0274397) (0.00859313)[ min ] [ medium ] [ max ] CEM 1 Brpf3 116.5 174.2 732.3 P ( S | Z, I ) = 0.02 Brpf1 348.8 448.2 773.7 Mean Corr = 0.31222 Kat6a 682.9 873.2 1774.5 Brd1 370.0 540.0 1198.1 Ing5 60.6 94.7 461.9 Meaf6 55.0 106.0 134.4 Kmt2b 458.2 651.6 1666.3 Spen 155.6 272.1 798.7 2410131K14Rik 2.8 53.5 108.1 Zkscan17 349.7 524.7 948.6 Ankrd26 139.5 217.8 521.0 CEM 1 + Smg7 396.4 516.1 1093.8 Top 10 Genes Kat6b 191.3 487.9 928.8 Tmcc1 44.0 114.4 292.2 Ubqln4 434.4 718.5 1467.4 Lbr 840.5 1266.8 11613.1

Null module GEO Series "GSE32386" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -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=GSE32386 Status: Public on Apr 01 2012 Title: Expression profiling of murine neuroblastoma in transgenic mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22764207 Summary & Design: Summary: Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK.

Overall design: Expression profiling of murine neuroblastoma driven by MYCN were compared to those driven by mutated ALK or both oncogenes. Mouse normal adrenal tissue served as a control.

Background corr dist: KL-Divergence = 0.0643, L1-Distance = 0.0382, L2-Distance = 0.0025, Normal std = 0.5410

0.775 Kernel fit Pairwise Correlations Normal fit

Density 0.387

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

66389_lo66977_ro (0.09113)66977_ru (0.0652897)70660_lu (0.0231234)74128_wlr (0.0617918)74128_wr (0.136054)74129_wl (0.187752)C57Bl6_1 (0.0846474)C57Bl6_2 (0.0647239)C57Bl6_3 (0.084553)86823-2x (0.0858903)82743-lo (0.0398928)77204-10 (0.0274673) (0.0476842) [ min ] [ medium ] [ max ] CEM 1 Brpf3 120.1 190.5 322.9 P ( S | Z, I ) = 0.02 Brpf1 610.1 954.5 1366.0 Mean Corr = 0.44052 Kat6a 541.1 1051.3 1534.2 Brd1 498.5 1001.0 1479.3 Ing5 50.6 57.0 93.7 Meaf6 48.5 73.2 117.9 Kmt2b 590.6 942.8 1434.3 Spen 176.2 256.4 324.8 2410131K14Rik 63.2 106.2 126.7 Zkscan17 575.3 1200.6 1644.8 Ankrd26 178.3 598.9 1081.1 CEM 1 + Smg7 575.3 1062.4 1506.0 Top 10 Genes Kat6b 391.6 893.8 1424.4 Tmcc1 82.7 110.9 326.3 Ubqln4 885.4 1180.5 1951.5 Lbr 990.6 2206.3 4251.8

Null module GEO Series "GSE17266" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 59 -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=GSE17266 Status: Public on Jan 12 2010 Title: Expression data from B6C3F1 mice treated with baclofen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.

Overall design: Mice were sacrificed by cervical dislocation after either a single dose (1day) or 5 daily doses (5 days) of either baclofen or 0.5% methylcellulose two hours after the last dose. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 59 arrays.

Background corr dist: KL-Divergence = 0.0198, L1-Distance = 0.0483, L2-Distance = 0.0033, Normal std = 0.7864

0.507 Kernel fit Pairwise Correlations Normal fit

Density 0.254

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

liver-vehicle-1day-repliver-baclofen-1day-repliver-baclofen-1day-rep 1liver-vehicle-1day-rep (0.0330468)liver-baclofen-1day-rep 1 (0.0262851)liver-vehicle-1day-rep 2 (0.0263061) 2liver-baclofen-1day-rep (0.024532)liver-vehicle-5day-rep 3 (0.0201116) 3liver-baclofen-5day-rep (0.0278621)liver-vehicle-5day-rep 4 (0.020014) 1liver-baclofen-5day-rep (0.0315682)liver-vehicle-5day-rep 1 (0.0172592) 2liver-baclofen-5day-rep (0.0239365)liver-vehicle-5day-rep 2 (0.0244683) 3liver-baclofen-5day-rep (0.0239513)liver-baclofen-5day-rep 3 (0.0171682) 4liver-baclofen-5day-rep (0.0198013)liver-baclofen-5day-rep 4 (0.018033)liver-baclofen-5day-rep 5 (0.0157211)bone 6 (0.0173974) marrow-vehicle-1day-repbone 7 (0.0240243) marrow-baclofen-1day-repbone 8 (0.0217414) marrow-vehicle-1day-repbone marrow-baclofen-1day-repbone 1 (0.0264931) marrow-vehicle-1day-repbone 1 (0.0115695) marrow-baclofen-1day-repbone 2 (0.00875933) marrow-vehicle-1day-repbone 2 (0.0071122) marrow-baclofen-1day-repbone 3 (0.0100545) marrow-vehicle-5day-repbone 3 (0.0176857) marrow-baclofen-5day-repbone 4 (0.0113356) marrow-vehicle-5day-repbone 4 (0.0118086) marrow-baclofen-5day-repbone 1 (0.01365) marrow-vehicle-5day-repbone 1 (0.0122651) marrow-baclofen-5day-repbone 2 (0.00778733) marrow-vehicle-5day-repbone 2 (0.0153765) marrow-baclofen-5day-repbone 3 (0.00868874) marrow-baclofen-5day-repbone 3 (0.0121015) marrow-baclofen-5day-repbone 4 (0.0100106) marrow-baclofen-5day-repbone 4 (0.0135582) marrow-baclofen-5day-repspleen-vehicle-1day-rep 5 (0.014841)spleen-baclofen-1day-rep 6 (0.00900633)spleen-vehicle-1day-rep 7 (0.0177347)spleen-baclofen-1day-rep 1 8 (0.0422847) (0.0108527)spleen-vehicle-1day-rep 1 (0.0233274)spleen-baclofen-1day-rep 2 (0.015321)spleen-vehicle-1day-rep 2 (0.00499555)spleen-baclofen-1day-rep 3 (0.0241001)spleen-vehicle-5day-rep 3 (0.00785355)spleen-baclofen-5day-rep 4 (0.00461361)spleen-vehicle-5day-rep 4 (0.00778555)spleen-baclofen-5day-rep 1 (0.0103626)spleen-vehicle-5day-rep 1 (0.0147768)spleen-baclofen-5day-rep 2 (0.0171673)spleen-vehicle-5day-rep 2 (0.0198867)spleen-baclofen-5day-rep 3 (0.0184142)spleen-baclofen-5day-rep 3 (0.010117)spleen-baclofen-5day-rep 4 (0.0218436)spleen-baclofen-5day-rep 4 (0.00921001)spleen-baclofen-5day-rep 5 (0.0132886) 6 (0.0249121) 7 (0.00544388) 8 (0.0203765)[ min ] [ medium ] [ max ] CEM 1 Brpf3 371.4 582.9 1135.1 P ( S | Z, I ) = 0.02 Brpf1 547.1 1087.0 1519.5 Mean Corr = 0.47731 Kat6a 604.3 1850.4 2663.9 Brd1 457.1 1153.2 1485.2 Ing5 50.9 93.3 165.5 Meaf6 120.4 160.1 239.9 Kmt2b 753.8 1154.4 1786.9 Spen 371.2 520.5 736.8 2410131K14Rik 58.1 81.2 110.0 Zkscan17 637.9 999.3 1304.5 Ankrd26 146.8 267.4 400.4 CEM 1 + Smg7 574.5 1019.3 1453.5 Top 10 Genes Kat6b 310.0 408.9 654.7 Tmcc1 156.5 396.1 800.3 Ubqln4 599.1 965.6 1371.1 Lbr 537.3 6434.1 16903.7

Null module GEO Series "GSE12454" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -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=GSE12454 Status: Public on Aug 01 2009 Title: The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18842153 Summary & Design: Summary: Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.

Overall design: At P0.5, n = 4 biological replicates of littermate-matched wt/ko pairs (for pair #2 there is one wt and 2 Atrx-null samples (2A & 2B) and we count this as 2 pairs).

