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: 5 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. Vps26b Vps26a Tbc1d5 Dscr3 Num ofGenesinQueryGeneset:5.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Snx8

Dscr3 Vps26a Snx8 Vps26b Tbc1d5 CEM 1(45datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 9030624J02Rik 0610031J06Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page1 Tmem55b Atp6v1b2 Atp6v0d1 Tspan14 Amdhd2 Lamtor1 Pip4k2c Slc46a3 Slc17a5 Slc36a1 Fam50a Hs1bp3 Vps26b Vps33a Vps26a Tbc1d5 Smpd2 Acot13 Pnpla7 Ostm1 Nhlrc3 Aagab Wdr81 Hmgcl Spg21 Casp9 Mroh1 Vps11 Rragc Dscr3 Appl2 Hsdl1 Pqlc2 Fnip2 Tom1 Napg Naga Hexb Neu1 Hexa Snx8 Hes6 Plin3 Arsa Ctns Ctsa Pigc Flcn 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE8621 [12] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE21711 [6] GSE31166 [6] GSE4043 [6] GSE48204 [6] GSE7348 [6] GSE15610 [12] GSE35260 [21] GSE8065 [18] GSE15872 [18] GSE26745 [24] GSE35318 [12] GSE32328 [24] GSE42877 [14] GSE14769 [24] GSE11723 [9] GSE9123 [8] GSE17647 [24] GSE20987 [12] GSE46854 [20] GSE30176 [12] GSE46185 [6] GSE30855 [6] GSE37907 [24] GSE36414 [8] GSE55809 [8] GSE14891 [8] GSE19684 [14] GSE43825 [31] GSE32986 [18] GSE33726 [48] GSE41925 [8] GSE47959 [8] GSE6383 [6] GSE40260 [6] GSE31378 [9] GSE20696 [8] GSE50603 [12] GSE7767 [6] GSE19836 [114] GSE27932 [14] GSE10182 [7] GSE42061 [12] GSE21861 [8] GSE16002 [9] GSE20391 [11] GSE40795 [50] GSE8788 [6] GSE5202 [12] GSE37000 [47] GSE33156 [18] GSE38031 [8] GSE32095 [24] GSE50687 [38] GSE4671 [28] GSE20177 [14] GSE5309 [7] GSE38257 [14] GSE15318 [24] GSE24121 [9] GSE17728 [12] GSE4034 [24] GSE16266 [6] GSE6789 [12] GSE16516 [18] GSE24061 [88] GSE33942 [12] GSE9247 [15] GSE11732 [15] GSE23496 [9] GSE9368 [12] GSE39886 [24] GSE12986 [10] GSE8156 [6] GSE11044 [6] GSE28593 [9] GSE27720 [6] GSE17256 [8] GSE43620 [8] GSE6933 [15] GSE20500 [6] GSE24789 [9] GSE19181 [6] GSE18042 [18] GSE34629 [6] GSE19732 [20] GSE20390 [6] GSE20604 [6] GSE17316 [12] GSE29262 [12] GSE32102 [49] GSE8683 [11] GSE8960 [18] GSE15767 [6] GSE8660 [6] GSE13869 [8] GSE40087 [15] GSE4288 [36] GSE9763 [20] GSE35044 [9] GSE37029 [15] GSE18115 [8] GSE4518 [12] GSE21393 [6] GSE4535 [6] GSE6065 [100] GSE44339 [14] GSE16684 [6] GSE20335 [8] GSE32330 [12] GSE4695 [6] GSE54056 [12] GSE45895 [27] GSE5232 [6] GSE9460 [26] GSE53480 [16] GSE46970 [15] GSE18064 [12] GSE10176 [6] GSE42591 [26] GSE9804 [9] GSE35785 [10] GSE52338 [12] GSE18322 [12] GSE30873 [6] GSE3554 [6] GSE38696 [8] GSE6116 [70] GSE45487 [9] GSE25088 [24] GSE9441 [36] GSE17796 [39] GSE36530 [6] GSE23178 [6] GSE31359 [8] GSE59319 [6] GSE17649 [36] GSE12073 [12] GSE23600 [10] GSE18395 [8] GSE30192 [6] GSE15871 [18] GSE23495 [6] GSE39770 [10] GSE16623 [6] GSE26616 [6] GSE46150 [8] GSE12536 [6] GSE21841 [18] GSE10273 [9] GSE2433 [10] GSE23006 [48] CEM+ CEM GSE34902 [6] GSE53986 [16] GSE28389 [20] GSE21900 [12] GSE26568 [6] GSE8512 [207] 0.0 GSE34324 [12] GSE7683 [12]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 18.03 18.08 18.22 18.30 18.40 18.82 18.93 18.98 18.99 19.13 19.48 19.70 19.78 19.82 19.88 19.90 19.99 20.24 20.31 20.45 20.95 21.06 21.13 21.15 21.74 21.75 22.06 22.40 22.49 22.99 23.24 23.31 23.61 23.65 24.32 24.95 25.34 25.42 25.70 26.09 26.13 26.36 27.12 28.87 32.71 1.0 Notes 1110034G24Rik D6Wsu163e Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page2 Atp6v1c1 Trappc12 Dnase1l1 Nudt16l1 Tmem18 Ppp1r21 Atp6ap1 Fam63b Slc38a9 Zfyve26 Gnpda1 Pcmtd2 Ube2q1 Coq10a Slc35f6 Mcoln1 Mms19 Rnf167 Uap1l1 Fam21 Manba Mpv17 Sumf1 Klhl24 Asah1 Vps18 Fbxo3 Foxo3 Fads1 Coro7 Cpt1a Naglu Galk2 Sgpl1 Lgmn Uckl1 Stk38 Hacl1 Gusb Plin2 Paox Tpp1 Cln6 Ttc5 Grn Mnt Taz Asl 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 12.50 12.52 12.55 12.71 12.77 12.80 12.92 13.13 13.20 13.44 13.45 13.63 13.71 13.97 14.17 14.37 14.58 14.78 14.83 14.83 14.88 15.04 15.13 15.27 15.56 15.62 15.65 15.69 15.72 15.72 15.73 15.81 15.93 15.96 16.25 16.53 16.61 16.66 16.76 16.93 17.24 17.29 17.44 17.49 17.51 17.56 17.77 17.87 17.92 17.95 1.0 Notes 5031439G07Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page3 AW549877 AI413582 Slc26a11 Fam134a Fam117a Commd4 Tmem51 Lamtor4 N4bp2l1 Hmg20a Wdsub1 Vipas39 Slc37a4 Lrsam1 Tex264 Scarb2 Pxmp4 Tmub2 Zfp839 Fbxl20 Fbxw4 Mapk3 Ddhd2 Lrrc57 Spsb2 Snx13 Vps39 Naa60 Mkrn1 Mfap3 Lace1 Uvrag Cnot8 Tpra1 Soat1 Tctn3 Tbcel Orai3 Chkb Npc1 Hscb Snx1 Psap Nek9 Sord Nbr1 Cuta Itfg3 Rit1 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 9.58 9.63 9.69 9.69 9.69 9.73 9.73 9.81 9.89 9.90 9.99 10.07 10.11 10.19 10.20 10.20 10.21 10.21 10.28 10.45 10.50 10.51 10.55 10.72 10.84 10.84 11.13 11.15 11.18 11.22 11.27 11.37 11.39 11.47 11.52 11.59 11.69 11.70 11.74 11.77 11.80 11.88 11.92 11.92 12.02 12.07 12.21 12.26 12.32 12.47 1.0 Notes 4632428N05Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page4 Suv420h2 Tmem86a Tmem206 Tmem175 Mapk1ip1 Smarcal1 Fam173a Txndc15 Tmem43 Ankrd46 Camk2g Plekhb2 Pla2g15 Hsd3b7 Unc119 Zdhhc9 Eif2ak3 Snapin Tatdn3 Slc8b1 Arrdc2 Zfp414 Slc2a8 Fam3a Dguok Acox1 Aaed1 Rab24 Snx30 Echs1 Vps35 Atraid Srpk2 Plod1 Il10rb Tigd2 Mdp1 Ubn1 Nagk Neil1 Glb1 Ctsd Alg1 Klc4 Dvl2 Ift46 Gba Gns Dbp 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 7.56 7.59 7.61 7.62 7.67 7.67 7.73 7.75 7.76 7.76 7.82 7.83 7.88 7.89 7.92 7.98 7.98 8.02 8.07 8.12 8.13 8.16 8.17 8.25 8.28 8.31 8.37 8.37 8.41 8.45 8.55 8.55 8.60 8.81 8.88 8.89 8.91 9.01 9.01 9.02 9.10 9.12 9.28 9.33 9.44 9.44 9.46 9.50 9.51 9.53 1.0 Notes Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page5 Tmem194b BC004004 Tgfbrap1 Tmem19 Txndc16 Zscan26 Ppip5k1 Rwdd2a Primpol Map2k5 Map3k4 Cc2d1b Asnsd1 Rab40c Rnase4 Akap8l Cd99l2 Camk1 Tecpr1 Pcnxl3 Inpp5k Myo7a Wdr41 Ccpg1 Pik3r4 Abca3 Fuca1 Gpd1l Mast3 Atp5s Dctn5 Phf20 Pomk Ypel3 Pqlc3 Fbxl4 Nprl2 Surf1 Dgkd Coq9 Hps3 Epg5 Pan2 Glg1 Idh1 Ilvbl Gaa Xpc Tk2 Hfe 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 6.06 6.06 6.11 6.20 6.21 6.22 6.23 6.24 6.24 6.26 6.37 6.41 6.44 6.46 6.49 6.55 6.63 6.68 6.69 6.69 6.70 6.81 6.82 6.83 6.89 6.94 6.99 7.03 7.05 7.10 7.14 7.14 7.14 7.15 7.17 7.18 7.21 7.34 7.34 7.40 7.41 7.41 7.41 7.44 7.51 7.51 7.51 7.55 7.55 7.56 1.0 Notes Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page6 Tmem256 Tmem144 Ctnnbip1 Slc25a11 Ccndbp1 Commd3 Tmem62 Tmem65 Tsc22d3 Rmnd5b Atp13a2 Mospd2 Slc38a7 Slc38a6 Myo18a Sh2d3c Sec22b Coro1b B3gnt1 Rassf2 Zfp362 Abcd1 Wdr11 Cebpa Ap5s1 Spns1 Vps53 Tpcn1 Tpgs1 Mtss1 Creg1 Numb Oma1 Atg14 Dctn2 Rufy1 Ypel5 Gga2 Yipf1 Vps8 Tep1 Oxr1 Rere Adi1 Rgl2 Cln8 Pef1 Ift52 Ifi30 Ski 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 4.82 4.83 4.86 4.87 4.88 4.93 4.95 4.96 4.97 5.00 5.02 5.02 5.04 5.07 5.08 5.15 5.18 5.26 5.26 5.31 5.35 5.40 5.40 5.41 5.44 5.46 5.46 5.48 5.48 5.53 5.55 5.57 5.61 5.66 5.67 5.84 5.85 5.92 5.92 5.93 5.94 5.95 5.96 5.96 5.99 6.01 6.02 6.04 6.05 6.05 1.0 Notes E430025E21Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page7 Rab11fip5 Tmem55a Fam134b Fam214a Ankrd12 Rmnd5a Aldh3a2 Trappc1 Cdc14b Vps9d1 Ormdl1 Mfsd12 Nudt18 Hgsnat Rmnd1 Dcaf11 Pnpla6 Pbxip1 Tnrc6c Tmppe Tmed3 Lamp1 Plk1s1 Slc9a6 Abhd5 Lrrc61 Hdac5 Rchy1 Sash3 Ndrg3 Mfsd5 Oxld1 Daglb Tmx2 Serf2 Hbp1 Apeh Kif1c Itgb5 Lmf1 Cbr3 Cbr1 Xpr1 Snrk Bin3 Clk2 Pld3 Narf Maf 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 3.42 3.56 3.58 3.62 3.63 3.65 3.69 3.71 3.76 3.79 3.82 3.82 3.87 3.87 3.90 3.92 3.95 3.96 3.97 4.01 4.01 4.02 4.07 4.25 4.25 4.26 4.28 4.28 4.28 4.31 4.32 4.34 4.35 4.37 4.37 4.41 4.43 4.50 4.53 4.57 4.61 4.63 4.65 4.65 4.68 4.73 4.73 4.76 4.81 4.81 1.0 Notes D430042O09Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page8 Tmem126b Gm12942 Slc25a45 Fam134c Trappc2l Ccdc181 Tbc1d20 Tbc1d16 Tbc1d17 Aspscr1 Akr1b10 Atp6v1a Slc35e3 Man2a2 Acad11 Fbxo25 Lman2l Mettl20 Nudt16 Prkag2 Hmha1 Smpd1 Dcaf17 Zfp512 Myo9b Gstm4 Stard9 Dhx16 Coasy Klhl22 Crebrf Vps41 Fcho2 Carkd Aifm2 Rpain Sf3b2 Pias2 Tldc1 Rnh1 Wdr7 Stat6 Pigs Iffo1 Siae Idua Tcta Nit1 Sfi1 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 2.03 2.05 2.07 2.07 2.13 2.14 2.17 2.20 2.21 2.33 2.35 2.39 2.39 2.39 2.39 2.41 2.44 2.48 2.50 2.51 2.54 2.54 2.54 2.55 2.60 2.61 2.61 2.62 2.66 2.67 2.71 2.71 2.77 2.81 2.84 2.85 2.87 2.89 2.92 2.95 2.97 3.01 3.03 3.04 3.11 3.17 3.26 3.33 3.33 3.35 1.0 Notes 1700021K19Rik 4931406C07Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page9 BC017643 Tmem230 Selenbp1 Fam168b Fam193b Commd6 Apobec1 Rps6ka1 Cd300lb Scamp3 Abhd12 Ddx26b Bckdha Fkbp1b Kdelc2 Zfand1 Plxdc1 Zfp277 Zfp524 Hpgds Renbp Ap3d1 Hebp1 Klhl17 Dhx32 Adcy9 Ncoa4 Adck2 Acox3 Cdpf1 Bbip1 Polg2 Tor4a Zbtb4 Ift140 Glyr1 Arl8b Actr8 Hadh Hps4 Tcn2 Twf2 Sirt3 Rtn3 Fnta Galt Mut Cat 0.0 1.0

GSE48338 [8] GSE30160 [6]

GSE35332 [12] Scale ofaveragePearsoncorrelations GSE22180 [60] GSE32334 [19] GSE21905 [6] GSE48811 [20] GSE47967 [18] GSE29081 [6] 0.2 GSE9975 [36] GSE56345 [9] GSE53077 [8] GSE22005 [23] GSE21996 [14] GSE8044 [6] GSE48397 [10] GSE34732 [12] GSE20372 [6] 0.4 GSE8513 [10] GSE4786 [9] GSE19885 [9] GSE12499 [10] GSE24683 [8] GSE30684 [6] GSE4718 [6] GSE12049 [6] GSE2197 [6] 0.6 GSE31004 [8] GSE46797 [6] GSE3296 [16] GSE39458 [6] GSE5582 [6] GSE6482 [9] GSE42565 [6] GSE52358 [8] GSE50439 [15] 0.8 GSE20100 [15] GSE11161 [6] GSE50865 [12] GSE6674 [15] Score 0.78 0.81 0.81 0.81 0.82 0.83 0.84 0.84 0.88 0.90 0.94 0.94 0.98 0.99 1.02 1.04 1.10 1.10 1.16 1.17 1.21 1.22 1.26 1.28 1.30 1.30 1.34 1.35 1.42 1.42 1.45 1.47 1.52 1.53 1.56 1.67 1.69 1.69 1.72 1.77 1.78 1.80 1.82 1.83 1.89 1.89 1.89 1.91 1.96 1.99 1.0 Notes 8430427H17Rik Symbol Num ofCEMGenes:5.Predicted483.SelectedDatasets:45.Strength:0.2 CEM 1,Geneset"[G]retromercomplex",Page10 Trp53inp1 Tmem218 Cdk5rap3 Fam120b Fam118b Hsd17b4 Csnk1g2 Arhgap9 Scamp5 Mospd1 Slc40a1 Map3k1 Man1c1 Scpep1 Trmt2b Rnf185 Samd8 Plxnb2 Arrdc1 Lactb2 Mrpl24 Osgep Mknk1 Neurl2 Pfkfb4 Ap1b1 Snx32 Btbd6 Abtb1 Wash Eml3 Ldb1 Dgkz Fig4 Ciz1 Araf Ufl1 0.0 1.0

GSE48338 [8] GSE30160 [6]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48338 Status: Public on Jun 03 2014 Title: Tpl2 promotes chemokine/chemokine receptor expression and macrophage migration during acute inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24713702 Summary & Design: Summary: In autoimmune diseases, accumulation of activated leukocytes correlates with inflammation and disease progression, and therefore, disruption of leukocyte trafficking is an active area of research. The protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Herein, we addressed the contribution of Tpl2 to the regulation of macrophage chemokine and chemokine receptor expression and subsequent migration in vivo using a mouse model of Tpl2 ablation. We found that gene expression of the chemokine ligands CCL2, CCL7, CXCL2, and CXCL3 as well as the chemokine receptors CCR1 and CCR5 were reduced in macrophages from the bone marrow and peritoneal cavities of tpl2-/- mice following stimulation with LPS. LPS stimulation repressed chemokine receptor expression of CCR1, CCR2 and CCR5. Notably, LPS-induced repression of CCR1 and CCR5 was significantly enhanced in Tpl2-deficient macrophages and was observed to be dependent upon Erk activation and independent of PI3K and mTOR signaling. Consistent with alterations in chemokine and chemokine receptor expression, tpl2-/- macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of both chemokine receptors and their ligands and provides further insight into how Tpl2 inhibition may disrupt inflammatory networks in vivo.

Overall design: microarray was used to profile the genome-wide expression patterns in Tpl2 wild-type and deficient macrophage.

