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: 14 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. C920025E04Rik H2-Q10 Azgp1 H2-M3 H2-Q2 H2-D1 H2-K1 Ulbp1 Procr H2-Bl Fcgrt Num ofGenesinQueryGeneset:14.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting B2m Mr1 Hfe

H2-K1 Fcgrt Hfe H2-Bl H2-Q2 H2-Q10 C920025E04Rik H2-M3 B2m Mr1 Azgp1 Ulbp1 Procr H2-D1 CEM 1(14datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 C920025E04Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page1 AA467197 Lgals3bp Hsd11b1 H2-Q10 Ifi27l2a Phf11d Psmb8 Psmb9 Dram1 Casp1 Casp4 Tapbp Azgp1 H2-M3 H2-Q2 Fxyd5 H2-Aa H2-D1 H2-K1 Icam1 Parp3 Pilrb1 Ulbp1 P2ry6 Irgm2 Tor3a Ifitm3 Procr H2-Bl Gbp2 Emr1 Fcgrt Slfn8 Cd74 Cd44 Cd68 Lcn2 Rtp4 B2m Ifi47 Ifi27 C1s Igtp Grn Ifit3 Mr1 Hfe Irf7 Irf8 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE45619 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43899 [12] GSE28389 [20] GSE24793 [8] GSE21137 [16] GSE23895 [18] GSE15794 [6] GSE38831 [7] GSE6223 [13] GSE19194 [14] GSE13103 [8] GSE29241 [6] GSE9330 [8] GSE18460 [16] GSE51213 [16] GSE15872 [18] GSE38074 [39] GSE33134 [31] GSE40260 [6] GSE5298 [8] GSE4029 [10] GSE23925 [6] GSE32386 [13] GSE34423 [40] GSE26299 [108] GSE22381 [12] GSE16675 [72] GSE16496 [102] GSE13753 [10] GSE6837 [8] GSE18586 [9] GSE3554 [6] GSE8039 [32] GSE14395 [24] GSE19616 [16] GSE42548 [29] GSE7342 [12] GSE43242 [10] GSE25286 [10] GSE17256 [8] GSE20577 [12] GSE13149 [25] GSE21576 [10] GSE25257 [6] GSE10965 [8] GSE17266 [59] GSE5334 [19] GSE33726 [48] GSE4926 [12] GSE15580 [14] GSE13526 [6] GSE27159 [8] GSE20954 [14] GSE1986 [17] GSE12730 [24] GSE5041 [8] GSE41759 [14] GSE9763 [20] GSE6285 [24] GSE29648 [10] GSE13874 [14] GSE18281 [33] GSE34765 [6] GSE9038 [24] GSE18660 [10] GSE10871 [32] GSE16874 [12] GSE19076 [12] GSE45618 [6] GSE35160 [6] GSE9443 [24] GSE39621 [51] GSE7897 [60] GSE31972 [6] GSE4535 [6] GSE11201 [18] GSE22005 [23] GSE9441 [36] GSE11358 [8] GSE4323 [6] GSE52542 [9] GSE28559 [30] GSE42264 [26] GSE17794 [44] GSE8295 [16] GSE30160 [6] GSE42601 [6] GSE11386 [15] GSE2019 [12] GSE47196 [6] GSE55356 [6] GSE17796 [39] GSE57543 [6] GSE30855 [6] GSE35734 [6] GSE16925 [15] GSE15624 [12] GSE14344 [6] GSE8249 [46] GSE41084 [6] GSE38224 [12] GSE32265 [6] GSE7333 [6] GSE27114 [6] GSE8726 [7] GSE19181 [6] GSE7424 [8] GSE3861 [6] GSE13071 [15] GSE10913 [6] GSE31744 [8] GSE10176 [6] GSE37975 [8] GSE33308 [10] GSE7694 [12] GSE25767 [6] GSE6210 [12] GSE51608 [6] GSE29318 [9] GSE48790 [8] GSE53951 [10] GSE16679 [8] GSE7767 [6] GSE6591 [15] GSE20302 [12] GSE52357 [8] GSE2250 [18] GSE17985 [8] GSE35396 [24] GSE31598 [12] GSE4193 [8] GSE6998 [32] GSE54653 [6] GSE4749 [6] GSE36336 [6] GSE19272 [30] GSE14481 [12] GSE15772 [8] GSE43381 [26] GSE54785 [6] GSE15155 [12] GSE35785 [10] GSE49346 [6] GSE12454 [13] GSE20372 [6] GSE27811 [9] GSE56777 [8] GSE36384 [12] GSE32598 [11] GSE9338 [42] GSE33770 [8] GSE23923 [8] CEM+ CEM GSE10528 [6] GSE23398 [7] GSE19885 [9] GSE34902 [6] GSE6065 [100] GSE23119 [9] 0.0 GSE21836 [8] GSE22006 [19]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 6.15 6.17 6.18 6.19 6.20 6.20 6.22 6.24 6.28 6.30 6.32 6.34 6.34 6.37 6.49 6.50 6.51 6.61 6.64 6.65 6.67 6.79 6.91 6.92 6.96 6.99 7.06 7.07 7.16 7.42 7.44 7.98 8.40 8.55 8.98 9.32 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page2 Serpina3n Cyp27a1 Themis2 S100a13 Psmb10 Ms4a6d Hsd3b7 S100a1 Tyrobp Akr1c6 Ptpn18 P2ry13 Adssl1 Ube2l6 Fcer1g Clec7a Cxcl10 Mpeg1 Tcirg1 Parp9 Oasl2 Fcgr1 Itgam Isg20 Gbp3 Gbp7 Gbp6 Cd86 Dtx3l Cd53 Stat6 Lpxn Lcp1 Tap1 Lyz2 Ctsd Ctsb Ctsh Pilra Ctss Ccl6 Ccl9 Pld4 Fgl2 Mlkl Ang Tlr2 Hck Tlr1 Ifit1 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 4.95 4.96 4.96 4.97 4.97 4.99 4.99 4.99 5.03 5.07 5.08 5.09 5.12 5.15 5.17 5.19 5.21 5.21 5.22 5.22 5.22 5.23 5.24 5.25 5.30 5.32 5.45 5.45 5.45 5.47 5.48 5.48 5.52 5.56 5.58 5.59 5.66 5.68 5.68 5.70 5.71 5.73 5.74 5.75 5.76 6.03 6.03 6.09 6.10 6.12 1.0 Notes 5430435G22Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page3 Adamdec1 Tnfrsf13b Tnfrsf1b Alox5ap Nckap1l Slc37a2 Slc11a1 Cyp4v3 Rnase4 H2-Ab1 S100a4 Gsdmd Parp12 Rnf213 Col5a3 Pyhin1 Mocos Nucb1 Oas1a Selplg Anxa4 Abcc3 Wdfy4 Fxyd1 Agmo Erap1 Fcgr3 Il15ra Ifi204 Nnmt Nlrc5 Oas2 Cd84 Bag3 Cd14 Phyh Slfn2 Sdc4 Tspo Tap2 Ly6a Ccr1 Ctsc Ncf4 Ifih1 Aif1 Xdh Tlr4 Clu 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 4.21 4.23 4.24 4.25 4.26 4.27 4.31 4.31 4.32 4.33 4.33 4.35 4.35 4.39 4.40 4.41 4.42 4.43 4.45 4.45 4.46 4.47 4.47 4.48 4.48 4.49 4.53 4.54 4.58 4.59 4.62 4.62 4.62 4.63 4.63 4.64 4.65 4.65 4.66 4.68 4.71 4.76 4.76 4.78 4.79 4.80 4.84 4.88 4.94 4.95 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page4 Tmem63a Serping1 Apobec1 Cyp2d22 Aldh1b1 Cyp4f13 Cd300lb Trim30a Slc15a3 Map3k8 Ms4a8a Abcb1a Gpr146 Clec2d Clec4d Tagln2 Lamp2 Plscr2 Nipal1 Rab32 Ephx1 Igfbp6 Thbs2 Gngt2 Gdf15 Zfp36 Apob Gch1 Cpn1 Rdh9 Cd3d Rgs1 Slfn4 Chil1 Slfn5 Slfn1 Aox3 Tifab Ctsw Qpct Ccr5 Bst2 Bcl3 Ccl2 Il4ra Ifi44 Slpi Fas Cfh C2 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 3.64 3.64 3.64 3.66 3.68 3.69 3.69 3.69 3.73 3.75 3.76 3.77 3.77 3.81 3.82 3.83 3.84 3.84 3.84 3.85 3.86 3.86 3.87 3.88 3.88 3.89 3.90 3.91 3.91 3.92 3.93 3.94 3.95 3.98 3.99 3.99 4.00 4.01 4.01 4.03 4.03 4.05 4.07 4.08 4.10 4.14 4.18 4.18 4.18 4.19 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page5 Hist2h2aa2 Ccdc109b Tmem154 Fam210b Slc25a45 Chchd10 Cyp2c50 Tnfrsf1a Trim30d Slc6a12 Slc46a3 Mybpc2 Sult2b1 Tm4sf1 Akr1b7 Osgin1 Pycard Prss16 Cebpd Apoc3 Hspb6 Ch25h Apoa4 Susd2 Acacb Cd163 Asah2 Usp18 Hgfac Naglu Ifngr1 Cideb Irgm1 Chia1 Plbd1 Tgfb1 Inhba Grina Ip6k3 Crip1 Sfrp4 Cd82 C1qc Hpse Nags Zbp1 Rras Hcst A2m Hp 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 3.31 3.31 3.31 3.31 3.31 3.31 3.32 3.32 3.32 3.32 3.32 3.36 3.37 3.37 3.37 3.38 3.39 3.41 3.41 3.41 3.41 3.42 3.43 3.47 3.48 3.48 3.48 3.49 3.50 3.51 3.51 3.51 3.52 3.54 3.55 3.55 3.55 3.56 3.56 3.57 3.57 3.57 3.57 3.58 3.58 3.59 3.60 3.62 3.63 3.63 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page6 Ceacam18 Fam114a1 Tmem173 AI607873 Unc93b1 Gm1123 Akr1c13 Slc36a2 Fam46c H2-DMa Casp12 Tbxas1 Lrrn4cl Agpat2 Apol7a Trim47 Pnpla7 Plxdc1 Stard5 Cebpb Ctla2b Apoa5 Stat5a Rab43 Calm4 Metrnl Gpr65 Creg1 Cryaa Gm2a Oasl1 Naip2 Hcls1 Ifitm6 C1qb Cd69 Ninj1 Tlr13 Lyg1 Msr1 Zg16 Ctsa Cst7 Ccl5 Itfg3 Itih1 Ifi35 Hpd Khk Il7r 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 2.92 2.92 2.94 2.96 2.96 2.98 2.98 2.98 3.01 3.01 3.02 3.02 3.03 3.04 3.04 3.04 3.05 3.05 3.05 3.05 3.05 3.08 3.08 3.09 3.10 3.10 3.10 3.12 3.15 3.15 3.15 3.15 3.15 3.17 3.20 3.21 3.22 3.22 3.23 3.24 3.24 3.25 3.25 3.26 3.27 3.29 3.30 3.30 3.30 3.30 1.0 Notes 1810033B17Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page7 BC021614 AF251705 Cyp4a12a Tmem219 S100a16 Clec4a3 Slc44a3 Slc10a6 Ms4a4c Ms4a6c Cd300lf Sqstm1 Sult1a1 Samd9l Mustn1 H2-Eb1 Prodh2 Clec4n Cxcl16 Lgals3 Crebl2 Apoc2 Pik3r5 Ddx60 Casp8 Wfdc1 Nr1d1 Nfkb2 Ptgs2 Amy1 Ptgs1 Gstt1 Galm Cmbl Upb1 Vnn3 Plin4 Vasn Saa4 Ly96 Mafk Fpr1 Fpr2 Ccl7 Mvp Gda Tlr7 Fyb Irf1 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 2.63 2.63 2.63 2.63 2.64 2.64 2.64 2.65 2.67 2.67 2.68 2.69 2.70 2.71 2.72 2.73 2.73 2.74 2.74 2.75 2.75 2.75 2.75 2.76 2.77 2.77 2.77 2.77 2.78 2.78 2.78 2.80 2.81 2.81 2.81 2.82 2.84 2.84 2.84 2.84 2.84 2.85 2.86 2.86 2.87 2.89 2.90 2.90 2.91 2.91 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page8 Tnfrsf11a Abhd14b Cacna1s Gpihbp1 Zc3h12a Clec12b Col16a1 Kazald1 Slc38a3 Galnt15 St8sia5 Ifi27l2b Ramp1 Zbtb7b Psme2 Fam3b Lpcat2 Lgals9 Man1a Aebp1 Sp100 Foxa3 Dhrs3 Sardh Paqr9 Mpzl3 Prss2 Pmp2 Pold4 Fcgr4 Stap1 Tnip2 Htr2b Gstt3 Csf3r Ptrh1 Nod1 C1qa Folr2 Aim1 Cd48 Tnxb Itgax Cbr3 Lrg1 Cast C8g Ier3 Tifa Cfp 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 2.23 2.23 2.23 2.24 2.25 2.26 2.26 2.27 2.27 2.28 2.28 2.29 2.30 2.31 2.33 2.34 2.37 2.38 2.39 2.40 2.40 2.40 2.41 2.42 2.44 2.44 2.44 2.45 2.46 2.48 2.48 2.48 2.49 2.49 2.49 2.50 2.51 2.52 2.52 2.53 2.53 2.54 2.55 2.56 2.57 2.58 2.60 2.60 2.62 2.62 1.0 Notes 1100001G20Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page9 AB124611 Krtap4-16 Cyp3a44 Tnfrsf18 Bhlhe40 Samsn1 Slc48a1 Ms4a4d Sh2d1a Echdc3 Scpep1 Tnfaip2 Gpr171 Atp8b4 Hgsnat Rab7l1 Clec5a Rasal3 Slc7a8 Naprt1 Agtr1a Myo1g Mrgprf Ms4a7 Kcnq1 Cd274 Msrb1 Glipr1 Acsl1 Vsig4 Tnni2 Krt25 Hint3 Rdh7 Cd97 Pon1 Spp1 Cd22 Thpo Mrc1 Fcna Ifna1 Blnk Lepr Oit3 Dap Rilp Nmi Agt 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 2.01 2.01 2.02 2.03 2.03 2.03 2.05 2.05 2.06 2.06 2.06 2.07 2.07 2.07 2.08 2.08 2.08 2.08 2.09 2.09 2.10 2.10 2.10 2.10 2.11 2.11 2.11 2.13 2.14 2.14 2.14 2.14 2.14 2.15 2.16 2.16 2.16 2.18 2.18 2.18 2.19 2.19 2.19 2.20 2.20 2.20 2.20 2.21 2.21 2.22 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page10 Tmem176a Adamtsl4 Gm11545 Ccdc88b Cyp2c65 Tnfrsf23 Clec4a2 Slc44a1 Sertad1 Cyp2d9 Acad11 Cyp2e1 Abca8a Sec16b Papss2 Cela3b Slamf9 Acsm5 Slc7a2 Slc9a1 Gng12 Niacr1 Abcc6 Rasa4 Timp1 Nr1h3 Gsta3 Herc6 Rem1 Pla1a Orai3 Nlrp3 Sftpd Cd36 Suox Stat2 Acp5 Fbp1 Igsf6 Ncf1 Csf1 Flnc Maff Mpo Ifi30 Gba Sil1 Gc Cfi F7 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 1.76 1.76 1.77 1.77 1.77 1.77 1.78 1.79 1.79 1.80 1.80 1.80 1.81 1.81 1.82 1.82 1.83 1.84 1.84 1.84 1.85 1.86 1.86 1.86 1.86 1.86 1.87 1.87 1.87 1.87 1.87 1.87 1.88 1.88 1.89 1.89 1.90 1.92 1.93 1.95 1.96 1.96 1.97 1.98 1.98 1.99 1.99 1.99 2.00 2.00 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page11 BC028528 Pla2g12b Tmprss6 Tmem37 Atp13a4 Sema4a Sdcbp2 Casp14 Rnase1 P2ry10 Slc7a7 Medag Kdelr3 Gstm1 Ahnak Cd8b1 Ddx58 Ephx2 C2cd2 Dnali1 Adck3 Pxdc1 Styxl1 Gpr34 F13a1 Lyve1 Gpld1 Asgr1 Oplah Smlr1 Zbtb4 Ecm1 Jsrp1 Cela1 Znfx1 Apoh Ccrl2 Aspg Kng1 Ucp2 Cd8a Milr1 Rorc Ftcd Itih2 Olr1 Atf3 C8b Eng Irf9 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 1.56 1.56 1.57 1.59 1.59 1.60 1.60 1.60 1.60 1.61 1.61 1.61 1.61 1.61 1.62 1.62 1.62 1.63 1.63 1.63 1.64 1.64 1.64 1.64 1.66 1.66 1.66 1.66 1.66 1.68 1.68 1.68 1.69 1.69 1.70 1.70 1.71 1.71 1.71 1.71 1.72 1.72 1.72 1.73 1.74 1.74 1.74 1.75 1.75 1.76 1.0 Notes A630033H20Rik 1110007C09Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page12 Krtap11-1 Tnfaip8l2 Cyp3a25 Serpinf2 Aldh3b1 Adam33 Slc26a3 Cyp8b1 Dnaja4 Pik3cg Iqsec2 Muc16 Reg3g Nfatc1 Dcpp3 Abcb4 Retnla Aadac Cd302 Lhfpl2 Timd2 Apobr Nupr1 Rrbp1 Prap1 Parvg Hacl1 Styk1 Muc2 H6pd Aoc3 Haao Shpk Junb Tchh Itga2 Ly6d Ly86 Retn Ckm Proz Cilp Des Vwf Igf1 Crp Il1a Hal 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 1.35 1.35 1.36 1.36 1.37 1.37 1.38 1.38 1.39 1.39 1.39 1.40 1.40 1.41 1.41 1.42 1.42 1.42 1.43 1.43 1.43 1.43 1.43 1.44 1.44 1.46 1.46 1.47 1.47 1.47 1.48 1.48 1.48 1.49 1.49 1.49 1.49 1.50 1.50 1.50 1.50 1.50 1.51 1.51 1.52 1.53 1.53 1.53 1.54 1.54 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page13 Serpina3g Serpina11 Arhgap30 Gm14137 Fam105a Serpind1 Akr1c14 Sdr42e1 Akr1c12 Spink12 Slc39a4 Ushbp1 Mmp13 Cryba4 Agpat9 Entpd1 Itpripl2 Aloxe3 Pnpla5 Lamb2 Slc2a9 Slc2a8 Lgals8 Krt33a Ptger4 Gstm2 Nkpd1 Abca1 Casp7 Fhad1 Lypd8 Fuca1 Odam Pbld1 Cidec Cybb Pdk4 Gdf2 Mbl2 Ncr1 Ereg Bst1 Klk6 Pld3 Il6ra Ins2 Pigr Gsn Rgn Cel 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 1.21 1.21 1.21 1.21 1.21 1.21 1.21 1.22 1.22 1.22 1.22 1.22 1.23 1.23 1.24 1.25 1.25 1.26 1.26 1.27 1.27 1.27 1.27 1.27 1.27 1.28 1.28 1.28 1.28 1.29 1.29 1.29 1.29 1.29 1.29 1.30 1.30 1.30 1.30 1.31 1.31 1.31 1.32 1.32 1.32 1.32 1.33 1.33 1.34 1.34 1.0 Notes 5430401F13Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page14 Tmem106a Ppp1r15a Serpinb8 Myadml2 Col14a1 Slco2a1 Sirpb1a Fbxw10 Sult1b1 Ptplad2 St3gal1 March2 Tfcp2l1 Gpr133 Cyp2f2 Atp12a Gdpd3 Ginm1 Myoz2 Retsat Hspb8 Ccdc3 Dapk2 Coro6 Mmp8 Thrsp Emp3 Sval1 Plac8 Krt6b Krt81 Birc3 Adh1 Bco2 Cyba Cpa1 Cd38 Cd3e Sod3 F13b Relb Gltp Cd9 Inf2 Fos Ly9 Cfd Fgr Il7 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 1.04 1.04 1.05 1.06 1.06 1.07 1.07 1.07 1.07 1.07 1.07 1.08 1.08 1.08 1.08 1.09 1.10 1.10 1.11 1.11 1.11 1.12 1.12 1.12 1.12 1.12 1.13 1.13 1.13 1.13 1.13 1.13 1.14 1.14 1.15 1.15 1.15 1.16 1.16 1.17 1.17 1.17 1.18 1.18 1.19 1.20 1.20 1.20 1.20 1.20 1.0 Notes 1700039E15Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page15 Serpina10 Tmem45b Tnfrsf11b Cyp2c70 Gm4980 Slco2b1 Tmbim1 Angptl7 Dennd3 Endod1 Guca1a Acaa1b Mfsd12 Parp14 Pbxip1 Shisa5 Myd88 Rab20 Scn1b Rab19 Asb11 Rab17 Fcgbp Marc2 Dhrs7 C3ar1 P2rx4 Pianp Klk11 Furin Chp2 Aspn Reg4 Yipf6 Cd28 Neu1 Ehd4 Ucp3 Tcn2 Gjb1 Kmo Ctsg Litaf Ctsf Cbs Adc Tlr6 Lbp Ltf 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.84 0.84 0.84 0.85 0.85 0.85 0.85 0.86 0.86 0.86 0.86 0.87 0.87 0.87 0.87 0.87 0.87 0.88 0.89 0.89 0.89 0.90 0.91 0.91 0.91 0.92 0.93 0.93 0.93 0.93 0.93 0.94 0.94 0.95 0.95 0.96 0.96 0.97 0.97 0.97 0.98 0.99 0.99 1.01 1.01 1.02 1.02 1.03 1.03 1.04 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page16 Tmem156 Atp6v0d2 Fam161a Serpinc1 Cyp3a13 S100a10 Ugt2b35 Plekhg6 Slc34a3 Rarres1 Angptl3 Tnfsf11 Nccrp1 Ugt2b5 Slc6a3 Lgals4 Bpifb1 Bpifb5 Wdr44 Sepp1 Klhl40 Crygd Pparg Cma1 Padi1 Il17rb Il10rb Itgbl1 Krt35 Rhod Bhmt Rhog Rbp7 Dpp4 Aoc1 Stat1 Apcs Aspa Pim1 Mlph Myot Urah Il2rg Inmt Il1r1 Brdt Cltb Ace Axl Tat 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.68 0.68 0.68 0.68 0.69 0.69 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.71 0.71 0.71 0.72 0.72 0.72 0.72 0.73 0.73 0.73 0.74 0.74 0.74 0.74 0.74 0.75 0.75 0.76 0.76 0.76 0.77 0.77 0.77 0.77 0.77 0.78 0.78 0.79 0.79 0.81 0.81 0.81 0.82 0.82 0.82 0.83 1.0 Notes C130050O18Rik A230050P20Rik 9030617O03Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page17 Serpina3c AI467606 Slc16a11 Adamts2 Scgb3a2 Cyp2c68 Cyp3a11 Slc31a2 Popdc3 Capns2 Ccdc63 Mettl7b Dnmt3l Trim15 Steap4 Clec3b Muc13 Robo4 Cd79b Dpep1 Acox2 Kcns1 Kcnk6 Nceh1 Card6 Acot3 Ptges Pqlc3 Fmo5 Orm1 Csf1r Krt26 Clrn3 Myh4 Hagh Pthlh Rdh1 Vnn1 Ass1 Tsku Hrh2 Nrap Mefv Nrg4 Arsa Klk7 Tst 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.55 0.55 0.55 0.55 0.55 0.55 0.56 0.56 0.56 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.58 0.58 0.58 0.58 0.58 0.59 0.59 0.59 0.60 0.60 0.60 0.60 0.60 0.61 0.62 0.62 0.62 0.63 0.63 0.63 0.64 0.65 0.65 0.65 0.65 0.66 0.66 0.66 0.66 0.66 0.66 0.67 0.67 1.0 Notes 0610009O20Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page18 Tmem150a Tmprss11f Serpina5 Tmprss4 Tnfrsf22 Pitpnm3 Adam15 Traf3ip2 Clec10a Pacsin3 Slc35d2 Stard10 Ms4a6b Ms4a10 Tspan1 Crybb3 Chmp5 Vkorc1 Acot12 Atp2a1 Acsm1 Cyp2j6 Pcp4l1 Enpp1 Bank1 Klhl30 Amelx Pdgfrl Dmkn Plod1 Lrp10 Klkb1 Stab1 Fosl2 Klrd1 Nkg7 Cd72 Aox1 Asb2 Psd4 Lcp2 Ncf2 Pld2 Lipc Pirb Hpn Tff3 Ghr F10 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.44 0.45 0.45 0.45 0.45 0.45 0.45 0.46 0.46 0.46 0.46 0.47 0.47 0.47 0.47 0.47 0.48 0.48 0.48 0.48 0.48 0.48 0.48 0.48 0.48 0.48 0.48 0.49 0.49 0.49 0.50 0.50 0.50 0.50 0.50 0.50 0.51 0.52 0.52 0.52 0.52 0.52 0.53 0.53 0.53 0.53 0.53 0.53 0.53 0.54 1.0 Notes 5430427O19Rik 2610528A11Rik 1300017J02Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page19 Tmem30b Tnfrsf12a Slc25a35 Fam132a Cyp2c44 Tmem53 Tspan10 Slc13a3 Guca2a Cyp4b1 Dusp19 Siglec1 Ptpn22 Tmco4 Zfp524 Masp1 Qsox1 Dedd2 Apoc4 Hilpda Anxa1 Copz2 Tpcn2 Foxs1 Il18bp Cdhr2 Ocel1 Cxcl9 Sprr3 Ikbke Nrn1l Rhoh Kynu Stom Cytip Sgcd Uba7 Itga5 Msln Proc Abi3 Il1rn Glul Auh Fgb Prlr Cp 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.29 0.29 0.30 0.30 0.30 0.30 0.31 0.31 0.32 0.33 0.33 0.33 0.34 0.34 0.34 0.35 0.35 0.36 0.36 0.36 0.36 0.36 0.36 0.37 0.37 0.38 0.38 0.38 0.38 0.39 0.39 0.39 0.40 0.40 0.41 0.41 0.41 0.41 0.41 0.41 0.42 0.42 0.42 0.43 0.43 0.43 0.43 0.43 0.44 0.44 1.0 Notes 2010003K11Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page20 Tmprss11e Arhgap31 Hist1h3i Slco1b2 Fam26e Mansc1 Cyp2g1 Ppp3cc Mtmr11 C77080 Fabp12 B3gnt8 Abi3bp Kctd11 Trim31 Rassf5 Tmed3 Krt33b Nlrp10 Nphp3 Acvrl1 Nfe2l2 Anxa5 Abca6 Ssc5d Tuba8 Fabp1 Timd4 Wisp2 Asgr2 Plbd2 Igfals Vwa8 Nlrp6 Adh7 Cpn2 Pon2 Pon3 Pdyn Prg4 Fgl1 Ltbr Hk3 Sp7 Dpt Btd Irf4 Plg Ltb 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.15 0.16 0.16 0.17 0.17 0.17 0.17 0.17 0.18 0.18 0.18 0.18 0.18 0.19 0.19 0.19 0.20 0.21 0.21 0.21 0.21 0.21 0.21 0.22 0.22 0.22 0.23 0.23 0.23 0.23 0.23 0.23 0.24 0.24 0.24 0.24 0.24 0.24 0.25 0.26 0.27 0.27 0.27 0.28 0.28 0.29 0.29 0.29 0.29 0.29 1.0 Notes 2310005G13Rik 1300002K09Rik Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page21 Adamtsl5 Ugt2b36 Akr1c19 Slc15a1 Man2b2 Abcb1b Capns1 Lurap1l Rabac1 Gprc5d Gpr182 Gpr116 B3gnt9 Calml4 Galnt6 Myo1c Arid5a Nlrp12 Bpifa2 Plscr1 Rgs10 Ephx3 Snx20 Fabp2 Gpr68 Tbx21 Arap1 Camp Cyth4 Soat1 Esyt1 Nrros Helz2 Krt80 Myh2 Krt84 Prelp Rdh5 Ldhd Sgca Tyk2 Otos Cym Qprt Mttp Glrx Uox Pzp 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE19729 [14] Scale ofaveragePearsoncorrelations GSE7764 [10] GSE23182 [12] GSE50603 [12] GSE55855 [6] GSE8828 [6] GSE24121 [9] 0.2 GSE19979 [6] GSE8044 [6] GSE22841 [12] GSE46875 [10] GSE52474 [154] GSE37658 [6] GSE38335 [9] GSE10813 [12] GSE9725 [16] 0.4 GSE23600 [10] GSE50824 [19] GSE51385 [8] GSE22927 [38] GSE18326 [8] GSE35091 [11] GSE11259 [9] GSE51628 [15] GSE43620 [8] 0.6 GSE7069 [8] GSE11723 [9] GSE19204 [6] GSE19657 [21] GSE42103 [9] GSE28093 [6] GSE42018 [8] GSE31208 [8] GSE35219 [6] 0.8 GSE51365 [28] GSE1983 [6] GSE17879 [6] GSE16684 [6] Score 0.03 0.03 0.03 0.03 0.03 0.03 0.04 0.04 0.05 0.05 0.05 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.07 0.07 0.07 0.08 0.08 0.08 0.08 0.08 0.09 0.09 0.10 0.10 0.11 0.11 0.12 0.12 0.12 0.12 0.12 0.13 0.13 0.13 0.13 0.13 0.14 0.14 0.15 0.15 0.15 0.15 0.15 0.15 1.0 Notes Symbol Num ofCEMGenes:14.Predicted1049.SelectedDatasets:Strength:0.2 CEM 1,Geneset"[G]MHCclassIproteincomplex",Page22 Whamm Fam20a Slc8b1 Myo7b Gapdh Npas1 Anxa3 Gpr84 P2ry2 Vsig2 Cd3g Cd37 Cys1 0.0 1.0