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0308, L2-Distance = 0.0011, Normal std = 0.6463

0.648 Kernel fit Pairwise Correlations Normal fit

Density 0.324

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

E13.5 wildE13.5 type wildE13.5 #1 type(0.193651) wildE13.5 #2 type(0.0378699) Atrx-nullE13.5 #3 (0.0961311) Atrx-null E13.5#1 (0.128925) Atrx-null P0.5#2 (0.0490425) wild P0.5#3 type (0.0981302) wild #1P0.5 type(0.0671487) wild #2P0.5 type(0.0469723) Atrx-null #3P0.5 (0.0424492) Atrx-null #1P0.5 (0.0566485) Atrx-null #2AP0.5 (0.0397005) Atrx-null #2B (0.0584599) #3 (0.0848712) [ min ] [ medium ] [ max ] CEM 1 Brpf3 95.5 138.4 207.1 P ( S | Z, I ) = 0.02 Brpf1 448.8 700.2 1003.7 Mean Corr = 0.56108 Kat6a 1982.3 2982.8 3725.7 Brd1 962.5 1397.2 1898.8 Ing5 79.0 110.4 212.0 Meaf6 107.7 120.4 194.1 Kmt2b 1855.5 2209.0 2383.9 Spen 402.3 553.7 677.7 2410131K14Rik 153.9 236.0 280.4 Zkscan17 685.8 1153.7 1463.3 Ankrd26 517.0 669.8 1051.6 CEM 1 + Smg7 527.8 900.8 1291.0 Top 10 Genes Kat6b 2116.4 2942.5 4478.3 Tmcc1 56.4 106.7 173.2 Ubqln4 1512.1 2048.3 2734.7 Lbr 931.7 1317.3 4874.7

Null module GEO Series "GSE27546" 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=GSE27546 Status: Public on Feb 28 2011 Title: Effects of HMGN variants on cellular transcription profile Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21278158 Summary & Design: Summary: HMGN (high mobility group N) is a family of intrinsically disordered nuclear proteins that binds to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family.

Here we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. The results reveal an HMGN-variant specific effect on the fidelity of the cellular transcription profile, indicating that functionally, the various HMGN subtypes are not fully redundant.

Overall design: RNA was collected from either primary knock-out MEFs or SV40-transformed MEFs and MIN6 cells over expressing various HMGN proteins and mutants and hybridized to Affymetrix arrays. We obtained a double ammount of HMGN proteins in MEFs and MIN6 cells by retroviral infection and subsequent selection procedure. We collected all infected cells (pools, not clones) in order to eliminate the effect of viral integration in the genome.

Background corr dist: KL-Divergence = 0.0270, L1-Distance = 0.0406, L2-Distance = 0.0025, Normal std = 0.6975

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

MEFs HMGN1MEFs HMGN1 knockMEFs outHMGN1 knockMEFs rep outHMGN1 1knockMEFs (0.0190359) rep outHMGN1 2WTMEFs (0.0200096) rep rep HMGN1 3WT MEFs 1(0.019611) (0.0189322) rep HMGN3 WT MEFs2 (0.0187139) rep HMGN3 knock MEFs3 (0.0177288) outHMGN3 knockMEFs rep outHMGN3 1knockMEFs (0.0208663) rep outHMGN3 2WTMEFs (0.0194265) rep rep HMGN3 3WT MEFs 1(0.0245734) (0.0208963) rep HMGN5 WT MEFs2 (0.0204011) rep HMGN5 knock MEFs3 (0.0239398) outHMGN5 knockMEFs rep outHMGN5 1knockMEFs (0.0213141) rep outHMGN5 2WTMEFs (0.0239273) rep rep HMGN5 3WT MEFs 1(0.0173263) (0.0190529) rep empty WT MEFs2 (0.0223411) rep vector empty MEFs3 (0.0228915) OEvector emptyMEFs rep OE1vector HMGN1 (0.0129503)MEFs rep OE2 HMGN1 (0.0190005)OEMEFs rep rep 3 HMGN1 (0.0125017)OE1MEFs (0.0317814) rep HMGN2 OE2MEFs (0.0291928) rep HMGN2 OE3MEFs (0.0341392) rep HMGN2 OE1MEFs (0.0097508) rep HMGN3a OE2MEFs (0.00783601) rep HMGN3a 3MEFs OE (0.0074879) rep HMGN3aMEFs OE1 (0.0181746) rep HMGN5MEFs OE2 (0.0155221) rep HMGN5 OEMEFs 3 (0.0190337) rep HMGN5 OE1MEFs (0.00772967) rep HMGN5SE OE2MEFs (0.00880971) rep HMGN5SE 3MEFs (0.0112732) OE repHMGN5SEMEFs OE1 (0.0219389) repHMGN1_N2swapMEFs OE2 (0.0163796) repHMGN1_N2swapMEFs 3 (0.0129906) HMGN1_N2swapMEFs rep 1 HMGN1_N3swap (0.0190962)MEFs rep 2 HMGN1_N3swap (0.0149551)MEFs rep 3 HMGN1_N3swap (0.0109109)MIN6 rep 1empty (0.01263)MIN6 rep vector 2empty (0.0132777)MIN6 rep OEvector 3empty (0.0114432)MIN6 rep OE1vector HMGN1 (0.0213262)MIN6 rep OE2 HMGN1 (0.0274302)OEMIN6 rep rep 3 HMGN1 (0.0248817)OE1MIN6 (0.0262527) rep HMGN3a OE2MIN6 (0.0277022) rep HMGN3a 3 MIN6OE (0.0300403) rep HMGN3a OE1 (0.0332254) rep OE2 (0.0307828) rep 3 (0.028565)[ min ] [ medium ] [ max ] CEM 1 Brpf3 265.5 430.4 752.3 P ( S | Z, I ) = 0.02 Brpf1 672.6 830.9 1062.3 Mean Corr = 0.50333 Kat6a 713.7 1606.9 2556.5 Brd1 573.6 964.8 1381.8 Ing5 34.2 60.8 187.8 Meaf6 52.4 126.4 254.4 Kmt2b 490.6 834.5 1023.0 Spen 205.5 280.6 434.3 2410131K14Rik 41.2 114.3 287.2 Zkscan17 576.7 925.2 2093.8 Ankrd26 167.9 359.5 546.2 CEM 1 + Smg7 519.1 751.6 1030.7 Top 10 Genes Kat6b 272.0 392.2 612.5 Tmcc1 45.4 66.8 127.8 Ubqln4 720.8 1172.3 3382.3 Lbr 1115.5 4361.3 6488.7

Null module GEO Series "GSE13223" 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=GSE13223 Status: Public on Nov 30 2008 Title: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 bone marrow expression data Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19118016 Summary & Design: Summary: F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues

Keywords: Basal transcription profiles

Overall design: Bone Marrow from adult F1 animals from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses was collected and arrayed on Affymetrics chip to identify basal differences in gene expression between the different genotypes

Background corr dist: KL-Divergence = 0.0268, L1-Distance = 0.0196, L2-Distance = 0.0004, Normal std = 0.6966

0.584 Kernel fit Pairwise Correlations Normal fit

Density 0.292

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

bone_marrow_akr1bone_marrow_akr2bone_marrow_akr3 (0.127411)bone_marrow_dba1 (0.246873)bone_marrow_dba2 (0.136951)bone_marrow_dba3 (0.188826) (0.0761252) (0.223815)[ min ] [ medium ] [ max ] CEM 1 Brpf3 1045.8 1479.5 1529.2 P ( S | Z, I ) = 0.01 Brpf1 684.9 1433.9 1611.6 Mean Corr = 0.30085 Kat6a 1907.6 2430.1 2666.2 Brd1 977.9 1016.0 1061.2 Ing5 35.8 49.4 64.7 Meaf6 156.6 170.7 242.2 Kmt2b 952.5 1820.0 2087.8 Spen 274.1 910.4 967.0 2410131K14Rik 37.5 47.8 50.0 Zkscan17 1039.4 1328.5 1621.5 Ankrd26 181.8 217.6 225.9 CEM 1 + Smg7 441.3 650.1 715.0 Top 10 Genes Kat6b 400.9 499.3 574.7 Tmcc1 154.8 287.1 353.7 Ubqln4 669.9 959.2 1224.1 Lbr 11321.2 13456.4 14046.2

Null module GEO Series "GSE16623" 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=GSE16623 Status: Public on Apr 11 2010 Title: Differential gene expression between ERRa KO and WT mouse kidneys Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19901197 Summary & Design: Summary: Estrogen-related receptor (ERR) alpha is an orphan nuclear receptor highly expressed in the kidneys. ERRalpha is implicated in renal sodium and potassium homeostasis and blood pressure regulation. We used microarray analysis to identify differentially expressed genes in ERR alpha knockout mice kidneys versus wild-type. The results provide insight on the roles of ERRalpha in the kidney.

Overall design: Three biological replicates of WT and ERRaKO were performed, for a total of 6 samples. 2-3 month old males of each genotype were used.