Background corr dist: KL-Divergence = 0.0154, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.8097

0.493 Kernel fit Pairwise Correlations Normal fit

Density 0.246

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

BMDM, BMDM,Tpl2 WT, BMDM,Tpl2 unstimulated, WT, BMDM,Tpl2 unstimulated, KO, BMDM,Tpl2 biologicalunstimulated, KO, BMDM,Tpl2 biologicalunstimulated, replicate WT, BMDM,Tpl2 biological LPS replicate WT, 1treated, BMDM, Tpl2(0.126167) biological LPS replicate KO, 2treated, biologicalTpl2(0.0937698) LPS replicate KO, 1treated, biological(0.161604) LPS replicate 2treated, biological(0.113046) replicate 1 (0.106887) biological[ minreplicate 2 (0.144343) replicate ]1 (0.173329) 2 (0.0808538)[ medium ] [ max ] CEM 1 Dscr3 1087.4 3243.2 3575.5 P ( S | Z, I ) = 1.00 Vps26a 4175.2 6006.5 6602.0 Mean Corr = 0.93597 Snx8 1023.2 4792.9 5458.2 Vps26b 263.6 794.8 896.4 Tbc1d5 94.2 225.5 279.5 Hsdl1 973.9 1935.5 2275.4 Slc36a1 242.1 1255.0 1339.3 Fam50a 1348.9 3721.0 4241.4 Flcn 373.1 2821.6 2896.4 Ostm1 1521.8 4155.9 4617.8 CEM 1 + Hmgcl 867.3 3186.6 3509.7 Top 10 Genes Amdhd2 1167.3 2537.7 3095.0 Appl2 545.5 4603.2 5679.7 Hexa 15275.8 21845.3 23709.7 Wdr81 1004.2 3891.3 4415.9

Null module GEO Series "GSE30160" 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=GSE30160 Status: Public on Jul 05 2011 Title: The RANK IVVY Motif-regulated Genes in Osteoclastogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: By carrying out a systematic structure/function study of the RANK cytoplasmic domain, we previously identified a specific 4-a.a. RANK motif (IVVY535-538) which plays a critical role in osteoclastogenesis by mediating commitment of macrophages to the osteoclast lineage. We have recently validated the role of this IVVY motif in osteoclastogenesis in vivo by generating knockin (KI) mice bearing inactivating mutations in the RANK IVVY motif. This microarray experiment was performed to determine whether the IVVY motif is involved in regulating gene expression in osteoclastogenesis.

We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

Overall design: Bone marrow macrophages isolated from wild-type (WT) or knockin (KI) mice were plated in 60-mm tissue culture dishes and treated with M-CSF (44ng/ml) and RANKL (100ng/ml) for 24 hours. Each genotype has three triplicates. Total RNA was isolated for microarray analysis using mouse chips (type 430.2.0) at the Microarray Shared Facility at the University of Alabama at Birmingham.

Background corr dist: KL-Divergence = 0.0193, L1-Distance = 0.0421, L2-Distance = 0.0019, Normal std = 0.8277

0.522 Kernel fit Pairwise Correlations Normal fit

Density 0.261

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild replicate typewild replicate 1 type (0.214542)knockin replicate 2 (0.112111)knockin replicate 3 (0.10021)knock replicate 1 (0.312484) in replicate 2 (0.120647) 3 (0.140007)[ min ] [ medium ] [ max ] CEM 1 Dscr3 1731.0 3854.3 4210.5 P ( S | Z, I ) = 1.00 Vps26a 3834.6 5623.4 6041.0 Mean Corr = 0.82685 Snx8 3050.0 5297.9 6032.7 Vps26b 694.7 856.6 960.3 Tbc1d5 242.8 261.5 308.9 Hsdl1 1449.7 2195.6 2382.6 Slc36a1 504.0 1641.6 1934.2 Fam50a 1542.1 1884.5 1976.4 Flcn 1180.7 2671.9 3482.4 Ostm1 2164.4 3112.9 3184.7 CEM 1 + Hmgcl 3025.7 3423.1 3698.4 Top 10 Genes Amdhd2 1235.6 2662.2 3082.5 Appl2 1828.9 4471.6 5432.0 Hexa 9122.7 15442.2 17283.9 Wdr81 1490.3 2829.3 3252.1

Null module GEO Series "GSE8621" 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=GSE8621 Status: Public on Aug 10 2007 Title: LPS tolerance in macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18086374 Summary & Design: Summary: Among the multiple mechanisms that control the intensity and duration of macrophage activation, the development of a state of refractoriness to a second stimulation in cells treated with LPS has long been recognized. Release of inhibitory cytokines and alterations in intracellular signaling pathways may be involved in the development of LPS tolerance. Although a number of molecules have been implicated, a detailed picture of the molecular changes in LPS tolerance is still missing. We have used a genome-wide gene expression analysis approach to (i) define which fraction of LPS target genes are subject to tolerance induction and (ii) identify genes that are expressed at high levels in tolerant macrophages. Our data show that in LPS tolerant macrophages the vast majority of LPS-induced gene expression is abrogated. The extent of tolerance induction varies for individual genes, and a small subset appears to be excepted. Compared to other negative control mechanisms of macrophages, e.g. IL-10-induced deactivation, LPS-tolerance inhibits a much wider range of transcriptional targets. Some previously described negative regulators of TLR-signaling (e.g. IRAK-M) were confirmed as expressed at higher levels in LPS-tolerant macrophages. In addition, we discuss other potential players in LPS tolerance identified in this group of genes.

Keywords: pre and restimulation with LPS, tolerance induction

Overall design: Cells were either prestimulated (1_X) or not (0_X) for 18h with 100 ng/ml LPS. Media was exchanged and after 2h rest, cells either restimulated (X_1) or not (X_0) with again 100 ng/ml LPS. This resulted in 4 experimental conditions: 0_0, 0_1, 1_0 and 1_1. There were 3 biological replicates done, resulting in 12 arrays altogether.

Background corr dist: KL-Divergence = 0.0499, L1-Distance = 0.0755, L2-Distance = 0.0102, Normal std = 0.6205

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.325

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

no_pre_no_restimulation_rep_Ano_pre_no_restimulation_rep_Bno_pre_no_restimulation_rep_Cno_pre_LPS_restimulation_rep_Ano_pre_LPS_restimulation_rep_B (0.0540762)no_pre_LPS_restimulation_rep_C (0.0616245)LPS_pre_no_restimulation_rep_A (0.13177)LPS_pre_no_restimulation_rep_B (0.131931)LPS_pre_no_restimulation_rep_C (0.189836)LPS_pre_LPS_restimulation_rep_A (0.146091)LPS_pre_LPS_restimulation_rep_B (0.10588)LPS_pre_LPS_restimulation_rep_C (0.0373577) (0.0852129) (0.017882) (0.0170442)[ min (0.0212958) ] [ medium ] [ max ] CEM 1 Dscr3 633.5 2396.0 3149.9 P ( S | Z, I ) = 1.00 Vps26a 4101.5 5593.3 6877.7 Mean Corr = 0.82536 Snx8 1082.6 3227.8 4460.1 Vps26b 232.9 956.5 1301.4 Tbc1d5 89.8 187.8 400.9 Hsdl1 975.4 2123.1 2805.9 Slc36a1 264.4 1462.0 3023.1 Fam50a 1141.5 1694.0 2709.5 Flcn 488.9 3157.8 4506.7 Ostm1 1257.1 3423.9 3724.0 CEM 1 + Hmgcl 1258.8 3343.1 4294.4 Top 10 Genes Amdhd2 816.4 1770.5 2330.4 Appl2 506.5 3110.7 4277.7 Hexa 13875.1 18486.3 21056.1 Wdr81 580.8 2355.7 3028.1

Null module GEO Series "GSE21711" 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=GSE21711 Status: Public on May 07 2010 Title: Effect of cholera toxin or forskolin on mouse bone marrow-derived dendritic cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20479237 Summary & Design: Summary: Bone marrow-derived dendritic cells from C57BL/6 mice were treated with 1 ug/ml cholera toxin, 10 uM forskolin or control medium for 2 h.

Overall design: drug treatment groups

Background corr dist: KL-Divergence = 0.0361, L1-Distance = 0.0260, L2-Distance = 0.0007, Normal std = 0.6542

0.629 Kernel fit Pairwise Correlations Normal fit

Density 0.314

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 controlmedium, choleramedium, biologicalcholera toxin, biological rep biologicalforskolin, toxin, 1 (0.094736) rep biologicalforskolin, 2 repbiological (0.237824) 1 (0.227329) repbiological rep 2 (0.301473) 1 (0.0628644) rep 2 (0.0757737)[ min ] [ medium ] [ max ] CEM 1 Dscr3 2313.5 3624.8 3954.9 P ( S | Z, I ) = 1.00 Vps26a 3095.4 3861.1 3924.2 Mean Corr = 0.79172 Snx8 1662.9 2102.9 2206.1 Vps26b 569.4 801.5 825.5 Tbc1d5 48.9 101.0 160.5 Hsdl1 1330.1 2051.1 2230.2 Slc36a1 354.5 1081.7 1404.3 Fam50a 1366.6 1704.1 1734.9 Flcn 1100.9 1898.8 2121.3 Ostm1 2605.6 2961.2 3125.3 CEM 1 + Hmgcl 2077.5 3097.8 3265.0 Top 10 Genes Amdhd2 829.0 906.9 1018.5 Appl2 1210.2 1830.6 2067.9 Hexa 10292.2 11058.5 11847.0 Wdr81 846.1 1525.9 1647.1

Null module GEO Series "GSE31166" 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=GSE31166 Status: Public on Dec 13 2012 Title: Expression data from inducible ES stable cell line Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23180766 Summary & Design: Summary: In order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the inducible not-tagged cell line.

Transcriptome analysis of the inducible transgenic mouse ES cell line.

The E13 inducible cell lines derived from parental EB3 cell line. The cell line EB3 was obtained from the laboratory of Dr Hitoshi Niwa as previously described in (Masui S et al., 2005).

Tthe specific mouse gene is E130012A19Rik.

Overall design: For the analysis on the inducible not-tagged cell line, total RNA was extracted from three biological replicates grown in medium deprived of Tetracycline for 48 hours; RNA extracted from un-induced clones was used as control.

Background corr dist: KL-Divergence = 0.0196, L1-Distance = 0.0228, L2-Distance = 0.0005, Normal std = 0.7644

0.539 Kernel fit Pairwise Correlations Normal fit

Density 0.270

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

CTL, biologicalCTL, biologicalCTL, replicate biologicalinducible replicate 1 (0.161623)inducible replicate clone,2 (0.157005)inducible biological clone,3 (0.217038) biological clone, replicate1 biological replicate2 (0.286075) replicate3 (0.089757)[ min (0.0885011) ] [ medium ] [ max ] CEM 1 Dscr3 658.0 902.7 1009.5 P ( S | Z, I ) = 1.00 Vps26a 1989.2 2749.7 3071.4 Mean Corr = 0.77327 Snx8 574.9 699.0 814.3 Vps26b 437.7 478.3 501.5 Tbc1d5 14.3 20.3 21.4 Hsdl1 602.1 681.7 771.6 Slc36a1 202.9 233.2 247.2 Fam50a 1811.0 1945.1 1976.6 Flcn 436.9 566.1 615.2 Ostm1 408.4 664.5 717.2 CEM 1 + Hmgcl 1145.8 1452.2 1645.5 Top 10 Genes Amdhd2 634.5 714.1 735.3 Appl2 392.6 642.9 740.4 Hexa 1455.2 2537.1 3234.5 Wdr81 261.3 296.8 303.5

Null module GEO Series "GSE4043" 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=GSE4043 Status: Public on Mar 07 2006 Title: Gene profiling analysis of Src chemical rescue Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16513984 Summary & Design: Summary: The restoration of catalytic activity to mutant enzymes by small molecules is well-established for in vitro systems. Here we show that the protein tyrosine kinase Src R388A mutant can be rescued in live cells using the small molecule imidazole. Cellular rescue of a v-Src homolog was rapid and reversible and conferred predicted oncogenic properties. Using chemical rescue in combination with mass spectrometry, six known Src kinase substrates were confirmed, and several new protein targets identified. Chemical rescue data suggests that c-Src is active under basal conditions. Rescue of R388A c-Src also allowed contributions of Src to the MAP kinase pathway to be clarified. This chemical rescue approach is likely to be of broad utility in cell signaling.

We were also interested in examining the impact of Src rescue on the kinetics of gene expression. Chronic gene expression changes in v-Src transformed colon cancer and NIH3T3 cells have been reported, but the chemical rescue method permits insights into rapid kinetic changes. We used gene microarray analysis of imidazole activated Src, 1 h after imidazole treatment of 8A7F cells as well as 6N7F control cells, a set of several genes show increases (>1.7-fold) at 1 h in the 8A7F cells and another set show decreases (>1.7-fold) at 1 h with minimal changes in 6N7F control cells. Thirteen of these genes were further analyzed using real-time RT-PCR and most of the genes tested showed similar changes using both techniques. These gene changes were not reported in cells chronically transformed with v-Src or rapidly stimulated with growth factors suggesting that rapid initiation of Src-mediated tyrosine phosphorylation may induce a specialized pattern of gene expression changes. However, these earlier experiments were done under different conditions which may also contribute to gene effects.

Keywords: time course, cell type comparison

Overall design: using Murine Genome MOE430 2.0 GeneChips as described in the Affymetrix website.

Background corr dist: KL-Divergence = 0.0386, L1-Distance = 0.0241, L2-Distance = 0.0006, Normal std = 0.6315

0.649 Kernel fit Pairwise Correlations Normal fit

Density 0.325

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

Src R388A/Y527F-0Src R388A/Y527F-1Src R388A/Y527F-12 hr Src(0.206613) D386N/Y527F-0 hr Src(0.154287) D386N/Y527F-1 hrSrc (0.0801497) D386N/Y527F-12 hr (0.029588) hr (0.0693984) hr (0.459964)[ min ] [ medium ] [ max ] CEM 1 Dscr3 1389.4 1689.4 2040.1 P ( S | Z, I ) = 1.00 Vps26a 3914.4 5651.8 7063.0 Mean Corr = 0.75487 Snx8 1039.2 1622.7 2489.1 Vps26b 600.9 683.7 866.6 Tbc1d5 10.7 26.7 62.5 Hsdl1 1574.2 1726.3 2034.1 Slc36a1 409.4 497.1 661.3 Fam50a 1934.9 2103.9 3350.3 Flcn 903.3 1174.0 1483.8 Ostm1 1062.0 1592.2 2543.9 CEM 1 + Hmgcl 1581.2 1755.8 1905.0 Top 10 Genes Amdhd2 564.4 712.4 1393.1 Appl2 1473.9 1819.7 1927.4 Hexa 2786.8 3022.4 5260.7 Wdr81 1153.1 1478.9 2041.1

Null module GEO Series "GSE48204" 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=GSE48204 Status: Public on Jul 26 2013 Title: Gene expression in epithelial, EMT (epithelial-mesenchymal transition) and MET (mesenchymal-epithelial transition) cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23878399 Summary & Design: Summary: NMuMG is an epithelial cell line that can be induced into EMT by TGF-Î² treatment or MET by TGF-Î² withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype.

Transcription factors that are regulated during EMT and its reverse process MET are candidate genes for the regulations of the EMT marker genes.

Overall design: NMuMG cells treated with vehicle, TGF-Î² for 11 days, or 11days of TGF-Î² treatment followed by TGF-Î² withdrawl for another 13 days. RNA from these 3 conditions of NMuMG were extracted and subject to microarray analysis

Background corr dist: KL-Divergence = 0.0249, L1-Distance = 0.0454, L2-Distance = 0.0022, Normal std = 0.8085

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl NMuMGNMuMG NMuMG cells, NMuMGreplicate cells cells, treated NMuMGreplicate cells 1 (0.0498939) treatedbyNMuMG cells 211 (0.0731446) days treatedby cells 11 with days treatedby 4ng/ml 11 with days by TGF-Î²,4ng/ml 11 with days [ TGF-Î²,4ng/mlfollowed minwith TGF-Î²,4ng/mlfollowed by ] TGF-Î² TGF-Î²,replicate by withdrawlTGF-Î² replicate 1[ (0.167578) withdrawlmedium for 2 another(0.115836) for another 13 days,] 13 replicate days, replicate[ 1 max(0.206453) 2 (0.387094) ] CEM 1 Dscr3 1002.8 1186.9 1965.0 P ( S | Z, I ) = 1.00 Vps26a 2143.6 2528.5 4299.5 Mean Corr = 0.77214 Snx8 557.8 716.3 1041.4 Vps26b 490.5 528.0 589.1 Tbc1d5 60.7 77.3 89.3 Hsdl1 620.5 914.5 1082.3 Slc36a1 383.5 527.4 681.3 Fam50a 1962.3 2513.0 4114.1 Flcn 366.8 456.7 772.9 Ostm1 1049.6 1532.4 2294.2 CEM 1 + Hmgcl 788.2 952.9 1171.2 Top 10 Genes Amdhd2 564.1 868.9 2939.6 Appl2 407.4 588.3 1772.4 Hexa 466.6 928.0 5515.9 Wdr81 691.2 1143.7 1847.6

Null module GEO Series "GSE7348" 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=GSE7348 Status: Public on Apr 22 2007 Title: Gene Expression in Naive and Tolerant Macrophages stimulated with LPS Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17538624 Summary & Design: Summary: The inflammatory response initiated by microbial products signaling through Toll-like receptors (TLRs) of the innate immune system is essential for host defense against infection. Because inflammation can be harmful to host tissues, the innate response is highly regulated. Negative regulation of TLR4, the receptor for bacterial lipopolysaccharide (LPS), results in LPS tolerance, defined as hyporesponsiveness to repeated stimulation with LPS. LPS tolerance is thought to protect the host from excessive inflammation by turning off TLR4 signal, which then shuts down TLR-induced genes. However, TLR signaling induces hundreds of genes with very different functions. We reasoned that genes with different functions should have different requirements for regulation. Specifically, genes encoding proinflammatory mediators should be transiently inactivated to limit tissue damage, while genes encoding antimicrobial effectors, which directly target pathogens, should remain inducible in tolerant cells to protect the host from infection. Using an in vitro system of LPS tolerance in macrophages, here we show that TLR-induced genes may indeed be divided into two distinct categories based on their functions and regulatory requirements. Further, we show these distinct groups are regulated by gene-specific, and not signal-specific mechanisms.

Keywords: Treatment Comparison

Overall design: We examined gene expression using affymetrix genechips in 3 groups of murine bone-marrow derived macrophages: Naive (untreated), Naive stimulated with LPS, and Tolerant stimulated with LPS. Two biological replicates were performed for each group.