GSE5891 [6] GSE30488 [52]

GSE45619 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE43899 [12] GSE28389 [20] GSE24793 [8] GSE21137 [16] GSE23895 [18] GSE15794 [6] GSE38831 [7] GSE6223 [13] GSE19194 [14] GSE13103 [8] GSE29241 [6] GSE9330 [8] GSE18460 [16] GSE51213 [16] GSE15872 [18] GSE38074 [39] GSE33134 [31] GSE40260 [6] GSE5298 [8] GSE4029 [10] GSE23925 [6] GSE32386 [13] GSE34423 [40] GSE26299 [108] GSE22381 [12] GSE16675 [72] GSE16496 [102] GSE13753 [10] GSE6837 [8] GSE18586 [9] GSE3554 [6] GSE8039 [32] GSE14395 [24] GSE19616 [16] GSE42548 [29] GSE7342 [12] GSE43242 [10] GSE25286 [10] GSE17256 [8] GSE20577 [12] GSE13149 [25] GSE21576 [10] GSE25257 [6] GSE10965 [8] GSE17266 [59] GSE5334 [19] GSE33726 [48] GSE4926 [12] GSE15580 [14] GSE13526 [6] GSE27159 [8] GSE20954 [14] GSE1986 [17] GSE12730 [24] GSE5041 [8] GSE41759 [14] GSE9763 [20] GSE6285 [24] GSE29648 [10] GSE13874 [14] GSE18281 [33] GSE34765 [6] GSE9038 [24] GSE18660 [10] GSE10871 [32] GSE16874 [12] GSE19076 [12] GSE45618 [6] GSE35160 [6] GSE9443 [24] GSE39621 [51] GSE7897 [60] GSE31972 [6] GSE4535 [6] GSE11201 [18] GSE22005 [23] GSE9441 [36] GSE11358 [8] GSE4323 [6] GSE52542 [9] GSE28559 [30] GSE42264 [26] GSE17794 [44] GSE8295 [16] GSE30160 [6] GSE42601 [6] GSE11386 [15] GSE2019 [12] GSE47196 [6] GSE55356 [6] GSE17796 [39] GSE57543 [6] GSE30855 [6] GSE35734 [6] GSE16925 [15] GSE15624 [12] GSE14344 [6] GSE8249 [46] GSE41084 [6] GSE38224 [12] GSE32265 [6] GSE7333 [6] GSE27114 [6] GSE8726 [7] GSE19181 [6] GSE7424 [8] GSE3861 [6] GSE13071 [15] GSE10913 [6] GSE31744 [8] GSE10176 [6] GSE37975 [8] GSE33308 [10] GSE7694 [12] GSE25767 [6] GSE6210 [12] GSE51608 [6] GSE29318 [9] GSE48790 [8] GSE53951 [10] GSE16679 [8] GSE7767 [6] GSE6591 [15] GSE20302 [12] GSE52357 [8] GSE2250 [18] GSE17985 [8] GSE35396 [24] GSE31598 [12] GSE4193 [8] GSE6998 [32] GSE54653 [6] GSE4749 [6] GSE36336 [6] GSE19272 [30] GSE14481 [12] GSE15772 [8] GSE43381 [26] GSE54785 [6] GSE15155 [12] GSE35785 [10] GSE49346 [6] GSE12454 [13] GSE20372 [6] GSE27811 [9] GSE56777 [8] GSE36384 [12] GSE32598 [11] GSE9338 [42] GSE33770 [8] GSE23923 [8] CEM+ CEM GSE10528 [6] GSE23398 [7] GSE19885 [9] GSE34902 [6] GSE6065 [100] GSE23119 [9] 0.0 GSE21836 [8] GSE22006 [19]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5891 Status: Public on Sep 22 2006 Title: Nuclear organization of active and inactive chromatin domains revealed by 4C technology Organism: Mus musculus Experiment type: Other Platform: GPL1261 Pubmed ID: 17033623 Summary & Design: Summary: The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We have developed 4C technology, or 3C-on-chip, which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active b-globin locus in fetal liver contacts mostly transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, while the inactive locus in fetal brain contacts different, transcriptionally silent, loci. A housekeeping gene in a gene dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.

Keywords: 4C technology

Overall design: Gene expression arrays were performed in triplicate, according to standard procedures (Affymetrix). 4C experiments were performed in duplo (biologically independent samples), dye swap was included. Hybriisation was performed on dedicated micro-arrays. Probes (60-mers) were selected from the sequences 100 bp up and downstream of HindIII sites. To prevent cross-hybridization, probes that had any similarity with highly abundant repeats (RepBase 10.09) were removed from the probeset. In addition, probes that gave more than two BLAST hits in the genome were also removed from the probeset. Sequence alignments were performed using MegaBLAST using the standard settings. A hit was defined as an alignment of 30 nt or longer.

Background corr dist: KL-Divergence = 0.0158, L1-Distance = 0.0653, L2-Distance = 0.0070, Normal std = 0.9745

0.409 Kernel fit Pairwise Correlations Normal fit

Density 0.205

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

E14.5_fetal_brain_1E14.5_fetal_brain_2E14.5_fetal_brain_3 (0.125027)E14.5_fetal_liver_1 (0.243467)E14.5_fetal_liver_2 (0.076073)E14.5_fetal_liver_3 (0.265405) (0.059809) (0.230219) [ min ] [ medium ] [ max ] CEM 1 H2-K1 46.2 2989.2 4028.8 P ( S | Z, I ) = 1.00 Fcgrt 47.7 541.2 960.4 Mean Corr = 0.76103 Hfe 37.1 315.4 491.5 H2-Bl 34.8 47.6 51.0 H2-Q2 27.0 35.3 41.2 H2-Q10 22.0 2611.4 4150.0 C920025E04Rik 19.4 21.0 22.9 H2-M3 43.6 58.4 73.3 B2m 24.2 31.0 66.1 Mr1 16.3 17.4 18.3 Azgp1 18.2 25.5 37.1 Ulbp1 18.6 21.1 22.0 Procr 40.3 52.3 115.4 H2-D1 12.7 13.5 13.8 H2-Aa 21.8 49.1 111.6 Cd68 17.7 405.3 561.5 Psmb9 22.9 92.2 151.3 Psmb8 21.3 134.6 203.6 Tapbp 365.1 981.1 1179.8 CEM 1 + Gbp2 16.6 189.8 229.7 Top 10 Genes Ifi27l2a 36.8 46.1 96.1 Igtp 24.8 3475.2 4142.9 Fxyd5 95.7 336.1 561.6 Ifit3 21.3 32.9 39.7

Null module GEO Series "GSE30488" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 52 -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=GSE30488 Status: Public on Aug 31 2012 Title: Expression data from E2f7/E2f8/E2f3a null placentas and embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22516201 Summary & Design: Summary: To understand the underlying cause and mechanisms of embryonic lethality observed in combined loss of E2f7 and E2f8, we compared global gene expression profiles of wild type, germline deleted and sox2-Cre/Cyp19-Cre deleted embryos and placentas.

Overall design: RNA was extracted from E10.5 embryos and placentas. Gene deletion in samples confirmed by PCR genotyping of DNA isolated from each sample.

Background corr dist: KL-Divergence = 0.0427, L1-Distance = 0.0236, L2-Distance = 0.0008, Normal std = 0.5868

0.680 Kernel fit Pairwise Correlations Normal fit

Density 0.340

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

E2f3a-/-;E2f7-/-;E2f8-/-E2f3a-/-;E2f7-/-;E2f8-/-E2f3a-/-;E2f7-/-;E2f8-/- E2f3a-/-;E2f7-/-;E2f8-/-embryo E2f3a-/-;E2f7-/-;E2f8-/-embryo 3a78KO E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 1 (0.0049081) E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 2 (0.00439611) E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 3 (0.00592333)E2f3a-/-;E2f7+/+;E2f8+/+ 3a78KO 4embryo (0.00957697)E2f3a+/+;E2f7-/-;E2f8-/- 5embryo 3KO (0.0043909) E2f3a+/+;E2f7-/-;E2f8-/-1 (0.0115279)embryo 3KO E2f3a+/+;E2f7-/-;E2f8-/-2 (0.00891411)embryo 3KO E2f3a+/+;E2f7-/-;E2f8-/-3 embryo (0.0110793) 3KO Cyp19Cre+;E2f7F/F;E2f8F/F4 embryo 78KO(0.00981799) Cyp19Cre+;E2f7F/F;E2f8F/F1 embryo 78KO(0.0128516) Cyp19Cre+;E2f7F/F;E2f8F/F2 embryo 78KO(0.0157357) Sox2Cre+;E2f7F/-;E2f8F/-3 78KO(0.0153193) embryo Sox2Cre+;E2f7F/-;E2f8F/-4 (0.00858191) embryo Cyp19Sox2Cre+;E2f7F/-;E2f8F/- embryo 1Cyp19 Sox2Cre+;E2f7F/-;E2f8F/-(0.00897803) embryo 2Cyp19 E2f3a+/+;E2f7+/+;E2f8+/+(0.0161998) embryo Sox2 3 E2f3a+/+;E2f7+/+;E2f8+/+(0.00976074) 1 embryo (0.0112705)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 2 embryo (0.0109756)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 3 embryo (0.011366)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 4 embryo (0.00800516)WT E2f3a+/+;E2f7+/+;E2f8+/+1 (0.0134217) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-2 (0.0157755) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-3 (0.0046616) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-4 (0.00449728) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-placenta5 (0.00524701) WT E2f3a-/-;E2f7-/-;E2f8-/-placenta6 3a78KO(0.00987664) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 1 (0.00993039) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 2 (0.00448118) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 3 (0.00541424)E2f3a-/-;E2f7+/+;E2f8+/+ 3a78KO placenta4 (0.00422473)E2f3a+/+;E2f7-/-;E2f8-/- placenta5 3KO (0.00395621)E2f3a+/+;E2f7-/-;E2f8-/- 1 placenta (0.123161) 3KOE2f3a+/+;E2f7-/-;E2f8-/- 2 placenta (0.0832971) 3KOE2f3a+/+;E2f7-/-;E2f8-/- placenta3 (0.0827833) 3KOCyp19Cre+;E2f7F/F;E2f8F/F placenta4 78KO(0.125384)Cyp19Cre+;E2f7F/F;E2f8F/F placenta1 78KO(0.0096787)Cyp19Cre+;E2f7F/F;E2f8F/F placenta2 78KO(0.00618017)Sox2Cre+;E2f7F/-;E2f8F/- 3 78KO(0.00696677) placentaSox2Cre+;E2f7F/-;E2f8F/- 4 (0.01073) placenta Sox2Cre+;E2f7F/-;E2f8F/-cyp 19 placenta 3Sox2Cre+;E2f7F/-;E2f8F/-Cyp19 (0.00794733) placenta 1E2f3a+/+;E2f7+/+;E2f8+/+Cyp19 (0.00905718) placenta sox2 2E2f3a+/+;E2f7+/+;E2f8+/+ (0.0071321) 1placenta (0.00625322)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 2placenta (0.00747165)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 3placenta (0.00411167)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 4placenta (0.00602024)WTE2f3a+/+;E2f7+/+;E2f8+/+ 1 (0.0046311)placenta WT 2 (0.00738901)placenta WT 3 (0.00437673)placenta WT 4 (0.0095458)placenta WT[ 5 min(0.0956918) WT 6 (0.101125) ] [ medium ] [ max ] CEM 1 H2-K1 1118.1 2262.9 9728.5 P ( S | Z, I ) = 1.00 Fcgrt 120.7 229.3 1915.0 Mean Corr = 0.67598 Hfe 40.5 65.6 240.2 H2-Bl 38.0 66.6 144.6 H2-Q2 7.2 11.0 27.3 H2-Q10 24.5 33.0 81.0 C920025E04Rik 18.6 26.6 37.9 H2-M3 92.1 123.7 564.3 B2m 30.1 47.3 131.3 Mr1 118.7 172.2 323.2 Azgp1 73.3 97.3 156.5 Ulbp1 40.0 66.4 131.2 Procr 94.1 6648.4 20017.9 H2-D1 15.7 25.5 35.8 H2-Aa 21.4 42.2 1011.2 Cd68 67.6 180.6 2663.2 Psmb9 52.5 86.5 696.3 Psmb8 45.2 91.2 1792.9 Tapbp 166.4 1666.9 3457.2 CEM 1 + Gbp2 11.8 23.4 651.0 Top 10 Genes Ifi27l2a 29.2 45.6 1654.1 Igtp 151.2 373.1 745.8 Fxyd5 147.2 745.4 3232.6 Ifit3 33.7 60.7 268.1

Null module GEO Series "GSE45619" 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=GSE45619 Status: Public on Mar 29 2013 Title: Expression analysis of GATA1s 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 GATA1s fetal liver and bone marrow

Background corr dist: KL-Divergence = 0.0282, L1-Distance = 0.0322, L2-Distance = 0.0012, Normal std = 0.7067

0.596 Kernel fit Pairwise Correlations Normal fit

Density 0.298

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

Gs_MKP_BM_1Gs_MKP_BM_2Gs_MKP_BM_3 (0.216081)Gs_MKP_FL_1 (0.199298)Gs_MKP_FL_2 (0.172533) Gs_MKP_FL_3(0.125476) (0.156124) (0.130487) [ min ] [ medium ] [ max ] CEM 1 H2-K1 1890.0 7155.5 7683.0 P ( S | Z, I ) = 1.00 Fcgrt 6.9 164.6 189.5 Mean Corr = 0.55526 Hfe 17.7 81.7 110.3 H2-Bl 4.7 18.4 26.6 H2-Q2 1.0 1.0 3.1 H2-Q10 3.9 48.6 271.7 C920025E04Rik 23.5 153.2 189.4 H2-M3 82.0 765.8 965.0 B2m 102.5 827.1 1129.0 Mr1 1.3 36.0 63.2 Azgp1 1.0 15.6 17.7 Ulbp1 33.4 63.5 95.5 Procr 18.0 41.4 74.3 H2-D1 5.9 12.1 20.4 H2-Aa 1.9 554.1 661.1 Cd68 170.2 473.4 757.0 Psmb9 349.4 3157.4 3388.1 Psmb8 715.9 2505.4 2695.4 Tapbp 3245.3 4865.7 5194.7 CEM 1 + Gbp2 16.8 409.8 534.5 Top 10 Genes Ifi27l2a 6.8 613.5 1015.1 Igtp 280.9 666.7 1477.0 Fxyd5 3947.0 5487.9 6040.4 Ifit3 20.5 56.1 65.9

Null module GEO Series "GSE43899" 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=GSE43899 Status: Public on Aug 30 2013 Title: Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23995680 Summary & Design: Summary: Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology.

Overall design: 9) cultured mouse cortical neurons treated with topotecan with or without subsequent drug washout, vs vehicle-treated controls.

Background corr dist: KL-Divergence = 0.0306, L1-Distance = 0.0234, L2-Distance = 0.0007, Normal std = 0.6443

0.619 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

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

Pre-normalization Quantiles

ICRF193_3´M_1ICRF193_3´M_2ICRF193_3´M_3 (0.0570523)ICRF193_3´M_vehicle_1 (0.0430328)ICRF193_3´M_vehicle_2 (0.0435284)ICRF193_3´M_vehicle_3Topotecan_300nM_1 (0.0617297)Topotecan_300nM_2 (0.0626932)Topotecan_300nM_3 (0.0532163) (0.0434276)Topotecan_300nM_vehicle_1 (0.130896)Topotecan_300nM_vehicle_2 (0.281681)Topotecan_300nM_vehicle_3 (0.0639638) (0.127534) (0.0312446)[ min ] [ medium ] [ max ] CEM 1 H2-K1 1252.1 4303.4 13280.5 P ( S | Z, I ) = 1.00 Fcgrt 282.4 354.8 729.6 Mean Corr = 0.52024 Hfe 75.1 103.5 218.2 H2-Bl 55.0 77.1 159.0 H2-Q2 80.3 253.6 726.2 H2-Q10 42.1 109.8 415.2 C920025E04Rik 30.9 90.6 643.1 H2-M3 164.3 206.0 508.5 B2m 24.6 31.0 38.2 Mr1 83.7 102.9 120.8 Azgp1 45.7 68.3 93.4 Ulbp1 24.3 40.4 42.9 Procr 91.1 131.7 406.8 H2-D1 15.6 20.8 24.9 H2-Aa 21.5 30.5 51.5 Cd68 144.1 350.1 2376.2 Psmb9 105.6 242.8 338.4 Psmb8 102.6 141.8 345.4 Tapbp 818.1 1115.7 2845.4 CEM 1 + Gbp2 87.2 113.3 235.0 Top 10 Genes Ifi27l2a 32.2 50.9 119.7 Igtp 144.4 291.9 707.5 Fxyd5 109.9 152.9 269.6 Ifit3 77.7 145.4 714.1

Null module GEO Series "GSE28389" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -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=GSE28389 Status: Public on Apr 05 2011 Title: [E-MTAB-368] Transcription profiling by array of mouse embryos at 8 different stages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21427719 Summary & Design: Summary: Transcription profiling of mouse development

The experiment were perfomed as a part of our Vertebrate Evo-Devo project. The aim of the project is to compare transcription profiles of normal (unmanipulated, wild-type, whole embryo) vertebrate embryos.

Overall design: Total RNA was collected from wild type C57BL/6 mice, whole embryos at 8 different stages (Stages:E7.5, E8.5, E9.5, E10.5, E12.5, E14.5, E16.5, E18.5), and hybridized to Affymetrix Mouse Genome 430 2.0 Array. All the stages contains data from 2 to 3 biological replications. Each staged-samples consists of pooled total RNA from several whole embryos.