Background corr dist: KL-Divergence = 0.0447, L1-Distance = 0.0165, L2-Distance = 0.0003, Normal std = 0.5914

0.678 Kernel fit Pairwise Correlations Normal fit

Density 0.339

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 biologicalWT biological replicateWT biological replicateERRa 1 (0.19656) KO replicateERRa 2 biological(0.0183357) KOERRa 3 biological(0.336354) replicate KO biological replicate 1 (0.109574) replicate 2 (0.118948) 3[ (0.220229) min ] [ medium ] [ max ] CEM 1 Brpf3 529.2 553.7 589.3 P ( S | Z, I ) = 0.01 Brpf1 400.1 453.2 474.5 Mean Corr = 0.44044 Kat6a 986.5 1120.7 1165.9 Brd1 514.5 548.6 559.6 Ing5 84.9 106.5 114.4 Meaf6 55.3 59.1 67.6 Kmt2b 550.5 577.4 615.6 Spen 364.8 401.2 421.2 2410131K14Rik 70.6 85.0 88.1 Zkscan17 610.9 694.4 742.4 Ankrd26 129.0 144.0 157.8 CEM 1 + Smg7 594.4 711.5 728.5 Top 10 Genes Kat6b 363.9 412.5 430.8 Tmcc1 34.1 38.0 41.7 Ubqln4 975.8 1017.0 1050.8 Lbr 1552.4 1780.9 2062.9

Null module GEO Series "GSE41997" 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=GSE41997 Status: Public on Dec 12 2013 Title: Expression data from Dmp1-GFP sorted osteocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24333171 Summary & Design: Summary: Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/Î²-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER˛– deletion mice (ER˛–˛Ocy/˛Ocy) were generated by mating ER˛– floxed mice with Dmp1-Cre mice to determine functions of ERÎ± in osteocytes. Trabecular bone mineral density of female, but not male ER˛–˛Ocy/˛Ocy mice was significantly decreased. Bone formation parameters in ER˛–˛Ocy/˛Ocy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERÎ± in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER˛–, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ER˛–˛Ocy/˛Ocy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or Î²-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERÎ± in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.

Overall design: Wild type and osteocyte-specific Estrogen Receptor alpha knock-out mice were generated. The number of both genotypes of mice was three. Calvarial osteocytes of both genotypes harboring Dmp1-GFP were extracted by sequential enzymatic digestion, followed by FACS Aria sorting and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling.

Background corr dist: KL-Divergence = 0.0479, L1-Distance = 0.0228, L2-Distance = 0.0006, Normal std = 0.5831

0.702 Kernel fit Pairwise Correlations Normal fit

Density 0.351

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

Osteocyte_WT,Osteocyte_WT,Osteocyte_WT, biologicalOsteocyte_ERaKO, biological rep1Osteocyte_ERaKO, biological(0.184384) rep2Osteocyte_ERaKO, (0.12449) rep3 biological (0.0595372) biological rep1 biological(0.262815) rep2 (0.224231) [rep3 min (0.144542) ] [ medium ] [ max ] CEM 1 Brpf3 104.4 123.6 165.3 P ( S | Z, I ) = 0.01 Brpf1 638.6 699.0 723.2 Mean Corr = 0.37503 Kat6a 589.6 710.3 864.6 Brd1 722.1 781.9 987.3 Ing5 35.3 83.3 99.9 Meaf6 78.6 119.7 166.0 Kmt2b 683.6 772.4 841.8 Spen 175.7 224.5 233.7 2410131K14Rik 6.3 12.9 34.4 Zkscan17 953.0 1104.4 1401.8 Ankrd26 268.1 322.0 371.4 CEM 1 + Smg7 598.9 697.8 768.9 Top 10 Genes Kat6b 779.3 1026.0 1115.6 Tmcc1 145.0 189.3 241.2 Ubqln4 529.4 638.9 683.8 Lbr 2469.1 2700.9 2931.0

Null module GEO Series "GSE12432" 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=GSE12432 Status: Public on Jul 12 2010 Title: Microarray data of prepubertal, peripubertal, and adult oocytes, and from GV and MII oocytes matured in vivo or in vitro Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Expression data from prepubertal, peripubertal, and adult derived mouse oocytes, and from germinal vesicle (GV), in vivo matured, and in vitro matured mouse oocytes.

Oocytes derived from prepubertal females, or oocytes matured in vitro, are less developmentally competent compared to adult derived, or in vivo matured, oocytes, indicated by decreased embryonic development. One potential mechanism for decreased developmental potetential in prepubertal or in vitro matured oocytes is inadequate or inappropriate RNA degradation during oocyte maturation (progression from GV to MII).

To investigate mechanisms involved in establishing oocyte cytoplasmic maturation and developmental competence, Affymetrix GeneChip microarrays were used.

Keywords: Oocyte developmental competence

Overall design: The study encompassed three experimental designs using female B6D2F1 mice: 1) In vitro matured oocytes were obtained from d20 (prepubertal), d26 (peripubertal), and 7-8 wk old (adult) mice; 2) in vivo and in vitro matured oocytes were obtained from d26 mice; and 3) GV, in vivo matured, and in vitro matured oocytes were obtained from 7-8 wk old mice. RNA was extracted from pools of 150 oocytes and hybridized onto the Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1390, L1-Distance = 0.0842, L2-Distance = 0.0153, Normal std = 0.4490

0.973 Kernel fit Pairwise Correlations Normal fit

Density 0.486

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

7-8 wk In7-8 Vivo, wk In d26Mmu01 Vitro, In Vitro, d26Mmu02(0.114848) In Mmu05 Vivo,7-8 (0.0557366) wk Mmu07 (0.027924) In7-8 Vivo, wk (0.0235715) GV, d26Mmu08 Mmu11In Vivo,d26 (0.0237059) (0.251142)In Mmu12 Vitro,d20 In Mmu13(0.0188322) Vitro,d26 In Mmu15(0.026956) Vitro,7-8 wk Mmu16(0.0122405) GV,7-8 wkMmu18 (0.0170887) Ind20 Vitro, (0.306393)In Vitro, 7-8Mmu19 wk Mmu22 Ind20 (0.0241851) Vivo, In (0.0522381) Vitro, Mmu23 Mmu24 (0.0377865) (0.00735252)[ min ] [ medium ] [ max ] CEM 1 Brpf3 29.6 76.0 230.5 P ( S | Z, I ) = 0.01 Brpf1 25.0 136.3 409.5 Mean Corr = 0.07780 Kat6a 5.9 73.7 413.7 Brd1 2085.5 6739.2 8744.7 Ing5 18.2 71.5 258.2 Meaf6 16.1 80.2 616.7 Kmt2b 236.4 1517.0 3866.1 Spen 49.4 161.7 300.8 2410131K14Rik 2.3 11.5 66.8 Zkscan17 34.9 560.6 3304.1 Ankrd26 863.9 2210.7 3653.5 CEM 1 + Smg7 50.0 385.0 696.6 Top 10 Genes Kat6b 530.8 1259.1 1853.0 Tmcc1 10.1 49.2 170.1 Ubqln4 139.8 253.7 578.8 Lbr 11770.7 17583.5 33429.1

Null module GEO Series "GSE23782" 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=GSE23782 Status: Public on Sep 15 2010 Title: Adult epidermal Notch activity induces dermal accumulation of stromal cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20940224 Summary & Design: Summary: K14NICDER transgenic and wildtype littermate mice were treated with 4OHT for 14 days to activate the transgene

Epidermis and dermis preparations from Transgenic and Wild type mice plus whole skin

Overall design: We sought to compare gene expression patterns in K14NICDER transgenic epidermis and dermis to wild type controls

Background corr dist: KL-Divergence = 0.0858, L1-Distance = 0.0370, L2-Distance = 0.0027, Normal std = 0.4638

0.860 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

Dermis Dermisfrom Wild Dermisfrom type Wild Dermis fromskin type rep1Wild Dermis fromskin (0.0318912)type rep2Transgenic Dermis fromskin (0.0418945) rep3Transgenic Epidermisfrom skin(0.0112105) Transgenic rep1Epidermis skin from (0.0225631) rep2Epidermis Wild skin from (0.0112062) type rep3Epidermis Wild fromskin (0.0463364) typeEpidermis rep1Wild fromskin (0.359709)typeEpidermis rep2Transgenic fromskin (0.0454832)Whole rep3Transgenic from skin(0.0900872) SkinWhole Transgenic rep1 from skin Skin Whole(0.0246352) Wildrep2 from skin Skin typeWhole(0.0763035) Wildrep3 fromrep1 Skin typeWhole(0.0144546) Wild(0.0288217) fromrep2 SkintypeWhole Transgenic(0.0543292) fromrep3 Skin Transgenic(0.0369977) from rep1 Transgenic (0.0346622) rep2 (0.0390792) rep3[ min (0.0303353) ] [ medium ] [ max ] CEM 1 Brpf3 227.1 392.3 794.6 P ( S | Z, I ) = 0.01 Brpf1 144.1 274.5 607.3 Mean Corr = 0.21028 Kat6a 1923.7 2679.2 3267.1 Brd1 678.1 1745.8 2843.5 Ing5 46.3 151.5 631.1 Meaf6 97.7 171.6 600.5 Kmt2b 247.6 342.1 551.6 Spen 30.1 92.7 173.9 2410131K14Rik 35.4 77.1 182.9 Zkscan17 172.8 312.1 467.6 Ankrd26 20.0 47.2 118.2 CEM 1 + Smg7 1974.7 2812.8 5887.8 Top 10 Genes Kat6b 119.9 323.2 466.1 Tmcc1 52.3 121.4 181.8 Ubqln4 775.6 2316.5 3405.9 Lbr 440.0 1936.4 2305.4

Null module GEO Series "GSE45618" 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=GSE45618 Status: Public on Mar 29 2013 Title: Expression analysis of BL6 murine megakaryocyte progenitors from bone marrow and fetal Liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.

kewywords: Mouse megakaryocyte progenitors

Overall design: Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from C57/BL6 murine fetal liver and bone marrow