Background corr dist: KL-Divergence = 0.0411, L1-Distance = 0.0357, L2-Distance = 0.0018, Normal std = 0.6261

0.647 Kernel fit Pairwise Correlations Normal fit

Density 0.323

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

Naive-rep2N+L, (0.367835) rep2T+L, (0.0858546) rep2Naive-rep1 (0.0616752)N+L, (0.0983329) rep1T+L, (0.295706) rep1 (0.0905961) [ min ] [ medium ] [ max ] CEM 1 Dscr3 775.5 3281.6 4157.5 P ( S | Z, I ) = 1.00 Vps26a 4186.9 4992.3 6180.4 Mean Corr = 0.74423 Snx8 968.4 2742.3 6867.6 Vps26b 259.9 880.6 1131.5 Tbc1d5 68.2 135.9 214.0 Hsdl1 875.6 1961.4 2420.5 Slc36a1 263.3 730.1 1040.8 Fam50a 1193.0 1937.4 2701.0 Flcn 168.3 1689.6 3265.1 Ostm1 2130.7 3656.6 4396.8 CEM 1 + Hmgcl 727.5 2347.8 4344.4 Top 10 Genes Amdhd2 950.1 1835.4 2070.4 Appl2 661.7 2190.7 5184.1 Hexa 12410.1 20782.7 27328.9 Wdr81 528.1 1662.1 2446.1

Null module GEO Series "GSE15610" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.823 Kernel fit Pairwise Correlations Normal fit

Density 0.411

0.000 CEM 1

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

Pre-normalization Quantiles

Control_untreated_replicateControl_untreated_replicateControl_untreated_replicateKnockout_untreated_replicate 1Knockout_untreated_replicate (0.158547) 2Knockout_untreated_replicate (0.0296459) 3Control_4h (0.118431)Control_4h 1 (0.0722693) lipopolysaccharide_replicateControl_4h 2 (0.0486591) lipopolysaccharide_replicateKnockout_4h 3 (0.0891381) lipopolysaccharide_replicateKnockout_4h lipopolysaccharide_replicateKnockout_4h 1 (0.0417838) lipopolysaccharide_replicate 2 (0.113083) lipopolysaccharide_replicate 3 (0.0734189) 1 [(0.112984) min 2 (0.0694403) ] 3 (0.0726002)[ medium ] [ max ] CEM 1 Dscr3 708.2 1905.3 2449.8 P ( S | Z, I ) = 1.00 Vps26a 2611.3 3711.0 4423.4 Mean Corr = 0.71195 Snx8 431.1 1820.9 2627.7 Vps26b 148.9 659.2 966.6 Tbc1d5 75.6 183.2 354.4 Hsdl1 817.4 1417.0 1877.2 Slc36a1 107.2 569.8 920.9 Fam50a 616.6 1506.9 1949.8 Flcn 179.3 870.6 1262.9 Ostm1 535.7 2505.9 3518.7 CEM 1 + Hmgcl 994.2 1986.3 2837.6 Top 10 Genes Amdhd2 194.9 799.4 1415.1 Appl2 190.4 1265.3 1615.0 Hexa 6166.3 8871.4 11044.1 Wdr81 477.5 1074.5 1799.1

Null module GEO Series "GSE35260" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 21 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35260 Status: Public on Mar 19 2013 Title: Functional dissection of the Paired domain of Pax6 distinct roles of subdomains in neurogenesis and proliferation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23404109 Summary & Design: Summary: The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex.

Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation.

Overall design: We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice

Background corr dist: KL-Divergence = 0.0555, L1-Distance = 0.0286, L2-Distance = 0.0013, Normal std = 0.5344

0.746 Kernel fit Pairwise Correlations Normal fit

Density 0.373

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

Pax6 mutantPax6 mutant(Small-eye;Pax6 mutant(Small-eye;Pax6 Sey) mutant(Small-eye; Controlrostral Sey) (Small-eye; cerebralControl rostralrostral Sey) cerebralControl rostralcerebral rostralcortex Sey) cerebralPax6 rostralcerebral rostralat cortexcortex embryonic mutant cerebralPax6 cerebral at atcortexcortex embryonicembryonic mutant(Leca2) dayPax6 at atcortexcortex embryonicembryonicE14, mutant (Leca2)rostral daydayPax6 atatbiological embryonic embryonicE14,E14 mutant (Leca2)cerebralrostral daydayControl (littermatebiological E14,replicateE14 (Leca2)cerebralrostral daycortexdayControl rostral(littermatebiological E14,replicateE14of cerebral1 rostral atPax6 cortexControl (0.0502802)cerebral rostral(littermate biologicalembryonic replicateof Sey cerebral2 atPax6 cortexPax6 (0.0700166)cerebralrostral cortexembryonicmutants), replicateof Sey daymutant3 atPax6 cortexPax6(0.0940706)cerebral at cortexembryonicmutants),E14, embryonic biological Sey daymutant(Leca4)4 at biologicalPax6(0.048053) at cortexembryonicmutants),E14, embryonic biological daymutant (Leca4)rostral biologicaldayreplicateControl at E14,replicate embryonic E14biological day (Leca4)cerebralrostral biologicaldayreplicateControl rostral(littermate 1 E14,replicate [WT_8] E141 cerebralrostral(0.00646739) biological cortexdayreplicateControl cerebral rostral(littermate 2 replicate [WT_9](0.0745703) E14of2 cerebral (0.000717118) atPax6 cortexControl cerebral rostral(littermate cortexembryonic3 replicate [WT_10](0.0655941) of 3Leca2 (0.0125576) atPax6 cortex cerebral rostral atcortexembryonic embryonic mutants), of4 (0.0766064)Leca2day (0.015201)atPax6 cerebral at cortexembryonicE14, embryonicmutants), Leca2day biologicalbiologicalday at cortexE14, embryonicmutants),E14 day biologicalbiologicalday[ (littermateat replicateE14,replicatemin embryonicE14 biologicalbiologicalday (littermate replicatereplicate 1E14of1] [WT_5](0.129771) Pax6day (littermate replicatereplicate 2E14of 2Leca4 [WT_6](0.0088372)(0.0643367) Pax6 (littermate[ 3mutants),of 3Leca4 medium[WT_7](0.00836643)(0.090147) Pax6 mutants),of Leca4 (0.0119169) biologicalPax6 mutants), Leca4 biological ]replicate mutants), biological replicate 1 [WT_1] biological[ replicatemax 2 [WT_2](0.03324) replicate 3] [WT_3](0.0327351) 4 [WT_4](0.0464435) (0.0600722) CEM 1 Dscr3 951.7 1340.7 1519.4 P ( S | Z, I ) = 1.00 Vps26a 1537.2 1918.1 2315.9 Mean Corr = 0.72861 Snx8 401.9 564.8 748.7 Vps26b 1524.7 1900.1 2369.8 Tbc1d5 19.5 32.4 62.8 Hsdl1 2773.8 3252.8 3632.7 Slc36a1 354.5 426.1 539.8 Fam50a 1442.0 1685.1 1884.3 Flcn 407.7 496.3 642.9 Ostm1 833.0 1453.6 1506.8 CEM 1 + Hmgcl 835.2 958.7 1170.0 Top 10 Genes Amdhd2 381.0 455.8 503.0 Appl2 812.3 1102.2 1423.0 Hexa 1094.2 1241.1 1381.7 Wdr81 583.7 737.9 876.9

Null module GEO Series "GSE8065" 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=GSE8065 Status: Public on Jun 12 2007 Title: Gene expression during early postnatal development of the small intestine Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18388184 Summary & Design: Summary: It was the purpose to analyse the changes in gene expression which occur in the mouse small intestine from the pre-weaning to the post-weaning stage. The gene expression was accordingly followed from postnatal day 4 to postnatal day 32.

Keywords: Time-course

Overall design: 6 time-points were defined corresponding to postnatal day 4, 7, 9, 11, 24 and 32. Ileal samples were taken from individual mice at each time-point. All layers of the small intestine were included in the sample. Three samples from individual mice were analysed by hybridization to Affymetrix GeneChips.

Background corr dist: KL-Divergence = 0.0658, L1-Distance = 0.0198, L2-Distance = 0.0006, Normal std = 0.5101

0.782 Kernel fit Pairwise Correlations Normal fit

Density 0.391

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

476_4d 478_4d(0.0162037) 480_4d(0.0182131) 481_7d(0.0569632) 484_7d(0.0326811) 488_7d(0.0338106) 486_9d(0.0150973) 488_9d(0.0416514) 490_9d(0.0519459) 496_11d(0.0556555)497_11d (0.0455885)498_11d (0.042407)1143_24d (0.0583651)1146_24d (0.045303)1279_32d (0.071411)1281_32d (0.0970867)1285_32d (0.10075)1148_24d (0.114716) (0.102151) [ min ] [ medium ] [ max ] CEM 1 Dscr3 1183.1 1876.4 2330.6 P ( S | Z, I ) = 1.00 Vps26a 2260.4 5239.7 6518.8 Mean Corr = 0.67526 Snx8 135.3 3739.1 5863.3 Vps26b 871.3 1167.7 1362.3 Tbc1d5 56.2 85.2 116.0 Hsdl1 784.6 1315.0 1511.0 Slc36a1 233.4 827.8 897.7 Fam50a 892.1 1624.1 2066.7 Flcn 267.0 1205.7 1457.9 Ostm1 879.5 1773.0 2075.3 CEM 1 + Hmgcl 3122.9 5583.0 6300.4 Top 10 Genes Amdhd2 1346.3 4540.7 5860.4 Appl2 959.5 2251.4 2733.2 Hexa 4400.0 24287.2 27063.6 Wdr81 519.2 1545.5 1918.2

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(0.0336673) rep2pylorus at biological E14.5, (0.0149472) rep3duodenum at biological E14.5, (0.0221648) rep1duodenum biological(0.0227235) at rep2 E14.5,duodenum (0.0217232) at rep3biological E14.5,stomach (0.0105936) at biological E14.5,stomach rep1 at E16.5, biological(0.0219923)stomach rep2 at biological E16.5, (0.0103033)pylorus rep3 at biological E16.5, (0.026241)rep1pylorus at E16.5, biological(0.012011) rep2pylorus at biological E16.5, (0.0216995) rep3duodenum at biological E16.5, (0.0221522) rep1duodenum biological(0.0287868) at rep2 E16.5,duodenum (0.0396904) at rep3biological E16.5, (0.00319208) at biological E16.5, rep1 biological(0.155751) rep2 (0.2267)[ rep3 min (0.305662) ] [ medium ] [ max ] CEM 1 Dscr3 1205.5 1477.8 2580.9 P ( S | Z, I ) = 1.00 Vps26a 1788.9 2050.3 3944.8 Mean Corr = 0.65738 Snx8 451.7 580.7 3917.5 Vps26b 855.0 1049.0 1693.4 Tbc1d5 57.6 117.6 198.1 Hsdl1 775.9 919.1 1142.4 Slc36a1 188.6 280.1 1094.3 Fam50a 948.7 1173.5 1484.5 Flcn 412.8 564.8 1003.0 Ostm1 327.4 428.8 1064.3 CEM 1 + Hmgcl 1413.9 3311.6 5570.7 Top 10 Genes Amdhd2 335.9 379.3 4316.8 Appl2 1259.2 1942.4 2715.9 Hexa 1780.7 2661.3 12816.6 Wdr81 458.9 550.0 1958.8

Null module GEO Series "GSE26745" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.968 Kernel fit Pairwise Correlations Normal fit

Density 0.484

0.000 CEM 1

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

Pre-normalization Quantiles

WT P7 mouseWT P7 cerebralmouseWT P7 cerebralmouseWT cortex, P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseFmr1 cortex,polyribosomalRNA, KO biologicalcerebralFmr1 cortex,polyribosomalRNA, P7 mouseKO biologicalFmr1 cortex,polyribosomalRNA, P7replicate cerebral mouseKO biologicalFmr1 polyribosomalRNA, P7replicate 1 cerebral mouseKO(0.0301509) cortex,biologicalFmr1 RNA, P7replicate 2 cerebral mouseKO(0.0108175) cortex,polyribosomalbiologicalFmr1 RNA, P7replicate 3 cerebral mouseKO(0.00933968) cortex,polyribosomalbiologicalWT P7replicate P74 cerebralmouse (0.075377) cortex,polyribosomalRNA,mouseWT replicate P75 biologicalcerebral (0.0779207) cortex,polyribosomalRNA,cerebralmouseWT P76 biological (0.0358746) cortex,polyribosomalRNA,cerebralmouse WT replicatecortex, P7 biological polyribosomalRNA,cerebralmouse WT replicatecortex,total 1 P7(0.0667548) biological cortical RNA,cerebralmouse WT replicatecortex,total 2 P7(0.0322568) biological cortical lysateRNA,cerebralmouse Fmr1 replicatecortex,total 3 (0.00634335) biological RNA,KOcortical lysatecerebral Fmr1 replicatecortex,total P74 biological(0.0404675) mouseRNA,KOcortical lysate Fmr1 replicatecortex,total P75 biological(0.0742608) cerebralmouseRNA,KOcortical lysatereplicateFmr1 total P76 biological(0.124186) cerebralmouseRNA,KO cortical cortex,lysatereplicateFmr1 1 P7 (0.057748) biological cerebralmouseRNA,KO cortex,totallysatereplicateFmr1 2 P7 (0.0189514) biologicalcortical cerebralmouseRNA,KO cortex,totalreplicate 3 P7 (0.0638127) biologicalcortical lysatecerebralmouse cortex,totalreplicate 4 (0.0402161) RNA,cortical lysatecerebral cortex,totalreplicate 5 biological (0.0164285) RNA,cortical lysate cortex,total[ 6 biological min(0.033889) RNA,cortical lysatereplicate total biological RNA,cortical ]lysatereplicate 1 (0.0469027) biological RNA, lysatereplicate 2 (0.030169) biological[ RNA, replicatemedium 3 (0.0297069) biological replicate 4 (0.0404211) replicate 5 (0.0120319)] 6 (0.0259733)[ max ] CEM 1 Dscr3 874.3 1372.0 2115.9 P ( S | Z, I ) = 1.00 Vps26a 1502.8 1756.6 2262.9 Mean Corr = 0.59449 Snx8 122.9 158.3 290.7 Vps26b 1450.4 2083.6 2800.1 Tbc1d5 15.2 17.2 19.7 Hsdl1 1203.5 1798.2 3311.1 Slc36a1 67.2 91.3 115.6 Fam50a 409.6 552.2 895.4 Flcn 364.0 580.1 808.9 Ostm1 272.5 434.6 628.2 CEM 1 + Hmgcl 146.1 367.2 668.6 Top 10 Genes Amdhd2 60.2 92.9 133.3 Appl2 108.4 182.5 237.2 Hexa 758.0 945.8 1292.4 Wdr81 37.9 47.2 54.8

Null module GEO Series "GSE35318" 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=GSE35318 Status: Public on Jul 10 2012 Title: p38a-dependent gene expression in dendritic cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22615377 Summary & Design: Summary: Gene expression in wild-type and p38a-knockout dendritic cells (DCs) were compared. Lymph node dendritic cells were isolated from mice, and left unstimulated and stimulated with Pam3CSK4, a toll-like receptor 2 agonist.

C57BL/6 wild-type mice, and dendritic cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of primary DCs.

Overall design: Gene expression 0, 2, and 4 h after stimulation was analyzed with each time point in duplicate.

Background corr dist: KL-Divergence = 0.1423, L1-Distance = 0.0306, L2-Distance = 0.0017, Normal std = 0.3824

1.043 Kernel fit Pairwise Correlations Normal fit

Density 0.522

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

KO TLR2LKO 0h-ATLR2LKO (0.153396) 0h-BTLR2LKO (0.054418) 2h-ATLR2LKO (0.0313256) 2h-BTLR2LKO (0.129978) 4h-ATLR2LWT (0.0264001) 4h-BTLR2LWT (0.0659215) 0h-ATLR2LWT (0.143573) 0h-BTLR2LWT (0.0131259) 2h-ATLR2LWT (0.129836) 2h-BTLR2LWT (0.153027) 4h-ATLR2L (0.00930083) 4h-B (0.0896984) [ min ] [ medium ] [ max ] CEM 1 Dscr3 781.4 1164.7 1395.2 P ( S | Z, I ) = 1.00 Vps26a 1609.8 2396.5 2811.2 Mean Corr = 0.55938 Snx8 449.3 545.4 848.3 Vps26b 242.3 429.7 557.2 Tbc1d5 88.1 211.5 321.3 Hsdl1 1476.4 1890.0 2339.8 Slc36a1 132.7 191.4 255.7 Fam50a 1207.5 1355.9 1802.8 Flcn 864.9 1139.4 1902.8 Ostm1 881.8 1088.1 1532.0 CEM 1 + Hmgcl 576.3 834.5 980.7 Top 10 Genes Amdhd2 230.2 431.0 751.6 Appl2 373.4 545.1 733.4 Hexa 2180.8 2685.3 3911.4 Wdr81 974.8 1127.1 1271.8

Null module GEO Series "GSE32328" 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=GSE32328 Status: Public on Sep 23 2011 Title: Macrophage response to serum in culture medium Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Most cell culture experiments utilize media containing fetal calf serum. Results are often interpreted regarding importance to human pathways. We studied gene expression in mouse macrophages grown in the absence of serum, and in fetal calf serum, mouse serum, and human serum using genome wide expression systems in resting conditions and after stimulation with lipopolysaccharide.

Overall design: We cultured mouse bone marrow derived macrophages in media containing no serum, or 5% fetal calf, or mouse or human serum. The experiment was performed in conditions without or with stimulation by LPS. We harvested the cells at 4 hours after stimulation and analyzed whole genome mRNA expression by microarray as a proxy for transcriptional responses. Three replicate experiments were performed.