Background corr dist: KL-Divergence = 0.0441, L1-Distance = 0.0355, L2-Distance = 0.0018, Normal std = 0.5966

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.353

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

[E-MTAB-368][E-MTAB-368] Mouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMousestage[E-MTAB-368] E7.5 developmentalMousestage[E-MTAB-368] 1 (0.0449125) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0783509) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.0278662) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0531021) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0316849) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0253832) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0284963) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.026371) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0245047) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0189823) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0127512) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0311095) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0132081) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0268032) developmentalMousestage 1 E14.5 (0.0190779) developmentalMousestage 2 E16.5 (0.022719) developmentalstage 1 E16.5(0.0377486) stage[ min 2 E18.5(0.0560941) stage 1] E18.5(0.213673) 2 (0.207161)[ medium ] [ max ] CEM 1 H2-K1 377.5 500.7 2329.3 P ( S | Z, I ) = 1.00 Fcgrt 77.3 288.5 4407.6 Mean Corr = 0.47495 Hfe 9.0 102.4 445.8 H2-Bl 4.1 32.4 64.0 H2-Q2 1.0 23.9 566.2 H2-Q10 19.8 70.3 1851.1 C920025E04Rik 5.6 35.8 73.4 H2-M3 26.3 114.2 220.4 B2m 11.6 48.8 151.0 Mr1 7.2 62.6 276.1 Azgp1 4.2 24.8 2983.8 Ulbp1 4.3 37.3 64.3 Procr 69.1 181.6 763.9 H2-D1 1.8 16.7 47.8 H2-Aa 2.4 20.4 161.8 Cd68 26.4 115.2 593.7 Psmb9 8.0 59.2 265.1 Psmb8 3.1 39.9 371.7 Tapbp 180.1 311.6 1375.3 CEM 1 + Gbp2 1.7 32.2 258.9 Top 10 Genes Ifi27l2a 2.7 58.9 586.3 Igtp 46.5 161.4 1044.4 Fxyd5 87.4 243.4 976.8 Ifit3 6.9 60.2 442.1

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 (0.130864)Neurons at (0.179363) 16h_untreatedtreatmentNeurons at 24h_T3 (0.033375)Neurons at 24h_untreated(0.0792349)treatmentNeurons at 48h_T3 (0.0595109) at 48h_untreated(0.0893493)treatment (0.217905) (0.210398)[ min ] [ medium ] [ max ] CEM 1 H2-K1 4739.9 13827.6 15565.0 P ( S | Z, I ) = 1.00 Fcgrt 540.5 1611.7 3441.7 Mean Corr = 0.44560 Hfe 125.0 676.4 779.1 H2-Bl 18.6 77.8 122.1 H2-Q2 5.0 9.5 25.6 H2-Q10 5.0 30.1 55.7 C920025E04Rik 18.1 80.3 139.1 H2-M3 257.5 630.5 1431.6 B2m 60.2 128.1 154.0 Mr1 47.2 134.5 260.8 Azgp1 7.0 9.0 27.6 Ulbp1 5.0 25.6 56.2 Procr 248.9 665.4 866.8 H2-D1 78.3 379.8 849.2 H2-Aa 5.0 5.0 5.0 Cd68 1227.8 3338.3 7059.6 Psmb9 422.6 921.8 1905.0 Psmb8 321.6 1299.1 1756.3 Tapbp 1864.1 5252.2 6954.7 CEM 1 + Gbp2 547.6 1524.3 2763.3 Top 10 Genes Ifi27l2a 203.9 766.0 1579.9 Igtp 925.2 1952.7 3127.6 Fxyd5 472.7 2699.6 3709.5 Ifit3 823.4 3427.6 6700.4

Null module GEO Series "GSE21137" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -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=GSE21137 Status: Public on Apr 20 2010 Title: Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20395962 Summary & Design: Summary: We compare here the neurodegenerative processes observed in the hippocampus of bitransgenic mice with chronically altered levels of cAMP-response element-binding protein (CREB) function. The combination of genome-wide transcriptional profiling of degenerating hippocampal tissue with microscopy analyses reveals that the sustained inhibition of CREB function in A-CREB mice is associated with dark neuron degeneration, whereas its strong chronic activation in VP16-CREB mice primarily causes excitotoxic cell death and inflammation. Furthermore, the meta-analysis with gene expression profiles available in public databases identifies relevant common markers to other neurodegenerative processes and highlights the importance of the immune response in neurodegeneration. Overall, these analyses define the ultrastructural and transcriptional signatures associated with these two forms of hippocampal neurodegeneration, confirm the importance of fine-tuned regulation of CREBdependent gene expression for CA1 neuron survival and function, and provide novel insight into the function of CREB in the etiology of neurodegenerative processes.

Overall design: For each mouse genome 430 2.0 gene expression array (Affymetrix, Santa Clara, CA, USA), total RNA was extracted from the hippocampi of three to four mice with the same age, sex, and genotype to produce one pooled sample. We analyzed three late A-CREB pooled samples (6-week-old mice) and three late VP16-CREB pooled samples (3-week-off dox) with their corresponding control littermate samples (three pooled samples for each strain). To compare with early changes, we included two pooled A-CREB early samples (3-week-old mice) and two pooled VP16-CREB early samples (1-week-off dox) with their corresponding control littermate samples. In the case of A-CREB mice, we used the dataset GSE14320. We prepared new samples from bitransgenic mice and control littermates 1 week after transgene induction and hybridized them to mouse genome 430 2.0 genechips. The arrays were hybridized, washed, and screened for quality according to the manufacturers protocol.

Background corr dist: KL-Divergence = 0.1496, L1-Distance = 0.0345, L2-Distance = 0.0023, Normal std = 0.3737

1.067 Kernel fit Pairwise Correlations Normal fit

Density 0.534

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 littermateControl littermate for VP16-CREBVP16-CREB littermate for VP16-CREBVP16-CREB for 3 3 weeks-induction VP16-CREBweeks-inducedVP16-CREB 3 3 weeks-induction weeks-inducedControl 3 3 weeks-induction weeks-induced Control samplelittermatesample VP16-CREBsample1 littermatesample1 (0.107679) (0.0599838)for VP16-CREB VP16-CREBsample2 sample2 (0.170704) (0.0632018)for 1 VP16-CREBweek-induced Control3 3 (0.185885) (0.0409378) 1 1 week-induction week-inducedControl littermate 1 week-inductionsampleControl littermate for sampleA-CREB1sampleA-CREB littermate(0.0425183) for A-CREB2 sample1 A-CREB 6(0.0280738) 6(0.0430865) weeks-old weeks-oldfor A-CREB 2 A-CREB6 6(0.0480983) weeks-old weeks-old sample sample 6 6 weeks-old weeks-old sample 1 sample1 (0.0462195) (0.0358129) sample 2 sample2 (0.019365) (0.0140761) 3 3 [(0.0503611) (0.0439971) min ] [ medium ] [ max ] CEM 1 H2-K1 748.6 1242.2 7635.6 P ( S | Z, I ) = 1.00 Fcgrt 357.1 520.1 642.5 Mean Corr = 0.41631 Hfe 178.3 274.4 373.3 H2-Bl 23.1 45.0 70.0 H2-Q2 1.1 24.6 109.7 H2-Q10 1.8 28.7 247.3 C920025E04Rik 6.6 54.7 841.9 H2-M3 123.7 241.3 794.3 B2m 3.6 35.8 148.6 Mr1 23.1 106.2 174.1 Azgp1 3.6 13.0 68.6 Ulbp1 1.5 31.2 69.1 Procr 7.6 44.1 82.6 H2-D1 1.4 7.4 32.5 H2-Aa 8.8 41.0 489.0 Cd68 267.1 426.7 2509.2 Psmb9 92.2 147.5 424.5 Psmb8 116.0 212.8 763.0 Tapbp 693.9 921.4 1323.5 CEM 1 + Gbp2 112.9 256.0 661.2 Top 10 Genes Ifi27l2a 52.9 196.9 1273.6 Igtp 189.9 249.9 607.6 Fxyd5 182.1 231.6 582.7 Ifit3 270.9 466.5 1743.7

Null module GEO Series "GSE23895" 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=GSE23895 Status: Public on Jan 19 2011 Title: Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21226930 Summary & Design: Summary: Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency.

Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 ´g Se/g diet.

Overall design: Rats or mice were fed Se-deficient diets supplemented with sodium selenite up to 5 ug Se/g diet for 28 or 35 days. Affymetrix Rat 230 2.0 and Mouse 430 2.0 Genome Arrays were used to analyze gene expression in liver in all studies plus kidney in the mouse study.

Background corr dist: KL-Divergence = 0.0133, L1-Distance = 0.0509, L2-Distance = 0.0031, Normal std = 0.9121

0.437 Kernel fit Pairwise Correlations Normal fit

Density 0.219

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

MouseLiver_SeDef_rep1MouseLiver_SeDef_rep2MouseLiver_SeDef_rep3MouseLiver_0.05ugSe_rep1 (0.0473918)MouseLiver_0.05ugSe_rep2 (0.0469883)MouseLiver_0.05ugSe_rep3 (0.046901)MouseLiver_0.2ugSe_rep1 (0.0570545)MouseLiver_0.2ugSe_rep2 (0.0498969)MouseLiver_0.2ugSe_rep3 (0.121983)MouseKidney_SeDef_rep1 (0.0320774)MouseKidney_SeDef_rep2 (0.054445)MouseKidney_SeDef_rep3 (0.0531998)MouseKidney_0.05ugSe_rep1 (0.0496892)MouseKidney_0.05ugSe_rep2 (0.0506201)MouseKidney_0.05ugSe_rep3 (0.0489523)MouseKidney_0.2ugSe_rep1 MouseKidney_0.2ugSe_rep2(0.0456893) MouseKidney_0.2ugSe_rep3(0.042358) (0.095218) (0.0512626) (0.0645696) (0.0417031)[ min ] [ medium ] [ max ] CEM 1 H2-K1 7880.9 30340.8 46779.8 P ( S | Z, I ) = 1.00 Fcgrt 2143.7 5856.2 6648.5 Mean Corr = 0.48437 Hfe 435.5 2355.6 3267.6 H2-Bl 207.6 565.4 1073.4 H2-Q2 16.6 24.5 36.1 H2-Q10 104.5 27424.5 33654.5 C920025E04Rik 88.2 114.3 160.9 H2-M3 469.4 661.5 1109.9 B2m 92.2 144.2 202.2 Mr1 273.3 418.6 536.9 Azgp1 1203.1 24802.5 28837.6 Ulbp1 50.7 78.3 98.2 Procr 82.2 159.7 244.9 H2-D1 65.1 88.4 133.6 H2-Aa 800.9 1516.6 6563.0 Cd68 136.8 265.3 798.6 Psmb9 389.1 1117.1 4709.5 Psmb8 607.6 1416.8 4915.9 Tapbp 864.2 1518.9 2592.4 CEM 1 + Gbp2 79.8 207.4 903.0 Top 10 Genes Ifi27l2a 364.6 608.8 1077.3 Igtp 1222.8 4225.7 21974.7 Fxyd5 342.1 460.8 698.4 Ifit3 500.2 671.6 1066.0

Null module GEO Series "GSE15794" 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=GSE15794 Status: Public on Apr 25 2009 Title: Gene expression profiles of E13 bladder neck/urethral compartments. (GUDMAP Series ID: 25) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of micro dissected tissues and FACS sorted cells plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here delineates the gene expression profiles of the mesenchymal and epithelial compartments of the E13 mouse bladder neck/urethral compartment.

Overall design: FVB/N mice were time mated. At embryonic day 13 mice were euthanized by decapitation and the bladders were microdissected and cut just below the ureters. Since the EDTA dissociation was ineffective, the bladder neck and urethra were collected and treated with 1 mg/ml trypsin in Tyrode’s solution for 20 minutes at 37´C. The layers were separated using a fine needle and rimming. The samples were placed in RLT and stored at -80´C. RNA was prepared and the Epicentre 2-round amplification scheme described under the Lessard Group Protocols on the GUDMAP pages were performed. The amplified RNA was examined with the Affymetrix GeneChip Mouse Genome 430 2.0 Array.

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0594, L2-Distance = 0.0048, Normal std = 0.7260

0.597 Kernel fit Pairwise Correlations Normal fit

Density 0.298

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

urothelium1_200209urothelium2_200209urothelium5_200209 (0.0633235)mesenchyme1_200209 (0.125797)mesenchyme2_200209 (0.103808)mesenchyme3_200209 (0.479897) (0.0711744) (0.156)[ min ] [ medium ] [ max ] CEM 1 H2-K1 319.7 594.5 4303.3 P ( S | Z, I ) = 1.00 Fcgrt 24.1 316.5 6884.0 Mean Corr = 0.36237 Hfe 4.8 111.7 932.0 H2-Bl 5.8 23.9 95.9 H2-Q2 0.5 23.1 1120.6 H2-Q10 15.9 36.8 659.3 C920025E04Rik 31.7 53.9 62.7 H2-M3 242.1 525.4 789.3 B2m 2.1 2.6 52.2 Mr1 5.4 40.9 84.2 Azgp1 2.9 14.8 401.3 Ulbp1 2.2 12.9 22.0 Procr 58.8 381.9 516.8 H2-D1 3.0 8.9 12.3 H2-Aa 4.4 31.5 272.1 Cd68 54.9 142.6 492.3 Psmb9 13.7 90.8 375.2 Psmb8 6.9 13.1 165.3 Tapbp 371.9 820.6 1645.7 CEM 1 + Gbp2 20.5 32.9 165.3 Top 10 Genes Ifi27l2a 3.5 22.0 77.2 Igtp 78.2 177.4 832.7 Fxyd5 15.4 58.8 252.8 Ifit3 17.3 59.8 192.5

Null module GEO Series "GSE38831" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38831 Status: Public on Dec 22 2013 Title: Deciphering genomic alterations in colorectal cancer through transcriptional subtype-based network analysis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24260186 Summary & Design: Summary: High-throughput genomic studies have identified thousands of genetic alterations in colorectal cancer (CRC). Distinguishing driver from passenger mutations is critical for developing rational therapeutic strategies. Because only a few transcriptional subtypes exist in previously studied tumor types, we hypothesize that highly heterogeneous genomic alterations may converge to a limited number of distinct mechanisms that drive unique gene expression patterns in different transcriptional subtypes. In this study, we defined transcriptional subtypes for CRC and identified driver networks/pathways for each subtype, respectively. Applying consensus clustering to a patient cohort with 1173 samples identified three transcriptional subtypes, which were validated in an independent cohort with 485 samples. The three subtypes were characterized by different transcriptional programs related to normal adult colon, early colon embryonic development, and epithelial mesenchymal transition, respectively. They also showed statistically different clinical outcomes. For each subtype, we mapped somatic mutation and copy number variation data onto an integrated signaling network and identified subtype-specific driver networks using a random walk-based strategy. We found that genomic alterations in the Wnt signaling pathway were common among all three subtypes; however, unique combinations of pathway alterations including Wnt, VEGF, Notch and TGF-beta drove distinct molecular and clinical phenotypes in different CRC subtypes. Our results provide a coherent and integrated picture of human CRC that links genomic alterations to molecular and clinical consequences, and which provides insights for the development of personalized therapeutic strategies for different CRC subtypes.

Overall design: To characterize the embryonic development of colon, we conducted a time course microarray study using the inbred C57BL/6 (Jackson Laboratories, Bar Harbor, ME) mice. Seven samples corresponding to the mouse colonic development from E13.5 to E18.5 and adult (eight week post-natal) were collected. RNA samples were submitted to the Vanderbilt Functional Genomics Shared Resource (FSGR, http://array.mc.vanderbilt.edu), where RNA was hybridized to the Affymetrix Mouse Genome 430 2.0 GeneChip Expression Arrays (Santa Clara, CA) according to manufacturers instructions. The RMA algorithm was used for data normalization. Mouse gene symbols were mapped to human gene symbols by the Human and Mouse Orthology list available from the Mouse Genome Informatics (http://www.informatics.jax.org/).

Background corr dist: KL-Divergence = 0.0290, L1-Distance = 0.0333, L2-Distance = 0.0015, Normal std = 0.7069

0.606 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

C57BL/6JE13.5C57BL/6JE14.5C57BL/6JE15.5 (0.0750557)C57BL/6JE16.5 (0.0946978)C57BL/6JE17.5 (0.133446)C57BL/6JE18.5 (0.0464553)C57BL/6JADULT (0.0398889) (0.111245) COLON (0.499211)[ min ] [ medium ] [ max ] CEM 1 H2-K1 76.7 612.0 4628.4 P ( S | Z, I ) = 1.00 Fcgrt 416.1 597.8 945.0 Mean Corr = 0.40103 Hfe 133.8 198.1 521.5 H2-Bl 53.9 73.3 122.4 H2-Q2 38.6 48.4 1280.8 H2-Q10 89.3 158.8 294.3 C920025E04Rik 59.8 76.8 131.7 H2-M3 315.3 369.7 433.1 B2m 75.6 87.1 128.1 Mr1 117.2 134.1 184.1 Azgp1 71.3 80.1 153.1 Ulbp1 66.9 69.4 79.5 Procr 299.1 408.6 635.0 H2-D1 73.1 99.4 117.5 H2-Aa 62.4 67.8 354.7 Cd68 132.4 156.5 268.3 Psmb9 65.0 90.5 163.6 Psmb8 127.7 143.2 477.1 Tapbp 1015.4 2108.1 9408.4 CEM 1 + Gbp2 38.9 43.8 215.5 Top 10 Genes Ifi27l2a 133.1 170.4 973.4 Igtp 699.8 859.3 2120.7 Fxyd5 228.7 357.2 580.8 Ifit3 119.6 120.6 365.3

Null module GEO Series "GSE6223" 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=GSE6223 Status: Public on Nov 18 2006 Title: Gene expression profiles of E14 bladder, urogenital sinus and urethra isolated from SMGA (Actg2) transgenic mice. (GUDMAP Series ID: 6) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of the embryonic day 14 bladder, urogenital sinus, and urethra.

Keywords: Gene expression comparison from developing regions of the mouse embryonic day 14 urogenital system

Overall design: Bladder, urogenital sinus, and urethra regions from embryonic day 14 SMGA/EGFP animals were microdissected and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.

Background corr dist: KL-Divergence = 0.0992, L1-Distance = 0.0390, L2-Distance = 0.0030, Normal std = 0.4599

0.867 Kernel fit Pairwise Correlations Normal fit

Density 0.434

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

060301_2BLAD060301_6BLADJS_8 (0.0473949) (0.0385682)060301_1UGS (0.0508791)060301_2UGS (0.10369)060301_6UGS (0.0220537)JS_7 (0.0312396) (0.0316953)JS_060301_1_UrethraJS_060301_2_UrethraJS_060301_6_Urethra 060301_RefRNA_(0.0483179) JS_5(0.0411093) (0.17292) JS_RefRNA(0.0247557) (0.195081) (0.192295) [ min ] [ medium ] [ max ] CEM 1 H2-K1 415.7 862.6 4496.8 P ( S | Z, I ) = 1.00 Fcgrt 149.6 833.2 8127.3 Mean Corr = 0.24922 Hfe 48.3 164.8 979.8 H2-Bl 3.6 27.6 178.1 H2-Q2 0.3 3.8 921.3 H2-Q10 8.5 27.2 682.0 C920025E04Rik 6.5 28.2 60.1 H2-M3 73.5 259.8 401.4 B2m 2.1 24.6 158.8 Mr1 6.5 194.7 713.6 Azgp1 5.1 56.7 750.8 Ulbp1 2.1 147.9 403.6 Procr 425.1 547.7 1805.9 H2-D1 5.8 18.7 60.9 H2-Aa 1.8 29.8 256.0 Cd68 37.4 79.9 567.9 Psmb9 36.5 81.8 226.0 Psmb8 2.8 27.7 306.7 Tapbp 301.1 494.8 1377.0 CEM 1 + Gbp2 8.0 47.7 473.5 Top 10 Genes Ifi27l2a 5.4 22.8 325.0 Igtp 140.1 204.0 792.9 Fxyd5 38.6 83.6 350.4 Ifit3 4.7 55.2 194.4

Null module GEO Series "GSE19194" 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=GSE19194 Status: Public on Mar 31 2010 Title: Cbfb/Runx1-repression independent blockage of differentiation and accumulation of Csf2rb expressing cells by Cbfb-MYH11 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20007544 Summary & Design: Summary: It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. However, knockin mice expressing Cbfb-MYH11 (Cbfb+/MYH11) showed defects in primitive hematopoiesis not seen in Cbfb null (Cbfb-/-) embryos indicating that Cbfb-MYH11 has repression independent activities as well.

To identify gene expression changes associated with this novel activity, we compared the gene expression profile in the blood cells of Cbfb+/MYH11 and Cbfb-/- embryonic day 12.5 (E12.5) embryos with that of their wildtype littermates.

Overall design: Cbfb-MYH11 chimeras were mated to C57/Bl6 females to generate Cbfb+/MYH11 (Cbfb+/MYH11) and Cbfb+/+ (WT) embryos. Cbfb+/- x Cbfb+/- matings were used to generate Cbfb+/+ (Cbfb+/+) and Cbfb-/- (Cbfb-/-) embryos. Blood from 8-10 E12.5 embryos of the same genotype was pooled, and RNA was isolated, labeled, and hybridized to Affymetrix Genechip mouse microarray (430 2.0) chips. 4 chips were used for both the Cbfb+/MYH11 and littermate control samples. 3 chips were used for the Cbfb-/- samples and littermate control samples.

Background corr dist: KL-Divergence = 0.0464, L1-Distance = 0.0796, L2-Distance = 0.0113, Normal std = 0.6373

0.626 Kernel fit Pairwise Correlations Normal fit

Density 0.313

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

Cbfb+/MYH11,Cbfb+/MYH11, technicalCbfb+/MYH11, technicalCbfb+/MYH11, replicate technicalWT, replicate 1technical (0.0372532) technicalWT, replicate 2technical (0.0488391) replicateWT, replicate 3technical (0.0972056) replicateWT, 1 (0.185154) 4technical (0.107878) replicateCbfb-/-, 2 (0.0832422) replicate Cbfb-/-, technical3 (0.0187831) Cbfb-/-, technical4 replicate(0.0166316) Cbfb+/+,technical replicate 1 (0.0348534)Cbfb+/+, technical replicate 2 (0.0172351)Cbfb+/+, technical replicate 3 (0.0144258) technical replicate 1 (0.103479) replicate 2 (0.116813) 3 (0.118207)[ min ] [ medium ] [ max ] CEM 1 H2-K1 3723.3 5611.4 7865.7 P ( S | Z, I ) = 0.96 Fcgrt 230.5 559.5 1239.6 Mean Corr = 0.65830 Hfe 61.8 102.4 245.7 H2-Bl 141.1 192.6 279.9 H2-Q2 34.5 43.4 55.2 H2-Q10 70.6 89.4 128.4 C920025E04Rik 51.7 79.2 167.7 H2-M3 123.8 191.4 284.3 B2m 67.0 83.3 153.1 Mr1 572.7 760.9 997.5 Azgp1 281.1 408.4 735.0 Ulbp1 73.2 100.2 151.5 Procr 117.6 327.7 499.1 H2-D1 57.5 63.3 106.1 H2-Aa 147.5 196.3 310.6 Cd68 187.8 255.5 526.3 Psmb9 114.2 204.1 301.3 Psmb8 85.5 146.9 285.2 Tapbp 1579.8 1855.3 2953.5 CEM 1 + Gbp2 37.6 55.3 72.9 Top 10 Genes Ifi27l2a 206.6 320.4 1588.8 Igtp 1800.9 3153.3 3430.6 Fxyd5 443.6 756.7 1401.6 Ifit3 257.1 338.4 643.0

Null module GEO Series "GSE13103" 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=GSE13103 Status: Public on Oct 08 2008 Title: Expression data from early mouse embryo eye development, specifically optic fissure. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19171890 Summary & Design: Summary: The different stages of the optic fissure can be clearly visualized by making sagittal sections through the mouse eye during early development which represent the optic fissure at open (E10.5), closing (E11.5) and fused (E12.5) states. Laser capture microdissection (LCM) was employed to dissect tissue from the margins of the optic fissure consisting of the outer (presumptive RPE) and inner (presumptive neurosensory retina) layers of the retina.

An approximately square-shaped block of optic fissure (50 x 50 mm) was dissected from each side of the fissure. Two rounds of linear amplification were performed on RNA isolated from each of the samples prior to microarray hybridization. Expression data were gathered in biological triplicate at E10.5, E11.5 and duplicate at E12.5, each array representing pooled optic fissure tissue from three embryos from a single litter. Expression signals were ascertained from 45,101 probe sets and normalized across arrays.

Keywords: Time course

Overall design: Differential gene expression over the course of three days in laser capture microdissected tissue from wild type mouse embryos.