Background corr dist: KL-Divergence = 0.0460, L1-Distance = 0.0371, L2-Distance = 0.0020, Normal std = 0.6078

0.669 Kernel fit Pairwise Correlations Normal fit

Density 0.335

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_MKP_BM_1WT_MKP_BM_2WT_MKP_BM_3 (0.0325324)WT_MKP_FL_1 (0.300164)WT_MKP_FL_2 (0.274869)WT_MKP_FL_3 (0.233461) (0.109566) (0.049408) [ min ] [ medium ] [ max ] CEM 1 Brpf3 223.4 347.2 457.7 P ( S | Z, I ) = 0.01 Brpf1 261.1 464.5 828.6 Mean Corr = 0.12611 Kat6a 2032.9 2650.3 3306.1 Brd1 1634.2 2609.7 3572.6 Ing5 402.6 652.4 889.4 Meaf6 104.3 362.2 481.2 Kmt2b 447.8 511.7 1228.1 Spen 75.7 112.5 182.9 2410131K14Rik 2.8 35.2 116.3 Zkscan17 431.7 559.0 673.0 Ankrd26 56.5 81.8 119.8 CEM 1 + Smg7 3102.5 4392.5 4768.9 Top 10 Genes Kat6b 55.7 131.4 161.5 Tmcc1 18.2 30.5 50.0 Ubqln4 5930.8 7249.8 7678.7 Lbr 3888.0 4484.5 4755.2

Null module GEO Series "GSE44175" 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=GSE44175 Status: Public on Feb 09 2013 Title: Expression data from mouse embyonic stem cell, neural progenitor and neuron Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23775126 Summary & Design: Summary: The effect of HMGN1 protein on gene expression of mouse ESC, NP and Neurons were investigated by comparing the transcriptome between Hmgn1+/+ and Hmgn1 -/- cells.

Overall design: three cell types, two genotypes, three reps per sample type

Background corr dist: KL-Divergence = 0.0123, L1-Distance = 0.0320, L2-Distance = 0.0019, Normal std = 0.8462

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

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

EmbyonicEmbyonic stemEmbyonic cell, stem Hmgn1+/+,Neural cell, stem Hmgn1+/+, progenitor,Neural cell, biological Hmgn1+/+, progenitor,Neural biological Hmgn1+/+, rep1 progenitor,Neuron, biological (0.0720045) Hmgn1+/+, rep2Neuron, biological Hmgn1+/+, (0.0607275) Hmgn1+/+, rep3Neuron, biological Hmgn1+/+, (0.0658218)rep1 biologicalEmbyonic biological(0.0131589)Hmgn1+/+, rep2 biologicalEmbyonic rep1(0.0156782) stem rep3 biological(0.0568564)Embyonic rep2cell,(0.0103659) stem (0.0652427)Hmgn1-/-,Neural rep3cell, stem (0.0595592)Hmgn1-/-, progenitor,Neural cell, biological Hmgn1-/-, progenitor,Neural biological Hmgn1-/-,rep1 progenitor,Neuron, biological(0.072125) Hmgn1-/-,rep2 biologicalNeuron, Hmgn1-/-, (0.0838619) Hmgn1-/-,rep3 biologicalNeuron, Hmgn1-/-, (0.10695)rep1 biological biological(0.00498674) Hmgn1-/-, rep2 biological rep1(0.00617233) rep3 biological(0.0793373) rep2(0.0278498) (0.100605) rep3[ min (0.0986975) ] [ medium ] [ max ] CEM 1 Brpf3 146.5 260.2 332.4 P ( S | Z, I ) = 0.01 Brpf1 515.7 1046.4 1320.1 Mean Corr = 0.32197 Kat6a 660.7 1050.8 1245.9 Brd1 688.9 835.8 1016.4 Ing5 31.7 56.7 85.3 Meaf6 62.9 118.1 174.2 Kmt2b 488.2 640.5 1140.3 Spen 144.5 188.1 451.6 2410131K14Rik 44.3 75.5 105.6 Zkscan17 886.5 1282.1 1434.6 Ankrd26 269.0 321.4 389.2 CEM 1 + Smg7 377.0 605.8 1247.2 Top 10 Genes Kat6b 494.5 1122.8 3229.1 Tmcc1 50.4 113.5 166.0 Ubqln4 444.5 1077.3 2368.2 Lbr 1962.2 7044.2 10909.2

Null module GEO Series "GSE13364" 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=GSE13364 Status: Public on Oct 28 2008 Title: Expression data from BWF1 mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20200542 Summary & Design: Summary: Microarray analysis was performed on BWF1 mice spleenocyte cells in control and pCONS treated mice.

Microarray analysis identified many genes differentially expressed in control vs pCONS treated mice spleenocytes. Some of the genes were uperegulated and some of the genes were down regulated. Microarray analysis was performed in CD4, CD8, and whole spleenocyte WBC cells.

Keywords: One week after pCONS injection

Overall design: RNA was isolated from the mice spleenocytes from control and pCONs treated mice one week after treatment.

Background corr dist: KL-Divergence = 0.0420, L1-Distance = 0.0205, L2-Distance = 0.0005, Normal std = 0.6072

0.660 Kernel fit Pairwise Correlations Normal fit

Density 0.330

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

CD4 NaÃ¯veCD4 pCONS(0.159495)CD8 NaÃ¯ve(0.00691035)CD8 pCONS(0.166331)WBC (0.191899)NaÃ¯veWBC pCONS(0.110914) (0.364451) [ min ] [ medium ] [ max ] CEM 1 Brpf3 275.0 386.1 575.1 P ( S | Z, I ) = 0.00 Brpf1 846.6 1630.0 1876.5 Mean Corr = 0.26489 Kat6a 2105.8 3994.0 4307.3 Brd1 900.9 1283.8 1579.2 Ing5 247.9 326.7 410.1 Meaf6 150.9 295.8 365.0 Kmt2b 1233.8 1912.7 2470.6 Spen 689.0 935.6 1176.8 2410131K14Rik 52.2 170.9 235.7 Zkscan17 397.1 897.2 1037.7 Ankrd26 364.9 450.3 671.7 CEM 1 + Smg7 1035.6 1136.5 1302.7 Top 10 Genes Kat6b 448.4 691.3 940.6 Tmcc1 89.0 245.4 283.0 Ubqln4 554.6 901.1 1011.0 Lbr 5495.6 8299.3 9215.3

Null module 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 "GSE3126" 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=GSE3126 Status: Public on Dec 31 2005 Title: Comparison of HNF4 null mouse embryonic livers with control mouse embryonic livers Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16714383 Summary & Design: Summary: To study the role of hepatic nuclear factor alpha (HNF4a in hepatogenesis, we used loxP-Cre technology to eliminate it from developing mouse livers.

A comparison of control and experimental livers revealed that hepatocytes lacking HNF4a_failed to fully differentiate. Specifically, HNF4a null liver cells failed to express genes that are markers of mature hepatocytes including Gys2, Pck1, and G6pc. These cells also failed to form normal cellular junctions, which are critical for establishment of the hepatic epithelium [Parviz et al. (2003) Nat.Genet. 34, 292-96]. Because HNF4a functions as a transcription factor, we hypothesized that it regulates liver development by controlling the expression of genes whose products are essential in executing cellular differentiation and morphogenesis. To identify these genes, we compared expression profiles between HNF4a null and wild type E18.5 fetal livers using Affymetrix gene arrays. We identified 564 genes whose expression was decreased by at least 2.5-fold and 34 genes whose expression was increased by at least 2.5-fold when HNF4a was eliminated from hepatocytes. These represent genes involved in diverse molecular pathways, reflecting the pleiotropic phenotype of HNF4a null livers. Our goal was to use the information from the gene arrays to define the mechanisms through which HNF4a controls the generation of the hepatic epithelium. We identified 27 genes from our list of downregulated genes with either defined or predicted roles in cellular junctions and/or adhesion. Most striking was that loss of HNF4a altered the expression of genes encoding proteins involved in virtually all types of cellular junctions including tight junctions (Cldn1, Cldn-2, Cldn-12, Ocln, F11r/Jam1, Cxadr, Crb3), adherens junctions (Cdh1), desmosomes (Dsc2, Pkp2, Krt2-8), and gap junctions (Gjb1, Gjb2). Using immunoblotting and immunohistochemistry, we found that the expression of proteins representing each of these junction types was reduced or absent. Analysis of these genes for the presence of putative HNF4a binding sites revealed that 25 of 27 contain such sites. We have used chromatin immunoprecipitation to confirm that HNF4a occupies several of these sites in vivo, including Cdh1, Cldn1, and F11r/Jam1. From these data, we conclude that HNF4a is a central mediator of the fully differentiated hepatocyte gene expression program and that it orchestrates the expression of cell junction and adhesion proteins required for establishing the hepatic epithelium.