Background corr dist: KL-Divergence = 0.0879, L1-Distance = 0.0267, L2-Distance = 0.0009, Normal std = 0.4698

0.856 Kernel fit Pairwise Correlations Normal fit

Density 0.428

0.000 CEM 1

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

Pre-normalization Quantiles

Human MouseLPS G (0.050722)LPSCalf GLPS (0.0224836)No G Serum (0.0296764)Human LPS MouseControlG (0.0432616) ControlCalf G (0.0280148) Control NoG (0.0440339) Serum G (0.0942172)Mouse Control ControlHuman G (0.0719017) CalfControlH (0.0145179) ControlNo H (0.0369513)Serum H (0.0619945)Mouse Control LPSHuman H H (0.0778044) (0.0395415) CalfLPS LPSH (0.0283755)No H Serum(0.0335165)Calf LPS LPS NoH I (0.0391558) (0.0340983)SerumHuman LPS MouseLPSI (0.0446895) I (0.0582947) LPSNo Serum I (0.024245)Calf Control ControlHuman I (0.0222817)I (0.0521106) MouseControl Control I (0.026395) I (0.0217167) [ min ] [ medium ] [ max ] CEM 1 Dscr3 539.6 1466.4 1993.5 P ( S | Z, I ) = 1.00 Vps26a 3035.2 3772.6 4514.5 Mean Corr = 0.51688 Snx8 735.2 2187.5 3358.3 Vps26b 572.2 1860.3 3049.7 Tbc1d5 15.3 20.7 27.7 Hsdl1 1014.5 1568.6 2638.5 Slc36a1 158.2 270.2 644.0 Fam50a 2107.7 3612.0 4955.1 Flcn 95.1 275.8 444.9 Ostm1 2407.3 4234.7 6106.7 CEM 1 + Hmgcl 255.7 661.3 1067.9 Top 10 Genes Amdhd2 2302.3 2827.8 4044.2 Appl2 358.1 674.6 1347.4 Hexa 20357.3 22356.2 25132.1 Wdr81 105.1 376.2 552.7

Null module GEO Series "GSE42877" 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=GSE42877 Status: Public on Dec 13 2012 Title: Expression data from mice peritoneal cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Sodium methyldithiocarbamate (SMD) is one of the most abundantly used conventional pesticides in the U.S. At dosages relevant to occupational exposure, it causes major effects on the immune system in mice, including a decreased resistance to sepsis. This lab has identified some of the mechanisms of action of this compound and some of the immunological parameters affected, but the global effects have not previously been assessed.

We used microarrays to analyze the effect of SMD on lipopolysaccharide-induced mediators important in innate immunity and inflammation and reveal a broad effect on expression of transcription factors involved in Toll-like Receptors 4 (TLR4) signaling.

Overall design: Female (C57Bl/6 x C3H F1) mice at 12-16 weeks old were housed in filter top shoebox cages with 5 mice per cage in a temperature (70-78´F) and humidity (40-60%) controlled environment. Then the mice were anesthetized with halothane and 50 ´l of SMD solution was placed on the nares. SMD was administered by inhalation at (1) 100 mg/kg, (2) 200 mg/kg or (3) 300 mg/kg. 30 minutes after administering SMD the mice were challenged with ultra pure LPS from Salmonella minnesota at 60 ´g/mouse (in PBS) intravenously in a tail vein.

Background corr dist: KL-Divergence = 0.1419, L1-Distance = 0.0366, L2-Distance = 0.0025, Normal std = 0.3931

1.020 Kernel fit Pairwise Correlations Normal fit

Density 0.510

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

LPS, biologicalLPS, biologicalLPS, rep1 biological(0.0686409)LPS+SMD rep2 (0.0482042)LPS+SMD rep3 at 100mg/kg,(0.0516396)LPS+SMD at 100mg/kg,LPS+SMD biological at 100mg/kg,LPS+SMD biological at rep1 200mg/kg,LPS+SMD biological(0.0508578) at rep2 200mg/kg,LPS+SMD biological(0.0408492) at rep3 200mg/kg,LPS+SMD biological(0.0329444) at rep1 300mg/kg,LPS+SMD biological(0.0312076) at rep2 300mg/kg,NaÃ¯ve, biological(0.0282528) at rep3 300mg/kg,NaÃ¯ve, rep1 biological(0.0440196) rep1 (0.266289) rep2 biological(0.0127247) rep2 (0.261273) (0.0538332) rep3 (0.0092643)[ min ] [ medium ] [ max ] CEM 1 Dscr3 641.9 1111.1 2541.6 P ( S | Z, I ) = 1.00 Vps26a 1917.0 2510.6 3032.1 Mean Corr = 0.57516 Snx8 176.5 332.4 1048.6 Vps26b 184.5 247.8 523.3 Tbc1d5 42.6 127.9 347.7 Hsdl1 1014.7 1453.8 2089.0 Slc36a1 95.6 205.2 573.7 Fam50a 855.7 1551.3 2223.4 Flcn 283.6 627.1 1355.5 Ostm1 1181.7 3372.9 4412.5 CEM 1 + Hmgcl 278.3 415.2 947.8 Top 10 Genes Amdhd2 10.2 111.2 253.2 Appl2 436.3 1243.0 4045.3 Hexa 10042.7 13299.0 18303.4 Wdr81 225.7 376.5 609.3

Null module GEO Series "GSE14769" 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=GSE14769 Status: Public on Mar 27 2009 Title: Time course of bone marrow-derived macrophages simulated with LPS Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19270711 Summary & Design: Summary: The innate immune system is a two-edged sword; it is absolutely required for host defense against infection, but if left uncontrolled can trigger a plethora of inflammatory diseases. Here we used systems biology approaches to predict and validate a gene regulatory network involving a dynamic interplay between the transcription factors NF-ÎºB, C/EBPÎ´, and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of Il6 and Cebpd genes and experimentally validated the prediction that the combination of an initiator (NF-ÎºB), an amplifier (C/EBPÎ´) and an attenuator (ATF3) forms a regulatory circuit that discriminates between transient and persistent Toll-like receptor 4-induced signals. Our results suggest a mechanism that enables the innate immune system to detect the duration of infection and to respond appropriately.

Overall design: Bone marrow-derived macrophages stimulated with LPS for 0, 20, 40, 60, 80, 120, 240 and 360 minutes.

Background corr dist: KL-Divergence = 0.0950, L1-Distance = 0.0642, L2-Distance = 0.0069, Normal std = 0.4890

0.914 Kernel fit Pairwise Correlations Normal fit

Density 0.457

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

LPS1-0 LPS1-120(0.0270198)LPS1-20 (0.015196)LPS1-40 (0.0202012)LPS1-60 (0.0232838)LPS1-80 (0.0130694)LPS2-0 (0.0167401) LPS2-20(0.0330264)LPS2-40 (0.04322)LPS2-60 (0.035605)LPS2-80 (0.00589946)LPS2-120 (0.0256353)LPS3-0 (0.0153093) LPS3-20(0.0344336)LPS3-40 (0.0345923)LPS3-60 (0.0208162)LPS3-80 (0.0117548)LPS3-120 (0.00747007)C57_A_LPS_240_min (0.0132431)C57_LPS_B_240_minC57_A_LPS_360_min (0.110187)C57_B_LPS-360 (0.105878)C57_LPS_C_240min (0.0814254)WT_LPS_240_min (0.0846386) (0.0625306) (0.158824) [ min ] [ medium ] [ max ] CEM 1 Dscr3 637.3 2005.5 2459.9 P ( S | Z, I ) = 1.00 Vps26a 3011.5 4726.3 5218.1 Mean Corr = 0.42317 Snx8 936.8 3917.8 4565.7 Vps26b 204.2 718.4 792.2 Tbc1d5 83.2 115.5 164.5 Hsdl1 754.8 1571.5 1869.1 Slc36a1 165.8 489.0 701.5 Fam50a 914.3 1755.1 2022.5 Flcn 192.7 1430.8 2364.3 Ostm1 802.4 2027.8 2385.3 CEM 1 + Hmgcl 1072.2 2703.8 3423.7 Top 10 Genes Amdhd2 847.7 1546.2 1760.2 Appl2 363.2 2473.4 3200.0 Hexa 13023.9 19304.5 21663.3 Wdr81 452.3 1566.2 2000.7

Null module GEO Series "GSE11723" 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=GSE11723 Status: Public on Jun 02 2009 Title: Role of Notch signaling on hematopoietic stem cell differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18786418 Summary & Design: Summary: Although Notch signaling has been clearly implicated in lymphoid differentiation, its role in myeloid lineages differentiation is unclear.

Expression data from hematopoietic stem cells plated on OP9 stroma expressing or not the Notch ligand Delta-like1. Results provide insight into the role of Notch signalling in megakaryocyte fate specification.

Keywords: Gene expression array-based (RNA / in situ oligonucleotide)

Overall design: LSK cells were co-cultured for 3 days on OP9, OP9-DL1 and OP9-DL1+CompoundE (gamma-secretase inhibitor) and expression analysis was performed.

Background corr dist: KL-Divergence = 0.0364, L1-Distance = 0.0225, L2-Distance = 0.0005, Normal std = 0.6430

0.637 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

LSK_OP9-GFP_Rep1LSK_OP9-GFP_Rep2LSK_OP9-GFP_Rep3 (0.0461343)LSK_OP9-DL1_Rep1 (0.0190391)LSK_OP9-DL1_Rep2 (0.0243802)LSK_OP9-DL1_Rep3 (0.168645)LSK_OP9-DL1+CompoundE_Rep1 (0.156935)LSK_OP9-DL1+CompoundE_Rep2 (0.131235)LSK_OP9-DL1+CompoundE_Rep3 (0.125786) (0.201726)[ min (0.126119) ] [ medium ] [ max ] CEM 1 Dscr3 272.2 589.1 787.3 P ( S | Z, I ) = 1.00 Vps26a 6154.5 7621.3 8473.8 Mean Corr = 0.34669 Snx8 1226.8 2627.3 3055.3 Vps26b 312.2 369.1 450.7 Tbc1d5 70.3 176.2 233.6 Hsdl1 1451.7 1612.8 1717.6 Slc36a1 380.0 602.4 694.7 Fam50a 883.7 1290.8 1579.1 Flcn 509.0 566.9 1030.8 Ostm1 7503.4 7980.6 8631.0 CEM 1 + Hmgcl 828.8 1337.1 1910.3 Top 10 Genes Amdhd2 708.4 1322.1 1915.8 Appl2 645.4 1073.6 1320.0 Hexa 4814.7 7837.9 9537.7 Wdr81 269.9 480.7 720.7

Null module GEO Series "GSE9123" 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=GSE9123 Status: Public on Sep 22 2007 Title: transcription factor PlagL2 regulates steps in chylomicron metabolism Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17983586 Summary & Design: Summary: Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. We report that the transcription factor Pleomorphic adenoma gene-like 2 (PLAGL2) is essential for this aspect of dietary lipid metabolism. PlagL2-/- mice die from post-natal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates essential and poorly understood aspects of dietary lipid absorption and its deficiency represents an authentic animal model with implications for amelioration of obesity or the metabolic syndrome.

Keywords: gene expression profiling analysis

Overall design: Total RNA was extracted from 4 knockout and 4 wild-type mouse small intestines at 18.5 dpc using the Macherey-Nagel Nucleospin kit. cRNA synthesis and labeling, hybridization to Affymetrix (Santa Clara, CA) MOE430 2.0 expression arrays, and data acquisition occurred on the Affymetrix GeneChip Instrument System.

Background corr dist: KL-Divergence = 0.0699, L1-Distance = 0.0190, L2-Distance = 0.0005, Normal std = 0.5060

0.788 Kernel fit Pairwise Correlations Normal fit

Density 0.394

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

PlagL2WT1PlagL2WT2 (0.170267)PlagL2WT3 (0.110834)PlagL2WT4 (0.0434317)PlagL2KO1 (0.17312)PlagL2KO2 (0.115277)PlagL2KO3 (0.0955868)PlagL2KO4 (0.1735) (0.117983) [ min ] [ medium ] [ max ] CEM 1 Dscr3 1421.2 2050.7 2398.4 P ( S | Z, I ) = 1.00 Vps26a 2237.2 3465.7 3810.0 Mean Corr = 0.26152 Snx8 505.1 1913.1 2913.5 Vps26b 702.7 1100.3 1786.2 Tbc1d5 103.7 150.5 251.0 Hsdl1 528.5 826.1 1067.0 Slc36a1 505.3 749.3 916.5 Fam50a 826.0 1087.2 1234.3 Flcn 745.7 1207.4 1612.4 Ostm1 464.8 685.6 960.0 CEM 1 + Hmgcl 2756.3 4612.1 5051.4 Top 10 Genes Amdhd2 672.3 1338.4 2405.1 Appl2 1769.0 2241.9 2910.4 Hexa 3853.4 8655.6 12625.1 Wdr81 501.9 893.2 1010.2

Null module GEO Series "GSE17647" 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=GSE17647 Status: Public on Aug 15 2009 Title: Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19574449 Summary & Design: Summary: High-density lipoproteins (HDLs) protect pancreatic Î² cells against apoptosis. This property might be related to the increased risk to develop diabetes in patients with low HDL blood levels. However, the mechanisms by which HDLs protect Î² cells are poorly characterized. Here we use a transcriptomic approach to identify genes differentially modulated by HDLs in Î² cells subjected to apoptotic stimuli.

Overall design: Starvation medium + HDL (prep. HDL GSK3 or HDL GSK4) [HDL.S]

Background corr dist: KL-Divergence = 0.3267, L1-Distance = 0.0543, L2-Distance = 0.0075, Normal std = 0.2719

1.467 Kernel fit Pairwise Correlations Normal fit

Density 0.734

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

V_GSK3.CM.replicate1V_GSK3.CM.replicate2V_GSK3.CM.replicate3HDL_GSK3.CM.replicate1 (0.0611299)HDL_GSK3.CM.replicate2 (0.0615119)HDL_GSK3.CM.replicate3 (0.0491851)V_GSK3.Starved.replicate1 (0.0380812)V_GSK3.Starved.replicate2 (0.0328027)V_GSK3.Starved.replicate3 (0.0596019)HDL_GSK3.Starved.replicate1 (0.0669583)HDL_GSK3.Starved.replicate2 (0.0634517)HDL_GSK3.Starved.replicate3 (0.06468)V_GSK4.CM.replicate1V_GSK4.CM.replicate2 (0.0497486)V_GSK4.CM.replicate3 (0.0380374)HDL_GSK4.CM.replicate1 (0.0249273)(0.0304987)HDL_GSK4.CM.replicate2 (0.042311)HDL_GSK4.CM.replicate3 (0.0420526)V_GSK4.Starved.replicate1 (0.0678147)V_GSK4.Starved.replicate2 (0.0179534)V_GSK4.Starved.replicate3 (0.0089555)HDL_GSK4.Starved.replicate1 (0.0156759)HDL_GSK4.Starved.replicate2 (0.0656041)HDL_GSK4.Starved.replicate3 (0.0246298) (0.0189194) (0.0205148)[ (0.0349543) min ] [ medium ] [ max ] CEM 1 Dscr3 1339.0 1627.0 2014.7 P ( S | Z, I ) = 1.00 Vps26a 1888.6 2401.5 2909.2 Mean Corr = 0.26092 Snx8 991.5 1244.9 1510.3 Vps26b 880.9 1090.3 1329.5 Tbc1d5 8.7 47.7 89.4 Hsdl1 1266.1 1579.9 2024.0 Slc36a1 552.4 743.4 885.6 Fam50a 1276.2 1600.9 2054.2 Flcn 337.4 740.2 979.9 Ostm1 1746.2 2232.1 2580.7 CEM 1 + Hmgcl 956.9 1335.5 1804.4 Top 10 Genes Amdhd2 222.4 311.8 467.4 Appl2 816.4 1008.7 1279.4 Hexa 4734.4 5758.9 6606.5 Wdr81 1029.1 1234.9 1541.0

Null module GEO Series "GSE20987" 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=GSE20987 Status: Public on May 10 2010 Title: Gene expression data of BCR-ABL1 transformed B cell precursors from BCL6 wild-type and BCL6 knockout mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21911423 Summary & Design: Summary: To elucidate the mechanism of BCL6-mediated pre-B cell survival signaling, we investigated the gene expression pattern in BCR-ABL1-transformed BCL6+/+ and BCL6-/- B cell precursors. Pharmacological inhibition of BCR-ABL1 was performed with the BCR-ABL1 kinase inhibitor STI571 (Imatinib).

Overall design: BCR-ABL1 transformed B cell precursors of BCL6 wildtype and BCL6 knockout mice were either treated with 10´M STI571 (Imatinib) for 16 hours or cultured in absence of STI571. Three samples for each condition were processed.

Background corr dist: KL-Divergence = 0.0587, L1-Distance = 0.0336, L2-Distance = 0.0015, Normal std = 0.5553

0.748 Kernel fit Pairwise Correlations Normal fit

Density 0.374

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

Bcl6 +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed B +/+cellBcl6 BCR-ABL1-transformed precursors B +/+cellBcl6 BCR-ABL1-transformed precursors B -/-cell - untreatedBcl6BCR-ABL1-transformed precursors B -/-cell - untreatedBcl6BCR-ABL1-transformed precursors 1B (0.0508331) -/-cell - untreatedBcl6BCR-ABL1-transformed precursors 2B (0.0767887) -/-cell - STI571Bcl6BCR-ABL1-transformed precursors B3 cell(0.0510878) -/- - treatedSTI571Bcl6BCR-ABL1-transformed precursors B cell -/- - treatedSTI5711BCR-ABL1-transformed precursors (0.148878)B cell - untreated treated2 precursors (0.105457)B cell - untreated 3 precursors 1(0.111125)B (0.078713) cell - untreated[ precursors 2B min(0.0440715) cell - STI571 precursors 3 (0.0720291) ]- treatedSTI571 - treatedSTI5711 (0.184213)[ mediumtreated2 (0.0483394) 3 (0.0284632) ] [ max ] CEM 1 Dscr3 1230.9 2059.5 3231.4 P ( S | Z, I ) = 1.00 Vps26a 1365.0 2226.5 2952.1 Mean Corr = 0.50181 Snx8 1023.5 1426.9 1829.4 Vps26b 258.2 380.3 489.1 Tbc1d5 91.3 120.8 142.0 Hsdl1 1023.3 1156.7 1541.5 Slc36a1 182.3 313.6 391.4 Fam50a 1038.5 1570.5 2441.4 Flcn 1004.4 1625.7 1818.4 Ostm1 1098.3 1873.3 2934.8 CEM 1 + Hmgcl 991.6 1542.7 1924.9 Top 10 Genes Amdhd2 592.9 681.7 994.8 Appl2 212.8 428.4 752.2 Hexa 61.9 107.3 169.0 Wdr81 638.3 1373.2 1735.6

Null module GEO Series "GSE46854" 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=GSE46854 Status: Public on Aug 04 2013 Title: Induction of the mouse germ cell fate by transcription factors in vitro [exp2] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23913270 Summary & Design: Summary: The germ cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have established a culture system that recapitulates the mouse germ-cell specification pathway: Using cytokines, embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) are induced into epiblast-like cells (EpiLCs) and then into primordial germ cell-like cells (PGCLCs) with capacity both for spermatogenesis and oogenesis, creating an opportunity for understanding and regulating mammalian germ cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous over-expression of three transcription factors (TFs), Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2Î³), directs EpiLCs, but not ESCs, swiftly and highly efficiently into a PGC state with endogenous transcription circuitry. The induction of the PGC state on EpiLCs minimally requires Prdm14 but not Blimp1 or Tfap2c. The TF-induced PGC state reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC specification in vivo and in vitro by cytokines including BMP4. Importantly, the TF-induced PGC-like cells robustly contribute to spermatogenesis and fertile offspring. Our findings provide not only a novel insight into the transcriptional logic that creates a germ cell state, but also a foundation for the TF-based reconstitution and regulation of mammalian gametogenesis.