Background corr dist: KL-Divergence = 0.0253, L1-Distance = 0.0380, L2-Distance = 0.0026, Normal std = 0.7071

0.564 Kernel fit Pairwise Correlations Normal fit

Density 0.282

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

Optic fissure_mouse_E10.5_AOptic fissure_mouse_E10.5_BOptic fissure_mouse_E10.5_COptic fissure_mouse_E11.5_AOptic (0.1674) fissure_mouse_E11.5_BOptic (0.0256799) fissure_mouse_E11.5_COptic (0.10769) fissure_mouse_E12.5_AOptic (0.496763) fissure_mouse_E12.5_B (0.0664788) (0.0449818) (0.0437113)[ (0.0472957) min ] [ medium ] [ max ] CEM 1 H2-K1 101.1 130.2 229.2 P ( S | Z, I ) = 0.96 Fcgrt 47.5 62.6 103.3 Mean Corr = 0.71968 Hfe 51.0 129.9 189.2 H2-Bl 26.9 34.7 60.2 H2-Q2 23.2 26.1 47.7 H2-Q10 39.6 44.6 67.5 C920025E04Rik 23.9 35.4 51.5 H2-M3 70.8 132.9 165.7 B2m 30.9 43.9 55.5 Mr1 87.6 126.7 299.2 Azgp1 67.1 93.6 259.4 Ulbp1 25.1 39.0 67.7 Procr 78.7 106.7 150.1 H2-D1 32.5 39.2 65.4 H2-Aa 32.9 37.0 65.7 Cd68 29.6 57.2 67.8 Psmb9 44.0 76.5 117.3 Psmb8 53.4 58.9 97.6 Tapbp 78.3 159.3 361.0 CEM 1 + Gbp2 22.7 33.9 63.2 Top 10 Genes Ifi27l2a 36.6 54.1 94.3 Igtp 254.7 333.9 558.4 Fxyd5 32.4 54.9 97.4 Ifit3 123.1 168.6 224.4

Null module GEO Series "GSE29241" 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=GSE29241 Status: Public on Nov 13 2011 Title: Dendritic cell lineage commitment is instructed by distinct cytokine signals Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22078373 Summary & Design: Summary: Dendritic cells (DC) develop from hematopoietic stem cells, which is guided by instructive signals through cytokines. DC development progresses from multipotent progenitors (MPP) via common DC progenitors (CDP) into DC. Flt3 ligand (Flt3L) signaling via the Flt3/Stat3 pathway is of pivotal importance for DC development under steady state conditions. Additional factors produced during steady state or inflammation, such as TGF-beta1 or GM-CSF, also influence the differentiation potential of MPP and CDP. Here, we studied how gp130, GM-CSF and TGF-beta1 signaling influence DC lineage commitment from MPP to CDP and further into DC. We observed that activation of gp130 signaling promotes expansion of MPP. Additionally, gp130 signaling inhibited Flt3L-driven DC differentiation, but had little effect on GM-CSF-driven DC development. The inflammatory cytokine GM-CSF induces differentiation of MPP into inflammatory DC and blocks steady state DC development. Global transcriptome analysis revealed a GM-CSF-driven gene expression repertoire that primes MPP for differentiation into inflammatory DC. Finally, TGF-beta1 induces expression of DC-lineage affiliated genes in MPP, including Flt3, Irf-4 and Irf-8. Under inflammatory conditions, however, the effect of TGF- beta1 is altered: Flt3 is not upregulated, indicating that an inflammatory environment inhibits steady state DC development. Altogether, our data indicate that distinct cytokine signals produced during steady state or inflammation have a different outcome on DC lineage commitment and differentiation.

Overall design: - GM-TNFa-DC_2

Background corr dist: KL-Divergence = 0.0220, L1-Distance = 0.0160, L2-Distance = 0.0003, Normal std = 0.7247

0.550 Kernel fit Pairwise Correlations Normal fit

Density 0.275

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

MultipotentMultipotent progenitorDendritic progenitorDendritic sample cell sampleDendritic sample1 cell (GM-MPP_1) sample1Dendritic (GM-DC_1)2 cell (GM-MPP_2) plus2 (0.193025)(GM-DC_2) cell TNFa (0.0961559) plus (0.167017) sample TNFa (0.177709) sample1 (GM-TNFa-DC_1)[ 2min (GM-TNFa-DC_2) ] (0.108203) (0.25789)[ medium ] [ max ] CEM 1 H2-K1 11035.4 36151.4 49251.0 P ( S | Z, I ) = 0.95 Fcgrt 318.0 624.4 4137.1 Mean Corr = 0.49202 Hfe 210.9 601.3 992.6 H2-Bl 71.2 140.7 163.5 H2-Q2 20.1 23.2 27.5 H2-Q10 32.0 35.4 38.1 C920025E04Rik 59.0 108.5 498.4 H2-M3 546.1 3685.0 4766.3 B2m 156.7 1262.9 2097.0 Mr1 181.8 598.8 939.3 Azgp1 116.1 126.7 139.6 Ulbp1 86.8 149.2 213.2 Procr 40.3 2650.8 16267.6 H2-D1 30.6 45.0 50.4 H2-Aa 149.9 5546.9 27628.6 Cd68 6444.2 24406.6 27431.6 Psmb9 1262.3 3121.1 3758.8 Psmb8 3919.7 8995.3 9868.8 Tapbp 2474.5 6879.2 10064.5 CEM 1 + Gbp2 130.2 3140.6 8773.5 Top 10 Genes Ifi27l2a 90.4 1317.3 3373.3 Igtp 460.6 661.3 986.2 Fxyd5 11292.2 17457.7 28455.8 Ifit3 104.1 187.7 944.8

Null module GEO Series "GSE9330" 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=GSE9330 Status: Public on Dec 15 2007 Title: Expression data from wild type and Ctip2-/- (Bcl11b) mutant mouse striatum at P0 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18199763 Summary & Design: Summary: Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntingtons disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.

Keywords: mutant analysis

Overall design: Matched regions of striatum from wild type and Ctip2-/- mice were obtained via 500 ´m diameter punch biopsies performed in the center of the developing striatum in acutely sectioned 300 ´m coronal slices of the brain at postnatal day 0 (P0). Sections were matched rostro-caudally between wild type and null mutant tissue, and fiduciary landmarks were used to assure reproducible microdissection of comparable regions. RNA was extracted using the StrataPrep Total RNA Mini Kit (Stratagene, La Jolla, CA), and RNA quality was assayed using a bioanalyzer (Agilent Technologies, Paola Alto, CA). To ensure reproducibility and biological significance, microarrays were performed with RNA samples from three independent wild type, one heterozygote, and four Ctip2-/- mice (biological replicates). Microarray data were normalized using the RMA function within Bioconductor (Irizarry et al., 2003). Statistical significance of gene expression differences between wild type and knockout was determined using Statistical Analysis of Micrarrays (SAM) (Tusher et al., 2001). Using a SAM d-score cutoff of > 2 or < -2, we selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance.

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0600, L2-Distance = 0.0051, Normal std = 0.7875

0.507 Kernel fit Pairwise Correlations Normal fit

Density 0.253

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

striatum_wildtype_1striatum_wildtype_2striatum_wildtype_3 (0.0358509)striatum_het_1 (0.283445)striatum_ctip2_KO_1 (0.124028)striatum_ctip2_KO_2 (0.173745)striatum_ctip2_KO_3 (0.0215955)striatum_ctip2_KO_4 (0.159246) (0.147611) (0.0544797)[ min ] [ medium ] [ max ] CEM 1 H2-K1 573.8 698.0 983.3 P ( S | Z, I ) = 0.34 Fcgrt 217.7 272.1 301.6 Mean Corr = 0.56703 Hfe 109.7 159.7 185.5 H2-Bl 56.0 74.5 81.1 H2-Q2 15.0 18.1 24.2 H2-Q10 41.2 55.5 68.0 C920025E04Rik 46.1 61.7 73.4 H2-M3 119.9 171.2 185.0 B2m 37.1 45.8 59.6 Mr1 157.7 238.6 310.3 Azgp1 222.4 345.4 490.8 Ulbp1 38.1 45.4 72.6 Procr 68.6 96.6 118.2 H2-D1 66.1 101.7 109.4 H2-Aa 87.7 114.2 158.8 Cd68 133.9 168.4 204.8 Psmb9 160.6 188.5 225.9 Psmb8 149.0 173.4 260.6 Tapbp 202.0 218.5 292.3 CEM 1 + Gbp2 62.6 88.3 117.1 Top 10 Genes Ifi27l2a 134.9 209.0 248.3 Igtp 166.3 244.4 277.8 Fxyd5 262.2 361.3 466.8 Ifit3 102.8 147.6 173.9

Null module GEO Series "GSE18460" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -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=GSE18460 Status: Public on Oct 08 2009 Title: Lactobacillus acidophilus induces virus immune defense genes in murine dendritic cells by a TLR-2 dependent mechanism Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20545783 Summary & Design: Summary: Lactobacilli are probiotics that, among other health promoting effects, have been ascribed immunostimulating and virus preventive properties. Certain lactobacilli species have been shown to possess strong IL-12 inducing properties. As IL-12 production depends on the up-regulation of type I interferons, we hypothesized that the strong IL-12 inducing capacity of L. acidophilus NCFM in murine bone marrow derived DC is caused by an up-regulation of IFN-Î², which subsequently stimulates the induction of IL-12 and the dsRNA binding toll like receptor (TLR)-3. The expression of the genes encoding IFN-Î², IL-12, IL-10 and TLR-3 in DC upon stimulation with L. acidophilus NCFM was measured. L. acidophilus NCFM induced a much stronger expression of ifn-Î², il-12 and il-10 compared to the synthetic dsRNA ligand Poly I:C, whereas the levels of expressed tlr-3 were similar. By the use of whole genome microarray gene expression, we investigated whether other genes related to the viral defence were up-regulated in DC upon stimulation with L. acidophilus NCFM and found that various virus defence related genes, both early and late, were among the strongest up-regulated genes. The IFN-Î² stimulating capability was also detected in another L. acidophilus strain, but was not a property of other probiotic bacteria tested (B. bifidum and E. coli nissle).The IFN-Î² inducing capacity was markedly reduced in TLR-2 -/- DCs, dependent on endocytosis and the major cause of the induction of il-12 and tlr-3 in L. acidophilus NCFM stimulated cells. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DC in a TLR-2 manner through induction of IFN- Î².

Overall design: In the experiment Lactobacillus NCFM were added to murine dendritic cells and stimulated for 4, 10 or 18 hours. These were compared to control experiment at the same timepoints. Experiments were run in triplicates except for control 10h and control 18h which were only in duplicate, giving a total of 16 arrays.

Background corr dist: KL-Divergence = 0.0592, L1-Distance = 0.0699, L2-Distance = 0.0103, Normal std = 0.5549

0.719 Kernel fit Pairwise Correlations Normal fit

Density 0.359

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

DC ncfmDC 4h ncfm rep1DC 4h (0.0290784) ncfm rep2DC 4h (0.0209115) ncfm rep3DC 10h (0.0104489) ncfm rep1DC 10h (0.0297531)ncfm rep2DC 10h (0.0448291)ncfm rep3DC 18h (0.038326)ncfm rep1DC 18h (0.13566)ncfm rep2DC 18h (0.192184)control rep3DC (0.100639)control4h rep1DC control4h (0.0508085) rep2DC control4h (0.0581175) rep3DC control10h (0.0702872)DC rep1 control10h (0.0933832)DC rep2 control18h (0.0350493) rep1 18h (0.0291242) rep2 (0.0614011)[ min ] [ medium ] [ max ] CEM 1 H2-K1 17530.5 25169.2 34210.2 P ( S | Z, I ) = 0.20 Fcgrt 406.8 867.3 1785.1 Mean Corr = 0.33653 Hfe 483.2 931.6 2513.6 H2-Bl 271.5 386.2 543.4 H2-Q2 64.7 83.2 112.5 H2-Q10 177.6 228.0 391.6 C920025E04Rik 280.3 387.1 963.3 H2-M3 1982.2 3924.4 6082.1 B2m 184.3 802.6 1295.4 Mr1 252.7 326.3 477.0 Azgp1 223.2 246.1 265.2 Ulbp1 162.5 205.5 257.0 Procr 849.3 6985.5 19464.9 H2-D1 116.7 158.2 185.4 H2-Aa 13876.5 16999.1 20243.5 Cd68 4513.1 7111.9 13384.7 Psmb9 2880.3 5493.9 9921.9 Psmb8 5673.3 8989.4 14311.5 Tapbp 5689.1 11013.8 16954.1 CEM 1 + Gbp2 3514.2 11508.9 22618.6 Top 10 Genes Ifi27l2a 992.5 6914.5 15770.4 Igtp 730.8 5444.4 8957.3 Fxyd5 5010.3 7619.1 11173.7 Ifit3 232.8 9241.6 17214.7

Null module GEO Series "GSE51213" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -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=GSE51213 Status: Public on Sep 26 2013 Title: Effect of chronic glucocorticoid (GC) treatment on neonatal mouse whole cerebellum and whole lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Dexamethasone (1ug/g, Dex) or vehicle (saline) injected into postnatal days 0-7 (P0 to P7) of C57BL6J mouse pups every day. Whole organ were harvested at P7.

Overall design: KEYWORDS: cell type comparison, treatment comparison.

Background corr dist: KL-Divergence = 0.0258, L1-Distance = 0.0164, L2-Distance = 0.0003, Normal std = 0.6871

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.290

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

whole cerebellumwhole cerebellumwhole with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone replicate with cerebellumwhole dexamethasone replicate with B39 cerebellumwhole vehicle(0.0616452) replicate with B49 cerebellumwhole vehiclereplicate(0.0458885) replicate with B50 lungwhole vehiclereplicate(0.0444163) B78with B52with lung (0.0418512)whole vehicle replicate(0.0438544)dexamethasone B79 with lung (0.0441106)whole replicatedexamethasone B80 with lung (0.0427283)whole dexamethasone B81replicate with lung (0.0351365)whole dexamethasone replicate with B28 lungwhole vehicle(0.0709774) replicate with B31 lungwhole vehiclereplicate(0.0638822) replicate with B40 lung vehiclereplicate(0.074647) B12with B46 (0.0824753) vehiclereplicate(0.0965602) B14 (0.0739804) replicate B19 [(0.117207) min B22 (0.0606395) ] [ medium ] [ max ] CEM 1 H2-K1 422.1 5805.9 7306.8 P ( S | Z, I ) = 0.01 Fcgrt 310.5 1285.7 1834.7 Mean Corr = 0.51568 Hfe 106.0 664.1 849.4 H2-Bl 38.4 45.3 59.4 H2-Q2 25.9 65.5 153.0 H2-Q10 31.3 46.6 89.2 C920025E04Rik 27.5 32.2 47.4 H2-M3 91.5 315.6 495.5 B2m 21.2 53.6 166.3 Mr1 124.3 170.0 306.2 Azgp1 48.0 63.8 140.4 Ulbp1 23.5 28.7 35.8 Procr 67.9 160.0 322.1 H2-D1 19.9 24.0 28.8 H2-Aa 30.4 59.3 765.7 Cd68 71.0 265.3 1885.9 Psmb9 71.0 346.6 634.6 Psmb8 69.5 685.2 1028.0 Tapbp 366.6 2122.6 3089.2 CEM 1 + Gbp2 33.8 499.2 755.5 Top 10 Genes Ifi27l2a 73.4 122.9 544.8 Igtp 128.9 705.6 997.6 Fxyd5 171.2 1276.9 3683.9 Ifit3 44.9 187.8 703.9

Null module GEO Series "GSE15872" 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=GSE15872 Status: Public on Oct 01 2009 Title: Dynamic patterning at the pylorus: formation of an epithelial intestine-stomach boundary in late fetal life Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19877272 Summary & Design: Summary: In the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4g, Creb3l3 and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan.

Overall design: Stomach, pylorus and duodenum tissue from E14.5 and E16.5 mouse embryos were collected for RNA extraction and hybridization on Affymetrix microarrays. We sought to study the gene expression profiles and identify genes and pathways enriched in these three tissues at two important developmental times.

Background corr dist: KL-Divergence = 0.0387, L1-Distance = 0.0489, L2-Distance = 0.0046, Normal std = 0.6254

0.638 Kernel fit Pairwise Correlations Normal fit

Density 0.319

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

stomachstomach at E14.5,stomach at biological E14.5,pylorus at biological E14.5, rep1pylorus at E14.5, biological(0.035552) rep2pylorus at biological E14.5, (0.0458932) rep3duodenum at biological E14.5, (0.0354755) rep1duodenum biological(0.0267726) at rep2 E14.5,duodenum (0.0275605) at rep3biological E14.5,stomach (0.0233769) at biological E14.5,stomach rep1 at E16.5, biological(0.025492)stomach rep2 at biological E16.5, (0.034513)pylorus rep3 at biological E16.5, (0.0238978)rep1pylorus at E16.5, biological(0.0182244) rep2pylorus at biological E16.5, (0.0600816) rep3duodenum at biological E16.5, (0.0350168) rep1duodenum biological(0.0357525) at rep2 E16.5,duodenum (0.0331802) at rep3biological E16.5, (0.0170546) at biological E16.5, rep1 biological(0.0987583) rep2 (0.161146)[ rep3 min (0.262253) ] [ medium ] [ max ] CEM 1 H2-K1 417.4 2398.5 9317.5 P ( S | Z, I ) = 0.00 Fcgrt 345.4 944.4 21406.1 Mean Corr = 0.40909 Hfe 80.6 188.7 286.8 H2-Bl 29.4 40.7 1693.4 H2-Q2 16.7 363.1 4749.8 H2-Q10 43.2 194.9 4619.9 C920025E04Rik 21.2 26.2 49.7 H2-M3 123.2 195.3 289.8 B2m 27.3 47.8 178.0 Mr1 141.7 172.1 234.2 Azgp1 59.5 84.4 132.5 Ulbp1 27.4 34.6 52.8 Procr 185.6 425.1 604.6 H2-D1 17.8 20.6 25.1 H2-Aa 30.3 40.6 87.6 Cd68 61.8 105.1 130.4 Psmb9 82.4 227.5 1283.4 Psmb8 72.6 114.8 697.3 Tapbp 504.3 1241.0 2887.8 CEM 1 + Gbp2 52.2 67.7 86.0 Top 10 Genes Ifi27l2a 108.0 177.8 400.5 Igtp 184.2 287.5 1274.5 Fxyd5 124.7 165.0 212.3 Ifit3 31.7 46.6 590.5

Null module GEO Series "GSE38074" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 39 -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=GSE38074 Status: Public on Aug 23 2012 Title: Scaling proprioceptor gene transcription by retrograde NT3 signaling Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23029089 Summary & Design: Summary: Transcriptional analysis of identified DRG subpopulations.

Cell-type specific intrinsic programs instruct neuronal subpopulations before target-derived factors influence later neuronal maturation. Retrograde neurotrophin signaling controls neuronal survival and maturation of dorsal root ganglion (DRG) sensory neurons, but how these potent signaling pathways intersect with transcriptional programs established at earlier developmental stages remains poorly understood. Here we determine the consequences of genetic alternation of NT3 signaling on genome-wide transcription programs in proprioceptors, an important sensory neuron subpopulation involved in motor reflex behavior. We find that the expression of many proprioceptor-enriched genes is dramatically altered by genetic NT3 elimination, independent of survival-related activities. Combinatorial analysis of gene expression profiles with proprioceptors isolated from mice expressing surplus muscular NT3 identifies an anticorrelated gene set with transcriptional levels scaled in opposite directions. Voluntary running experiments in adult mice further demonstrate the maintenance of transcriptional adjustability of genes expressed by DRG neurons, pointing to life-long gene expression plasticity in sensory neurons.

Overall design: We combined a mouse line expressing GFP under the control of the TrkC promoter (BAC transgene approach) with various NT3 signaling mutants in order to identify the transcriptional changes in identified subpopulations of dorsal root ganglia (DRG) neurons. Sorted cells were processed for RNA extraction and hybridization on Affymetrix microarrays. Analysis was performed a postnatal (p) day p0. Subsequent analysis focused on the transcriptional profile of DRG neuron subpopulations at specific lumbar levels. Additional work addressed the transcriptional changes in whole DRG in adult mice with and without physical exercise.

Background corr dist: KL-Divergence = 0.0769, L1-Distance = 0.0455, L2-Distance = 0.0046, Normal std = 0.4814

0.829 Kernel fit Pairwise Correlations Normal fit

Density 0.414

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

DRG_BaxKO_P0_TrkC+_rep1DRG_BaxKO_P0_TrkC+_rep2DRG_BaxKO_P0_TrkC-_rep1DRG_BaxKO_P0_TrkC-_rep2 DRG_NT3KO-BaxKO_P0_TrkC+_rep1(0.0218205) DRG_NT3KO-BaxKO_P0_TrkC+_rep2(0.0130525) (0.0200063)DRG_NT3KO-BaxKO_P0_TrkC-_rep1 (0.0166901)DRG_NT3KO-BaxKO_P0_TrkC-_rep2DRG_wildtype_P0_TrkC+_rep1DRG_wildtype_P0_TrkC+_rep2 (0.015806)DRG_wildtype_P0_TrkC-_rep1 (0.0163139) DRG_wildtype_P0_TrkC-_rep2(0.122433) DRG_mlcNT3_P0_TrkC+_rep1(0.0255518) (0.0335208)DRG_mlcNT3_P0_TrkC+_rep2 (0.0126507)DRG_mlcNT3_P0_TrkC-_rep1 (0.0108491)DRG_mlcNT3_P0_TrkC-_rep2 (0.00548398)DRG_wildtype_L1_adult_TrkC+_rep1 (0.0169723)DRG_wildtype_L1_adult_TrkC+_rep2 (0.0144705) DRG_wildtype_L1_adult_TrkC+_rep3(0.0126021) DRG_wildtype_L5_adult_TrkC-_rep1(0.0183654)DRG_wildtype_L5_adult_TrkC-_rep2 DRG_wildtype_L5_adult_TrkC-_rep3(0.0436768) DRG_wildtype_L1_EEadult_TrkC+_rep1(0.0189352) DRG_wildtype_L1_EEadult_TrkC+_rep2(0.0167941) (0.0412773)DRG_wildtype_L1_EEadult_TrkC+_rep3 (0.0906662)DRG_wildtype_L5_EEadult_TrkC-_rep1 (0.0571368)DRG_wildtype_L5_EEadult_TrkC-_rep2DRG_wildtype_L5_EEadult_TrkC-_rep3 (0.0433626)DRG_wildtype_L1_P0_TrkC+_rep1 (0.0220476)DRG_wildtype_L5_P0_TrkC+_rep1 (0.0235152)DRG_wildtype_L1_P0_TrkC-_rep1 (0.0411406)DRG_wildtype_L5_P0_TrkC-_rep1 (0.0229295)DRG_wildtype_L5_P0_TrkC+_rep2 (0.0295512) (0.00821211)DRG_wildtype_L1_P0_TrkC-_rep2 (0.0145739)DRG_wildtype_L5_P0_TrkC-_rep2 (0.0145244)DRG_wildtype_L1_P0_TrkC+_rep2 (0.0198912)DRG_wildtype_L5_P0_TrkC+_rep3 (0.0304717)DRG_wildtype_L1_P0_TrkC-_rep3 (0.0165774)DRG_wildtype_L5_P0_TrkC-_rep3 (0.0153458) (0.00885493) (0.0150218) (0.0177327)[ min (0.0111727) ] [ medium ] [ max ] CEM 1 H2-K1 105.1 338.4 3080.9 P ( S | Z, I ) = 0.00 Fcgrt 47.5 110.7 1279.9 Mean Corr = 0.50632 Hfe 32.1 119.7 803.5 H2-Bl 25.0 31.4 49.7 H2-Q2 9.0 12.4 16.0 H2-Q10 16.2 21.0 39.9 C920025E04Rik 18.3 26.2 45.7 H2-M3 47.4 213.6 877.4 B2m 27.4 40.7 245.7 Mr1 76.8 114.5 216.5 Azgp1 47.0 68.4 122.9 Ulbp1 18.3 25.0 48.3 Procr 25.7 50.3 226.2 H2-D1 14.0 20.4 30.6 H2-Aa 19.4 31.6 265.3 Cd68 20.7 37.1 172.8 Psmb9 39.3 66.7 247.3 Psmb8 38.6 52.8 233.4 Tapbp 371.4 1158.6 1556.1 CEM 1 + Gbp2 16.1 27.6 689.6 Top 10 Genes Ifi27l2a 40.5 93.0 650.6 Igtp 160.6 410.8 3413.0 Fxyd5 63.9 109.0 538.9 Ifit3 31.6 64.2 931.7

Null module GEO Series "GSE33134" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 31 -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=GSE33134 Status: Public on Dec 31 2011 Title: Protective gene expression changes elicited by an inherited defect in photoreceptor structure. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To investigate pathogenic mechanisms in such instances, we have characterized rod photoreceptor and retinal gene expression changes in response to a defined insult to photoreceptor structure, using the retinal degeneration slow (rds) mouse model. Global gene expression profiling was performed on flow-sorted rds and wild-type rod photoreceptors immediately prior and subsequent to times at which OSs are normally elaborated. Dysregulated genes were identified via microarray hybridization, and selected candidates were validated using quantitative PCR analyses. We identified a single key gene, Egr1, that was dysregulated in a sustained fashion in rds rod photoreceptors and in the retina. Egr1 upregulation was associated with microglial activation and migration, into the outer retina at times subsequent to the major peak of photoreceptor cell death. Interestingly, this response was accompanied by neurotrophic factor upregulation. We hypothesize that activation of Egr1 and neurotrophic factors represents a protective immune mechanism, contributing to the characteristically slow retinal degeneration of the rds mouse model.