Keywords: E18.5 fetal hnf4 null and control mouse livers

Overall design: comparison of three hnf4 null livers to three control

Background corr dist: KL-Divergence = 0.0251, L1-Distance = 0.0111, L2-Distance = 0.0001, Normal std = 0.6969

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

HNF4 Control_8HNF4 Control_1192HNF4 (0.100592) Control_1193HNF4 (0.0354675) Null_61HNF4 (0.200726) Null_1191 (0.41271)HNF4 Null_1195 (0.0475474) (0.202957) [ min ] [ medium ] [ max ] CEM 1 Brpf3 281.1 322.8 562.4 P ( S | Z, I ) = 0.00 Brpf1 368.2 476.2 551.1 Mean Corr = 0.47279 Kat6a 688.0 825.5 956.0 Brd1 348.0 374.9 498.7 Ing5 59.5 76.9 82.1 Meaf6 78.2 117.1 141.7 Kmt2b 491.8 569.5 704.3 Spen 477.9 565.1 1092.6 2410131K14Rik 194.3 256.4 287.5 Zkscan17 460.3 499.2 589.7 Ankrd26 239.8 320.0 363.6 CEM 1 + Smg7 510.8 623.6 720.8 Top 10 Genes Kat6b 192.9 229.9 318.3 Tmcc1 49.6 93.8 130.5 Ubqln4 580.7 676.7 821.0 Lbr 5295.3 7066.5 7409.4

Null module GEO Series "GSE57425" 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=GSE57425 Status: Public on May 09 2014 Title: Gene expression data of livers from C57BL/6 fed a normal diet or high-fat-diet Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Obesity is tightly associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms of obesity-induced fatty liver remain largely unknown.In order to identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, we performed a clustering analysis of Affymetrix arrays,which revealed that a number of mRNAs were dys-regulated in the livers of mice fed a high-fat diet (HFD), compared with mice fed a normal chow diet (ND).

Overall design: To identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, male C57BL/6 mice aged 8 weeks were fed a normal diet (ND) or high-fat-diet (HFD) containing 60 Kcal% of fat for 12 weeks. Then mice were sacrificed and total RNAs were isoloated from hepatic tissues. Affymetrix array hybridisation and scanning were performed using Mouse Genome 430 2.0 chips.Total RNA samples obtained from six mice per group (ND and HFD) and pooled by each of the two were used for microarray analysis.

Background corr dist: KL-Divergence = 0.0199, L1-Distance = 0.0231, L2-Distance = 0.0008, Normal std = 0.7367

0.542 Kernel fit Pairwise Correlations Normal fit

Density 0.271

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

Normal Normaldiet 1 (0.164323) Normaldiet 2 (0.0374712) Highdiet 3fat (0.391885)High diet fat1 (0.050829)High diet fat2 (0.119808) diet 3 (0.235684) [ min ] [ medium ] [ max ] CEM 1 Brpf3 359.1 466.1 623.1 P ( S | Z, I ) = 0.00 Brpf1 331.3 443.2 526.5 Mean Corr = 0.41319 Kat6a 540.9 730.2 775.0 Brd1 267.3 370.9 433.3 Ing5 70.3 86.7 118.7 Meaf6 78.0 94.3 112.8 Kmt2b 340.3 403.0 527.9 Spen 287.8 327.2 395.4 2410131K14Rik 73.3 103.3 110.9 Zkscan17 520.4 860.1 924.9 Ankrd26 163.9 188.9 223.5 CEM 1 + Smg7 263.3 322.8 497.4 Top 10 Genes Kat6b 218.8 263.7 399.8 Tmcc1 93.4 119.6 153.5 Ubqln4 748.1 776.0 976.6 Lbr 329.4 393.6 450.0

Null module GEO Series "GSE9249" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 28 -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=GSE9249 Status: Public on Nov 01 2007 Title: Gene expression analysis of B-NHL from ˛»MYC, ˛»MYC/I´HABCL6, ˛»MYC/AIDKO and ˛»MYC/I´HABCL6/AIDKO mouse models Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18066064 Summary & Design: Summary: Most human B cell lymphomas (B-NHL) are derived from germinal centers (GCs), the structure where B-cells undergo class switch recombination (CSR) and somatic hypermutation (SHM) and are selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant somatic hypermutation, which appear to arise from mistakes occurring during CSR and SHM. To ascertain the role of CSR and SHM in lymphomagenesis, we crossed three oncogene-driven (MYC, BCL6, MYC/BCL6) mouse models of B cell lymphoma with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both processes.

We show that AID deficiency prevents BCL6-dependent, GC-derived B-NHL, while it has no impact on the formation of MYC-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of both CSR- and SHM-mediated structural alterations, including cMYC-IgH chromosomal translocations and aberrant SHM. These results demonstrate that AID is required for GC-derived lymphomagenesis, providing direct support to the notion that errors in AID-mediated antigen-receptor gene modification events represent major contributors to the pathogenesis of human B-NHL.

Keywords: Phenotypic characterization of tumors developing in oncogene-driven mouse models of lymphomas

Overall design: Nodal B-NHL from 5 MYC, 7 MYC/AIDKO, 12 MYC/HABCL6 and 6 MYC/HABCL6/AIDKO mice were analyzed in this study. Total RNA was extracted from frozen tumor biopsies and processed according to Affymetrix standard protocols

Background corr dist: KL-Divergence = 0.3116, L1-Distance = 0.0597, L2-Distance = 0.0098, Normal std = 0.2778

1.436 Kernel fit Pairwise Correlations Normal fit

Density 0.718

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

LymphomaLymphoma lambdaLymphoma lambdaMYCtgLymphoma lambda1MYCtg (0.0488782)Lymphoma lambda2MYCtg (0.0200044)Lymphoma lambda3MYCtg (0.0696815)Lymphoma lambda4MYCtg (0.00559201)Lymphoma lambda5MYCtg/AIDKO (0.0174141)Lymphoma lambdaMYCtg/AIDKOLymphoma lambda1MYCtg/AIDKO (0.127167)Lymphoma lambda2MYCtg/AIDKO (0.0331359)Lymphoma lambda3MYCtg/AIDKO (0.0141731)Lymphoma lambda4MYCtg/I´HABCL6KI (0.0197779)Lymphoma lambda5MYCtg/I´HABCL6KI (0.0551558)Lymphoma lambdaMYCtg/I´HABCL6KILymphoma 1 lambda(0.00801821)MYCtg/I´HABCL6KILymphoma 2 lambda(0.0448011)MYCtg/I´HABCL6KILymphoma 3 lambda(0.103292)MYCtg/I´HABCL6KILymphoma 4 lambda(0.0367241)MYCtg/I´HABCL6KILymphoma 5 lambda(0.0347523)MYCtg/I´HABCL6KILymphoma 6 lambda(0.0677887)MYCtg/I´HABCL6KILymphoma 7 lambda(0.013997)MYCtg/I´HABCL6KILymphoma 8 lambda(0.0157245)MYCtg/I´HABCL6KILymphoma 9 lambda(0.00427603)MYCtg/I´HABCL6KILymphoma 10 lambdaMYCtg/I´HABCL6KI/AIDKO (0.00712746)Lymphoma 11 lambdaMYCtg/I´HABCL6KI/AIDKO (0.0569099)Lymphoma 12 lambdaMYCtg/I´HABCL6KI/AIDKO (0.0236693)Lymphoma lambdaMYCtg/I´HABCL6KI/AIDKO 1 lambda(0.0461949)MYCtg/I´HABCL6KI/AIDKO 2 (0.0177954)MYCtg/I´HABCL6KI/AIDKO 3 (0.0481527)[ 4min (0.023545) 5 (0.0199734)] 6 (0.0162775)[ medium ] [ max ] CEM 1 Brpf3 72.6 185.7 362.4 P ( S | Z, I ) = 0.00 Brpf1 917.7 1610.6 2158.7 Mean Corr = 0.36226 Kat6a 946.1 1565.5 2503.8 Brd1 558.3 938.3 1509.6 Ing5 48.9 165.0 227.1 Meaf6 107.2 165.0 362.0 Kmt2b 659.0 1317.6 2374.0 Spen 195.7 521.0 1050.8 2410131K14Rik 9.8 54.9 127.0 Zkscan17 343.9 1307.9 2120.6 Ankrd26 224.7 471.2 713.8 CEM 1 + Smg7 671.1 998.6 1640.6 Top 10 Genes Kat6b 337.9 549.2 1445.4 Tmcc1 77.4 155.4 493.2 Ubqln4 1401.8 2045.9 2703.0 Lbr 7675.2 13234.4 17109.6

Null module GEO Series "GSE30868" 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=GSE30868 Status: Public on Feb 23 2013 Title: Parthenogenetic stem cells for tissue-engineered heart repair Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23434590 Summary & Design: Summary: Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.