Overall design: Aim of this analysis is identification of genes whose expression was altered by each of key transcription factor for transcription factor-induced primordial germ cells (TF-PGCLCs) induction (Blimp1 (B), Prdm14 (P14), and Tfap2c (A)). Both of epiblast-like cells (EpiLCs) (Hayashi et al., 2011, Cell) and aggregates of EpiLCs cultured with doxycycline on day 1 were harvested for 5 cell lines, including BP14A (Clone #3-3), B (#2-4), P14 (#7-109), A (#8-2), and the parental clone (BVSCR26rtTA embryonic stem cells). Total RNA was isolated and analyzed. Two biological duplicates for each cell type were included.

Background corr dist: KL-Divergence = 0.1480, L1-Distance = 0.0511, L2-Distance = 0.0045, Normal std = 0.3974

1.068 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

EpiLCs,EpiLCs, ParentalEpiLCs, BP14A clone,EpiLCs, (cloneB 36H, (clone rep1 EpiLCs,#3-3), P14 #2-4), (0.0287604) (clone 36H,Parental A36H, (clone rep1 #7-109), rep1BP14A clone(0.0253812) #8-2), (0.0232004) 36H, (cloneB+Doxycycline, 36H, (clone rep1 rep1 #3-3)P14 (0.0232437) #2-4) (0.0391343) (clone+Doxycycline, +Doxycycline,day1,A (clone #7-109) rep1EpiLCs, #8-2) (0.0152009) +Doxycycline,day1, day1,+Doxycycline,EpiLCs, Parental rep1 rep1EpiLCs, (0.106544)BP14A clone,(0.0588865) day1, day1,EpiLCs, (cloneB 36H, rep1 (clone rep1 rep2 (0.0528128)EpiLCs,#3-3), P14 #2-4),(0.00865875) (0.0372902) (clone 36H,Parental A36H, (clone rep2 #7-109), rep2BP14A clone(0.0384414) #8-2), (0.0396629) 36H, (cloneB+Doxycycline, 36H, (clone rep2 rep2 #3-3)P14 (0.0292798) #2-4) (0.0381667) (clone+Doxycycline, +Doxycycline,day1,A (clone #7-109) rep2 #8-2) (0.0139787) +Doxycycline,day1, day1,+Doxycycline, rep2 rep2 (0.234261) (0.0939368) day1, day1,[ rep2min rep2 (0.0494472) (0.0437121) ] [ medium ] [ max ] CEM 1 Dscr3 781.3 1438.8 2084.6 P ( S | Z, I ) = 1.00 Vps26a 1198.1 2150.7 3308.0 Mean Corr = 0.20825 Snx8 596.6 835.1 1031.8 Vps26b 420.4 561.0 622.1 Tbc1d5 23.8 41.5 116.6 Hsdl1 221.4 409.0 742.1 Slc36a1 113.1 176.4 223.9 Fam50a 1479.2 1932.0 2388.3 Flcn 586.3 1753.3 2265.4 Ostm1 306.7 503.9 622.1 CEM 1 + Hmgcl 803.8 906.2 1021.1 Top 10 Genes Amdhd2 356.2 692.6 1374.1 Appl2 190.1 269.8 306.9 Hexa 787.2 3410.8 6435.1 Wdr81 395.2 580.3 803.9

Null module GEO Series "GSE30176" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30176 Status: Public on Jul 19 2011 Title: Retinoic acid (RA) induction time-course to profile gene expression during mES cell differentiation. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21764852 Summary & Design: Summary: Murine ES cell gene expression before RA induction are used to compare gene expression for time-points of 2, 4, 6hrs post-induction.

Overall design: KH2 ES Cell RA Differentiation Time-course

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

0.814 Kernel fit Pairwise Correlations Normal fit

Density 0.407

0.000 CEM 1

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

Pre-normalization Quantiles

WT-A (0.079897)WT-B (0.123668)WT-C (0.0425366)2HR-A (0.0598038)2HR-B (0.124129)2HR-C (0.0908088)4HR-A (0.0600046)4HR-B (0.0536044)4HR-C (0.0357109)6HR-A (0.135276)6HR-B (0.138116)6HR-C (0.056446) [ min ] [ medium ] [ max ] CEM 1 Dscr3 1013.9 1428.2 1668.4 P ( S | Z, I ) = 1.00 Vps26a 1920.0 2416.9 2707.7 Mean Corr = 0.20374 Snx8 787.7 1135.5 1220.6 Vps26b 701.0 770.6 853.5 Tbc1d5 31.1 70.0 94.8 Hsdl1 817.4 1011.0 1145.0 Slc36a1 213.2 270.1 304.4 Fam50a 1265.9 1445.7 1615.2 Flcn 642.3 717.9 909.8 Ostm1 745.4 873.7 1117.7 CEM 1 + Hmgcl 758.1 935.1 1038.8 Top 10 Genes Amdhd2 617.7 673.9 776.7 Appl2 730.2 836.1 1078.9 Hexa 1633.1 2960.4 3953.5 Wdr81 664.9 721.4 772.6

Null module GEO Series "GSE46185" 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=GSE46185 Status: Public on Apr 19 2013 Title: Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell identity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23824597 Summary & Design: Summary: Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.

Overall design: Mock-transfected and GATA3 siRNA-transfected Th2 and Th2-4th cells are profiled for mRNA expression

Background corr dist: KL-Divergence = 0.0332, L1-Distance = 0.0373, L2-Distance = 0.0018, Normal std = 0.6839

0.604 Kernel fit Pairwise Correlations Normal fit

Density 0.302

0.000 CEM 1

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

Pre-normalization Quantiles

Th2 (controlTh2 (control siRNA)Th2 (Gata3 siRNA)(0.154395)Th2-4th siRNA) a-TCRTh2-4th (control a-TCR stimTh2-4th (control siRNA)(0.0539588) stim (Gata3(0.10719) siRNA)(0.49278) siRNA) a-TCR a-TCR stim (0.123418) stim[ min (0.068258) ] [ medium ] [ max ] CEM 1 Dscr3 459.5 639.2 2247.8 P ( S | Z, I ) = 0.98 Vps26a 598.3 718.3 1598.5 Mean Corr = 0.27456 Snx8 203.5 288.9 333.8 Vps26b 397.4 559.0 1124.4 Tbc1d5 175.1 234.4 478.1 Hsdl1 260.8 459.5 1098.8 Slc36a1 231.3 394.3 734.0 Fam50a 620.7 772.0 1502.4 Flcn 275.9 327.7 720.0 Ostm1 865.8 1423.1 2324.7 CEM 1 + Hmgcl 460.9 538.8 1419.5 Top 10 Genes Amdhd2 195.4 435.9 1537.8 Appl2 97.7 256.9 1175.7 Hexa 918.1 1722.9 4592.3 Wdr81 496.5 807.3 1189.8

Null module GEO Series "GSE30855" 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=GSE30855 Status: Public on Sep 01 2011 Title: Establishment of Enhancer Repertoires that Orchestrate the Myeloid and Lymphoid Cell Fates (gene expression dataset 1) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21903424 Summary & Design: Summary: Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are pre-marked by H3K4me1 in multipotent progenitors. However, H3K4me1 levels at a subset of enhancers are elevated during developmental progression, resulting in evolving enhancer repertoires that we propose orchestrate the myeloid and B cell fates.

Overall design: To characterize Id2-HPCs, we performed microarray analysis using RNA derived from cultured E2A-deficient cells, EBF-deficient cells and Id2-HPCs. Id2-HPC cells were cultured in IMDM medium supplemented with 10% FCS/2% PSG/Î²-me and IL7, Flt3-ligand, and SCF cytokines on S17 feeder cells in a humidified incubator at 37 degrees C with 5% CO2. Id2-HPC expanded cells were depleted of small (<1-5%) numbers of CD19-, CD25- and CD11b-positive cells by auto-MACS. E2A -/- and EBF -/- cells were cultured in IMDM supplemented with 10% FCS/2% PSG/Î²-me on S17 feeder cells in the presence of IL-7, Flt3-ligand, and SCF cytokines in a humidified incubator at 37 degree C with 5% CO2.

Background corr dist: KL-Divergence = 0.0252, L1-Distance = 0.0216, L2-Distance = 0.0004, Normal std = 0.7208

0.568 Kernel fit Pairwise Correlations Normal fit

Density 0.284

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

UninducedUninduced Id2-HPC,Cultured Id2-HPC, biologicalCultured E2A-deficient, biologicalCultured replicateE2A-deficient,Cultured replicatebiologicalEBF-deficient, 1 (0.14042) biologicalEBF-deficient, 2 replicate(0.288674) biological replicate 1 (0.232284) biological replicate 2 [(0.224332) min replicate 1 (0.024287) ] 2 (0.0900036)[ medium ] [ max ] CEM 1 Dscr3 1109.9 1555.8 1650.2 P ( S | Z, I ) = 0.98 Vps26a 1993.1 2245.4 3301.2 Mean Corr = 0.23903 Snx8 319.0 439.8 763.4 Vps26b 1524.4 1678.6 1973.5 Tbc1d5 78.9 174.5 458.9 Hsdl1 1026.5 1182.3 1284.6 Slc36a1 302.3 408.5 417.5 Fam50a 670.0 773.8 843.9 Flcn 1373.8 1894.1 2693.6 Ostm1 2115.7 2334.6 2611.1 CEM 1 + Hmgcl 1223.5 1745.6 1905.7 Top 10 Genes Amdhd2 759.7 865.3 959.9 Appl2 925.4 1090.1 2359.6 Hexa 2873.1 5282.8 8552.5 Wdr81 446.3 665.5 815.1

Null module GEO Series "GSE37907" 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=GSE37907 Status: Public on May 11 2012 Title: Expression data from murine hematopoietic cells expressing BCR-ABL alone, NUP98-HOXA9 alone, BCR-ABL and NUP98-HOXA9, or null for both oncogenes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22863534 Summary & Design: Summary: Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown.

Using a genetically defined mouse model of acute leuekmia, we investigated the regulated of genes downstream of the cooperative oncogenic interaction between BCR-ABL and NUP98-HOXA9 and identified a unique gene signature abberrantly expression in leukemia.

Overall design: Total RNA was isolated from hematopoietic cells transduced with BCR-ABL and Nup98-HOXA9 retroviruses and transplanted into recipient mice. Bone marrow cells were purified by GFP (BCR-ABL) and YFP (NUP98-HOXA9) using FACS.

Background corr dist: KL-Divergence = 0.1944, L1-Distance = 0.0342, L2-Distance = 0.0020, Normal std = 0.3407

1.171 Kernel fit Pairwise Correlations Normal fit

Density 0.586

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

BCR-ABLBCR-ABL neg, BCR-ABLNUP98-HOXA9 neg, BCR-ABLNUP98-HOXA9 neg, BCR-ABL NUP98-HOXA9neg neg, replicate BCR-ABL NUP98-HOXA9neg neg, replicate 1 BCR-ABL+ NUP98-HOXA9 neg(0.0352831) neg, replicate 2 BCR-ABL+ NUP98-HOXA9 neg(0.0163769) replicate replicate 3BCR-ABL+ neg(0.101219) replicate replicate 1 4 BCR-ABL+ (0.0218526) neg(0.0776663) replicate replicate 2 5 BCR-ABL+(0.144807) (0.0637394) replicate 3 6 BCR-ABL+(0.0148704) (0.024042) replicate 4 NUP98-HOXA9+(0.03287) replicate 5 NUP98-HOXA9+(0.0159184) 6 NUP98-HOXA9+(0.04219) replicateNUP98-HOXA9+ replicate 1 (0.0530217)NUP98-HOXA9+ replicate 2 (0.0575759)NUP98-HOXA9+ replicate 3 (0.0416632)BCR-ABL+, replicate 4 (0.0286701)BCR-ABL+, replicate 5 NUP98-HOXA9+ (0.0387109)BCR-ABL+, 6 NUP98-HOXA9+ (0.0488887)BCR-ABL+, NUP98-HOXA9+ replicateBCR-ABL+, NUP98-HOXA9+ replicate BCR-ABL+,1 (0.0239729) NUP98-HOXA9+ replicate 2 (0.0451632) NUP98-HOXA9+ replicate 3 (0.00906772) replicate 4 (0.0181621) replicate [5 (0.0280605)min 6 (0.0162084) ] [ medium ] [ max ] CEM 1 Dscr3 636.4 1085.2 1417.4 P ( S | Z, I ) = 0.96 Vps26a 3226.0 3755.0 4099.9 Mean Corr = 0.52223 Snx8 1154.9 1571.3 2116.8 Vps26b 720.8 935.9 1181.5 Tbc1d5 47.5 97.6 163.9 Hsdl1 1369.2 1797.8 2111.2 Slc36a1 263.8 505.9 722.8 Fam50a 1365.8 1720.0 1943.8 Flcn 362.5 452.4 546.5 Ostm1 3488.9 3909.4 4454.7 CEM 1 + Hmgcl 841.4 993.2 1293.0 Top 10 Genes Amdhd2 1307.8 1693.2 2025.2 Appl2 403.7 538.0 709.5 Hexa 3500.0 4943.1 5951.6 Wdr81 485.5 632.5 758.1

Null module GEO Series "GSE36414" 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=GSE36414 Status: Public on Mar 08 2013 Title: Gene expression changes induced in the stromal cell line EL08-1D2 by co-culture with leukemic B cells (CLL) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23328482 Summary & Design: Summary: Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-Î²II and the subsequent activation of NF-ÎºB in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC-Î² knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-Î²II- NF-ÎºB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-Î²II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.

We used microarrays to determine gene expression changes induced by co-culturing with leukemic B-cells (CLL) in EL08-1D2 cells.

Overall design: We compared EL08-1D2 cells co-cultured for 5 days with leukemic B-cells to EL08-1D2 mono-cultured cells by microarray analysis on Affymetrix MG-430_2.0 arrays.

Background corr dist: KL-Divergence = 0.0805, L1-Distance = 0.0211, L2-Distance = 0.0007, Normal std = 0.4750

0.840 Kernel fit Pairwise Correlations Normal fit

Density 0.420

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

EL08-1D2EL08-1D2 rep1 EL08/V128(0.200121) rep2 EL08/V131(0.314376) (0.0249415)EL08/V190 (0.114449)EL08/V172 (0.076431)EL08/V163 (0.0855983)EL08/V211 (0.0269549) (0.157128) [ min ] [ medium ] [ max ] CEM 1 Dscr3 1634.9 1893.7 2415.0 P ( S | Z, I ) = 0.95 Vps26a 2278.7 2627.7 3356.0 Mean Corr = 0.56717 Snx8 580.0 653.1 946.7 Vps26b 801.9 944.7 1156.7 Tbc1d5 93.9 145.1 166.9 Hsdl1 526.5 660.5 831.1 Slc36a1 400.0 466.8 547.5 Fam50a 1977.5 2354.7 2781.7 Flcn 441.6 633.9 891.3 Ostm1 1680.2 1835.9 2199.7 CEM 1 + Hmgcl 411.9 557.4 617.2 Top 10 Genes Amdhd2 685.4 889.5 1406.5 Appl2 3167.7 4371.2 5833.5 Hexa 7707.8 9185.4 11932.5 Wdr81 797.4 1109.4 1332.9

Null module GEO Series "GSE55809" 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=GSE55809 Status: Public on Mar 12 2014 Title: Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines. The finding is confirmed in 2 human epithelial cell lines, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium. NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine.

Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis.

Overall design: Cells from mouse epithelial cell line CT26 were cultured either alone, or with RAW macrophages in a system which allowed no physical contact but exchange of soluble factors between the cell types. The experiment was peformed twice.

Background corr dist: KL-Divergence = 0.0280, L1-Distance = 0.0347, L2-Distance = 0.0014, Normal std = 0.7125

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

CT26_cells_alone_rep1CT26_macrophage_coculture_rep1RAW_macrophage_alone_rep1RAW_macrophage_CT26_coculture_rep1 (0.0911147)CT26_cells_alone_rep2CT26_macrophage_coculture_rep2 (0.133301)RAW_macrophage_alone_rep2 (0.0680565)RAW_macrophage_CT26_coculture_rep2 (0.0895079) (0.206721) (0.179094) (0.0806653)[ min ](0.15154) [ medium ] [ max ] CEM 1 Dscr3 1107.6 1410.0 1676.2 P ( S | Z, I ) = 0.95 Vps26a 2280.5 3416.5 3545.8 Mean Corr = 0.69105 Snx8 585.7 977.3 1391.1 Vps26b 538.6 714.2 845.3 Tbc1d5 65.7 142.4 173.4 Hsdl1 675.1 770.3 883.9 Slc36a1 183.1 277.3 496.4 Fam50a 958.9 1063.8 1318.8 Flcn 405.5 532.6 636.9 Ostm1 1010.7 1317.8 1698.8 CEM 1 + Hmgcl 638.8 2378.0 3479.8 Top 10 Genes Amdhd2 346.1 505.0 925.9 Appl2 187.9 563.4 703.3 Hexa 1948.9 5705.2 9225.8 Wdr81 350.8 516.3 748.9

Null module GEO Series "GSE14891" 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=GSE14891 Status: Public on Feb 19 2009 Title: Expression data of LPS-stimulated macrophages from wild-type and Zc3h12a-/- mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19322177 Summary & Design: Summary: Lipopolysaccharide (LPS), a Toll-like receptor (TLR) 4 ligand, induces the expression of various genes including proinflammatory cytokines, and the expression is modified by the presence of Zc3h12a.