Overall design: We had two conditions WT and Rds-KO at 4 different time points: postnatal (P) 6, P9, P14 and P21.

Background corr dist: KL-Divergence = 0.0735, L1-Distance = 0.0832, L2-Distance = 0.0128, Normal std = 0.6445

0.619 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

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

Pre-normalization Quantiles

Rds at postRds atnatal postRds day atnatal 6,postRds biological day atnatal 6,postRds biological day atnatalreplicate 6,postRds biological day atnatalreplicate 16,postRds (0.0131493) biological day atnatalreplicate 29,postRds (0.022149) biological day atnatalreplicate 39,postRds (0.0247332) biological day atnatalreplicate 49,postRds (0.0306003) biological day atnatalreplicate 19,postRds (0.00807361) biological day atnatalreplicate 214,postRds (0.0015505) daybiological atnatalreplicate 314,postRds (0.00986571) daybiological atnatal replicate 414,postRds (0.00298272) daybiological atnatal replicate 14,post Rds1 (0.0163506) daybiological atnatal replicate 21,post Rds2 (0.00154075) daybiological atnatal replicate 21,post WT3 (0.00629918) daybiological at natal replicate post21, WT4 (0.0684598) daybiological atnatal replicate post21, WT1 day(0.00223046) biological atnatal replicate6,post WT2 biological day(0.0475974) atnatal replicate6,post WT3 biological day(0.00418243) atnatalreplicate 6,post WT4 biological day(0.0740399) atnatalreplicate 16,post WT(0.00621039) biological day atnatalreplicate 29,post WT(0.0257268) biological day atnatalreplicate 39,post WT(0.035853) biological day atnatalreplicate 49,post WT(0.0347529) biological day atnatalreplicate 19,post WT(0.0091544) biological day atnatalreplicate 214,post WT(0.141612) daybiological atnatalreplicate 314,post WT(0.226532) daybiological atnatal replicate 414,post WT(0.0477855) daybiological atnatal replicate 21,post 1WT (0.00922796) daybiological atnatal replicate 21,post 2 (0.038273) daybiological natal replicate 21, 3 (0.00908953) daybiological replicate 21, 1 (0.0113385) biological replicate 2[ (0.00803523) min replicate 3 (0.0560009) ] 4 (0.00660386)[ medium ] [ max ] CEM 1 H2-K1 45.2 57.4 76.2 P ( S | Z, I ) = 0.00 Fcgrt 47.4 61.5 122.3 Mean Corr = 0.64643 Hfe 83.8 109.3 162.5 H2-Bl 45.0 57.7 83.9 H2-Q2 45.4 60.3 294.8 H2-Q10 45.0 58.2 144.7 C920025E04Rik 51.8 125.8 491.1 H2-M3 47.6 99.4 314.7 B2m 45.2 56.8 90.9 Mr1 45.1 55.4 79.6 Azgp1 45.4 59.2 148.3 Ulbp1 45.7 65.3 182.9 Procr 45.3 57.2 77.3 H2-D1 44.7 63.7 509.8 H2-Aa 44.9 55.3 79.1 Cd68 45.3 58.8 83.3 Psmb9 45.4 55.4 80.9 Psmb8 45.6 57.6 102.2 Tapbp 197.9 1805.7 3335.1 CEM 1 + Gbp2 45.1 57.1 89.2 Top 10 Genes Ifi27l2a 45.2 55.5 94.4 Igtp 45.5 56.0 90.5 Fxyd5 45.3 57.5 77.7 Ifit3 46.8 59.0 108.1

Null module GEO Series "GSE40260" 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=GSE40260 Status: Public on Aug 17 2013 Title: Microarray using CD31+/CD41-/CD45- cells from E9.5 mouse heart tube, caudal half and yolk sac Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23463007 Summary & Design: Summary: Hematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here, we examined the hemogenic activity of the developing endocardium. Mouse heart explants generated myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arose from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and was transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, were expressed in and required for the hemogenic activity of the endocardium. Together, these data suggest that a subset of endocardial and yolk sac endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors.

Overall design: Two independent biological duplicates of freshly isolated mouse tissues (caudal half, heart tube, yolk sac) were sorted for CD31+/CD41-/CD45- cells.

Background corr dist: KL-Divergence = 0.0387, L1-Distance = 0.0296, L2-Distance = 0.0012, Normal std = 0.6347

0.642 Kernel fit Pairwise Correlations Normal fit

Density 0.321

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

Caudal Caudalhalf, biological Hearthalf, biological tube,Heart replicate biological tube,Yolk replicate 1 biological(0.131289) sac, replicateYolk biological2 (0.0760781) sac, replicate 1 biological (0.124186) replicate 2 (0.134071) replicate 1 (0.18636) 2[ (0.348016) min ] [ medium ] [ max ] CEM 1 H2-K1 169.5 605.8 1324.5 P ( S | Z, I ) = 0.00 Fcgrt 20.5 40.9 1999.3 Mean Corr = 0.35597 Hfe 16.6 36.6 111.4 H2-Bl 3.9 9.3 9.7 H2-Q2 0.8 1.0 1.9 H2-Q10 3.3 4.0 9.2 C920025E04Rik 4.9 8.6 13.9 H2-M3 26.8 38.7 100.4 B2m 22.2 49.5 110.7 Mr1 13.3 20.6 82.1 Azgp1 1.5 2.3 3.8 Ulbp1 145.7 492.8 1022.0 Procr 619.5 1290.3 2610.2 H2-D1 3.7 6.0 7.5 H2-Aa 3.5 4.9 6.6 Cd68 61.5 194.7 254.6 Psmb9 8.3 12.3 24.8 Psmb8 7.2 11.5 30.6 Tapbp 271.4 525.3 1003.8 CEM 1 + Gbp2 1.6 4.1 5.8 Top 10 Genes Ifi27l2a 9.5 12.7 21.9 Igtp 6.4 13.7 56.5 Fxyd5 1124.4 2782.1 2821.0 Ifit3 20.1 41.4 288.9

Null module GEO Series "GSE5298" 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=GSE5298 Status: Public on Jul 14 2006 Title: Development of heart valves requires Gata4 expression in endothelial-derived cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16914500 Summary & Design: Summary: Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart disease. At localized swellings of extracellular matrix known as the endocardial cushions, the endothelial lining of the heart undergoes an epithelial to mesenchymal transition (EMT) to form mesenchymal progenitors of the AV valves. Further growth and differentiation of these mesenchymal precursors results in formation of portions of the atrial and ventricular septae, and generation of thin, pliable valves. The transcription factor Gata4 is expressed in the endothelium and mesenchyme of the AV valves. Using a Tie2-Cre transgene, we selectively inactivated Gata4 within endothelial-derived cells. Mutant endothelium failed to undergo EMT, resulting in hypocellular cushions. Mutant cushions had decreased levels of Erbb3, an EGF-family receptor essential for EMT in the atrioventricular cushions. In Gata4 mutant embryos, Erbb3 downregulation was associated with impaired activation of Erk, which is also required for EMT. Expression of a Gata4 mutant protein defective in interaction with Friend of Gata (FOG) cofactors rescued the EMT defect, but resulted in decreased proliferation of mesenchyme and hypoplastic cushions that failed to septate the ventricular inlet. We demonstrate two novel functions of Gata4 in development of the AV valves. First, Gata4 functions as an upstream regulator of an Erbb3-Erk pathway necessary for EMT, and second, Gata4 acts to promote cushion mesenchyme growth and remodeling.

Keywords: genetic modification

Overall design: For RNA analysis, four mutant and four control RNA samples were prepared (Pico-Pure RNA Isolation Kit, Arcturus), each consisting of 10 microdissected AVCs. Probe was prepared from 50 ng total RNA using an isothermal amplification protocol (NuGen), and hybridized to Affymetrix Mouse 430 2.0 microarrays. Two control samples were excluded because of excessive noise.

Background corr dist: KL-Divergence = 0.0176, L1-Distance = 0.0303, L2-Distance = 0.0014, Normal std = 0.7687

0.519 Kernel fit Pairwise Correlations Normal fit

Density 0.260

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

AVC_control_rep1AVC_control_rep2AVC_control_rep3 (0.101849)AVC_control_rep4 (0.278405)AVC_mutant_rep1 (0.211496)AVC_mutant_rep2 (0.0486486)AVC_mutant_rep3 (0.135352)AVC_mutant_rep4 (0.0734101) (0.0874849) (0.0633538)[ min ] [ medium ] [ max ] CEM 1 H2-K1 93.3 193.5 565.5 P ( S | Z, I ) = 0.00 Fcgrt 7.9 106.6 379.0 Mean Corr = 0.51798 Hfe 6.2 70.3 104.9 H2-Bl 4.9 43.9 103.6 H2-Q2 145.1 200.8 544.7 H2-Q10 1.0 52.1 204.0 C920025E04Rik 2.6 26.7 118.1 H2-M3 11.3 90.7 195.8 B2m 7.2 45.2 256.7 Mr1 3.3 19.2 327.6 Azgp1 3.5 8.5 38.7 Ulbp1 19.2 84.2 134.3 Procr 32.2 89.5 444.1 H2-D1 7.5 80.8 209.6 H2-Aa 3.2 60.3 120.1 Cd68 23.6 52.5 185.9 Psmb9 2.8 42.7 104.6 Psmb8 1.9 9.3 62.7 Tapbp 717.0 857.5 1073.7 CEM 1 + Gbp2 3.2 25.6 116.9 Top 10 Genes Ifi27l2a 2.7 21.2 44.8 Igtp 43.6 178.4 409.0 Fxyd5 333.5 443.3 545.8 Ifit3 4.4 67.6 226.2

Null module GEO Series "GSE4029" 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=GSE4029 Status: Public on May 01 2006 Title: Basonuclin: A novel mammalian maternal effect gene Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16624857 Summary & Design: Summary: Keywords: RNAi knockdown

Overall design: Basonuclin-deficient oocytes were created by a mouse transgenic RNAi approach, which knocks down basonuclin mRNA level specifically in oocytes. Microarray analysis was performed on total RNA from four non-transgenic (control) and six transgenic (basonuclin-deficient) oocyte samples (approximately 50 oocytes per sample).

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0871, L2-Distance = 0.0111, Normal std = 0.6253

0.699 Kernel fit Pairwise Correlations Normal fit

Density 0.350

0.000 CEM 1

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

Pre-normalization Quantiles

Non-TransgenicNon-TransgenicNon replicate -TransgenicNon-Transgenic replicate 1 (0.368846)RNAi replicate 2 (0.12844)-TransgenicRNAi replicate 7 -Transgenic(0.108454)RNAi replicate8 (0.0801423)-TransgenicRNAi replicate 4-Transgenic (0.10396)RNAi replicate 5-Transgenic (0.0264138)RNAi replicate 6-Transgenic (0.0373175) replicate 11 (0.0573732) replicate 12 (0.0697826) 13 [(0.0192711) min ] [ medium ] [ max ] CEM 1 H2-K1 34.2 52.9 85.6 P ( S | Z, I ) = 0.00 Fcgrt 11.8 12.5 15.5 Mean Corr = 0.48379 Hfe 15.0 16.5 19.7 H2-Bl 28.2 31.8 58.8 H2-Q2 17.6 21.0 26.8 H2-Q10 20.0 24.0 34.9 C920025E04Rik 26.0 29.6 40.5 H2-M3 41.7 43.4 46.3 B2m 9.7 10.6 12.2 Mr1 5.9 6.3 6.9 Azgp1 62.4 68.9 94.3 Ulbp1 9.8 10.5 12.2 Procr 11.3 12.1 15.7 H2-D1 4.5 4.8 5.1 H2-Aa 111.0 548.8 1053.8 Cd68 9.5 10.0 18.0 Psmb9 7.4 7.8 8.3 Psmb8 9.1 9.5 9.9 Tapbp 30.8 42.3 86.9 CEM 1 + Gbp2 8.7 9.1 10.1 Top 10 Genes Ifi27l2a 38.1 44.6 56.1 Igtp 30.3 32.7 36.5 Fxyd5 11.4 12.2 13.7 Ifit3 20.2 22.1 25.0

Null module GEO Series "GSE23925" 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=GSE23925 Status: Public on Sep 07 2010 Title: Gene expression in germinal center light zone, dark zone, and naÃ¯ve B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21074050 Summary & Design: Summary: Microarrays of gene expression in mouse germinal center B cells photoactivated in the light zone or dark zone, and of naÃ¯ve cells for comparison.

We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of the germinal center.

Overall design: Light and dark zone cells were photoactivated in day 7 germinal centers and sorted by flow cytometry. NaÃ¯ve splenic B cells(IgD+CD19+) were sorted for comparison.

Background corr dist: KL-Divergence = 0.0123, L1-Distance = 0.0424, L2-Distance = 0.0027, Normal std = 0.8861

0.450 Kernel fit Pairwise Correlations Normal fit

Density 0.225

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

light zone,light biological zone,dark biological zone, replicatedark biological zone, replicatenaive, 1 (0.0529135) biological replicatebiologicalnaive, 2 (0.0530874) replicatebiological 1 replicate(0.0879623) 2 replicate(0.0952798) 1 (0.237508) 2 (0.473249)[ min ] [ medium ] [ max ] CEM 1 H2-K1 16571.9 23704.9 46749.6 P ( S | Z, I ) = 0.00 Fcgrt 203.9 285.8 1058.0 Mean Corr = 0.43982 Hfe 57.4 70.9 117.7 H2-Bl 109.5 126.7 304.0 H2-Q2 25.8 31.8 35.6 H2-Q10 52.9 70.8 158.1 C920025E04Rik 331.7 531.6 610.3 H2-M3 2540.3 3405.1 6081.1 B2m 575.3 670.2 2845.8 Mr1 121.9 172.7 300.0 Azgp1 83.4 110.2 226.8 Ulbp1 60.4 79.0 181.4 Procr 58.3 81.6 105.7 H2-D1 53.7 69.8 132.9 H2-Aa 24736.9 29884.2 61665.6 Cd68 58.4 208.4 338.4 Psmb9 5144.8 6573.3 9416.8 Psmb8 8642.4 12534.4 15473.1 Tapbp 3037.5 4608.1 7741.0 CEM 1 + Gbp2 116.3 558.8 1406.0 Top 10 Genes Ifi27l2a 4031.9 7894.5 33419.3 Igtp 749.2 1023.9 4154.6 Fxyd5 370.3 522.7 2736.0 Ifit3 99.5 358.2 1419.8

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 (0.0229815)66977_ru (0.0233358)70660_lu (0.0339471)74128_wlr (0.0548715)74128_wr (0.0417415)74129_wl (0.032413)C57Bl6_1 (0.018566)C57Bl6_2 (0.253333)C57Bl6_3 (0.14947)86823-2x (0.120522)82743-lo (0.140096)77204-10 (0.0592214) (0.0495014) [ min ] [ medium ] [ max ] CEM 1 H2-K1 925.4 2367.5 15383.7 P ( S | Z, I ) = 0.00 Fcgrt 222.3 396.5 2469.4 Mean Corr = 0.35866 Hfe 76.1 242.8 2220.4 H2-Bl 36.6 51.9 72.6 H2-Q2 10.6 11.6 16.4 H2-Q10 25.5 277.2 3152.0 C920025E04Rik 23.7 35.1 44.3 H2-M3 105.6 207.7 675.0 B2m 24.6 31.6 71.3 Mr1 72.8 111.6 314.9 Azgp1 58.0 80.6 1883.8 Ulbp1 38.0 46.4 55.3 Procr 163.4 399.9 1749.9 H2-D1 19.7 25.5 34.2 H2-Aa 94.4 361.5 1263.2 Cd68 160.0 677.9 1054.6 Psmb9 147.3 202.0 1264.1 Psmb8 159.5 297.9 1622.2 Tapbp 442.8 677.6 4337.5 CEM 1 + Gbp2 50.0 128.2 1135.2 Top 10 Genes Ifi27l2a 73.5 196.7 7972.0 Igtp 157.1 317.1 2983.4 Fxyd5 129.2 476.8 1161.7 Ifit3 62.3 80.3 533.1

Null module GEO Series "GSE34423" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 40 -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=GSE34423 Status: Public on Dec 14 2011 Title: Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice [Expression array]. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21455306 Summary & Design: Summary: Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.

Overall design: 2932 days old male B6C3F1/Crl (C57BL/6 x C3H/He ) mice were obtained from Charles River Laboratories (Germany). Animals were allowed to acclimatise for 5 days prior to being randomly divided into two treatment groups (n = 10) and phenobarbital (Sigma 04710, 0.05% (w/v) in drinking water) was administered to one group through ad libitum access to drinking water for 28 days. Mice were checked daily for activity and behavior and sacrificed on the last day of dosing (day 28). Blood was withdrawn for PK analysis and target (liver) and non-target (kidney) tissues removed, split into several sections, frozen in liquid nitrogen and stored at 80´C for subsequent analyses. Total RNA from liver and kidney was purified and processed for Affymetrix gene expression profiling while genomic DNA was prepared for promoter array based methylome analysis using the Methylated DNA immunoprecipitation (MeDIP) procedure. Remaining tissue material was used for chromatin immunoprecipitation (ChIP) to analyze histone modifications at individual promoters. Plasma samples were also collected to evaluate phenobarbital exposure in individual animals by LC-MS.

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0729, L2-Distance = 0.0087, Normal std = 0.5583

0.829 Kernel fit Pairwise Correlations Normal fit

Density 0.415

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

PB_Kidney_Control_5PB_Kidney_Control_1PB_Kidney_Control_9 PB_Kidney_Control_4(0.0199581) PB_Kidney_Control_10(0.0271424) PB_Kidney_Control_8(0.0181217) PB_Kidney_Control_3(0.0247401)PB_Kidney_Control_7 (0.0226894) PB_Kidney_Control_2(0.0123212) PB_Kidney_Control_6(0.0212547) PB_Liver_Control_10(0.0240952) PB_Liver_Control_9(0.0221568) PB_Liver_Control_2(0.0184905) (0.0214652)PB_Liver_Control_3 (0.0345868)PB_Liver_Control_6 (0.0713671)PB_Liver_Control_5 (0.0422182)PB_Liver_Control_4 (0.0129906)PB_Liver_Control_8 (0.0240021)PB_Liver_Control_1 (0.01949)PB_Liver_Control_7 (0.0248182)PB_Kidney_treated_20 (0.0186363)PB_Kidney_treated_18 (0.0450712)PB_Kidney_treated_12PB_Kidney_treated_11 (0.0237228)PB_Kidney_treated_17 (0.0161269)PB_Kidney_treated_16 (0.0247225)PB_Kidney_treated_14 (0.0195604)PB_Kidney_treated_15 (0.0190511)PB_Kidney_treated_13 (0.0189413)PB_Kidney_treated_19 (0.0200643)PB_Liver_treated_12 (0.0206469)PB_Liver_treated_13 (0.0179635)PB_Liver_treated_14 (0.0152708) (0.024785)PB_Liver_treated_15 (0.0259874)PB_Liver_treated_11 (0.028125)PB_Liver_treated_16 (0.0306966)PB_Liver_treated_18 (0.0340651)PB_Liver_treated_19 (0.0268509)PB_Liver_treated_20 (0.0322251)PB_Liver_treated_17 (0.0317656) (0.0154079) (0.0284048)[ min ] [ medium ] [ max ] CEM 1 H2-K1 2603.5 13816.2 19203.3 P ( S | Z, I ) = 0.00 Fcgrt 2075.0 3136.6 3698.9 Mean Corr = 0.21216 Hfe 370.7 1655.1 3215.6 H2-Bl 92.8 283.5 760.7 H2-Q2 3.3 21.1 79.8 H2-Q10 50.6 33008.5 45933.2 C920025E04Rik 4.4 62.6 107.7 H2-M3 151.7 249.5 392.7 B2m 55.6 145.0 319.3 Mr1 12.1 72.5 214.7 Azgp1 1025.0 41344.3 52184.5 Ulbp1 3.3 20.1 91.9 Procr 18.5 107.7 239.5 H2-D1 3.3 28.5 105.0 H2-Aa 169.4 547.5 942.2 Cd68 72.7 149.3 353.8 Psmb9 111.3 552.0 1013.2 Psmb8 152.7 693.3 1233.8 Tapbp 1255.4 2218.9 3129.1 CEM 1 + Gbp2 54.3 166.4 321.3 Top 10 Genes Ifi27l2a 190.6 387.0 1326.8 Igtp 368.5 1767.1 5877.3 Fxyd5 209.4 343.0 420.9 Ifit3 303.6 527.3 804.5

Null module GEO Series "GSE26299" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 108 -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=GSE26299

Background corr dist: KL-Divergence = 0.0440, L1-Distance = 0.0244, L2-Distance = 0.0009, Normal std = 0.5775 GEO Series "GSE22381" 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=GSE22381 Status: Public on Jul 01 2011 Title: Identification of downstream transcriptional targets of Dlx5 during early mouse inner ear (otocyst/otic vesicle) development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21227998 Summary & Design: Summary: Several transcription factors are known to be expressed in discrete regions of the otic vesicle and Dlx5 is one of those that is expressed highly in the presumptive dorsal vestibular region. Mice lacking Dlx5 have vestibular defects. Specifically, they fail to form the endolymphatic duct (a defect visible as early as E10) as well as the anterior and posterior semi-circular canals. The lateral canal does form but is smaller, whereas the saccule, the utricle and the cochlea appear relatively normal. The goal of this study was to use microarrays to identify differentially expressed genes between wild-type and Dlx5-null otic vesicles microdissected from E10 and 10.5 and identify downstream targets of Dlx5 by searching the immediate 3kb promoter regions of the differentially expressed genes for homeodomain binding sites followed by chromatin immunoprecipitation in an otic vesicle-derived cell line over-expressing Dlx5.

Normal vestibular morphogenesis is compromised in mice lacking Dlx5, a member of the Distal-less family of homeobox transcription factors. We identified its direct downstream targets in the developing mouse inner ear by gene expression profiling wild-type and Dlx5 null otic vesicles from embryonic stages E10 and E10.5. Four hundred genes were differentially expressed in mutants when compared to wild-type in at least one of the two stages. To further constrain the list of likely direct targets of Dlx5, we examined the genomic DNA sequences in the 3kb promoter regions immediately proximal to the transcriptional start sites of these genes. We searched for (i) one or more previously described binding site for Dlx5, (ii) one or more novel 12bp-long motifs with a canonical homeodomain response element (HDRE) shared by promoters of two or more genes, and (iii) 100% conservation of the 12bp-long HDRE-containing motifs in promoter regions of human orthologs. Forty genes passed one or more of these filters, 12 of which are known to be expressed in the developing otic vesicle in domains that at least partially overlap with that of Dlx5 in one or both stages that we examined. Chromatin immunoprecipitation using a Dlx5 antibody confirmed direct binding of Dlx5 to promoter regions of seven of these genes (Atbf1, Bmper, Large, Lrrtm1, and Msx1, all of which were down-regulated in mutants, and Ebf1 and Lhx1, both of which were up-regulated in mutants) in an otic vesicle-derived cell line over-expressing Dlx5. Gene expression profiling of this cell line showed that Bmper and Lrrtm1 transcripts were up-regulated, further supporting their identification as direct targets of Dlx5 activity.