Overall design: - ESC_3

Background corr dist: KL-Divergence = 0.0306, L1-Distance = 0.0233, L2-Distance = 0.0006, Normal std = 0.6786

0.607 Kernel fit Pairwise Correlations Normal fit

Density 0.303

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

ParthenogeneticParthenogeneticParthenogenetic stem Embryoidcells stem sample Embryoidcells stem body sample1 Embryonic(PSC_1)cells (EB) body sample2assays Embryonic(PSC_2) (EB)(0.0433533) stem 3assaysof Embryonic(PSC_3) parthenogenetic(0.0996923) cells stem of sample parthenogenetic(0.134695) cells stem sample1 (ESC_1)cells stem sample2 cells (ESC_2) (0.142193)stem sample [3 cells (ESC_3) min(0.0553162) sample1 (EB_PSC_1) (0.0552091)] 2 (EB_PSC_2) (0.211645)[ medium (0.257896) ] [ max ] CEM 1 Brpf3 305.8 483.8 653.8 P ( S | Z, I ) = 0.00 Brpf1 594.2 967.8 1113.0 Mean Corr = 0.54175 Kat6a 422.2 793.4 1166.3 Brd1 940.4 1165.9 1411.0 Ing5 41.9 66.4 74.0 Meaf6 112.0 175.4 319.7 Kmt2b 470.0 1012.1 1567.9 Spen 197.7 410.2 817.0 2410131K14Rik 63.9 84.5 108.4 Zkscan17 1098.6 1877.1 2252.5 Ankrd26 238.1 292.7 310.1 CEM 1 + Smg7 269.6 513.0 981.1 Top 10 Genes Kat6b 796.2 3570.6 4590.2 Tmcc1 90.7 108.1 207.4 Ubqln4 473.0 1494.1 3151.2 Lbr 4570.9 8329.7 9021.6

Null module GEO Series "GSE35077" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 26 -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=GSE35077 Status: Public on Mar 13 2012 Title: A gene expression database for retinal neuron subtypes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22407321 Summary & Design: Summary: The goal of this experiment was to define gene expression patterns of thirteen mouse retinal neuron subsets, labeled by expression of fluorescent proteins in transgenic mice.

Overall design: Neurons expressing xFPs were purified by flow cytometry. Thirteen different neuron subtypes were compared. Two biological replicates, originating from different litters, were collected for each cell type. RNA was extracted from sorted cells and prepared for hybridization to Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1251, L1-Distance = 0.0402, L2-Distance = 0.0027, Normal std = 0.4194

0.991 Kernel fit Pairwise Correlations Normal fit

Density 0.495

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

StarburstStarburst amacrine,BD amacrine, RGCs, rep1BD (0.0253015)rep1RGCs, rep2MP-positive (0.0408953) (0.0164678)rep2MP-positive (0.0403055) amacrine,MP-positive amacrine, MP-positiverep1 bipolars,(0.0487118) AIIrep2 amacrine bipolars,(0.0424925) rep1AII amacrine (0.013088) cells, rep2Cdh3 rep1(0.0249378) cells,BACCdh3 (0.0354758) RGCrep2 BACIsl2+ subset,(0.109171) RGC RGCs,Isl2+ subset,rep1 rep1RGCs, (0.0370449)J glycinergicrep2 (0.0485721) rep2 (0.0413497)J glycinergic (0.0400626) ACJ-RGCs, subset, ACJ-RGCs, rep1 subset,rep1 (0.0498863) ON(0.0399273) rep2 rep2 bipolar (0.0232325) ON(0.0432582) bipolarcells,PaxCre rep1 cells, (0.0174144)PaxCreGABAergic rep2 (0.0413808)W3GABAergic RGCs, ACW3 subset, rep1RGCs, ACW7 (0.0167109)subset,rep1 rep2RGCs, (0.0570697)W7 (0.0420831)rep2 rep1RGCs, (0.0441159) (0.0331051) rep2 (0.0279389) [ min ] [ medium ] [ max ] CEM 1 Brpf3 4.4 58.5 269.5 P ( S | Z, I ) = 0.00 Brpf1 146.9 356.1 584.1 Mean Corr = -0.10996 Kat6a 516.9 1419.9 2893.6 Brd1 929.0 1550.5 2940.7 Ing5 8.8 31.4 54.7 Meaf6 41.3 123.4 504.2 Kmt2b 712.8 944.8 1122.3 Spen 33.0 156.0 317.4 2410131K14Rik 24.9 51.6 104.9 Zkscan17 491.1 849.4 2107.9 Ankrd26 219.7 945.4 1837.7 CEM 1 + Smg7 885.1 1642.2 3955.5 Top 10 Genes Kat6b 436.9 1077.5 2518.3 Tmcc1 61.0 132.9 447.8 Ubqln4 718.9 1383.7 4474.6 Lbr 776.3 1082.3 2844.6

Null module GEO Series "GSE51385" 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=GSE51385 Status: Public on Oct 18 2013 Title: Expression profiling of ProB and PreB cells in Ebf1 heterozygous mouse bone marrow Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24078629 Summary & Design: Summary: Loss of one allele of Ebf1 impairs pre-B cell (B220+CD19+CD43low/negIgM-) expansion. In order to better understand the underlying cause of the reduced pre-B cell compartment in Ebf1+/- mice, we sorted pro-B (B220+CD19+CD43highIgM- ) as well as pre-B cells from Wt and Ebf1 heterozygote mutant mice and performed Affymetrix based microarray gene expression analysis.

While the overall gene expression patterns as well as Pax5 expression in Wt and Ebf1 pro-B cells were similar, gene set enrichment (GSE) analysis of the microarray data suggested a reduced expression of cell division (p<0.001) and mitosis (p<0.001) genes in the Ebf1+/- pre-B cells as compared to their Wt counterparts. This in combination with rather normal expression of B-lineage genes in Ebf1+/- pre-B cells opens for the possibility that the phenotypic loss of pre-B cells in Ebf1+/- mice could be a result of reduced expansion of progenitors rather than by a differentiation block.

Overall design: RNA was extracted from 20,000 or 25000 purified adult bone marrow cells using the RNAeasy microkit. RNA was labeled and amplified by dual amplification and hybridized to Affymetrix microarray MOE430_2, according to AffymetrixTM GeneChip Expression Analysis Technical Manual. Probe level expression values were calculated using the RMA algorithm.

Background corr dist: KL-Divergence = 0.0357, L1-Distance = 0.0280, L2-Distance = 0.0014, Normal std = 0.6198

0.644 Kernel fit Pairwise Correlations Normal fit

Density 0.322

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

Ebf1 heteroEbf1 PreB_1heteroEbf1 PreB_2(0.0975007)heteroEbf1 ProB_2(0.116448)heteroWT PreB_2 ProB_1(0.0939234)WT PreB_1(0.0633025) (0.0852433)WT ProB_1(0.342241)WT ProB_2(0.0531421) (0.148199) [ min ] [ medium ] [ max ] CEM 1 Brpf3 179.6 213.1 244.7 P ( S | Z, I ) = 0.00 Brpf1 663.5 912.7 1540.8 Mean Corr = 0.46485 Kat6a 1200.1 1843.0 2134.2 Brd1 662.9 848.0 1072.7 Ing5 33.8 43.7 53.5 Meaf6 181.5 269.8 427.6 Kmt2b 899.1 1138.7 1619.5 Spen 369.0 484.4 635.4 2410131K14Rik 49.8 64.5 81.9 Zkscan17 1624.3 3275.9 3529.5 Ankrd26 80.2 189.0 267.8 CEM 1 + Smg7 400.9 514.7 713.8 Top 10 Genes Kat6b 323.2 386.8 467.0 Tmcc1 197.4 282.4 579.2 Ubqln4 815.0 1203.1 1398.5 Lbr 8988.3 14738.3 15961.4

Null module GEO Series "GSE56755" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -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=GSE56755 Status: Public on Apr 18 2014 Title: The Cellular and Molecular Origin of Tumor-associated Macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24812208 Summary & Design: Summary: Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an alternatively activated phenotype. TAM differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.

Overall design: In the MMTV-PyMT spontaneous mammary tumor model, we found the key Notch transcriptional regulator, RBPJ, to be required for TAM terminal differentiation from inflammatory monocytes. The bulk myeloid cell population that remains in CD11cCreRbpj fl/fl mice (the cells in ""Rbpj KO"" samples), represents monocytes that have begun their differentiation into macrophages, but are unable to terminally differentiate due to the lack of Rbpj.

Background corr dist: KL-Divergence = 0.0672, L1-Distance = 0.0289, L2-Distance = 0.0015, Normal std = 0.5079

0.785 Kernel fit Pairwise Correlations Normal fit

Density 0.393

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

splenicDC_PCA_rep1splenicDC_PCA_rep2TAM_PCA_rep1 (0.217425)TAM_PCA_rep2 (0.0921791)MTM_CD11bhi_rep1 (0.0711567)MTM_CD11bhi_rep2 (0.0517635)TAM_CD11blo_rep1 (0.0825941)TAM_CD11blo_rep2 (0.0924276)TAM_CD11blo_rep3 (0.0240301)Rbpj_KO_rep1 (0.0298951)Rbpj_KO_rep2 (0.047365) Rbpj_WT_rep1(0.0815965) Rbpj_WT_rep2(0.0722739) (0.0375117) (0.0997817) [ min ] [ medium ] [ max ] CEM 1 Brpf3 237.3 435.4 635.1 P ( S | Z, I ) = 0.00 Brpf1 1280.6 1552.8 1969.9 Mean Corr = 0.46619 Kat6a 518.7 1199.5 2418.9 Brd1 505.0 695.7 1300.8 Ing5 34.6 51.6 78.3 Meaf6 149.2 199.7 278.8 Kmt2b 659.6 837.3 2024.9 Spen 188.4 373.2 665.3 2410131K14Rik 39.3 80.1 101.1 Zkscan17 655.7 957.8 1568.9 Ankrd26 91.5 171.8 279.9 CEM 1 + Smg7 313.4 631.1 934.0 Top 10 Genes Kat6b 320.3 489.7 683.9 Tmcc1 110.5 240.9 548.6 Ubqln4 372.4 552.9 939.6 Lbr 2330.2 4898.0 6291.2

Null module GEO Series "GSE32311" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -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=GSE32311 Status: Public on Nov 13 2011 Title: Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis Organism: Mus musculus Experiment type: Genome binding/occupancy profiling by high throughput sequencing Platform: GPL1261 Pubmed ID: 22080921 Summary & Design: Summary: Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks.