We used microarrays to examine influence of Zc3h12a deficiency in LPS-inducible gene expression.

Keywords: Time course after LPS (100 ng/ml) stimulation

Overall design: Peritoneal macrophages from wild-type and Zc3h12a-/- mice were stimulated with LPS for 0, 1, 2 and 4 hours, followed by RNA extraction. Then hybridization on affymetrix microarrays was performed.

Background corr dist: KL-Divergence = 0.0555, L1-Distance = 0.0263, L2-Distance = 0.0011, Normal std = 0.5497

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWild-type macrophagesWild-type macrophagesWild-type 0h macrophages (0.216704)Zc3h12aKO_macrophages_0h 1h macrophages (0.0429352)Zc3h12aKO_macrophages_1h 2h (0.104709)Zc3h12aKO_macrophages_2h 4h (0.0830249)Zc3h12aKO_macrophages_4h (0.198158) (0.0180791) (0.102286)[ (0.234104) min ] [ medium ] [ max ] CEM 1 Dscr3 358.4 675.8 1508.2 P ( S | Z, I ) = 0.95 Vps26a 9183.9 10717.2 12474.1 Mean Corr = 0.67786 Snx8 210.9 599.8 833.2 Vps26b 107.0 309.1 452.6 Tbc1d5 42.6 53.4 55.6 Hsdl1 817.4 1132.1 1825.2 Slc36a1 63.3 184.0 325.4 Fam50a 449.0 1134.1 1665.1 Flcn 95.0 238.4 575.6 Ostm1 5267.1 8904.2 10528.5 CEM 1 + Hmgcl 124.4 251.1 461.4 Top 10 Genes Amdhd2 552.7 1191.5 2186.0 Appl2 352.3 3992.3 6482.7 Hexa 24217.6 30457.1 39399.0 Wdr81 64.4 219.7 398.8

Null module GEO Series "GSE19684" 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=GSE19684 Status: Public on Jun 16 2010 Title: Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20516124 Summary & Design: Summary: The morphogen and mitogen, Sonic Hedgehog, activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of naÃ¯ve mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development.

Keywords: disease state analysis

Overall design: 14 samples, 1 time series, 2 engineered Medulloblastoma tumors

Background corr dist: KL-Divergence = 0.0925, L1-Distance = 0.0252, L2-Distance = 0.0009, Normal std = 0.4558

0.875 Kernel fit Pairwise Correlations Normal fit

Density 0.438

0.000 CEM 1

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

Pre-normalization Quantiles

GNPs expressingGNPs expressingGNPs Math1-ER expressingGNPs Math1-ER treatedexpressingGNPs Math1-ER treatedwithexpressingGli1 Math1-ERTamoxifen engineered treatedwithGli1 Math1Tamoxifen engineered with forGli1 Medulloblastoma, DNA-binding 8noTamoxifen engineeredhours Tamoxifen forAtoh1 Medulloblastoma, 24 (0.184791) hoursengineered forAtoh1 mutantMedulloblastoma, treatment4 hoursbiological(0.117634) engineeredAtoh1 treated Medulloblastoma,(0.0500802) biological(0.0778537) engineered granulereplicate with Medulloblastoma, biological Tamoxifen granulereplicateneuron 1 Medulloblastoma,(0.015205) biological granule replicateneuronprecursors, for2 (0.0948896) 4 biologicalhours neuronprecursors, 3replicate (0.0956385) biological (0.102969)biological precursors, replicate 1 biological(0.0547347) replicate replicate 2 biological(0.0637204)[ replicate min1 3(0.0344681) (0.0295331) replicate 2 ](0.039307) 3 (0.0391752)[ medium ] [ max ] CEM 1 Dscr3 737.2 951.5 1369.0 P ( S | Z, I ) = 0.94 Vps26a 1173.9 1503.6 1812.9 Mean Corr = 0.09414 Snx8 269.8 382.2 569.9 Vps26b 865.0 1186.1 1824.0 Tbc1d5 100.8 210.6 316.8 Hsdl1 1015.3 1315.6 1490.1 Slc36a1 269.5 339.4 478.3 Fam50a 957.6 1145.2 1623.4 Flcn 248.4 469.4 736.2 Ostm1 335.0 658.9 940.6 CEM 1 + Hmgcl 531.0 739.7 873.1 Top 10 Genes Amdhd2 76.5 196.2 332.8 Appl2 855.0 1825.8 3404.4 Hexa 480.5 1042.2 1754.8 Wdr81 390.7 470.3 602.4

Null module GEO Series "GSE43825" 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=GSE43825 Status: Public on Dec 31 2013 Title: Gene expression profiles from mammary tissue of control mice, small K5˛N˛†cat hyperplasia, large K5˛N˛†cat hyperplasia and K5˛N˛†cat tumor Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Basal-like breast cancer is a heterogeneous disease characterised by the expression of basal cell markers, no oestrogen or progesterone receptor expression and a lack of HER2 overexpression. Recent studies have linked activation of the Wnt/beta-catenin pathway to basal-like breast cancer. Transgenic mice expressing N-terminally truncated stabilised beta-catenin in the mammary basal/myoepithelial cell layer (K5deltaNbetacat strain) develop mammary hyperplasias that progress to invasive carcinomas. Histological and microarray analyses of these lesions have revealed their high similarity to a subset of basal-like human breast tumours with squamous differentiation. As in human basal-like carcinomas, the Myc pathway was found to be activated in the mammary lesions of K5deltaNbetacat mice. Mammosphere and transplantation assays showed that a basal cell population with stem/progenitor characteristics was amplified in K5deltaNbetacat mouse preneoplastic glands. Myc deletion from the mammary basal layer of K5deltaNbetacat mice abolished both basal cell regenerative capacity and tumorigenesis. These results show that Myc is essential for beta-catenin-induced stem cell amplification and tumorigenesis and that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumours.

Overall design: mammary tissue from K5˛N˛†cat mice were dissected at successive stages of development (small hyperplasia (n=5), large hyperplasia (n=5), tumor (n=11) and control (n=4)) for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0953, L1-Distance = 0.0371, L2-Distance = 0.0022, Normal std = 0.4542

0.902 Kernel fit Pairwise Correlations Normal fit

Density 0.451

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

K5˛N˛†catK5˛N˛†cat miceK5˛N˛†cat tumor miceK5˛N˛†cat 1 tumor (0.00990885) miceK5˛N˛†cat 2 tumor (0.00896534) miceK5˛N˛†cat 3 tumor (0.00944726) miceK5˛N˛†cat 4 tumor (0.0234997) miceK5˛N˛†cat 5 tumor (0.00617221) miceK5˛N˛†cat 6 tumor (0.0150967) miceK5˛N˛†cat 7 tumor (0.00485339) miceK5˛N˛†cat 8 tumor (0.00651058) miceK5˛N˛†cat 9 tumor (0.00459525) miceK5˛N˛†cat 10 tumor (0.0152291)smallK5˛N˛†cat 11 hyperplasia (0.00933866)smallK5˛N˛†cat hyperplasia small 1K5˛N˛†cat (0.00163843) hyperplasia small 2K5˛N˛†cat (0.00807855) hyperplasia small 3K5˛N˛†cat (0.00843034) hyperplasia Large 4K5˛N˛†cat (0.0162227) hyperplasia Large 5K5˛N˛†cat (0.0132793) hyperplasia Large 1K5˛N˛†cat (0.0128956) hyperplasia Large 2Control (0.0108554) hyperplasia Large 3Control mice (0.00486067) hyperplasia 1 4Control (0.0233754)mice (0.0198027) 2 5Control (0.0364533)mice (0.0160854) 3 sorted (0.01446)mice 4 basal sorted(0.011718) cells basalsorted Control cells basalsorted Control mice cells basalsorted 1 Control (0.127806)mice cells basalsorted 2 K5creL/L (0.113221)mice cells basal 3 K5creL/L(0.106727) micecells K5creL/L1 (0.0707497)mice 2 (0.106193)mice[ min3 (0.16353) ] [ medium ] [ max ] CEM 1 Dscr3 153.7 1092.5 1297.6 P ( S | Z, I ) = 0.93 Vps26a 584.7 1783.8 2858.0 Mean Corr = 0.09656 Snx8 43.4 486.9 638.7 Vps26b 527.7 778.2 3677.2 Tbc1d5 11.0 240.7 345.9 Hsdl1 18.2 595.8 1121.6 Slc36a1 5.0 371.9 614.2 Fam50a 725.7 976.4 2048.7 Flcn 45.9 597.0 882.8 Ostm1 508.6 1189.9 1671.0 CEM 1 + Hmgcl 160.1 1201.2 2088.5 Top 10 Genes Amdhd2 14.3 369.7 588.1 Appl2 313.4 1616.4 2825.3 Hexa 534.5 3957.2 6652.7 Wdr81 5.8 643.8 937.4

Null module GEO Series "GSE32986" 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=GSE32986 Status: Public on Oct 15 2011 Title: Synergism between curdlan and GM-CSF in mouse dendritic cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22250091 Summary & Design: Summary: A simultaneous engagement of different pathogen recognition receptors provides a tailor made adaptive immunity for an efficient defence against distinct pathogens. For example, cross talk of TLR and c-type lectin signalling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-ÎºB. Here, we extend this principle to a strong synergism between the Dectin-1 agonist, curdlan, and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature which converts immature DCs to potent effector DCs. A variety of cytokines (IL-1Î², IL-6, TNF-Î±, IL-2 and IL-12p70), costimulatory molecules (CD80, CD86, CD40 and CD70), chemokines (CxCl1, CxCl2, CxCl3, CCl12, CCl17) as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, Dectin-1, Dectin-2 and Pentraxin 3 are strongly up-regulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IKBÎ± phosphorylation, in its rapid degradation and in enhanced nuclear translocation of all NF-ÎºB subunits. We further identified MAPK ERK, as one possible integration site of both signals, since its phosphorylation was clearly augmented when curdlan was co-applied with GM-CSF. Our data demonstrate that the immunomodulatory activity of curdlan requires an additional signal provided by GM-CSF to successfully initiate a robust Î²-glucan specific cytokine and chemokine response. The integration of both signals clearly prime and tailor a more effective innate and adaptive response against invading microbes and fungi.

Overall design: CD11b+ fraction of FLT3L generated BM DCs (3-4 x106) were stimulated for 4 hours with 100 or 1 Î¼g/ml curdlan in presence or absence of 5 ng/ml GM-CSF in triplicates.

Background corr dist: KL-Divergence = 0.1193, L1-Distance = 0.0322, L2-Distance = 0.0015, Normal std = 0.4232

0.966 Kernel fit Pairwise Correlations Normal fit

Density 0.483

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

BMDC-Unstimulated-1BMDC-Unstimulated-2BMDC-Unstimulated-3 BMDC-GMCSF-1(0.0928179) BMDC-GMCSF-2(0.107201) BMDC-GMCSF-3(0.0927016) (0.0685516)BMDC-Curdlan1-1 (0.0138957)BMDC-Curdlan1-2 (0.0436841)BMDC-Curdlan1-3 (0.0458441)BMDC-Curdlan100-1 (0.0391779)BMDC-Curdlan100-2 (0.0403739)BMDC-Curdlan100-3 (0.0143759)BMDC-Curdlan1/GMCSF-1 (0.0354879)BMDC-Curdlan1/GMCSF-2 (0.0365377)BMDC-Curdlan1/GMCSF-3BMDC-Curdlan100/GMCSF-1 (0.0137323)BMDC-Curdlan100/GMCSF-2 (0.0373163)BMDC-Curdlan100/GMCSF-3 (0.0397005) (0.128823) (0.0865485) (0.0632304)[ min ] [ medium ] [ max ] CEM 1 Dscr3 1046.8 1427.3 1775.3 P ( S | Z, I ) = 0.92 Vps26a 3180.8 3594.2 3973.8 Mean Corr = 0.52605 Snx8 2106.3 2285.4 2723.8 Vps26b 510.9 682.5 858.6 Tbc1d5 144.6 201.0 237.0 Hsdl1 1226.9 1531.2 1837.4 Slc36a1 421.2 664.9 1068.5 Fam50a 1902.9 2200.8 2549.6 Flcn 869.6 1094.4 1340.6 Ostm1 3368.1 3933.1 4514.0 CEM 1 + Hmgcl 1280.3 1644.1 2040.6 Top 10 Genes Amdhd2 966.0 1284.4 1671.8 Appl2 1353.7 2299.9 3176.3 Hexa 12616.4 14182.0 15944.0 Wdr81 2043.8 2386.7 2840.4

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 (0.0265169)RNAZT4Polysomal Sample 1at (0.0154593)RNAZT6Polysomal Sample 1at (0.0428426)RNAZT8Polysomal Sample 1at (0.0286425)RNAZT10Polysomal 1atSample (0.0224594)RNAZT12Polysomal atSample 1 RNA ZT14(0.0112269)Polysomal atSample 1 RNA ZT16(0.0365835)Polysomal atSample 1 RNA ZT18(0.011219)Polysomal atSample 1 RNA ZT4(0.00592371)Polysomal Sample at 1 RNA ZT6(0.00994457)Polysomal Sample 2at (0.0483844)RNAZT8Polysomal Sample 2at (0.0159891)RNAZT10Polysomal 2atSample (0.052706)RNAZT12Polysomal atSample 2 RNA ZT14(0.0135546)Polysomal atSample 2 RNA ZT20(0.0153867)Polysomal atSample 2 RNA ZT22(0.0166978)Polysomal atSample 1 RNA ZT16(0.0284017)Polysomal atSample 1 RNA ZT18(0.0234461)Total atSample 2 RNA ZT20(0.0267698) RNATotal atSample 2 at ZT22(0.00578792) RNAZT0Total Sample 2Sample at (0.0234759) RNAZT2Total 2Sample 1at (0.0342584) (0.0159761)RNAZT4Total Sample 1at (0.0241055)RNAZT6Total Sample 1at (0.0222334)RNAZT8Total Sample 1at (0.0162024)RNAZT10Total 1atSample (0.0166596)RNAZT12Total atSample 1 RNA ZT14(0.0137611)Total atSample 1 RNA ZT0(0.00516385)Total Sample at 1 RNA ZT2(0.0114308)Total Sample 2at (0.0213679)RNAZT4Total Sample 2at (0.0148108)RNAZT6Total Sample 2at (0.0141082)RNAZT8Total Sample 2at (0.0170869)RNAZT10Total 2atSample (0.00673126)RNAZT12Total atSample 2 RNA ZT14(0.0341976)Total atSample 2 RNA ZT16(0.00925042)Total atSample 2 RNA ZT18(0.021469)Total atSample 1 RNA ZT20(0.011792)Total atSample 1 RNA ZT22(0.021476)Total atSample 1 RNA ZT16(0.0166752)Total atSample 1 RNA ZT18(0.0201576)Total atSample 2 RNA ZT20(0.0213563)Polysomal atSample 2 ZT22(0.0203633)Polysomal RNASample 2 (0.0222965) at RNAZT0 2 (0.0159718) Sample at ZT2 Sample 2 (0.0342682)[ 2 min(0.0354111) ] [ medium ] [ max ] CEM 1 Dscr3 612.0 1150.0 1805.1 P ( S | Z, I ) = 0.93 Vps26a 867.5 1422.8 2748.2 Mean Corr = 0.05775 Snx8 300.0 451.1 643.9 Vps26b 471.9 775.2 1460.5 Tbc1d5 5.0 93.2 195.0 Hsdl1 324.3 500.6 605.8 Slc36a1 258.6 499.0 771.9 Fam50a 663.9 1019.3 1526.6 Flcn 187.3 444.4 843.8 Ostm1 263.3 586.8 832.7 CEM 1 + Hmgcl 5109.4 8213.3 15053.3 Top 10 Genes Amdhd2 386.2 741.2 1894.1 Appl2 448.8 725.3 1195.8 Hexa 1138.7 2903.1 4811.8 Wdr81 464.9 850.0 1583.7

Null module GEO Series "GSE41925" 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=GSE41925 Status: Public on Dec 01 2012 Title: Transcription factor AP-2 gamma is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23136388 Summary & Design: Summary: We characterzised global changes in gene expresseion between 8 cell embryos and blastocysts to identify potential genes required for blastocyst formation.

Overall design: Expression data from mouse 8-cell embryos and blastocysts. Eight-cell embryos and blastocysts were obatained from B6D2F1 female X B6D2F1 male. We analyzed a total of four samples at both stages.

Background corr dist: KL-Divergence = 0.0169, L1-Distance = 0.0482, L2-Distance = 0.0027, Normal std = 0.8501

0.514 Kernel fit Pairwise Correlations Normal fit

Density 0.257

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

8-cell staged8-cell mousestaged8-cell wholemousestaged8-cell embryos wholemousestagedBlastocyst embryos wholemouse repBlastocyst 1staged embryos(0.0693161) whole repBlastocyst 2mousestaged embryos(0.0983454) repBlastocyst 3wholemousestaged (0.158221) rep embryos 4wholemousestaged (0.155679) embryos wholemouse rep 1 embryos(0.101671) whole rep[ 2 embryos(0.105551)min rep 3 (0.137512) ]rep 4 (0.173703)[ medium ] [ max ] CEM 1 Dscr3 490.6 1998.2 2360.4 P ( S | Z, I ) = 0.88 Vps26a 4897.0 6956.5 7850.6 Mean Corr = 0.47645 Snx8 704.0 841.6 1067.8 Vps26b 205.2 456.0 644.3 Tbc1d5 5.5 103.3 135.5 Hsdl1 258.5 2367.7 2559.7 Slc36a1 91.9 160.5 182.8 Fam50a 2939.7 4162.8 5063.9 Flcn 174.2 424.2 683.0 Ostm1 1265.7 1875.0 2370.0 CEM 1 + Hmgcl 499.8 3711.6 4125.2 Top 10 Genes Amdhd2 227.6 2912.4 3744.8 Appl2 52.1 1180.2 1401.4 Hexa 2630.9 10527.6 12177.2 Wdr81 932.7 3931.4 5909.3

Null module GEO Series "GSE47959" 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=GSE47959 Status: Public on Jul 25 2014 Title: NKT-10 cells represent a novel invariant NKT cell subset with regulatory characteristics Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 25061873 Summary & Design: Summary: We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD.