Overall design: Otic vesicles from wild-type and Dlx5-null embryos were microdissected from mouse developmental stages E10 and E10.5 and expression profiled in duplicate for each stage and genotype. Dlx5-transfected and empty vector-transfected 2B1 cell line samples were also profiled in duplicate (independent cell cultures).

Background corr dist: KL-Divergence = 0.0129, L1-Distance = 0.0464, L2-Distance = 0.0028, Normal std = 0.8888

0.449 Kernel fit Pairwise Correlations Normal fit

Density 0.224

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

E10_otic_vesicle_wt_replicate1E10_otic_vesicle_wt_replicate2E10_otic_vesicle_mut_replicate1E10_otic_vesicle_mut_replicate2E10.5_otic_vesicle_wt_replicate1 (0.0484623)E10.5_otic_vesicle_wt_replicate2 (0.0611634)E10.5_otic_vesicle_mut_replicate1 (0.0621517)E10.5_otic_vesicle_mut_replicate2 (0.0693705)2B1_Dlx5_replicate1 (0.0460158)2B1_Dlx5_replicate2 (0.0708319)2B1_empty_vector_replicate1 (0.066829) (0.122729)2B1_empty_vector_replicate2 (0.0275961) (0.153126) (0.145722) [(0.126002) min ] [ medium ] [ max ] CEM 1 H2-K1 2738.4 4394.9 74529.3 P ( S | Z, I ) = 0.00 Fcgrt 103.8 271.4 1793.6 Mean Corr = 0.27390 Hfe 50.2 111.0 549.4 H2-Bl 188.9 326.4 586.0 H2-Q2 11.5 18.4 41.2 H2-Q10 52.3 96.0 109.8 C920025E04Rik 46.9 66.3 106.3 H2-M3 169.7 260.4 8298.3 B2m 12.8 19.3 202.5 Mr1 150.2 216.9 293.2 Azgp1 103.0 138.3 179.2 Ulbp1 51.6 71.1 173.9 Procr 24.1 37.0 372.8 H2-D1 16.7 27.0 48.4 H2-Aa 41.5 51.2 68.7 Cd68 169.5 213.1 301.7 Psmb9 147.7 177.4 8434.6 Psmb8 68.6 84.1 3612.1 Tapbp 41.0 69.6 1227.6 CEM 1 + Gbp2 16.1 20.2 1362.1 Top 10 Genes Ifi27l2a 58.0 92.1 1856.8 Igtp 216.0 504.6 4186.8 Fxyd5 63.1 107.4 215.5 Ifit3 60.1 89.9 3497.5

Null module GEO Series "GSE16675" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 72 -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=GSE16675 Status: Public on Nov 17 2010 Title: The influence of segmental copy number variation on tissue transcriptomes through development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21084671 Summary & Design: Summary: A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes mapping within. They were shown to also affect the expression of genes located on their flanks, sometimes at great distance. Here, we show by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained throughout life. However, we find that some brain-expressed genes appear to be under compensatory loops only at specific time-points, indicating that the influence of CNVs on these genes is modulated through development. We also observe that CNV genes are significantly enriched upon transcripts that show variable time-course of expression in different strains. Thus modifying the number of copy of a gene not only potentially alters its expression level, but possibly also its time of expression.

Keywords: comparative genomic

Overall design: Expression from brain and liver tissues from C57BL/6J, DBA2/J and 129S2 mouse strains at different developmental time points.

Background corr dist: KL-Divergence = 0.0580, L1-Distance = 0.0593, L2-Distance = 0.0060, Normal std = 0.5608

0.711 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

129_E14.5_brain_rep1129_E14.5_brain_rep2129_E14.5_brain_rep3 B6_E14.5_brain_rep1(0.00719932) B6_E14.5_brain_rep2(0.00749715) B6_E14.5_brain_rep3(0.00586399) (0.00674077)D2_E14.5_brain_rep1 (0.00708227)D2_E14.5_brain_rep2 (0.00610388)D2_E14.5_brain_rep3 (0.00568491)129_E14.5_liver_rep1 (0.00764939)129_E14.5_liver_rep2 (0.00488382)129_E14.5_liver_rep3 (0.00289627)B6_E14.5_liver_rep1 (0.00250413)B6_E14.5_liver_rep2 (0.00266126)B6_E14.5_liver_rep3 (0.00252984)D2_E14.5_liver_rep1 (0.0039038)D2_E14.5_liver_rep2 (0.00282809)D2_E14.5_liver_rep3 (0.00223749)129_P1_brain_rep1 (0.00412215)129_P1_brain_rep2 (0.00242451)129_P1_brain_rep3 (0.00499974)B6_P1_brain_rep1 (0.00591133)B6_P1_brain_rep2 (0.00618096)B6_P1_brain_rep3 (0.00533989)D2_P1_brain_rep1 (0.00610816)D2_P1_brain_rep2 (0.00627868)D2_P1_brain_rep3 (0.00637457)129_P1_liver_rep1 (0.00619463)129_P1_liver_rep2 (0.00763898)129_P1_liver_rep3 (0.0180849)B6_P1_liver_rep1 (0.0118839)B6_P1_liver_rep2 (0.00702149)B6_P1_liver_rep3 (0.00724242)D2_P1_liver_rep1 (0.0062052)D2_P1_liver_rep2 (0.00749649)D2_P1_liver_rep3 (0.0110651)129_P7_brain_rep1 (0.0106701)129_P7_brain_rep2 (0.0133477)129_P7_brain_rep3 (0.00480194)B6_P7_brain_rep1 (0.00541358)B6_P7_brain_rep2 (0.00474155)B6_P7_brain_rep3 (0.00669636)D2_P7_brain_rep1 (0.00643405)D2_P7_brain_rep2 (0.0055237)D2_P7_brain_rep3 (0.0062953)129_P7_liver_rep1 (0.0055681)129_P7_liver_rep2 (0.00577351)129_P7_liver_rep3 (0.0428254)B6_P7_liver_rep1 (0.027916)B6_P7_liver_rep2 (0.0300482)B6_P7_liver_rep3 (0.063998)D2_P7_liver_rep1 (0.0254252)D2_P7_liver_rep2 (0.0176058)D2_P7_liver_rep3 (0.0186321)129_P90_brain_rep1 (0.0527803)129_P90_brain_rep2 (0.0227045)129_P90_brain_rep3 (0.0113617)B6_P90_brain_rep1 (0.0160655)B6_P90_brain_rep2 (0.011238)B6_P90_brain_rep3 (0.0165805)D2_P90_brain_rep1 (0.013631)D2_P90_brain_rep2 (0.0131208)D2_P90_brain_rep3 (0.0133619)129_P90_liver_rep1 (0.00940442)129_P90_liver_rep2 (0.0136937)129_P90_liver_rep3 (0.0494874)B6_P90_liver_rep1 (0.04124)B6_P90_liver_rep2 (0.0416295)B6_P90_liver_rep3 (0.0296826)D2_P90_liver_rep1 (0.029218)D2_P90_liver_rep2 (0.0328918)D2_P90_liver_rep3 (0.0264775) (0.020808) (0.0240666)[ min ] [ medium ] [ max ] CEM 1 H2-K1 370.2 1637.7 35180.2 P ( S | Z, I ) = 0.00 Fcgrt 245.8 812.5 4644.5 Mean Corr = 0.46380 Hfe 115.3 416.2 2952.6 H2-Bl 30.7 95.8 1591.2 H2-Q2 9.0 27.5 397.4 H2-Q10 25.8 2737.1 33821.5 C920025E04Rik 31.2 51.3 244.6 H2-M3 191.4 293.5 1174.3 B2m 19.7 65.2 331.8 Mr1 130.3 204.4 455.0 Azgp1 110.1 240.2 39782.6 Ulbp1 33.8 61.1 78.2 Procr 36.3 112.9 452.9 H2-D1 23.5 48.4 69.4 H2-Aa 37.9 89.4 3838.7 Cd68 99.1 253.2 1161.1 Psmb9 61.2 165.2 5648.7 Psmb8 82.7 254.2 7802.7 Tapbp 419.6 763.3 6287.3 CEM 1 + Gbp2 24.3 102.8 6761.1 Top 10 Genes Ifi27l2a 32.9 94.6 2898.0 Igtp 131.5 612.1 16094.3 Fxyd5 131.1 410.4 884.1 Ifit3 37.4 221.2 1029.5

Null module GEO Series "GSE16496" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 102 -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=GSE16496

Background corr dist: KL-Divergence = 0.3007, L1-Distance = 0.0716, L2-Distance = 0.0154, Normal std = 0.2865 GEO Series "GSE13753" 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=GSE13753 Status: Public on Jun 08 2009 Title: E2F4 cooperates with pRB in the development of extra-embryonic, not embryonic, tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues.

Keywords: genetically modified tissue comparison

Overall design: In one experiment, embryonic Day 13.5 placentas from wild-type and Rb -/- knock-out mice were compared. In the second experiment, embronic day 11.5 placentas from wild-type and Rb -/-;E2f4 -/- double knock-out mice were compared.

Background corr dist: KL-Divergence = 0.0302, L1-Distance = 0.0398, L2-Distance = 0.0027, Normal std = 0.6625

0.602 Kernel fit Pairwise Correlations Normal fit

Density 0.301

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

Day11.5_Placenta_WT_183-1Day11.5_Placenta_WT_150-8Day11.5_Placenta_WT_172-6Day11.5_Placenta_RbE2f4NULL_169-4 (0.0556235)Day11.5_Placenta_RbE2f4NULL_183-6 (0.0935448)Day11.5_Placenta_RbE2f4NULL_183-10 (0.0815401)Day13.5_Placenta_RbNULL_2Day13.5_Placenta_RbNULL_3Day13.5_Placenta_WT_4 (0.0676349)Day13.5_Placenta_WT_5 (0.0728072) (0.196121) (0.0503573) (0.0891377) (0.152979) (0.140254)[ min ] [ medium ] [ max ] CEM 1 H2-K1 3367.9 5870.8 8665.6 P ( S | Z, I ) = 0.00 Fcgrt 21.5 28.8 374.0 Mean Corr = 0.33249 Hfe 14.4 18.1 82.2 H2-Bl 22.4 31.9 42.8 H2-Q2 14.1 19.4 23.7 H2-Q10 11.3 16.6 32.2 C920025E04Rik 15.7 17.8 29.1 H2-M3 20.6 28.0 61.9 B2m 13.6 20.8 48.1 Mr1 10.0 15.6 35.2 Azgp1 15.8 19.8 21.5 Ulbp1 14.1 20.1 46.6 Procr 9949.7 20137.9 29400.5 H2-D1 5.6 6.5 8.3 H2-Aa 11.9 18.4 26.2 Cd68 177.8 714.1 1747.5 Psmb9 19.2 37.5 90.6 Psmb8 20.3 26.7 69.6 Tapbp 3895.6 4756.3 5466.9 CEM 1 + Gbp2 16.6 27.1 52.2 Top 10 Genes Ifi27l2a 19.7 30.6 64.9 Igtp 33.7 102.5 600.9 Fxyd5 216.8 383.8 729.7 Ifit3 36.9 76.6 98.8

Null module GEO Series "GSE6837" 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=GSE6837 Status: Public on Jan 31 2007 Title: Expression data from wild type (wt) and Ikbke knockout (Ikke) embryonic fibroblasts (EF) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17332413 Summary & Design: Summary: WT and Ikbke-/- EF cells were stimulated with recombinant interferon beta for 6 hours. Cells lacking IKKe kinase show a defect in a subset of interferon stimulated gene transcription

Keywords: comparative study

Overall design: WT and Ikbke cells were either stimulated and left untreated to compare their response to interferon.

Background corr dist: KL-Divergence = 0.0231, L1-Distance = 0.0545, L2-Distance = 0.0038, Normal std = 0.8315

0.536 Kernel fit Pairwise Correlations Normal fit

Density 0.268

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

unstimulatedunstimulated embryonicstimulated embryonicstimulated fibroblasts embryonicstimulated fibroblasts embryonic WT, stimulatedfibroblasts biologicalembryonic KO, stimulatedfibroblasts biologicalembryonicWT, rep1 stimulatedfibroblasts biological embryonicWT,(0.0642734) rep1 fibroblasts biological embryonicrep1WT,(0.0660879) fibroblasts biological(0.092691) rep2KO, fibroblasts biological (0.0530062) rep3KO,[ biological (0.0688785) min rep1KO, biological(0.417141) rep2] (0.0912057) rep3 (0.146716)[ medium ] [ max ] CEM 1 H2-K1 125.7 2361.3 23885.0 P ( S | Z, I ) = 0.00 Fcgrt 283.3 511.8 3097.1 Mean Corr = 0.36562 Hfe 6.6 97.3 1439.8 H2-Bl 5.4 46.9 271.3 H2-Q2 1.4 27.5 114.7 H2-Q10 2.2 57.4 8310.9 C920025E04Rik 10.9 31.8 120.9 H2-M3 90.9 343.9 560.9 B2m 39.3 251.0 470.3 Mr1 33.9 187.9 269.6 Azgp1 7.2 41.5 9441.2 Ulbp1 8.2 61.3 86.6 Procr 471.1 633.1 780.3 H2-D1 6.6 52.8 106.1 H2-Aa 7.3 21.1 5183.2 Cd68 3.0 84.1 1184.8 Psmb9 5.9 168.9 2716.1 Psmb8 16.3 306.1 3398.9 Tapbp 874.8 4550.7 10823.7 CEM 1 + Gbp2 33.5 1579.6 5328.4 Top 10 Genes Ifi27l2a 4.4 12.5 6880.5 Igtp 29.5 2778.7 8421.7 Fxyd5 2297.0 2513.7 2869.7 Ifit3 96.9 12731.4 21842.2

Null module GEO Series "GSE18586" 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=GSE18586 Status: Public on Jun 18 2012 Title: Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22700822 Summary & Design: Summary: We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.

Keywords: Diet intervention study

Overall design: Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.

Background corr dist: KL-Divergence = 0.0644, L1-Distance = 0.0264, L2-Distance = 0.0008, Normal std = 0.5278

0.773 Kernel fit Pairwise Correlations Normal fit

Density 0.386

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

SI1, 2 wksSI1, on 2 wksaSI1, HF-PO on 2 wksa SI2, dietHF-OO on 2(0.144258) wksaSI2, dietHF-SO on 2 (0.0916706) wksa SI2, dietHF-PO on 2(0.196347) wksa SI3, dietHF-OO on 2(0.036229) wksaSI3, dietHF-SO on 2 (0.0697801) wksa SI3, dietHF-PO on 2(0.0401592) wksa dietHF-OO on (0.122508) a dietHF-SO (0.150681) diet (0.148367)[ min ] [ medium ] [ max ] CEM 1 H2-K1 20783.2 23782.1 27291.0 P ( S | Z, I ) = 0.00 Fcgrt 1962.6 2762.2 3550.6 Mean Corr = 0.37065 Hfe 189.9 295.0 504.5 H2-Bl 532.1 1841.1 2227.2 H2-Q2 6308.1 11518.9 13222.6 H2-Q10 123.7 1970.5 4308.6 C920025E04Rik 246.9 328.7 392.6 H2-M3 315.0 385.8 505.1 B2m 312.7 436.7 734.8 Mr1 12.2 17.2 23.2 Azgp1 5.7 10.6 55.1 Ulbp1 9.4 32.3 54.7 Procr 21.8 108.6 199.5 H2-D1 2.1 23.8 39.9 H2-Aa 2270.1 4398.3 5806.9 Cd68 114.6 216.7 314.6 Psmb9 1275.9 1775.1 3349.3 Psmb8 1915.6 2874.2 4596.1 Tapbp 7708.1 8847.7 10285.5 CEM 1 + Gbp2 174.5 328.9 606.1 Top 10 Genes Ifi27l2a 298.7 473.0 817.7 Igtp 563.0 1034.5 2834.2 Fxyd5 151.1 288.1 446.6 Ifit3 233.1 474.2 1287.3

Null module GEO Series "GSE3554" 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=GSE3554 Status: Public on Nov 04 2005 Title: Microarray Analysis of Retinal Gene Expression in the DBA/2J Model of Glaucoma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16505032 Summary & Design: Summary: Purpose: The DBA/2J mouse is a model for secondary angle-closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure (IOP). We sought to correlate changes in retinal gene expression with glaucoma-like pathology by performing microarray analysis of retinal RNA from DBA/2J mice at 3 months before disease onset, and at 8 months, after IOP elevation. Methods: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months. Results: There were changes in expression of 68 genes, with 32 genes increasing and 36 genes decreasing at 8 months versus 3 months. Upregulated genes were associated with immune response, glial activation, signaling and gene expression, while down-regulated genes included multiple crystallin genes. Significant changes in 9 upregulated genes and 2 downregulated genes were confirmed by quantitative RT-PCR, with some showing changes in expression by 5 months. Conclusions: DBA/2J retina shows evidence for glial activation and an immune-related response following IOP elevation, similar to what has been reported following acute elevation of IOP in other models.

Keywords: retina, glaucoma, DBA/2J, elevated intraocular pressure

Overall design: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months.

Background corr dist: KL-Divergence = 0.0472, L1-Distance = 0.0372, L2-Distance = 0.0019, Normal std = 0.6520

0.647 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

retina_DBA_543L_8mo_rep1retina_DBA_544R_8mo_rep2retina_DBA_552R_8mo_rep3retina_DBA_1024L_3mo_rep1 (0.0671419)retina_DBA_1025L_3mo_rep2 (0.246401)retina_DBA_1026L_3mo_rep3 (0.208578) (0.264634) (0.115362) [(0.0978825) min ] [ medium ] [ max ] CEM 1 H2-K1 109.1 129.1 210.5 P ( S | Z, I ) = 0.00 Fcgrt 107.8 138.8 144.4 Mean Corr = 0.39608 Hfe 413.3 469.5 519.2 H2-Bl 26.9 27.7 29.9 H2-Q2 20.7 21.2 21.3 H2-Q10 26.1 26.7 38.6 C920025E04Rik 24.0 25.6 28.2 H2-M3 26.4 38.9 41.6 B2m 28.6 31.6 35.9 Mr1 22.0 22.5 22.7 Azgp1 38.9 40.5 46.9 Ulbp1 29.8 30.5 36.6 Procr 22.6 25.8 30.4 H2-D1 33.1 33.7 39.3 H2-Aa 23.9 31.4 47.2 Cd68 63.2 64.8 84.5 Psmb9 21.7 22.2 27.5 Psmb8 60.3 65.1 75.7 Tapbp 6666.4 7291.5 8348.6 CEM 1 + Gbp2 22.5 23.1 26.1 Top 10 Genes Ifi27l2a 47.6 50.1 69.8 Igtp 92.3 128.1 136.2 Fxyd5 88.4 101.7 108.7 Ifit3 215.8 269.9 317.4

Null module GEO Series "GSE8039" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 32 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8039 Status: Public on Oct 30 2007 Title: Gene Expression in Transgenic Mice Expressing CD30L on T Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: CD30L and CD30 are cell-surface glycoproteins in the TNF and TNFR superfamilies, respectively. Their expression is limited to immune cells and is tightly regulated. Cell surface expression of CD30 is restricted to subpopulations of activated T and B cells. CD30L is expressed primarily on activated T cells and subpopulations of B cells. The significance of CD30/CD30L interactions in immune regulation is not fully understood. Reported activities of CD30/CD30L in immune responses imply roles in regulation of secondary memory and antibody responses. Depending on the experimental system, both positive and negative regulation of immunoglobulin class switching and antibody production have been reported. Additionally, the biological activity of CD30/CD30L in animals has been difficult to assess due to the restricted and tightly regulated expression of this receptor-ligand pair. We generated transgenic mice with constitutive T cell specific overexpression of CD30L as a tool to help unravel the consequences of CD30/CD30L interactions in vivo. CD30L transgenic mice displayed a phenotype and responses to antigen challenge supporting a role for CD30/CD30L in promoting immunoglobulin class switching and antibody production. CD30L transgenic mice had increased numbers of germinal centers, elevated class-switched immunoglobulin isotypes, increased germinal center B cells and plasma cells, upregulation of genes indicative of B-cell activity, and exaggerated antibody responses to immune challenge. Interestingly, despite the heightened B-cell activity in CD30L transgenic mice, CD30L overexpression on T cells did not result in overt autoimmunity. Our results demonstrate that overexpression of CD30L on T cells promotes T cell-dependent B cell responses characterized by secondary antibody responses.

Keywords: Transgenic vs. wild-type

Overall design: Spleen, thymus, mesenteric lymph nodes and peripheral lymph nodes where samples from both CD30L transgenic and non-transgenic littermates (4 mice per group.)

Background corr dist: KL-Divergence = 0.1279, L1-Distance = 0.0705, L2-Distance = 0.0114, Normal std = 0.4192

1.108 Kernel fit Pairwise Correlations Normal fit

Density 0.554

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

T1 CD2-CD30LT2 CD2-CD30L C1peripheral peripheral C2peripheral peripherallymph lymphC3 node peripherallymph node lymphC4 (0.0182679) nodeperipheral (0.0152063) node lymphT3 (0.00996283) CD2-CD30L (0.0155455) node lymphT4 CD2-CD30L (0.035719) node C3peripheral mesenteric (0.0189313) C4peripheral mesentericlymph T3lymph nodemesenteric lymph node T4lymph (0.0115825) nodemesenteric (0.0207862) nodelymphT1 (0.0123134) CD2-CD30L (0.037475) node lymphT2 CD2-CD30L (0.0310972) node C1mesenteric mesenteric (0.0210605) C2mesenteric mesenteric lymph T1lymph CD2-CD30L node lymph node T2lymph (0.0317691) CD2-CD30L node (0.0145471) node C1spleen (0.00856793) spleen (0.0871253) C2(0.0138893)spleen (0.0172069)spleen T3(0.0173965) CD2-CD30L(0.0103847)T4 CD2-CD30L C3spleen spleen C4(0.0123661)spleen (0.0130494)spleen C3(0.0184936) (0.0165461)ThymusC4 Thymus (0.0704925)T3 CD2-CD30L (0.0623492)T4 CD2-CD30L T1Thymus CD2-CD30L T2Thymus (0.0691822) CD2-CD30L C1Thymus (0.05741) Thymus C2Thymus (0.0594297) Thymus (0.055512) (0.0481184) (0.0682163) [ min ] [ medium ] [ max ] CEM 1 H2-K1 9926.9 17482.3 27781.8 P ( S | Z, I ) = 0.00 Fcgrt 421.5 2040.1 4856.1 Mean Corr = 0.04384 Hfe 314.6 1549.6 2099.2 H2-Bl 34.9 378.0 656.6 H2-Q2 3.2 47.3 2753.0 H2-Q10 2.4 346.0 1451.3 C920025E04Rik 201.2 490.4 1196.6 H2-M3 822.1 3529.7 4613.4 B2m 350.0 1377.6 2601.9 Mr1 1.8 16.2 500.3 Azgp1 1.9 2.6 386.9 Ulbp1 3.2 37.0 144.7 Procr 10.3 714.7 1279.7 H2-D1 48.2 110.2 343.5 H2-Aa 3205.0 11920.1 17908.5 Cd68 756.7 2097.5 3175.0 Psmb9 3378.8 5942.5 7430.1 Psmb8 3635.0 5861.4 8203.7 Tapbp 3338.0 7778.3 9821.9 CEM 1 + Gbp2 957.0 1942.0 2995.4 Top 10 Genes Ifi27l2a 2121.1 6540.7 9181.0 Igtp 2294.5 2980.1 4807.8 Fxyd5 3253.2 5843.7 8877.0 Ifit3 333.6 643.5 2739.6

Null module GEO Series "GSE14395" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14395 Status: Public on Sep 11 2009 Title: Gender-specific gene repression of PPAR-alpha KO mice in liver and heart Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19729835 Summary & Design: Summary: Most metabolic studies are conducted in male animals; thus, the molecular mechanism controlling gender-specific pathways has been neglected, including sex-dependent responses to peroxisome proliferator-activated receptors (PPARs). Here we show that PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and inflammation. In males, this effect is reproduced by the administration of synthetic PPARalpha ligand. Using the steroid hydroxylase gene Cyp7b1 as a model, we elucidated the molecular mechanism of this PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggers the interaction of PPARalpha with the GA-binding protein alpha bound to the target promoter. Histone deacetylase is then recruited, and histones and adjacent Sp1-binding site are methylated. These events result in the loss of Sp1-stimulated expression, and thus the down-regulation of Cyp7b1. Physiologically, this repression confers protection against estrogen-induced intrahepatic cholestasis, paving the way for a novel therapy against the most common hepatic disease during pregnancy.