We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage.

Overall design: 8 samples (mouse DP thymocytes from wt, and different stage after Ikaros inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0. Examination of different histone modifications and binding sites for Ikaros, Mi2beta in wild type DP thymocytes, and Ikaros knockout thymocytes.

Background corr dist: KL-Divergence = 0.0614, L1-Distance = 0.0258, L2-Distance = 0.0011, Normal std = 0.5185

0.769 Kernel fit Pairwise Correlations Normal fit

Density 0.385

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

DP wt thymocyte,DP wt thymocyte,DP biologicalwt thymocyte,Ikaros biological rep1KOIkaros thymocyte biological(0.0581056) rep2KOIkaros thymocyte (0.0603498) rep3stageKOIkaros thymocyte (0.0294966) 1, stagedominant Ikarosbiological 1, stagedominant Ikarosbiological negative rep1 1, dominant Ikaros biological(0.104309) negative rep2thymocyte dominantIkaros (0.263583) negative rep3thymocyte dominantstage (0.0229992) negative thymocyte 2 stage(16 negative thymocyted), 2 biological stage(16 thymocyted), 2 biological stage[(27 rep1min d), 2 biologicalstage(0.156628)(27 rep2 d),] 3, biological(0.182676) biological rep1 (0.0398509) rep2[ rep1 medium (0.0182264) (0.0637756) ] [ max ] CEM 1 Brpf3 323.0 454.7 760.2 P ( S | Z, I ) = 0.00 Brpf1 768.7 2216.7 2416.0 Mean Corr = 0.16493 Kat6a 1085.9 3259.9 4550.0 Brd1 686.4 1381.1 2323.3 Ing5 78.3 102.2 156.2 Meaf6 142.1 192.8 206.3 Kmt2b 488.1 2147.6 3275.3 Spen 152.9 652.7 931.5 2410131K14Rik 61.7 93.3 126.4 Zkscan17 796.1 1102.6 1427.9 Ankrd26 172.0 403.8 626.7 CEM 1 + Smg7 530.5 849.0 1466.4 Top 10 Genes Kat6b 409.9 1431.8 2918.0 Tmcc1 178.1 223.9 882.0 Ubqln4 878.1 992.1 1360.1 Lbr 8637.7 12412.7 16925.6

Null module GEO Series "GSE26668" 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=GSE26668 Status: Public on Mar 23 2011 Title: Expression data from E13.5 Fz4-/-Fz8-/- and Fz4+/+Fz8-/- kidneys Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21343368 Summary & Design: Summary: Fz4 and Fz8 cooperate in regulating the branching morhpogenesis of the developing kidney during mouse embryonic development, hence determines the eventual kidney size.

We used microarrays to study the global gene expression profiles regulated by Fz4 and Fz8 signaling during early kidney development, and to understand the collaboration between the signaling events mediated by Fz4 and Fz8

Overall design: Kidney rudiments were dissected from E13.5 mouse embryos for RNA extraction and hybridization on Affymetrix MOE430.2 arrays. Three biological replicates of each genotype were analyzed.

Background corr dist: KL-Divergence = 0.0193, L1-Distance = 0.0128, L2-Distance = 0.0002, Normal std = 0.7424

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

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

Fz4Fz8 Fz4Fz8DKO C1 Fz4Fz8DKO (0.113223) C2 Fz4Fz8DKO (0.0953983) C3 Fz4Fz8DKO (0.306174) M1 Fz4Fz8DKO (0.162615) M2 DKO (0.143466) M3 (0.179124) [ min ] [ medium ] [ max ] CEM 1 Brpf3 1283.8 1649.9 1753.6 P ( S | Z, I ) = 0.00 Brpf1 439.9 462.2 618.0 Mean Corr = 0.30815 Kat6a 1860.5 2442.2 3174.2 Brd1 2225.9 2523.2 3035.1 Ing5 30.0 51.1 76.4 Meaf6 53.2 86.2 103.7 Kmt2b 347.2 540.1 728.5 Spen 123.4 270.7 316.5 2410131K14Rik 52.4 96.7 128.4 Zkscan17 483.8 613.8 771.3 Ankrd26 260.1 411.4 608.6 CEM 1 + Smg7 6026.6 6706.2 7478.1 Top 10 Genes Kat6b 1133.1 1217.3 1541.4 Tmcc1 225.4 302.3 344.9 Ubqln4 2377.7 3227.4 3785.8 Lbr 2957.3 3586.7 3954.2

Null module GEO Series "GSE12986" 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=GSE12986 Status: Public on Feb 01 2010 Title: Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20081188 Summary & Design: Summary: To identify whether Cdx2 or Gata3 can activate trophoblast specific gene expression when expressed in R1 ES cells. To assess the dependency of Gata3 activity on Cdx2, Gata3 was also expressed in Cdx2-null ES cells.

Keywords: gene expression

Overall design: a fusion construct of either Cdx2 or Gata3 and the tamoxifen responsive estrogen receptor ligand binding domain was expressed in R1 ES cells. Cell were induced with tamoxifen for 6 days to activate the transcription factor and cultured under trophoblast stem cell conditions

Background corr dist: KL-Divergence = 0.0488, L1-Distance = 0.0298, L2-Distance = 0.0015, Normal std = 0.5634

0.708 Kernel fit Pairwise Correlations Normal fit

Density 0.354

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

Gata3_H4Gata3_A3 (0.0577335)Gata3_D3 (0.139348)Gata3_F2 (0.0426845)Cdx2_E1 (0.0439752)Cdx2_H2 (0.238376)Gata3_Cdx2_null_11 (0.0724264)Gata3_Cdx2_null_3Gata3_Cdx2_null_9 (0.0549239)R1_control (0.0420444) (0.220408) (0.0880789) [ min ] [ medium ] [ max ] CEM 1 Brpf3 149.3 222.5 254.8 P ( S | Z, I ) = 0.00 Brpf1 599.1 993.5 1485.9 Mean Corr = 0.43013 Kat6a 799.8 1044.9 1240.4 Brd1 985.4 1455.7 1717.4 Ing5 321.5 429.6 574.5 Meaf6 187.5 206.0 336.9 Kmt2b 969.8 1356.7 1965.4 Spen 444.3 690.9 925.8 2410131K14Rik 63.1 79.4 129.5 Zkscan17 846.4 1589.0 1791.9 Ankrd26 310.9 412.5 536.8 CEM 1 + Smg7 722.3 975.2 1339.4 Top 10 Genes Kat6b 606.8 1065.5 3275.9 Tmcc1 48.3 54.6 104.1 Ubqln4 1053.2 1486.4 1744.4 Lbr 4805.3 5685.4 7772.0