Overall design: Group 1 (Ctr_unstim) = iNKT cells from C57BL/6 control mice and left unstimulated / Group 2 (Ctr_stim) = iNKT cells from C57BL/6 control mice and injected 1h before purification with 1ug aGalCer i.v. / Group 3 (Pre_unstim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and left unstimulated / Group 4 (Pre_stim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and injected 1h before purification with 1ug aGalCer i.v. / Sample were prepared in duplicates in two independent experiments.

Background corr dist: KL-Divergence = 0.0389, L1-Distance = 0.0167, L2-Distance = 0.0004, Normal std = 0.6079

0.656 Kernel fit Pairwise Correlations Normal fit

Density 0.328

0.000 CEM 1

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

Pre-normalization Quantiles

Ctr_unstim_1Ctr_unstim_2 (0.0691426)Ctr_stim_1 (0.216536)Ctr_stim_2 (0.220182)Pre_unstim_1 (0.255702)Pre_unstim_2 (0.0817201)Pre_stim_1 (0.070956)Pre_stim_2 (0.0148108) (0.0709505) [ min ] [ medium ] [ max ] CEM 1 Dscr3 215.9 785.4 919.8 P ( S | Z, I ) = 0.81 Vps26a 1728.9 2544.0 3143.8 Mean Corr = 0.47893 Snx8 157.5 434.6 545.7 Vps26b 623.2 930.1 1222.6 Tbc1d5 120.4 204.8 253.8 Hsdl1 532.9 1508.3 2682.4 Slc36a1 187.8 401.9 503.6 Fam50a 1149.6 1409.5 1890.3 Flcn 329.6 454.9 504.2 Ostm1 2795.0 3974.1 5098.4 CEM 1 + Hmgcl 326.3 617.9 754.9 Top 10 Genes Amdhd2 221.6 303.0 501.2 Appl2 883.6 1326.2 2063.6 Hexa 1214.8 1787.4 2076.5 Wdr81 136.7 371.6 440.6

Null module GEO Series "GSE6383" 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=GSE6383 Status: Public on Mar 12 2007 Title: Mouse small intestine epithelium vs. mesenchyme Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17299133 Summary & Design: Summary: During organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.

Keywords: comparative genomic hybridization: epithelium vs. mesenchyme

Overall design: Mouse small intestine (E18.5) is separated to epithelium and mesenchyme. Total RNA is extracted from epithelium and mesenchyme. There are 6 samples in this microarray experiment: 3 for epithelium and 3 for mesenchyme. Samples are hybridized the affymetrix Mouse Genome 430 2.0 Array. We compare the gene expression between epithelium and mesenchyme to study the gene expression profiles in these two compartments.

Background corr dist: KL-Divergence = 0.0057, L1-Distance = 0.0149, L2-Distance = 0.0002, Normal std = 0.9832

0.414 Kernel fit Pairwise Correlations Normal fit

Density 0.207

0.000 CEM 1

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

Pre-normalization Quantiles

small intestinesmall intestine smallEPI-MES intestine smallEPI-MES Epi intestineA small EPI-MES(0.175899) Epi intestineB small Mes(0.217009) Epi A intestineC (0.150163) Mes(0.0756362) B (0.187432) Mes C (0.193861)[ min ] [ medium ] [ max ] CEM 1 Dscr3 821.4 1164.1 1466.5 P ( S | Z, I ) = 0.72 Vps26a 1612.4 3072.1 3611.1 Mean Corr = 0.39935 Snx8 801.8 2813.8 3072.1 Vps26b 806.2 1247.6 1368.3 Tbc1d5 202.0 225.7 248.1 Hsdl1 698.0 808.1 945.5 Slc36a1 493.5 1224.8 1536.0 Fam50a 698.0 967.6 1086.1 Flcn 570.1 823.1 1191.2 Ostm1 654.8 766.4 967.6 CEM 1 + Hmgcl 1395.9 3528.9 4445.7 Top 10 Genes Amdhd2 325.6 2495.3 2813.8 Appl2 926.1 1989.7 2328.2 Hexa 2127.6 8891.5 9312.8 Wdr81 1133.9 1684.6 1891.1

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(0.218912) sac, replicateYolk biological2 (0.116178) sac, replicate 1 biological (0.148441) replicate 2 (0.0602193) replicate 1 (0.281291) 2[ (0.174958) min ] [ medium ] [ max ] CEM 1 Dscr3 347.3 455.7 945.3 P ( S | Z, I ) = 0.72 Vps26a 1028.6 1223.3 1977.8 Mean Corr = 0.32764 Snx8 510.5 855.4 4805.0 Vps26b 2058.0 2301.7 2694.4 Tbc1d5 8.9 15.1 21.9 Hsdl1 143.8 326.4 667.2 Slc36a1 16.7 32.0 120.5 Fam50a 881.3 1541.4 1898.9 Flcn 67.1 103.1 131.1 Ostm1 134.7 632.2 1419.6 CEM 1 + Hmgcl 157.5 293.2 690.4 Top 10 Genes Amdhd2 445.8 756.5 803.1 Appl2 171.7 407.0 468.8 Hexa 4506.7 8080.0 15515.4 Wdr81 8.5 11.5 12.7

Null module GEO Series "GSE31378" 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=GSE31378 Status: Public on Aug 16 2013 Title: Host cell gene expression in Human respiratory syncytial virus (HRSV) infected mouse macrophage cells at 4, 24 hours post infection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23506210 Summary & Design: Summary: We used the microarray data to analyze host cells response on mouse macrophage cells infected with HRSV

Overall design: The HRSV infected mouse macrophage cells were harvested at 4 and 24 hpi and RNA extraction was performed using standard protocol as described by Affymetrix. The aim of this experiment is to analyze host cell response to HRSV infection.

Background corr dist: KL-Divergence = 0.0597, L1-Distance = 0.0481, L2-Distance = 0.0032, Normal std = 0.5745

0.745 Kernel fit Pairwise Correlations Normal fit

Density 0.372

0.000 CEM 1

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

Pre-normalization Quantiles

HRSV infectedHRSV infected HRSVmouse infected HRSVmacrophagemouse infected HRSVmacrophagemouse at infected HRSVmacrophagemouse 0H, biological at infected HRSVmacrophagemouse 0H, biological at infected HRSVmacrophagerep1mouse 0H, biological (0.192688)at infected HRSVmacrophagerep2mouse 4H, biological (0.11206)at infected macrophagerep3mouse 4H, biological (0.131527)at macrophagerep1mouse 4H, biological (0.132885)at macrophagerep2 24H, (0.112395)atbiological [rep3 24H, min (0.125493)atbiological 24H,rep1 ] biological(0.061824) rep2 (0.058431) rep3[ medium (0.0726962) ] [ max ] CEM 1 Dscr3 1232.4 2223.9 3474.3 P ( S | Z, I ) = 0.69 Vps26a 2856.4 3651.5 4171.1 Mean Corr = 0.55966 Snx8 1721.1 2595.4 3049.5 Vps26b 382.4 617.2 894.1 Tbc1d5 59.0 86.7 163.7 Hsdl1 1411.1 2322.6 2898.7 Slc36a1 600.7 693.9 2048.6 Fam50a 1124.8 1322.6 1488.4 Flcn 1048.5 1368.5 2842.0 Ostm1 2968.5 3900.4 4757.2 CEM 1 + Hmgcl 1729.2 2141.2 2592.4 Top 10 Genes Amdhd2 1251.4 1686.8 2738.3 Appl2 1051.4 1461.0 3269.7 Hexa 12634.3 17101.4 23471.1 Wdr81 1521.4 2029.7 3204.5

Null module GEO Series "GSE20696" 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=GSE20696 Status: Public on Sep 30 2010 Title: Expression profiling of 3T3-L1 adipogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20887899 Summary & Design: Summary: 3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogeneic media.

Overall design: Two technical replicates from four time points relative to induction of adipogenesis (day 0)

Background corr dist: KL-Divergence = 0.0408, L1-Distance = 0.0317, L2-Distance = 0.0012, Normal std = 0.6378

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.325

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

3T3-L1_t1_rep13T3-L1_t1_rep23T3-L1_t2_rep1 (0.0667458)3T3-L1_t2_rep2 (0.0907591)3T3-L1_t3_rep1 (0.171151)3T3-L1_t3_rep2 (0.222124)3T3-L1_t4_rep1 (0.12017)3T3-L1_t4_rep2 (0.0901772) (0.111719) (0.127154) [ min ] [ medium ] [ max ] CEM 1 Dscr3 2013.0 2964.1 3870.2 P ( S | Z, I ) = 0.66 Vps26a 2209.5 2904.3 3159.3 Mean Corr = 0.42599 Snx8 507.3 709.9 1036.4 Vps26b 908.8 1095.1 1306.8 Tbc1d5 89.4 213.0 265.2 Hsdl1 336.5 375.8 433.8 Slc36a1 98.5 225.5 260.0 Fam50a 1711.4 2480.6 3241.2 Flcn 542.7 920.9 1681.1 Ostm1 813.4 1140.6 1330.2 CEM 1 + Hmgcl 1176.9 2118.5 3020.7 Top 10 Genes Amdhd2 167.8 766.5 1188.3 Appl2 596.6 2586.3 3244.6 Hexa 2858.2 5291.8 11498.1 Wdr81 331.1 607.9 1057.3

Null module GEO Series "GSE50603" 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=GSE50603 Status: Public on Sep 05 2013 Title: Effect of L-Proline on mouse embryonic stem cells (ESCs) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24319666 Summary & Design: Summary: We found that the non-essential amino acid L-Proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells (ESCs) into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic stem cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the transcriptome

We used microarrays to elucidate whether a diverse transcriptional program is the basis of the morphological and motility differences between ESCs and L- Proline treated ESCs (PiCs)

Overall design: Total RNA was extracted from Control (ESCs) and L-Proline treated mouse embryonic stem cells (PiCs) and hybridized on Affimetrix microarrays.

Background corr dist: KL-Divergence = 0.0532, L1-Distance = 0.0337, L2-Distance = 0.0015, Normal std = 0.5680

0.739 Kernel fit Pairwise Correlations Normal fit

Density 0.369

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

ESCs_biologicalESCs_biologicalESCs_biological rep1aESCs_biological (0.0160602) rep1bESCs_biological (0.0386742) rep1cESCs_biological (0.0432642) rep2aPiCs_biological (0.0763493) rep2bPiCs_biological (0.112323) rep2cPiCs_biological (0.0664175)rep1a PiCs_biological(0.074307) rep1b PiCs_biological(0.202184) rep1c PiCs_biological(0.185986) rep2a (0.059445) rep2b (0.0531124) rep2c (0.0718778)[ min ] [ medium ] [ max ] CEM 1 Dscr3 1043.6 1422.4 1843.6 P ( S | Z, I ) = 0.59 Vps26a 2287.9 3375.6 3711.1 Mean Corr = 0.59207 Snx8 886.7 1221.6 1571.8 Vps26b 482.8 614.0 767.0 Tbc1d5 63.1 72.8 125.2 Hsdl1 519.0 789.3 945.7 Slc36a1 222.4 304.8 371.9 Fam50a 1031.3 1153.3 1209.2 Flcn 730.3 1119.8 1244.6 Ostm1 528.7 789.8 1125.1 CEM 1 + Hmgcl 824.3 978.5 1092.2 Top 10 Genes Amdhd2 422.1 802.0 1106.7 Appl2 488.4 612.3 730.0 Hexa 1562.2 2868.3 4173.6 Wdr81 413.8 564.9 644.0

Null module GEO Series "GSE7767" 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=GSE7767 Status: Public on Jul 15 2007 Title: Differential transcription of ip Chlamydia infected C57BL6J and DBA2J mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17641048 Summary & Design: Summary: C57BL/6J mice were 105-fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5 Mbp region on chromosome 11 encoding a cluster of three p47GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype, implicating the non-redundant role of these p47GTPases. C57BL/6J and DBA/2J exhibited a difference in IFNg dependent chlamydial control, which was reversible by Iigp2 siRNA knockdown. Microarrays of infected peritoneal lavage revealed >10 fold up regulation of neutrophil recruiting chemokines in susceptible mice and >100 fold increase in macrophage differentiation genes in resistant mice, indicating that susceptibility pattern involves stimulation of different inflammatory cell recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived lethal challenge confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Results indicate that these p47GTPases have cell autonomous effects, which results in vastly different inflammatory stimulation leading to either recovery or death.

Keywords: Comparative disease state analysis

Overall design: C57BL/6J and DBA2J mice (4 mice each) were infected I.p. with 10E4 IFU of Chlamydia psittaci then peritoneal lavage was collected on day 3 post infection. Cells were centrifuged then treated with Trizol for total RNA extraction.

Background corr dist: KL-Divergence = 0.0126, L1-Distance = 0.0218, L2-Distance = 0.0006, Normal std = 0.8222

0.485 Kernel fit Pairwise Correlations Normal fit

Density 0.243

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

C57BL6JC57BL6J mice C57BL6Jinfected mice DBA2Jinfected peritoneal mice DBA2Jmiceinfected peritoneal lavage infected DBA2Jmice peritoneal daylavage infected peritoneal mice 3pi, daylavage biologicalinfected peritoneal 3pi, lavage day biological peritoneal repeat3pi, daylavage biological 3pi, [2repeat (0.10481)daylavage minbiological 3pi, 3repeat (0.166926)day biological ] repeat3pi, 5 (0.269209) biological 1repeat (0.183091)[ 2mediumrepeat (0.16585) 3 (0.110114) ] [ max ] CEM 1 Dscr3 1116.9 1561.0 1681.1 P ( S | Z, I ) = 0.56 Vps26a 3346.0 3862.1 4424.9 Mean Corr = 0.32758 Snx8 1032.1 1365.5 1456.5 Vps26b 391.1 637.0 679.5 Tbc1d5 243.1 418.2 420.3 Hsdl1 736.9 960.9 1182.9 Slc36a1 731.7 898.5 908.4 Fam50a 1375.0 1581.5 1797.1 Flcn 521.7 900.9 1103.8 Ostm1 2366.0 2750.0 3353.4 CEM 1 + Hmgcl 1198.6 1672.8 2069.7 Top 10 Genes Amdhd2 907.2 1456.5 1672.8 Appl2 846.4 1358.7 1365.5 Hexa 5435.7 9485.0 10276.9 Wdr81 736.9 1103.6 1118.3

Null module GEO Series "GSE19836" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 114 -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=GSE19836

Background corr dist: KL-Divergence = 0.3225, L1-Distance = 0.0725, L2-Distance = 0.0153, Normal std = 0.2720 GEO Series "GSE27932" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.712 Kernel fit Pairwise Correlations Normal fit

Density 0.356

0.000 CEM 1

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

Pre-normalization Quantiles

Lung EC,Lung control, EC,Lung control, rep1 EC,Lung (0.0273644) experimental, rep2 EC,Liver (0.0168851) experimental, sinusoidalLiver rep1 sinusoidal (0.0186601)Liver rep2EC, sinusoidalcontrol, (0.00924509)Liver EC, sinusoidalcontrol, rep1Liver EC, (0.073388) sinusoidalcontrol, rep2Liver EC, (0.0683954) sinusoidalexperimental, rep3Thymus, EC, (0.0460876) experimental,Thymus, EC,control, rep1 experimental,Thymus, control, rep1(0.0657363) rep2 Thymus,(0.116823) experimental, rep2(0.0659889) rep3 (0.153036) experimental, (0.0706881) rep1 (0.121361) rep2 (0.146341)[ min ] [ medium ] [ max ] CEM 1 Dscr3 751.4 1644.1 2495.8 P ( S | Z, I ) = 0.54 Vps26a 874.3 2182.7 3178.0 Mean Corr = -0.08996 Snx8 186.7 500.1 1741.4 Vps26b 319.2 450.3 878.4 Tbc1d5 70.5 120.1 224.0 Hsdl1 617.5 1334.0 4324.4 Slc36a1 308.9 443.7 696.2 Fam50a 871.5 1146.5 2736.4 Flcn 1876.7 2447.1 4336.0 Ostm1 1034.0 1676.9 2747.2 CEM 1 + Hmgcl 1755.9 2397.6 2717.5 Top 10 Genes Amdhd2 198.8 729.4 947.0 Appl2 282.7 872.1 1612.8 Hexa 865.0 3364.9 11069.3 Wdr81 825.9 905.7 1014.1

Null module GEO Series "GSE10182" 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=GSE10182 Status: Public on Mar 15 2008 Title: MDP- and Pam3CSK4-induced genes in naÃ¯ve and tolerant macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18261938 Summary & Design: Summary: Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization.

The transcriptome induced via Nod2 stimulation is greatly expanded in TLR2-tolerant macrophages.

Keywords: self and cross tolerance by MDP or Pam3CSK4

Overall design: Genes induced by Pam3CSK4 or MDP were selected based on a three-fold increase over expression levels in unstimulated macrophages. Tolerized genes are defined as genes downregulated more than 2-fold in tolerant macrophages stimulated with Pam3CSK4 or MDP.