Keywords: Genetic modification

Overall design: Expression profile difference between male and female PPARalpha wild-type and knock-out mice in liver and heart (3 pools of 4 animals in each group). Wild-type (12 males and 12 females) and knock-out PPARalpha SV129 mice (12 males and 12 females) approximately 10 to 12 weeks of age were killed at ZT14 and their livers and hearts quickly removed and frozen.

Background corr dist: KL-Divergence = 0.0171, L1-Distance = 0.0604, L2-Distance = 0.0059, Normal std = 0.8714

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

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_male_WT_pool1Liver_male_WT_pool2Liver_male_WT_pool3 Liver_male_KO_pool4(0.0253511) Liver_male_KO_pool5(0.0389686) Liver_male_KO_pool6(0.0315389) Liver_female_WT_pool7(0.0263296) Liver_female_WT_pool8(0.0390221) Liver_female_WT_pool9(0.0474475)Liver_female_KO_pool10 (0.0281046)Liver_female_KO_pool11 (0.0551965)Liver_female_KO_pool12 (0.039545)Heart_male_WT_pool1 (0.0471506)Heart_male_WT_pool2 (0.0379003)Heart_male_WT_pool3 (0.053151)Heart_male_KO_pool4 (0.0480765)Heart_male_KO_pool5 (0.0310298)Heart_male_KO_pool6 (0.0580013)Heart_female_WT_pool7 (0.0497659)Heart_female_WT_pool8 (0.0477486)Heart_female_WT_pool9 (0.0589469)Heart_female_KO_pool10 (0.0294733)Heart_female_KO_pool11 (0.0347384)Heart_female_KO_pool12 (0.0636981) (0.0411421) (0.0289041) (0.038769)[ min ] [ medium ] [ max ] CEM 1 H2-K1 5811.8 46959.7 59860.2 P ( S | Z, I ) = 0.00 Fcgrt 1991.7 5676.3 9156.6 Mean Corr = 0.34016 Hfe 468.9 1398.3 1842.9 H2-Bl 111.6 238.1 597.0 H2-Q2 72.8 91.2 109.4 H2-Q10 90.5 50677.0 59930.7 C920025E04Rik 87.7 106.8 145.4 H2-M3 149.6 180.5 226.4 B2m 84.8 136.0 156.6 Mr1 249.4 359.5 585.8 Azgp1 166.8 66920.7 79702.5 Ulbp1 99.4 126.6 152.1 Procr 115.5 159.0 237.0 H2-D1 83.9 105.5 116.0 H2-Aa 168.3 337.4 536.8 Cd68 134.1 223.5 372.3 Psmb9 217.7 316.8 506.5 Psmb8 351.6 568.0 1101.3 Tapbp 3706.7 4228.1 7039.3 CEM 1 + Gbp2 105.4 245.5 431.8 Top 10 Genes Ifi27l2a 169.0 1266.1 3255.9 Igtp 716.9 1357.0 2496.2 Fxyd5 234.1 494.1 793.7 Ifit3 203.4 314.8 468.0

Null module GEO Series "GSE19616" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -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=GSE19616 Status: Public on Jul 20 2010 Title: Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy (testing dataset) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20630075 Summary & Design: Summary: The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.

Overall design: Control skin was compared with skin tumors arising in k14Cre;p53loxP/loxP and k14Cre;p53loxP/loxP;pRbloxP/loxP animals, giving a mouse p53-tumor signature

Background corr dist: KL-Divergence = 0.1802, L1-Distance = 0.0477, L2-Distance = 0.0056, Normal std = 0.3576

1.116 Kernel fit Pairwise Correlations Normal fit

Density 0.558

0.000 CEM 1

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

Pre-normalization Quantiles

Control_skin_1Control_skin_2Control_skin_3 (0.0848857)Control_skin_4 (0.0305929)p53_tumor1 (0.0384981)p53_tumor2 (0.0324851) (0.0390963)p53_tumor3 (0.0493071)p53_tumor4 (0.118204)p53_tumor5 (0.074867)p53_tumor6 (0.305624)p53_tumor7 (0.0394264)pRbp53_tumor1 (0.032313)pRbp53_tumor2pRbp53_tumor3 (0.0332532)pRbp53_tumor4 (0.0241493)pRbp53_tumor5 (0.0439043) (0.0300358) (0.0233582) [ min ] [ medium ] [ max ] CEM 1 H2-K1 4599.2 12994.4 33425.6 P ( S | Z, I ) = 0.00 Fcgrt 464.1 1559.7 3853.4 Mean Corr = 0.12417 Hfe 114.5 621.5 1260.0 H2-Bl 64.2 74.6 251.8 H2-Q2 17.6 19.0 776.9 H2-Q10 44.5 54.2 66.2 C920025E04Rik 34.8 41.1 630.7 H2-M3 240.8 1087.6 1881.9 B2m 144.2 331.7 1134.2 Mr1 264.9 451.4 808.5 Azgp1 60.8 78.0 107.4 Ulbp1 43.6 86.2 385.4 Procr 100.2 509.5 1863.5 H2-D1 24.5 32.9 57.3 H2-Aa 346.2 7303.0 21306.3 Cd68 340.3 1399.2 3493.6 Psmb9 323.2 886.9 5635.5 Psmb8 770.3 2514.3 12415.9 Tapbp 1008.7 3521.4 6147.2 CEM 1 + Gbp2 122.1 1007.3 5863.3 Top 10 Genes Ifi27l2a 484.0 1198.9 8505.2 Igtp 245.4 732.3 11039.2 Fxyd5 530.3 1697.2 4968.7 Ifit3 183.3 555.9 8844.9

Null module GEO Series "GSE42548" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 29 -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=GSE42548 Status: Public on May 22 2013 Title: TH-MYCN Mice with Caspase-8 Deficiency Develop Advanced Neuroblastoma with Bone Marrow Metastasis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23536557 Summary & Design: Summary: Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression.

Overall design: Survey of spontateous 24 NB tumors and 5 bone marrow samples in wt and transgenic mice.

Background corr dist: KL-Divergence = 0.0350, L1-Distance = 0.0336, L2-Distance = 0.0021, Normal std = 0.6306

0.633 Kernel fit Pairwise Correlations Normal fit

Density 0.316

0.000 CEM 1

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

Pre-normalization Quantiles

primaryprimary abdominalprimary abdominal NBprimary tumorabdominal NB ttt010primary tumorabdominal NB (0.0464178) ttt012primary tumorabdominal NB (0.0151333) ttt013primary tumorabdominal NB (0.0156658) ttt015primary tumorabdominal NB (0.00525551) ttt016primary tumorabdominal NB (0.0111259) ttt017primary tumorabdominal NB (0.0379878) ttt018primary tumorabdominal NB (0.012341) ttt019primary tumorabdominal NB (0.0177566) ttt020primary tumorabdominal NB (0.0169202) ttt021primary tumorabdominal NB (0.0153468) ttt100primary tumorabdominal NB (0.0086933) ttt101primary tumorabdominal NB (0.0282109) ttt102primary tumorabdominal NB (0.0105838) ttt104primary tumorabdominal NB (0.0220121) ttt105primary tumorabdominal NB (0.00788436) ttt106primary tumorabdominal NB (0.0177853) ttt107primary tumorabdominal NB (0.0131485) ttt108Total tumorabdominal NB bone(0.00967379) ttt109aTotal tumor marrow NB bone (0.0348259)ttt110primary tumor marrow ttt112 (0.0126753) ttt111primary abdominal (0.183897) ttt114a (0.0100456)primary abdominal (0.145989)NBTotal tumorabdominal NB bone ttt115Total tumor marrow NB bone(0.00806401) ttt116Total tumor marrow ttt118 bone(0.00986847) ttt117 (0.0680807)marrow ttt119 (0.00967764) (0.130106) ttt120a (0.0748281)[ min ] [ medium ] [ max ] CEM 1 H2-K1 802.9 2173.4 17143.1 P ( S | Z, I ) = 0.00 Fcgrt 146.1 342.7 1135.7 Mean Corr = 0.43476 Hfe 83.3 221.7 993.1 H2-Bl 24.7 32.2 78.7 H2-Q2 15.0 17.9 21.8 H2-Q10 23.4 35.4 925.4 C920025E04Rik 28.5 37.4 210.1 H2-M3 110.1 152.0 488.3 B2m 25.4 40.3 517.2 Mr1 66.7 96.1 198.0 Azgp1 44.5 54.5 87.9 Ulbp1 28.0 35.5 65.5 Procr 61.5 179.0 353.2 H2-D1 23.5 32.7 45.6 H2-Aa 58.5 199.3 2088.6 Cd68 395.4 911.3 2213.6 Psmb9 82.4 164.3 2871.4 Psmb8 90.8 176.3 2474.6 Tapbp 280.7 501.0 4136.4 CEM 1 + Gbp2 32.7 74.5 892.5 Top 10 Genes Ifi27l2a 33.3 356.3 4334.6 Igtp 122.4 200.6 12708.0 Fxyd5 126.3 281.1 3516.8 Ifit3 47.5 71.1 282.0

Null module GEO Series "GSE7342" 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=GSE7342 Status: Public on Mar 23 2007 Title: Expression data from p38 knock out versus wild type fetal liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17468757 Summary & Design: Summary: The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional p38alpha alleles, we investigated its function in postnatal development and tumorigenesis. When p38alpha is specifically deleted in the mouse embryo, fetuses develop to term but die shortly after birth, likely due to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha display increased proliferation, resulting from sustained activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Importantly, in chemical-induced liver cancer development, mice with liver-specific deletion of p38alpha show enhanced hepatocyte proliferation and tumor development that also correlates with JNK/c-Jun upregulation. Furthermore, increased proliferation of p38alpha-deficient hepatocytes and tumor cells is suppressed by inactivation of JNK or c-Jun. These results reveal a novel mechanism whereby p38alpha negatively regulates cell proliferation through antagonizing the JNK/c-Jun pathway in multiple cell types and in liver cancer development.

We used microarrays to identifiy differental regulated genes by p38alpha in fetal liver cells

Keywords: time course

Overall design: Wild type and p38 deficient fetal liver cell were used for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0482, L1-Distance = 0.0409, L2-Distance = 0.0034, Normal std = 0.5674

0.703 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

p38alphap38alpha knockp38alpha out knock fetalp38alpha out knockliver fetal p38alphaE13.5, out wildliver fetal typebiological p38alphaE13.5, wildliver fetal typebiological p38alphaE13.5, liverwildrep1 fetal E13.5, typebiologicalp38alpha(0.0626432) liverknockrep2 fetal biological E13.5, p38alpha(0.102103) out liverknockrep3 fetal biological E13.5, p38alpha(0.0761689) outrep1 knockliver fetal biological(0.123411) p38alphaE15.5, outrep2 wildliver fetal (0.051032)typebiological p38alphaE15.5, rep3 wildliver fetal (0.0538489)typebiological E15.5, liverwildrep1 fetal E15.5, typebiological(0.10684) liver rep2 fetal biological E15.5, (0.0436994) liver rep3 biological E15.5, (0.105754)[ rep1 min biological(0.058825) rep2 ] (0.0805331) rep3 (0.135141)[ medium ] [ max ] CEM 1 H2-K1 1696.4 2359.7 2755.8 P ( S | Z, I ) = 0.00 Fcgrt 658.5 986.9 1141.6 Mean Corr = 0.46006 Hfe 144.9 369.5 526.0 H2-Bl 36.7 50.1 60.1 H2-Q2 15.5 17.2 27.0 H2-Q10 2510.0 6186.4 7303.1 C920025E04Rik 23.0 33.1 41.1 H2-M3 96.3 136.5 166.4 B2m 95.3 130.0 153.2 Mr1 166.9 206.4 271.7 Azgp1 50.7 213.0 411.7 Ulbp1 35.0 42.9 52.0 Procr 67.5 95.6 144.5 H2-D1 28.3 31.3 36.6 H2-Aa 40.1 64.4 85.2 Cd68 230.1 393.0 560.5 Psmb9 104.7 254.9 347.0 Psmb8 203.0 332.2 411.3 Tapbp 924.2 1326.0 1485.4 CEM 1 + Gbp2 120.5 168.1 237.6 Top 10 Genes Ifi27l2a 71.5 137.0 271.1 Igtp 321.7 538.8 1319.9 Fxyd5 436.2 515.6 572.9 Ifit3 88.2 121.1 185.8

Null module GEO Series "GSE43242" 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=GSE43242 Status: Public on Jan 21 2014 Title: Effect of osteoblast-specific constitutive activation of beta-catenin or deletion of FoxO1 on gene expression in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24429522 Summary & Design: Summary: The gene expression of mice with osteoblast-specific beta-catenin activation or FoxO1 deactivation are each compared to that of Wt.

Overall design: C. Osteoblast specific FoxO1 deleted mice (n=3)

Background corr dist: KL-Divergence = 0.1216, L1-Distance = 0.0309, L2-Distance = 0.0017, Normal std = 0.4052

0.985 Kernel fit Pairwise Correlations Normal fit

Density 0.492

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

a.wt.1 (0.0357952)a.wt.2 (0.0721078)a.wt.3 (0.105853)a.wt.4 (0.0438803)b.bcat.1b.bcat.2 (0.0944353)b.bcat.3 (0.0650603)c.FoxO1.1 (0.0859823)c.FoxO1.2 (0.0279542)c.FoxO1.3 (0.103954) (0.364978) [ min ] [ medium ] [ max ] CEM 1 H2-K1 1292.5 1741.8 13743.3 P ( S | Z, I ) = 0.00 Fcgrt 2676.4 3011.4 3606.6 Mean Corr = 0.06983 Hfe 392.4 463.5 1087.2 H2-Bl 17.8 45.8 96.8 H2-Q2 1.0 3.5 15.8 H2-Q10 9.2 67.5 115.1 C920025E04Rik 22.1 39.0 80.2 H2-M3 206.0 281.3 1198.0 B2m 80.8 121.6 1165.3 Mr1 45.1 103.7 153.9 Azgp1 4.8 7.3 64.7 Ulbp1 14.8 78.6 115.0 Procr 258.9 305.8 356.1 H2-D1 2.1 19.0 39.0 H2-Aa 92.8 138.7 1464.8 Cd68 1293.3 1694.1 2330.3 Psmb9 110.4 156.1 3318.8 Psmb8 139.7 197.6 4348.9 Tapbp 1035.6 1444.4 8003.7 CEM 1 + Gbp2 175.6 260.7 10857.8 Top 10 Genes Ifi27l2a 121.6 453.9 3273.1 Igtp 392.4 558.8 22326.1 Fxyd5 2695.5 2969.9 3227.0 Ifit3 145.7 181.8 5171.8

Null module GEO Series "GSE25286" 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=GSE25286 Status: Public on May 01 2012 Title: mRNA expression profile in a murine model of hyperoxia-induced bronchopulmonary dysplasia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia.

Overall design: Replicated time course of mouse lung development at 2 time points (P14, P29). Three replicates per time point for bronchopulmonary dysplasia induced by hyperoxia mouse lung, and two replicates per time point for wild type mouse lung. This dataset represents the mRNA expression profiling component of the study.

Background corr dist: KL-Divergence = 0.0273, L1-Distance = 0.0359, L2-Distance = 0.0021, Normal std = 0.6782

0.588 Kernel fit Pairwise Correlations Normal fit

Density 0.294

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

P14-WT-lung1P14-WT-lung2 (0.115766)P14-BPD-lung1 (0.0579984)P14-BPD-lung2P14-BPD-lung3 (0.0812802)P29-WT-lung1 (0.0736022)P29-WT-lung2 (0.0826956) (0.228062)P29-BPD-lung1 (0.235626)P29-BPD-lung2P29-BPD-lung3 (0.0561135) (0.0484982) (0.020358) [ min ] [ medium ] [ max ] CEM 1 H2-K1 3073.0 8219.1 17807.4 P ( S | Z, I ) = 0.00 Fcgrt 1500.6 1759.8 2695.6 Mean Corr = 0.35495 Hfe 597.2 670.6 1086.2 H2-Bl 74.9 91.7 133.3 H2-Q2 95.4 185.0 359.3 H2-Q10 25.8 28.8 35.3 C920025E04Rik 48.2 71.1 81.4 H2-M3 454.7 576.5 1183.1 B2m 79.1 161.1 345.5 Mr1 306.3 382.8 809.6 Azgp1 90.1 129.9 269.7 Ulbp1 37.2 46.7 56.9 Procr 156.8 525.3 835.8 H2-D1 21.0 26.3 38.7 H2-Aa 2291.0 5083.0 11120.8 Cd68 217.4 428.9 1219.1 Psmb9 298.7 674.0 1571.8 Psmb8 703.7 1347.4 2542.2 Tapbp 2454.7 3398.2 4224.8 CEM 1 + Gbp2 478.4 1013.9 1961.4 Top 10 Genes Ifi27l2a 213.2 579.5 1093.4 Igtp 362.9 837.9 1059.5 Fxyd5 832.3 1354.4 2118.9 Ifit3 363.3 1351.5 2129.5

Null module GEO Series "GSE17256" 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=GSE17256 Status: Public on Dec 04 2009 Title: Comparison of gene expression profiles between human and mouse monocyte subsets [mouse data] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19965649 Summary & Design: Summary: Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPARÎ³ signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.

Overall design: The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChipÂ® 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 4 separate times for 4 biological replicates. The two major monocyte subsets (CD16- and CD16+) were isolated from venous heparinized blood from apparently healthy human volunteers using MACS technology with all reagents and tools from Miltenyi Biotec. Three separate donors were hybridized three different times to Affymetrix U133 Plus 2.0 array.

Background corr dist: KL-Divergence = 0.0564, L1-Distance = 0.0247, L2-Distance = 0.0007, Normal std = 0.5574

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

Gr1hi 1 Gr1hi(0.177024) 2 Gr1hi(0.10579) 3 Gr1hi(0.146307) 4 Gr1lo(0.0917034) 1 Gr1lo(0.0696828) 2 Gr1lo(0.100209) 3 Gr1lo(0.164212) 4 (0.145071) [ min ] [ medium ] [ max ] CEM 1 H2-K1 20550.5 30695.9 35578.0 P ( S | Z, I ) = 0.00 Fcgrt 1575.0 2813.9 3567.5 Mean Corr = 0.36782 Hfe 3170.9 14412.8 15121.7 H2-Bl 344.8 389.8 432.0 H2-Q2 24.2 26.3 27.9 H2-Q10 127.3 151.2 169.4 C920025E04Rik 179.3 316.7 377.5 H2-M3 2282.1 2583.9 2980.1 B2m 423.0 722.8 867.5 Mr1 206.9 229.5 256.0 Azgp1 238.2 281.5 314.0 Ulbp1 90.6 112.3 130.2 Procr 114.9 145.9 152.5 H2-D1 130.3 188.1 228.7 H2-Aa 3814.3 12794.6 14758.3 Cd68 9308.8 11676.5 12608.8 Psmb9 3303.5 3592.5 4791.9 Psmb8 8353.4 8888.1 10365.5 Tapbp 7570.7 8600.7 8980.3 CEM 1 + Gbp2 859.8 1697.3 2452.3 Top 10 Genes Ifi27l2a 9987.0 19008.0 23830.8 Igtp 1341.4 1934.5 2187.7 Fxyd5 16256.8 18152.4 18690.3 Ifit3 693.0 2730.4 2968.5

Null module GEO Series "GSE20577" 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=GSE20577 Status: Public on Dec 01 2010 Title: Gestational taurine supplementation of mice: effect on offspring gene expression in liver and skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams.

We hypothesized that gestational taurine supplementation would affect gene expression level in 4w offspring liver and skeletal muscle.

Overall design: Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed at 4 weeks of age and liver and quadriceps skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau). The liver and muscle samples were normalized separately.

Background corr dist: KL-Divergence = 0.0243, L1-Distance = 0.0507, L2-Distance = 0.0039, Normal std = 0.7351

0.543 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

4 week 4liver, week untreated, 4liver, week untreated, 4liver, biologicalweek untreated, 4liver, biologicalweek replicate in 4liver,utero biologicalweek replicate in 1taurine 4liver,(0.0696183)utero week replicate in 2taurinesupplementation, 4skeletal(0.0836153)utero week 3taurinesupplementation, 4skeletal (0.0870316)muscle, week supplementation, 4skeletal muscle, weekuntreated,biological 4skeletal muscle, weekuntreated,biological biologicalreplicate 4skeletal muscle, weekuntreated,biological biologicalreplicate 1skeletal replicate muscle, (0.171011)in utero biologicalreplicate 2 replicate muscle, (0.0733189)in 1taurine (0.100874)utero 3 replicate (0.0496083)in 2taurinesupplementation, (0.0565134)utero[ 3taurineminsupplementation, (0.0799185) supplementation, ] biological biological replicate[ mediumbiological replicate 1 (0.0534437) replicate 2 (0.0863487) ] 3 (0.0886987)[ max ] CEM 1 H2-K1 1993.0 20594.7 25165.9 P ( S | Z, I ) = 0.00 Fcgrt 964.2 2790.8 4545.0 Mean Corr = 0.34245 Hfe 461.5 1780.2 2226.6 H2-Bl 54.6 102.5 239.1 H2-Q2 32.1 50.1 58.6 H2-Q10 66.4 22536.6 41459.6 C920025E04Rik 49.9 64.9 92.3 H2-M3 163.5 292.0 465.2 B2m 58.7 177.6 286.0 Mr1 232.1 369.5 524.1 Azgp1 76.5 22953.3 39537.2 Ulbp1 53.1 63.8 114.9 Procr 121.6 538.5 864.5 H2-D1 43.4 56.3 68.6 H2-Aa 59.8 136.9 786.2 Cd68 97.9 449.0 2594.4 Psmb9 185.1 475.2 775.2 Psmb8 309.4 569.3 1133.3 Tapbp 1433.9 3321.3 5447.4 CEM 1 + Gbp2 84.5 151.4 342.1 Top 10 Genes Ifi27l2a 273.1 634.6 1491.5 Igtp 326.9 1124.7 2536.3 Fxyd5 207.4 370.1 880.3 Ifit3 146.5 304.3 623.0

Null module GEO Series "GSE13149" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 25 -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=GSE13149 Status: Public on Oct 30 2008 Title: Multi-stage analysis of gene expression in C57/B6 mouse liver development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19015022 Summary & Design: Summary: The liver performs a number of essential functions for life. The development of such a complex organ relies on finely regulated gene expression profiles which change over time in the development and determine the phenotype and function of the liver.

We used high-density oligonucleotide microarrays to study the gene expression and transcription regulation at 14 time points across the C57/B6 mouse liver development, which include E11.5 (embryonic day 11.5), E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5, Day0 (the day of birth), Day3, Day7, Day14, Day21, and normal adult liver. With these data, we made a comprehensive analysis on gene expression patterns, functional preferences and transcriptional regulations during the liver development.

Keywords: time course

Overall design: Totally 25 microarrays have been used in this experiment, and 11 of the 14 time points have two technique repeat experiments.