Null module GEO Series "GSE40156" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 42 -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=GSE40156 Status: Public on Oct 30 2013 Title: Transcript atlases reveal that artery tertiary lymphoid organs but not secondary lymphoid organs control key steps of atherosclerosis T cell immunity in aged apoe-/- mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Tertiary lymphoid organs (TLOs) emerge in response to nonresolving inflammation but their roles in adaptive immunity remain unknown. Here, we explored artery TLOs (ATLOs) to delineate atherosclerosis T cell responses in apoe-/- mice during aging. Though the T cell repertoire showed systemic age-associated contractions in size and modifications in subtype composition and activation, wt and apoe-/- mice were equally affected. In contrast, ATLOs - but not wt aortae, apoe-/- aorta segments without ATLOs or atherosclerotic plaques - promoted T cell recruitment, altered characteristics of T cell motility, primed and imprinted T cells in situ, generated CD4+/FoxP3-, CD4+/FoxP3+, CD8+/FoxP3- effector and central memory cells, and converted naÃ¯ve CD4+/FoxP3- T cells into induced Treg cells. ATLOs also showed substantially increased antigen presentation capability by conventional dendritic cells (DCs) and monocyte-derived DCs but not by plasmacytoid DCs. Thus, the senescent immune system specifically employs ATLOs to control dichotomic atherosclerosis T cell immune responses. We assembled transcriptome maps of wt and apoe-/- aortae and aorta-draining RLNs and identified ATLOs as major sites of atherosclerosis-specific T cell responses during aging: Transcriptome atlases of wt and apoe-/- abdominal aortae and associated draining RLNs were constructed from laser capture microdissection (LCM)-based whole genome mRNA expression microarrays yielding 6 maps: wt adventitia (tissue-1); wt RLN (tissue-2); apoe-/- ATLOs (tissue-3); apoe-/- RLN (tissue-4); apoe-/- adventitia without adjacent plaques (tissue-5), and plaques (tissue-6). Several two-tissue comparisons within the transcriptome atlases are noteworthy: Unexpectedly, transcriptomes of wt and apoe-/- RLNs were virtually identical; additonal data revealed that transcriptomes of RLNs were strikingly similar to those of inguinal LNs which do not drain the aorta adventitia (as shown of India ink injection experiments of surgically exposed aortae); in sharp contrast, wt adventitia versus ATLOs revealed 1405 differentially expressed transcripts many of which encoded members of GO terms immune response and inflammatory response; the ATLO-plaque comparison also showed > 1000 differentially expressed transcripts; however, wt adventitia versus apoe-/- adventitia without plaque showed few genes (< 5 % of differentially expressed transcripts of the wt adventitia-ATLO comparison). Thus, the aorta transcriptome atlases support the conclusion that neither aorta-draining apoe-/- RLNs nor ILNs participate in atherosclerosis-specific T cell responses. In addition, they demonstrate that T cell responses in the diseased aorta are highly territorialized. Finally, these data show that the immune responses carried out in ATLOs differ significantly from those carried out in plaques. We next identified three major clusters within the transcriptome atlases through ANOVA analyses and application of strict filters: An adventitia cluster, a plaque/ATLO cluster, and a LN/plaque cluster. The total number of differentially expressed genes in each cluster were examined for GO terms immune response, inflammatory response, T cell activation, positive regulation of T cell response, and T cell proliferation. Within the adventitia cluster, similarities of transcriptomes of wt adventitia and apoe-/- adventitia without associated plaque versus ATLOs indicate that a robust number of immune response-regulating genes are selectively expressed in ATLOs which are located within a distance of few ´m of the adventitia without associated plaques indicating a very high degree of territoriality of the atherosclerosis T cell response. Furthermore, unlike the total number of differentially regulated transcripts, the majority of transcripts among GO terms immune response and inflammatory response, was up-regulated. Inspection of the plaque/ATLO cluster provided further information: The majority of immune response regulating genes where expressed at a higher level in ATLOs when compared to plaques though plaques also contained a significant number of immune response regulating genes; the reverse is true for genes regulating inflammation. Finally, the lymph node cluster revealed that though the majority of immune response regulating genes resides in both wt and apoe-/- RLNs (with little differences between them) ATLOs express a selected set of immune response regulating genes at a higher level when compared to LNs. In addition, the inflammatory component of ATLOs when compared to LNs is documented by the finding that many more genes regulating inflammation reside in ATLOs even when compared to those of plaques.

Key words:

T cell response in atherosclerosis; Laser capture microdissection; transcriptome atlas of atherosclerosis.

Citations:

GrÃ¤bner R. et al. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J Exp Med 2009 Jan 16;206(1):233-48. PMID: 19139167;

Moos M. et al. The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2386-91. Epub 2005 Sep 22. PMID: 16179593;

Beer M. et al. Laser-capture microdissection of hyperlipidemic/ApoE-/- mouse aorta atherosclerosis. Methods Mol Biol. 2011;755:417-28. PMID: 21761324;

Weih F. et al. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis. Front Physiol. 2012;3:226. Epub 2012 Jul 6. PMID: 22783198.

Overall design: Wild-type and apoE-deficient mice on the C57BL/6J genetic background were maintained on a standard mouse chow. Total aortae were removed at the age of 6 (n=3), 32 (n=3), or 78 (n=3) w and microarrays were prepared from total RNA extracts or extracts of atherosclerotic lesions and adventitiae obtained by the use of a laser dissection microscope. In addition, aorta associated LNs or distant LNs were prepared from both mouse genotypes.

Background corr dist: KL-Divergence = 0.1004, L1-Distance = 0.0740, L2-Distance = 0.0098, Normal std = 0.4788

0.955 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

wt-Aorta-32-weeks-1wt-Aorta-32-weeks-3apoE-Aorta-32-weeks-1 (0.0210364)apoE-Aorta-32-weeks-2 (0.0146568)apoE-Aorta-32-weeks-3wt-Aorta-32-weeks-2 (0.020154)wt-Aorta-6-weeks-1 (0.0186192)wt-Aorta-6-weeks-2 (0.023094) (0.0179786)wt-Aorta-6-weeks-3 (0.0101394)apoE-Aorta-6-weeks-1 (0.00676455)apoE-Aorta-6-weeks-2 (0.0124363)apoE-Aorta-6-weeks-3 wt-Aorta-78-weeks-1(0.0248639) wt-Aorta-78-weeks-2(0.0406778) wt-Aorta-78-weeks-3(0.0144075) (0.0211082)apoE-Aorta-78-weeks-1 (0.0231786)apoE-Aorta-78-weeks-2 (0.0258048)apoE-Aorta-78-weeks-3apoE-Spleen-32-weeks-1 (0.0313938)apoE-Spleen-32-weeks-2 (0.0309266)apoE-Spleen-32-weeks-3 (0.0501685)apoE-Spleen-78-weeks-1 (0.0521507)apoE-Spleen-78-weeks-2 (0.00650828)apoE-Spleen-78-weeks-3 (0.0198761)wt-Spleen-32-weeks-1 (0.015557)wt-Spleen-32-weeks-2 (0.0171491)wt-Spleen-32-weeks-3 (0.00613892) wt-Spleen-78-weeks-1(0.0273671) wt-Spleen-78-weeks-2(0.0229552) wt-Spleen-78-weeks-3(0.0966507) apoE-Blood-32-weeks-1(0.00551323) apoE-Blood-32-weeks-2(0.00505043) apoE-Blood-32-weeks-3(0.00641746)apoE-Blood-78-weeks-1 (0.0275032)apoE-Blood-78-weeks-2 (0.0394672)apoE-Blood-78-weeks-3 (0.0242096)wt-Blood-32-weeks-1 (0.0202381)wt-Blood-32-weeks-2 (0.0237988)wt-Blood-32-weeks-3 (0.0202363) (0.0289416)wt-Blood-78-weeks-1 (0.0253945)wt-Blood-78-weeks-2 (0.0191197)wt-Blood-78-weeks-3 (0.0342582) (0.0265461) (0.0215435)[ min ] [ medium ] [ max ] CEM 1 Brpf3 66.7 167.8 560.3 P ( S | Z, I ) = 0.00 Brpf1 471.2 1108.9 1914.0 Mean Corr = 0.42750 Kat6a 1209.3 2351.5 3448.0 Brd1 702.6 1130.2 1638.3 Ing5 75.7 201.3 343.2 Meaf6 113.0 220.9 308.3 Kmt2b 985.4 1984.3 2419.2 Spen 273.2 496.0 703.6 2410131K14Rik 72.6 142.5 194.3 Zkscan17 482.5 694.4 992.9 Ankrd26 252.3 452.0 662.8 CEM 1 + Smg7 841.6 1220.0 1751.7 Top 10 Genes Kat6b 652.1 970.4 1613.3 Tmcc1 186.3 341.8 965.4 Ubqln4 608.1 782.4 1021.5 Lbr 1462.3 6421.9 10665.7

Null module GEO Series "GSE30176" 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=GSE30176 Status: Public on Jul 19 2011 Title: Retinoic acid (RA) induction time-course to profile gene expression during mES cell differentiation. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21764852 Summary & Design: Summary: Murine ES cell gene expression before RA induction are used to compare gene expression for time-points of 2, 4, 6hrs post-induction.

Overall design: KH2 ES Cell RA Differentiation Time-course

Background corr dist: KL-Divergence = 0.0719, L1-Distance = 0.0287, L2-Distance = 0.0010, Normal std = 0.5040

0.814 Kernel fit Pairwise Correlations Normal fit

Density 0.407

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-A (0.130389)WT-B (0.12353)WT-C (0.147298)2HR-A (0.0638955)2HR-B (0.0389626)2HR-C (0.117761)4HR-A (0.0396655)4HR-B (0.0322549)4HR-C (0.0424123)6HR-A (0.0822259)6HR-B (0.0704375)6HR-C (0.111167) [ min ] [ medium ] [ max ] CEM 1 Brpf3 466.1 605.8 704.0 P ( S | Z, I ) = 0.00 Brpf1 1461.3 1658.6 1946.1 Mean Corr = 0.01893 Kat6a 1636.7 1958.2 2240.8 Brd1 704.9 949.7 1109.9 Ing5 67.5 81.6 104.5 Meaf6 164.6 256.6 336.3 Kmt2b 1445.5 1873.6 2048.0 Spen 661.3 1139.6 2394.2 2410131K14Rik 104.5 146.9 166.6 Zkscan17 1672.3 1815.4 1916.0 Ankrd26 219.7 394.6 456.7 CEM 1 + Smg7 2448.9 3304.5 3601.9 Top 10 Genes Kat6b 3694.2 3895.7 4415.9 Tmcc1 56.7 89.0 118.3 Ubqln4 2555.1 3139.4 3233.3 Lbr 8837.5 9741.1 10740.7

Null module