Background corr dist: KL-Divergence = 0.0435, L1-Distance = 0.0246, L2-Distance = 0.0007, Normal std = 0.6065

0.679 Kernel fit Pairwise Correlations Normal fit

Density 0.339

0.000 CEM 1

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

Pre-normalization Quantiles

BMDM_untreated_3h_rep2BMDM_unpretreated-MDP_3h_rep2BMDM_unpretreated-Pam3CSK4_3h_rep2BMDM_MDP-MDP_3h_rep2 (0.206489)BMDM_MDP-Pam3CSK4_3h_rep2BMDM_Pam3CSK4-MDP_3h_rep2 (0.0221024)BMDM_Pam3CSK4-Pam3CSK4_3h_rep2 (0.0804511) (0.20176) (0.273271) (0.106855)[ min (0.109072)] [ medium ] [ max ] CEM 1 Dscr3 2016.1 2904.7 3302.3 P ( S | Z, I ) = 0.51 Vps26a 5556.7 6349.6 6808.4 Mean Corr = 0.57203 Snx8 2815.8 4125.6 6710.2 Vps26b 604.4 881.1 995.4 Tbc1d5 40.4 44.6 48.9 Hsdl1 1250.2 1556.0 1904.7 Slc36a1 802.1 930.7 1030.0 Fam50a 2558.7 2852.8 3908.4 Flcn 860.0 1268.0 1536.0 Ostm1 2367.9 2972.4 3470.4 CEM 1 + Hmgcl 2094.2 3167.1 3255.5 Top 10 Genes Amdhd2 1606.3 1819.2 2095.7 Appl2 1611.6 2866.2 3522.1 Hexa 20066.5 24076.0 26115.8 Wdr81 1516.4 2024.8 2412.1

Null module GEO Series "GSE42061" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.895 Kernel fit Pairwise Correlations Normal fit

Density 0.448

0.000 CEM 1

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

Pre-normalization Quantiles

Macrophages_hyperlipid_blank_rep1Macrophages_hyperlipid_blank_rep2Macrophages_hyperlipid_blank_rep3Macrophages_hyperlipid_Pg_rep1Macrophages_hyperlipid_Pg_rep2 Macrophages_hyperlipid_Pg_rep3(0.066415) Macrophages_normallipid_blank_rep1(0.0346677) Macrophages_normallipid_blank_rep2(0.0579601) (0.0436839)Macrophages_normallipid_blank_rep3 (0.0470198)Macrophages_normallipid_Pg_rep1 (0.0943517)Macrophages_normallipid_Pg_rep2Macrophages_normallipid_Pg_rep3 (0.146476) (0.191502) (0.0689319) (0.0406662) (0.115896)[ min (0.0924298) ] [ medium ] [ max ] CEM 1 Dscr3 1763.9 2852.2 3608.0 P ( S | Z, I ) = 0.51 Vps26a 4423.7 4936.8 5645.4 Mean Corr = 0.30259 Snx8 1442.3 1780.6 2509.2 Vps26b 370.5 687.0 908.2 Tbc1d5 25.2 65.2 119.1 Hsdl1 1758.9 2093.8 2650.2 Slc36a1 344.9 616.4 1045.1 Fam50a 2617.6 3402.3 3947.1 Flcn 1002.6 1326.3 1755.3 Ostm1 3188.2 4625.8 5548.4 CEM 1 + Hmgcl 1258.6 2363.1 2661.4 Top 10 Genes Amdhd2 1736.0 1990.5 2487.0 Appl2 851.8 1525.4 2237.5 Hexa 19025.8 22595.2 25309.4 Wdr81 889.0 1270.6 1727.3

Null module GEO Series "GSE21861" 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=GSE21861 Status: Public on Nov 15 2010 Title: The transcription factors STAT5a/b negatively regulate cell proliferation through the activation of cdkn2b and cdkn1a expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21038417 Summary & Design: Summary: Although the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a key cell cycle inhibitor. These experiments therefore shed a light on the context-specific role of STAT5a/b as tumor suppressors.

Overall design: Control and Stat5a/b-null embryonic fibroblasts (MEFs) cells were stimulated w/o a GH including two biological replications per group (Total four groups)

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0466, L2-Distance = 0.0026, Normal std = 0.8018

0.546 Kernel fit Pairwise Correlations Normal fit

Density 0.273

0.000 CEM 1

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

Pre-normalization Quantiles

KO+GH_Bio-2WT-_Bio-3 replication-05-17-10KO-_Bio-2 replication-05-17-10WT+GH_Bio-3 replication-05-17-10KO+GH_Bio-3 (0.213168) replication-05-17-10WT-_Bio-2 (0.0978769) replication-5-17-10KO-_Bio-3 (0.0743134) replication-05-17-10WT+GH_Bio-2 replication-05-17-10 (0.117085) (0.214091) replication-05-17-10 (0.0413968) (0.139975)[ min (0.102094) ] [ medium ] [ max ] CEM 1 Dscr3 2545.3 3148.9 3568.8 P ( S | Z, I ) = 0.45 Vps26a 4056.9 5188.5 5972.5 Mean Corr = 0.62789 Snx8 931.0 1003.2 1383.0 Vps26b 893.2 1310.6 1552.5 Tbc1d5 31.6 38.6 63.3 Hsdl1 744.5 1011.7 1126.6 Slc36a1 442.4 561.1 621.2 Fam50a 1447.4 1669.1 1734.4 Flcn 1002.0 1313.4 1426.2 Ostm1 1130.7 2422.8 2680.9 CEM 1 + Hmgcl 824.3 1307.1 1341.5 Top 10 Genes Amdhd2 876.2 1307.2 1649.0 Appl2 906.5 1196.0 1308.4 Hexa 6199.9 8494.2 8976.3 Wdr81 944.9 1247.0 1351.1

Null module GEO Series "GSE16002" 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=GSE16002 Status: Public on Sep 30 2010 Title: Molecular Events Initiating B Cell Fate Specification Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20971928 Summary & Design: Summary: Functional genomics comparison of EBFko, Pax5ko, and RAG2ko cell lines.

Identify gene signatures associated with specfication and commitment to the B cell fate.

Overall design: Cultured cells harvested and for RNA extraction and hybridization to Affymetrix 430 2.0 Arrays.

Background corr dist: KL-Divergence = 0.0727, L1-Distance = 0.0236, L2-Distance = 0.0008, Normal std = 0.5007

0.797 Kernel fit Pairwise Correlations Normal fit

Density 0.398

0.000 CEM 1

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

Pre-normalization Quantiles

EBFko-1EBFko-2 (0.0317867)EBFko-3 (0.0751033)Pax5ko-1 (0.0876513)Pax5ko-2 (0.047438)Pax5ko-3 (0.11577)RAG2ko-1 (0.0459456)RAG2ko-2 (0.152295)RAG2ko-3 (0.183546) (0.260464) [ min ] [ medium ] [ max ] CEM 1 Dscr3 1019.4 1331.7 2147.3 P ( S | Z, I ) = 0.42 Vps26a 1017.5 1835.0 1896.7 Mean Corr = -0.16820 Snx8 408.6 447.8 767.2 Vps26b 308.0 1035.0 1162.2 Tbc1d5 84.8 167.5 208.0 Hsdl1 623.9 787.4 949.2 Slc36a1 88.0 189.9 280.9 Fam50a 1052.8 1162.2 1464.3 Flcn 529.3 783.3 1087.2 Ostm1 1000.3 1143.3 1449.7 CEM 1 + Hmgcl 700.6 1273.4 1655.3 Top 10 Genes Amdhd2 157.5 301.2 431.6 Appl2 52.1 309.3 1212.5 Hexa 105.5 2099.2 4303.6 Wdr81 278.9 591.2 774.3

Null module GEO Series "GSE20391" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20391 Status: Public on Jun 16 2010 Title: Comprehensive expression profiling across primary fetal liver terminal erythroid differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20231426 Summary & Design: Summary: Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).

Overall design: Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationexplained in part by impaired cell cycle progression as well as increased apoptosisand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesissuch as alpha-globin and mitoferrin 1demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

Background corr dist: KL-Divergence = 0.0629, L1-Distance = 0.0458, L2-Distance = 0.0040, Normal std = 0.5380

0.745 Kernel fit Pairwise Correlations Normal fit

Density 0.373

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

sorted-R1sorted-R2 cells,sorted-R3 repl cells, 1 sorted-R5(0.124977) repl cells, 1 sorted-R1(0.0797847) repl cells, 1 sorted-R2(0.0409801) repl cells, 1 sorted-R3(0.0493214) repl cells, 2 sorted-R4(0.242015) repl cells, 2 sorted-R5(0.0872969) repl cells, 2 sorted-R2(0.148312) repl cells, 1 sorted-R3(0.0674707) repl cells, 2 (0.1224) repl cells, 3 (0.015244) repl 3 (0.0221976)[ min ] [ medium ] [ max ] CEM 1 Dscr3 308.6 697.9 1776.7 P ( S | Z, I ) = 0.37 Vps26a 1079.7 1759.6 2513.9 Mean Corr = 0.56923 Snx8 144.2 415.2 530.5 Vps26b 241.0 564.8 1163.7 Tbc1d5 56.0 152.0 347.2 Hsdl1 394.2 860.3 2300.1 Slc36a1 16.8 238.9 466.0 Fam50a 414.0 1308.3 1626.1 Flcn 205.4 483.2 712.2 Ostm1 527.0 957.5 1517.1 CEM 1 + Hmgcl 951.4 2053.3 3515.7 Top 10 Genes Amdhd2 52.7 453.3 1046.8 Appl2 70.9 299.2 596.8 Hexa 509.5 1500.8 4946.6 Wdr81 669.8 2924.2 4798.4

Null module GEO Series "GSE40795" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 50 -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=GSE40795 Status: Public on Oct 12 2012 Title: Transcriptomic Dose Response Changes in Female Mouse and Rat Lungs following Chloroprene Exposure Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23125180 Summary & Design: Summary: ˆ-chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of multi-organ tumors in mouse and rat cancer bioassays. A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12.8 ppm while a small, but not statistically significant, increase was observed in female rats only at the highest exposure concentration of 80 ppm. The metabolism of chloroprene results in the generation of reactive epoxides and the rate of overall chloroprene metabolism is highly species dependent. To identify potential key events in the mode-of-action of chloroprene lung tumorigenesis, dose response and time course gene expression microarray measurements were made in the lungs of female mice and female rats. The gene expression changes were analyzed using both a traditional analysis of variance approach followed by pathway enrichment analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross-species differences in tumor incidence and transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day. The closer correspondence of the transcriptional changes with the tumor response are likely due to their reflection of the overall balance between metabolic activation and detoxication reactions whereas the current tissue dose surrogate reflects only oxidative metabolism.

Overall design: Female mice (B6C3F1/Crl) were exposed to chloroprene (CAS 126-99-8) by whole-body inhalation exposure at 0, 0.3, 2, 13, or 90 ppm. Exposures were performed for 6 hr/day, 5 days per week. The animals were sacrified at 5 days or 19 days (15 exposure days) post initiation of exposure. The right lung was excised and gene expression microarray analysis was performed using Affymetrix Mouse 430_2 arrays. Female rats (F344/NCrl) were exposed to chloroprene (CAS 126-99-8) by whole-body inhalation exposure at 0, 5, 30, 90, or 200 ppm. Exposures were performed for 6 hr/day, 5 days per week. The animals were sacrified at 5 days or 19 days (15 exposure days) post initiation of exposure. The right lung was excised and gene expression microarray analysis was performed using Affymetrix Rat 230_2 arrays.

Background corr dist: KL-Divergence = 0.1693, L1-Distance = 0.0369, L2-Distance = 0.0026, Normal std = 0.3558

1.121 Kernel fit Pairwise Correlations Normal fit

Density 0.561

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

RT_03_5d_118_Lung_CLPR03_RSTSRP805RT_03_5d_119_Lung_CLPR-03_RSTSRP805RT_03_5d_120_Lung_CLPR-03_RSTSRP805RT_03_5d_121r_Lung_CLPR03_RSTSRP805RT_0_15d_109_Lung_ACO2_RSTSRP805RT_0_15d_110_Lung_ACO2_RSTSRP805 (0.0090279)RT_0_15d_111A_Lung_ACO2_RSTSRP805 RT_0_15d_112A_Lung_ACO2_RSTSRP805(0.013745) RT_0_15d_113r_Lung_ACO2_RSTSRP805(0.0150268) RT_0_5d_101_Lung_ACO1_RSTSRP805(0.0170084) (0.195106)RT_0_5d_102_Lung_ACO1_RSTSRP805 (0.00724687)RT_0_5d_103_Lung_ACO1_RSTSRP805 (0.00640876)RT_0_5d_104_Lung_ACO1_RSTSRP805 (0.00672572)RT_0_5d_105_Lung_ACO1_RSTSRP805 (0.00866863)RT_13_15d_157_Lung_CLPR13_RSTSRP805 (0.00341557)RT_13_15d_158_Lung_CLPR13_RSTSRP805 (0.0131194)RT_13_15d_159_Lung_CLPR13_RSTSRP805 (0.0239104)RT_13_15d_160_Lung_CLPR13_RSTSRP805 (0.000581027)RT_13_15d_161_Lung_CLPR13_RSTSRP805 (0.00368404)RT_13_5d_149_Lung_CLPR-13_RSTSRP805 RT_13_5d_151_Lung_CLPR-13_RSTSRP805(0.00889516) RT_13_5d_152_Lung_CLPR-13_RSTSRP805(0.00928154) RT_13_5d_153_Lung_CLPR-13_RSTSRP805(0.0124511) RT_13_5d_154_Lung_CLPR13_RSTSRP805(0.00902198) RT_2_15d_141_Lung_CLPR2_RSTSRP805(0.0360953) RT_2_15d_142_Lung_CLPR2_RSTSRP805(0.00967657) RT_2_15d_143r_Lung_CLPR2_RSTSRP805(0.0207293) RT_2_15d_144_Lung_CLPR2_RSTSRP805(0.0020651) RT_2_15d_145_Lung_CLPR2_RSTSRP805(0.000695828) (0.0173971)RT_2_5d_133_Lung_CLPR-2_RSTSRP805 (0.0238023)RT_2_5d_134_Lung_CLPR-2_RSTSRP805 (0.00802148)RT_2_5d_135_Lung_CLPR-2_RSTSRP805 (0.022994)RT_2_5d_136_Lung_CLPR2_RSTSRP805 (0.00519483)RT_2_5d_137_Lung_CLPR-2_RSTSRP805 (0.00652361)RT_90_15d_177_Lung_CLPR90_RSTSRP805 (0.0160846)RT_90_15d_178A_Lung_CLPR90_RSTSRP805 (0.00784628)RT_90_15d_179_Lung_CLPR90_RSTSRP805 (0.0152972)RT_90_15d_180_Lung_CLPR90_RSTSRP805 (0.0191969)RT_90_15d_181A_Lung_CLPR90_RSTSRP805 (0.022298)RT_90_5d_165_Lung_CLPR-90_RSTSRP805 RT_90_5d_166_Lung_CLPR-90_RSTSRP805(0.0368309)RT_90_5d_167_Lung_CLPR90_RSTSRP805 (0.00581973) RT_90_5d_168_Lung_CLPR-90_RSTSRP805(0.0546961) RT_90_5d_169_Lung_CLPR-90_RSTSRP805(0.0311056)RT_03_15d_125_Lung_CLPR03_RSTSRP805 (0.0301412) RT_03_15d_126A_Lung_CLPR03_RSTSRP805(0.0857312) RT_03_15d_127A_Lung_CLPR03_RSTSRP805(0.0313516) (0.034338)RT_03_15d_128_Lung_CLPR03_RSTSRP805 RT_03_15d_129_Lung_CLPR03_RSTSRP805(0.0164709) RT_03_5d_117_Lung_CLPR-03_RSTSRP805(0.00990347) (0.00856528) (0.00772382) (0.00731396) [(0.0295182) min (0.00905358) ] (0.00419377)[ medium ] [ max ] CEM 1 Dscr3 1070.6 1343.5 1835.9 P ( S | Z, I ) = 0.35 Vps26a 877.5 1578.9 2004.8 Mean Corr = -0.08473 Snx8 539.4 655.5 860.3 Vps26b 528.3 671.9 983.0 Tbc1d5 123.9 200.7 269.2 Hsdl1 1067.0 1266.4 1728.4 Slc36a1 349.0 420.6 531.3 Fam50a 1054.6 1260.2 1546.2 Flcn 775.6 949.1 1098.3 Ostm1 1203.0 1424.3 1731.2 CEM 1 + Hmgcl 1495.6 1722.7 2399.9 Top 10 Genes Amdhd2 509.5 654.3 1028.5 Appl2 1826.7 2296.7 3164.1 Hexa 3469.8 4202.6 5164.8 Wdr81 935.4 1173.7 1740.9

Null module GEO Series "GSE8788" 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=GSE8788 Status: Public on Aug 17 2007 Title: Comparison of gene expression pattern between Wild-type and Trib1-deficient mice (Gene chip data for JEM 20070183) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17724128 Summary & Design: Summary: The purpose of this experiment was to compare the gene expression pattern between wild-type and Trib1-deficient macrophages in response to LPS.

Keywords: Comparison of gene expression pattern between Wild-type and Trib1-deficient mice

Overall design: Two samples to define ""LPS-inducible gene"" and 4 samples (2 for wild-type and the rests for Trib1-deficient mice) for comparison.

Background corr dist: KL-Divergence = 0.0435, L1-Distance = 0.0258, L2-Distance = 0.0009, Normal std = 0.6043

0.666 Kernel fit Pairwise Correlations Normal fit

Density 0.333

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWT macrophage macrophageTrib1 #1Trib1 mediumWild-type LPS #1 (0.143381)Trib1 KO (0.499094) macrophage macrophage #2Trib1 Wild-type #2 KO LPS treated macrophage macrophage (0.0189206) with LPS LPS LPS (0.155508) (0.0915216) [(0.0915747) min ] [ medium ] [ max ] CEM 1 Dscr3 1735.3 2205.9 2718.0 P ( S | Z, I ) = 0.27 Vps26a 4191.2 5928.6 8302.9 Mean Corr = 0.54344 Snx8 1204.9 1639.9 3088.8 Vps26b 266.0 431.1 506.4 Tbc1d5 27.9 51.9 84.1 Hsdl1 1177.7 1480.7 1722.7 Slc36a1 235.6 305.9 833.9 Fam50a 558.2 765.4 1567.3 Flcn 468.8 721.5 1218.9 Ostm1 2163.3 3891.8 4492.3 CEM 1 + Hmgcl 932.5 1517.4 2265.4 Top 10 Genes Amdhd2 943.9 1718.9 2769.1 Appl2 290.6 356.7 795.4 Hexa 19689.5 29453.3 30463.0 Wdr81 774.8 896.9 1269.7

Null module