Background corr dist: KL-Divergence = 0.0590, L1-Distance = 0.0653, L2-Distance = 0.0079, Normal std = 0.5560

0.718 Kernel fit Pairwise Correlations Normal fit

Density 0.359

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_development_E11.5_rep1Liver_development_E11.5_rep2Liver_development_E12.5_rep1Liver_development_E12.5_rep2Liver_development_E13.5_rep1 (0.0647712)Liver_development_E13.5_rep2 (0.0589784)Liver_development_E14.5_rep1 (0.0755634)Liver_development_E14.5_rep2 (0.0289551)Liver_development_E15.5_rep1 (0.0171782)Liver_development_E15.5_rep2 (0.0235646)Liver_development_E16.5_rep1 (0.0341566)Liver_development_E16.5_rep2 (0.0190531)Liver_development_E17.5_rep1 (0.0103068)Liver_development_E17.5_rep2 (0.0140301)Liver_development_E18.5_rep1 (0.00903657)Liver_development_Day0_rep1 (0.0320991)Liver_development_Day0_rep2 (0.00692105)Liver_development_Day3_rep1 (0.0129393)Liver_development_Day3_rep2 (0.0740269)Liver_development_Day7_rep1 (0.0191054)Liver_development_Day14_rep1 (0.00436508)Liver_development_Day21_rep1 (0.029606)Liver_development_Day21_rep2 (0.0535402)Liver_development_NL_rep1 (0.0728566)Liver_development_NL_rep2 (0.0919236) (0.0305351) (0.0486115) (0.0860812) (0.0817952)[ min ] [ medium ] [ max ] CEM 1 H2-K1 1462.7 2643.1 23307.1 P ( S | Z, I ) = 0.00 Fcgrt 509.3 1191.1 4237.3 Mean Corr = 0.53522 Hfe 152.8 792.5 1741.8 H2-Bl 105.5 189.2 309.9 H2-Q2 57.7 73.8 83.8 H2-Q10 1209.5 8112.7 25830.1 C920025E04Rik 84.0 115.3 156.4 H2-M3 177.8 312.5 528.4 B2m 114.0 174.0 476.3 Mr1 138.3 191.0 269.3 Azgp1 306.6 7113.9 29188.6 Ulbp1 90.1 114.2 145.3 Procr 147.3 199.6 445.7 H2-D1 94.8 126.6 173.0 H2-Aa 126.5 184.2 577.9 Cd68 173.1 420.3 1060.3 Psmb9 117.0 228.4 774.5 Psmb8 188.2 330.1 1256.3 Tapbp 694.5 1532.6 3924.7 CEM 1 + Gbp2 121.7 184.2 513.9 Top 10 Genes Ifi27l2a 283.3 557.1 1186.9 Igtp 346.4 1027.9 3505.3 Fxyd5 425.0 613.2 878.7 Ifit3 141.7 306.5 660.6

Null module GEO Series "GSE21576" 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=GSE21576 Status: Public on Sep 01 2010 Title: Expression profiles of laser dissected colon tumor samples of wild-type mice and vil-Cre-Bcl9-/-/Bcl9l-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20682801 Summary & Design: Summary: To investigate the impact of ablating Bcl9/Bcl9l on tumorigenesis, 6-8- week-old mice were exposed first to a single dose dimethylhydrazine (DMH, 44 mg/kg body weight), which is metabolized in the liver to carcinogenic azoxymethane (AOM), followed by 7 days oral administration of 2 % dextrane sulfate sodium (DSS) in the drinking water. This regimen results in the emergence of dysplastic adenomas, which progress to differentiated adenocarcinomas that are morphologically similar to human colorectal adenocarcinomas and typically harbor ˛†-catenin stabilizing mutations of GSK3ˆ phosphorylation sites. Accordingly, these tumors present hallmarks of active Wnt signaling such as accumulation of nuclear Î²-catenin and expression of Wnt target genes.

Overall design: Total RNA of laser dissected samples from five different tumors each of two wild-type mice and three vil-Cre-Bcl9-/-/Bcl9l-/- mice was collected and resulting amplified cDNA hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Samples are labeled as follows: Genotype_TumorID_MouseID_UniqueID.

Background corr dist: KL-Divergence = 0.1042, L1-Distance = 0.0294, L2-Distance = 0.0015, Normal std = 0.4299

0.928 Kernel fit Pairwise Correlations Normal fit

Density 0.464

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

vil-Cre-Bcl9-/-/Bcl9l-/-vil-Cre-Bcl9-/-/Bcl9l-/-vil-Cre-Bcl9-/-/Bcl9l-/- tumorvil-Cre-Bcl9-/-/Bcl9l-/- 258, tumorvil-Cre-Bcl9-/-/Bcl9l-/- mouse 257, tumorwildtype, 04mouse 256,(0.0977956) tumorwildtype, tumor 02mouse 195,(0.13889) tumorwildtype, 254, tumor 02mouse mouse255,(0.0763951)wildtype, 215, tumor 99mouse 72mouse(0.0997362)wildtype, 216,(0.130125) tumor 04 72mouse(0.133663) 191,(0.0440516) tumor 72mouse 229,(0.0898028) 72mouse (0.110469) 82[ (0.079071) min ] [ medium ] [ max ] CEM 1 H2-K1 6727.8 12489.0 17036.8 P ( S | Z, I ) = 0.00 Fcgrt 342.3 651.3 812.7 Mean Corr = 0.24077 Hfe 143.6 231.3 360.5 H2-Bl 36.2 58.5 93.5 H2-Q2 18.8 110.2 497.1 H2-Q10 63.3 274.9 397.7 C920025E04Rik 64.4 97.3 153.3 H2-M3 623.4 2176.5 2804.7 B2m 162.7 1129.3 2132.0 Mr1 98.4 133.0 326.6 Azgp1 33.1 46.5 70.0 Ulbp1 113.7 206.4 324.9 Procr 1447.0 2440.8 2993.7 H2-D1 16.9 20.0 23.2 H2-Aa 405.8 1572.9 5674.5 Cd68 184.8 234.6 255.3 Psmb9 499.5 4605.9 10371.1 Psmb8 384.8 4391.2 9235.3 Tapbp 2610.1 4720.4 7590.2 CEM 1 + Gbp2 39.3 1136.7 4962.8 Top 10 Genes Ifi27l2a 63.1 193.4 278.5 Igtp 217.4 3310.1 8942.9 Fxyd5 454.4 854.9 1021.0 Ifit3 189.6 1055.6 3021.8

Null module GEO Series "GSE25257" 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=GSE25257 Status: Public on Nov 11 2010 Title: Expression data from wild-type and Zmpste24-/- mouse embryonic fibroblasts (MEFs) at an early passage (passage 3, P3) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Zmpste24 is a metalloproteinase processing prelamin A into mature lamin A, a nuclear structure protein. Zmpste24-/- mice which accumulate prelamin A in cells recapitulate accelerated aging phenotypes observed in human premature aging disorder, Hutchinson Gilford progeria sydrome (HGPS). Zmpste24-/- mouse embryonic fibroblasts (MEFs) exhibited genomic instabiliy and accelerated aging at cellular level, which is premature senescence.

We performed microarray analysis on Zmpste24-/- MEFs, compared to wild-type littermates' MEFs, at an early passage (P3), which is a pre-symptom stage before cellular senescence occurs in the mutant MEFs, in order to examine gene expression profile and figure out the underneath mechanism triggering the premature aging process.

Overall design: Early passage wild-type and Zmpste24-/- MEFs were collected for RNA extraction, the quality of RNAs were determinded by Electrophoresis Assay (2100 Bioanalyzer, Agilent) and RNA extractions were used for hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0217, L1-Distance = 0.0450, L2-Distance = 0.0023, Normal std = 0.8008

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

WT1 (0.265909)WT2 (0.0907119)WT3 (0.111018)NT1 (0.202595)NT2 (0.0841004)NT3 (0.245665) [ min ] [ medium ] [ max ] CEM 1 H2-K1 1449.4 2166.0 4511.2 P ( S | Z, I ) = 0.00 Fcgrt 515.8 689.4 2685.1 Mean Corr = 0.29546 Hfe 163.9 201.8 719.3 H2-Bl 13.7 32.3 44.8 H2-Q2 1.0 1.0 6.1 H2-Q10 6.0 21.7 25.1 C920025E04Rik 34.1 47.8 101.1 H2-M3 237.1 333.4 394.2 B2m 38.1 53.5 79.2 Mr1 113.5 166.2 275.2 Azgp1 6.0 13.4 38.9 Ulbp1 9.6 22.9 37.2 Procr 800.9 985.5 1780.1 H2-D1 5.1 14.8 22.3 H2-Aa 5.7 10.3 32.8 Cd68 157.6 219.2 578.5 Psmb9 29.3 51.0 115.9 Psmb8 93.1 164.4 310.0 Tapbp 947.3 1100.6 2780.3 CEM 1 + Gbp2 175.6 200.1 222.1 Top 10 Genes Ifi27l2a 32.5 182.2 379.9 Igtp 130.9 318.9 575.8 Fxyd5 978.7 2937.6 3807.1 Ifit3 105.2 163.7 786.3

Null module GEO Series "GSE10965" 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=GSE10965 Status: Public on Mar 29 2008 Title: Comparison of the transcriptional profiles of the retinal pigmental epithelium/choroid from young and old mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18523633 Summary & Design: Summary: To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration.

Keywords: age-related change

Overall design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals

Background corr dist: KL-Divergence = 0.0376, L1-Distance = 0.0149, L2-Distance = 0.0002, Normal std = 0.6113

0.653 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

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

Pre-normalization Quantiles

RPE/choroid_young_rep1RPE/choroid_young_rep2RPE/choroid_young_rep3RPE/choroid_young_rep4 (0.0986062)RPE/choroid_old_rep1 (0.0908842)RPE/choroid_old_rep2 (0.129884)RPE/choroid_old_rep3 (0.088877)RPE/choroid_old_rep4 (0.100092) (0.146082) (0.303568) (0.0420066)[ min ] [ medium ] [ max ] CEM 1 H2-K1 4441.3 7314.8 9951.3 P ( S | Z, I ) = 0.00 Fcgrt 1695.1 1833.0 2219.6 Mean Corr = 0.22711 Hfe 1299.9 1434.2 1548.5 H2-Bl 136.3 153.5 189.5 H2-Q2 18.5 21.0 24.6 H2-Q10 73.5 87.3 103.3 C920025E04Rik 69.8 81.5 98.3 H2-M3 538.0 732.4 962.1 B2m 130.8 210.7 289.3 Mr1 380.6 453.6 503.9 Azgp1 313.8 399.8 461.0 Ulbp1 89.7 110.7 120.2 Procr 765.9 910.3 1053.0 H2-D1 71.3 81.3 102.6 H2-Aa 772.5 1154.4 1517.3 Cd68 2159.8 5792.5 7081.1 Psmb9 464.8 583.7 1053.7 Psmb8 584.7 1015.0 1534.3 Tapbp 2812.5 3640.9 4367.5 CEM 1 + Gbp2 729.3 916.3 1705.9 Top 10 Genes Ifi27l2a 1134.8 1385.6 1855.6 Igtp 920.2 1346.4 2922.4 Fxyd5 1239.6 2016.0 2682.9 Ifit3 2385.9 3882.5 5570.3

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 (0.0310697)liver-baclofen-1day-rep 1 (0.0224355)liver-vehicle-1day-rep 2 (0.029525) 2liver-baclofen-1day-rep (0.0263379)liver-vehicle-5day-rep 3 (0.02513) 3liver-baclofen-5day-rep (0.0276625)liver-vehicle-5day-rep 4 (0.024125) 1liver-baclofen-5day-rep (0.0267481)liver-vehicle-5day-rep 1 (0.0184462) 2liver-baclofen-5day-rep (0.0248534)liver-vehicle-5day-rep 2 (0.0217759) 3liver-baclofen-5day-rep (0.0413122)liver-baclofen-5day-rep 3 (0.0261215) 4liver-baclofen-5day-rep (0.0208831)liver-baclofen-5day-rep 4 (0.0309239)liver-baclofen-5day-rep 5 (0.0270512)bone 6 (0.0201644) marrow-vehicle-1day-repbone 7 (0.0212157) marrow-baclofen-1day-repbone 8 (0.018476) marrow-vehicle-1day-repbone marrow-baclofen-1day-repbone 1 (0.016896) marrow-vehicle-1day-repbone 1 (0.0104772) marrow-baclofen-1day-repbone 2 (0.0114528) marrow-vehicle-1day-repbone 2 (0.00780826) marrow-baclofen-1day-repbone 3 (0.0114085) marrow-vehicle-5day-repbone 3 (0.0109983) marrow-baclofen-5day-repbone 4 (0.016623) marrow-vehicle-5day-repbone 4 (0.0119201) marrow-baclofen-5day-repbone 1 (0.0104681) marrow-vehicle-5day-repbone 1 (0.0113653) marrow-baclofen-5day-repbone 2 (0.00925021) marrow-vehicle-5day-repbone 2 (0.0101903) marrow-baclofen-5day-repbone 3 (0.0123992) marrow-baclofen-5day-repbone 3 (0.0109718) marrow-baclofen-5day-repbone 4 (0.0118379) marrow-baclofen-5day-repbone 4 (0.0123154) marrow-baclofen-5day-repspleen-vehicle-1day-rep 5 (0.0149067)spleen-baclofen-1day-rep 6 (0.00748547)spleen-vehicle-1day-rep 7 (0.00916322)spleen-baclofen-1day-rep 1 8 (0.00700907) (0.010285)spleen-vehicle-1day-rep 1 (0.017667)spleen-baclofen-1day-rep 2 (0.00927946)spleen-vehicle-1day-rep 2 (0.0179601)spleen-baclofen-1day-rep 3 (0.020809)spleen-vehicle-5day-rep 3 (0.020062)spleen-baclofen-5day-rep 4 (0.0120291)spleen-vehicle-5day-rep 4 (0.0129616)spleen-baclofen-5day-rep 1 (0.0181693)spleen-vehicle-5day-rep 1 (0.0154511)spleen-baclofen-5day-rep 2 (0.00842968)spleen-vehicle-5day-rep 2 (0.0149943)spleen-baclofen-5day-rep 3 (0.0149794)spleen-baclofen-5day-rep 3 (0.0135013)spleen-baclofen-5day-rep 4 (0.015041)spleen-baclofen-5day-rep 4 (0.0134212)spleen-baclofen-5day-rep 5 (0.0130497) 6 (0.019502) 7 (0.0116463) 8 (0.0115575)[ min ] [ medium ] [ max ] CEM 1 H2-K1 7976.5 17622.1 21040.8 P ( S | Z, I ) = 0.00 Fcgrt 601.7 1393.9 5072.9 Mean Corr = 0.16793 Hfe 536.6 1167.3 2685.7 H2-Bl 66.2 125.6 441.0 H2-Q2 16.4 19.5 29.9 H2-Q10 177.5 954.3 34124.1 C920025E04Rik 46.2 95.7 375.5 H2-M3 263.2 712.1 2219.8 B2m 78.9 311.3 2681.0 Mr1 162.2 212.4 527.0 Azgp1 96.5 127.9 41846.8 Ulbp1 36.6 60.7 86.5 Procr 37.6 64.0 725.9 H2-D1 22.1 28.7 43.0 H2-Aa 151.4 2536.4 26451.1 Cd68 148.3 1498.1 3043.6 Psmb9 467.2 2493.2 4258.0 Psmb8 1113.8 3445.9 7171.6 Tapbp 3624.9 5020.9 8190.6 CEM 1 + Gbp2 49.7 302.3 963.4 Top 10 Genes Ifi27l2a 255.6 3186.4 10085.7 Igtp 1349.1 2150.1 3653.8 Fxyd5 202.3 3684.7 8915.4 Ifit3 222.1 510.2 1628.9

Null module GEO Series "GSE5334" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 19 -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=GSE5334 Status: Public on Jul 22 2006 Title: Gene expression profiling of whole ovary in embryonic (gestional day 11, 12, 14, 16 & 18) and postnatal day 2 mice. (GUDMAP Series ID: 5) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events.

Keywords: developmental time course

Overall design: Day to day comparison in whole ovary throughout development with triplicates at each time point. Each sample is a pair of ovaries from a single animal and each animal is taken from a different dam (with the exception of gd11 sample numbers 18 and 19 which come from the same dam).

Background corr dist: KL-Divergence = 0.1760, L1-Distance = 0.0465, L2-Distance = 0.0050, Normal std = 0.3897

1.061 Kernel fit Pairwise Correlations Normal fit

Density 0.530

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

KPL_pnd2_1_ovary_Mouse430_2_KWGU011601_aKPL_pnd2_2_ovary_Mouse430_2_KWGU011601_aKPL_pnd2_3_ovary_Mouse430_2_KWGU011601_aKPL_gd18_4_ovary_Mouse430_2_KWGU011601_aKPL_gd18_5_ovary_Mouse430_2_KWGU011601_aKPL_gd18_6_ovary_Mouse430_2_KWGU011601_aKPL_gd16_7_ovary_Mouse430_2_KWGU011601_a (0.0824354)KPL_gd16_8_ovary_Mouse430_2_KWGU011601_a (0.0359073)KPL_gd16_9_ovary_Mouse430_2_KWGU011601_a (0.0435933)KPL_gd14_10_ovary_Mouse430_2_KWGU011601_a (0.0292919)KPL_gd14_11_ovary_Mouse430_2_KWGU011601_a (0.0165874)KPL_gd14_12_ovary_Mouse430_2_KWGU011601_a (0.0547165)KPL_gd12_13_ovary_Mouse430_2_KWGU011601_a (0.0734398)KPL_gd12_14_ovary_Mouse430_2_KWGU011601_a (0.0149639)KPL_gd12_15_ovary_Mouse430_2_KWGU011601_a (0.019921)KPL_gd11_16_ovary_Mouse430_2_KWGU011601_a (0.0246654)KPL_gd11_18_ovary_Mouse430_2_KWGU011601_a (0.0403783)KPL_gd11_19_ovary_Mouse430_2_KWGU011601_a (0.0217996)KPL_pnd0.5_20_refLitter_Mouse430_2_KWGU011601_a (0.0151867) (0.027954) (0.0226399) (0.0541518)[ min (0.0311424) ] (0.0319091)[ (0.359316) medium ] [ max ] CEM 1 H2-K1 374.4 959.3 4032.2 P ( S | Z, I ) = 0.00 Fcgrt 572.7 1591.5 13608.0 Mean Corr = 0.31840 Hfe 69.8 198.2 415.3 H2-Bl 17.5 39.6 187.1 H2-Q2 1.0 32.8 824.0 H2-Q10 1.9 32.2 989.0 C920025E04Rik 2.2 18.1 81.9 H2-M3 87.1 158.2 612.8 B2m 56.8 104.3 173.9 Mr1 7.7 91.4 163.1 Azgp1 5.2 15.7 423.1 Ulbp1 20.3 39.2 67.8 Procr 71.4 350.2 744.9 H2-D1 1.6 15.5 48.8 H2-Aa 4.2 34.4 785.9 Cd68 77.3 117.8 696.9 Psmb9 16.8 74.4 243.9 Psmb8 4.9 21.4 254.5 Tapbp 249.9 692.1 1400.1 CEM 1 + Gbp2 31.3 197.7 534.5 Top 10 Genes Ifi27l2a 8.3 79.8 241.8 Igtp 170.3 392.4 990.0 Fxyd5 59.5 149.2 495.5 Ifit3 5.8 76.6 191.4

Null module GEO Series "GSE33726" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 48 -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=GSE33726 Status: Public on Dec 01 2012 Title: The circadian clock coordinates ribosome biogenesis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23300384 Summary & Design: Summary: Evolutionary conserved biological rhythms play a fundamental role in the physiology and behavior of all light-sensitive organisms. Generation of rhythmic expression of clock-controlled genes is orchestrated by a molecular circadian clock constitutes by interconnected negative feedback loops of transcription factors. In this study, we want to characterize gene which also present a rhythmic translation through the characterization of genes with a rhythmic polysomal/total RNA ratio.

Overall design: Analyze of gene expression in liver total RNA and polysomal RNA harvested every 2 hrs during 2 series of 48 hrs, 2 mice per samples

Background corr dist: KL-Divergence = 0.2369, L1-Distance = 0.0556, L2-Distance = 0.0060, Normal std = 0.3249

1.304 Kernel fit Pairwise Correlations Normal fit

Density 0.652

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

PolysomalPolysomal RNAPolysomal at RNAZT0Polysomal Sample at RNAZT2Polysomal Sample 1at (0.0190512)RNAZT4Polysomal Sample 1at (0.0149623)RNAZT6Polysomal Sample 1at (0.0145632)RNAZT8Polysomal Sample 1at (0.0267973)RNAZT10Polysomal 1atSample (0.0174567)RNAZT12Polysomal atSample 1 RNA ZT14(0.0158232)Polysomal atSample 1 RNA ZT16(0.017287)Polysomal atSample 1 RNA ZT18(0.0151248)Polysomal atSample 1 RNA ZT4(0.0191771)Polysomal Sample at 1 RNA ZT6(0.0134445)Polysomal Sample 2at (0.0149449)RNAZT8Polysomal Sample 2at (0.0277539)RNAZT10Polysomal 2atSample (0.0119706)RNAZT12Polysomal atSample 2 RNA ZT14(0.0213618)Polysomal atSample 2 RNA ZT20(0.0293723)Polysomal atSample 2 RNA ZT22(0.020325)Polysomal atSample 1 RNA ZT16(0.0295587)Polysomal atSample 1 RNA ZT18(0.0188757)Total atSample 2 RNA ZT20(0.0141255) RNATotal atSample 2 at ZT22(0.0134283) RNAZT0Total Sample 2Sample at (0.0171645) RNAZT2Total 2Sample 1at (0.0179109) (0.0150165)RNAZT4Total Sample 1at (0.0169843)RNAZT6Total Sample 1at (0.0120906)RNAZT8Total Sample 1at (0.00808075)RNAZT10Total 1atSample (0.0129286)RNAZT12Total atSample 1 RNA ZT14(0.0101509)Total atSample 1 RNA ZT0(0.0356325)Total Sample at 1 RNA ZT2(0.0151613)Total Sample 2at (0.0401806)RNAZT4Total Sample 2at (0.0217627)RNAZT6Total Sample 2at (0.0204644)RNAZT8Total Sample 2at (0.0158565)RNAZT10Total 2atSample (0.0106177)RNAZT12Total atSample 2 RNA ZT14(0.0216318)Total atSample 2 RNA ZT16(0.0230594)Total atSample 2 RNA ZT18(0.0239979)Total atSample 1 RNA ZT20(0.0242871)Total atSample 1 RNA ZT22(0.0214007)Total atSample 1 RNA ZT16(0.036533)Total atSample 1 RNA ZT18(0.0397264)Total atSample 2 RNA ZT20(0.0375733)Polysomal atSample 2 ZT22(0.0395556)Polysomal RNASample 2 (0.0224538) at RNAZT0 2 (0.0226807) Sample at ZT2 Sample 2 (0.0250849)[ 2 min(0.0166086) ] [ medium ] [ max ] CEM 1 H2-K1 15691.9 26392.5 38629.3 P ( S | Z, I ) = 0.00 Fcgrt 2083.5 3286.3 4408.2 Mean Corr = 0.37382 Hfe 1180.3 2334.9 3626.6 H2-Bl 65.3 152.2 307.5 H2-Q2 5.0 29.3 84.2 H2-Q10 17205.9 24436.9 34387.2 C920025E04Rik 5.0 54.5 103.1 H2-M3 171.6 419.9 754.8 B2m 5.0 153.0 422.5 Mr1 7.6 64.3 181.0 Azgp1 25723.3 32646.5 45939.8 Ulbp1 5.0 26.0 81.3 Procr 7.8 78.1 180.1 H2-D1 5.0 23.5 96.7 H2-Aa 121.4 708.3 2259.8 Cd68 113.8 440.5 1127.8 Psmb9 1037.5 2389.4 5353.2 Psmb8 905.9 2567.6 5679.5 Tapbp 1773.2 3266.0 5856.5 CEM 1 + Gbp2 154.9 364.1 868.8 Top 10 Genes Ifi27l2a 153.8 844.7 3686.8 Igtp 1065.3 2304.3 11699.3 Fxyd5 79.1 229.5 514.9 Ifit3 476.3 861.6 2488.9

Null module