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: 88 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. Num ofGenesinQueryGeneset:88.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Adcyap1r1 Arhgap17 Marveld2 Marveld3 Shroom2 Arhgef2 Frmd4a Pard3b Pard6g Pard6b Amotl2 Amotl1 Gm626 Pard6a Micall2 Cldn18 Cldn12 Cldn22 Cldn10 Cldn19 Cldn16 Cldn14 Cldn15 Cldn11 Cldn23 Sympk Pmp22 Epcam Plxdc1 Nphp1 Nphp4 Tgfbr1 Synpo Ddx58 Rab13 Cxadr Magi1 Magi2 Magi3 Pard3 Cgnl1 Cldn5 Cldn2 Cldn6 Cldn8 Cldn4 Cldn3 Cldn7 Cyth1 Cldn9 Cldn1 Ash1l Prkcz Esam Wnk3 Wnk4 Lin7b Lin7a Tjap1 Lin7c Mpp7 Mpp5 Jam3 Jam2 Amot Mpdz Clmp Ubn1 Cdh5 Ank3 Aoc1 Traf4 Bves Vapa Tbcd Mtdh Igsf5 Inadl Ocln Dlg1 Ect2 F11r Tjp1 Tjp2 Tjp3 Strn Cgn Apc

Cldn7 Epcam Marveld2 Cldn3 Cldn4 Pard6b Ocln Tjp3 Tjp2 F11r Inadl Cldn23 Prkcz Shroom2 Cldn8 Igsf5 Cldn6 Magi3 Tjp1 Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam Singletons CEM 1(137datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 2610528J11Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page1 Tmem30b Marveld2 Arhgef16 Shroom2 Tmprss2 Sowahb Mapk13 Pard6b Ap1m2 Cldn23 Epcam Galnt3 Spint2 Spint1 Cdcp1 Kcnk1 Rab25 Erbb3 Magi3 Esrp2 Esrp1 Cldn6 Cldn8 Cldn4 Cldn3 Cldn7 Prss8 Ripk4 Prkcz Grhl2 Tmc4 Krt18 Cdh1 Dsg2 Lad1 Tnk1 Igsf5 Inadl Grb7 Mal2 Ocln St14 F11r Tjp1 Tjp2 Tjp3 Krt7 Krt8 Irf6 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE6837 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE31313 [22] GSE35247 [15] GSE12618 [6] GSE12881 [6] GSE27675 [14] GSE17797 [19] GSE1983 [6] GSE34206 [8] GSE10659 [6] GSE20577 [12] GSE16380 [8] GSE10589 [6] GSE3501 [6] GSE31106 [18] GSE15794 [6] GSE51628 [15] GSE7069 [8] GSE3822 [16] GSE8024 [8] GSE26290 [12] GSE17263 [6] GSE29798 [6] GSE48884 [12] GSE22040 [9] GSE54349 [6] GSE34839 [6] GSE28593 [9] GSE11221 [9] GSE11382 [10] GSE6383 [6] GSE19979 [6] GSE51213 [16] GSE24295 [7] GSE9977 [24] GSE5309 [7] GSE16110 [16] GSE50813 [24] GSE15326 [10] GSE17796 [39] GSE23502 [8] GSE7810 [9] GSE34729 [6] GSE17096 [20] GSE17097 [20] GSE52474 [154] GSE31004 [8] GSE30684 [6] GSE15808 [29] GSE42565 [6] GSE8828 [6] GSE37658 [6] GSE14753 [6] GSE51080 [18] GSE25828 [8] GSE56755 [13] GSE55028 [6] GSE5671 [18] GSE11628 [12] GSE10290 [24] GSE27455 [12] GSE4189 [14] GSE18586 [9] GSE28664 [17] GSE41925 [8] GSE15069 [15] GSE2019 [12] GSE51483 [45] GSE50439 [15] GSE4816 [12] GSE12499 [10] GSE50603 [12] GSE16925 [15] GSE30488 [52] GSE24291 [6] GSE48790 [8] GSE56482 [8] GSE31940 [8] GSE12986 [10] GSE19616 [16] GSE31561 [36] GSE45143 [6] GSE27429 [8] GSE54774 [12] GSE7309 [12] GSE26771 [12] GSE17102 [9] GSE46211 [18] GSE40609 [28] GSE46209 [21] GSE15267 [8] GSE8488 [15] GSE17513 [12] GSE21247 [60] GSE26446 [8] GSE6290 [37] GSE18281 [33] GSE29632 [42] GSE26076 [12] GSE16364 [6] GSE38754 [40] GSE5976 [12] GSE13044 [59] GSE6933 [15] GSE13302 [30] GSE38831 [7] GSE55622 [22] GSE47872 [6] GSE30247 [16] GSE32095 [24] GSE42601 [6] GSE59437 [30] GSE14458 [12] GSE11259 [9] GSE35961 [12] GSE11186 [33] GSE45968 [6] GSE31359 [8] GSE23845 [15] GSE23408 [39] GSE9725 [16] GSE4002 [13] GSE39583 [21] GSE46169 [30] GSE13963 [15] GSE4734 [61] GSE16496 [102] GSE12078 [8] GSE18135 [18] GSE11274 [20] GSE19925 [6] GSE25737 [6] GSE22506 [12] GSE17266 [59] GSE27717 [11] GSE31598 [12] GSE24207 [73] GSE32223 [12] GSE37431 [6] GSE48382 [10] GSE49346 [6] GSE10776 [15] GSE38048 [20] GSE13235 [9] GSE13408 [14] GSE17297 [32] GSE30561 [6] GSE34351 [12] GSE35226 [12] GSE19091 [6] GSE39233 [40] GSE6589 [11] CEM+ CEM GSE20372 [6] GSE23200 [6] GSE10806 [11] GSE19076 [12] GSE6210 [12] GSE27848 [16] 0.0 GSE10989 [6] GSE13032 [18]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 22.58 22.71 23.16 23.36 23.94 24.95 25.45 25.66 25.67 25.79 25.90 26.28 26.46 26.51 26.76 27.59 27.75 28.80 28.91 28.96 29.39 29.83 29.90 30.74 31.38 32.12 33.06 33.40 33.55 34.60 36.94 1.0 Notes 2310030G06Rik 0610040J01Rik 1810019J16Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page2 Tmem184a Cdc42bpg Epb4.1l4b Tmem125 Camsap3 AI661453 Ccdc120 Tmem54 Arhgap8 Plekha7 Tacstd2 Arhgef5 Krtcap3 Stard10 Lrrc16a Cyb561 C77080 Tfcp2l1 Cnksr1 Rassf7 Sh3yl1 Eps8l2 Lamc2 Rhpn2 Macc1 Hook1 Eppk1 Epha1 Nipal2 Elmo3 Wfdc2 Fxyd3 Ptpn3 Rasef Stap2 Krt19 Pkp3 Dsc2 Llgl2 Crb3 Perp Cblc Klc3 Stx3 Ildr1 Elf3 Ehf 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 13.94 14.40 14.42 14.66 14.76 14.82 14.83 15.05 15.15 15.28 15.28 15.32 15.45 15.48 15.55 15.60 15.66 15.89 15.97 16.12 16.17 16.39 16.43 16.63 16.85 17.16 17.18 17.37 18.06 18.12 18.75 18.94 19.14 19.17 19.35 19.39 20.09 20.16 20.21 20.34 20.56 20.75 20.80 21.17 21.30 21.50 21.58 21.81 22.06 22.57 1.0 Notes 4930506M07Rik 2010107G23Rik 5730559C18Rik 2010300C02Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page3 AA986860 Tmem139 Sh3bgrl2 Cep170b Baiap2l1 Plekhh1 Fam84b Slc44a4 Mansc1 Serinc2 Gyltl1b Cmtm8 Smagp Rnf128 Fgfbp1 Vsig10 Lamb3 Myo5b Myh14 Hook2 Ckmt1 Ap1s3 Nfe2l3 Rab15 Usp43 Elovl7 Foxa1 Prr15l Gipc2 Mpzl3 Mpzl2 Pof1b Grhl1 Map7 Pvrl2 Tuft1 Pawr F2rl1 Agrn Evpl Tgfa Pls1 Etl4 Mal Ppl Ezr 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 9.17 9.18 9.24 9.24 9.31 9.54 9.59 9.68 9.71 9.96 10.04 10.04 10.07 10.11 10.19 10.25 10.27 10.28 10.28 10.37 10.81 10.85 10.96 11.08 11.11 11.11 11.32 11.39 11.41 11.67 11.69 11.75 11.80 12.05 12.30 12.44 12.60 12.68 12.92 13.02 13.03 13.29 13.37 13.40 13.48 13.54 13.60 13.60 13.62 13.80 1.0 Notes Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page4 Slc22a23 Ccdc64b Slc9a3r1 Dnase2a Samd10 Slc39a4 Slc44a3 Unc13b Ccdc68 Sh2d4a Arfgef1 Cmtm4 Rbm47 Atp2c2 Plxnb1 Rassf6 Lama5 Ttc39a Prom1 Myo5c Celsr1 Trpm4 Capn5 Abca3 Anxa4 Rab17 Exph5 H2-Q2 Pex26 Sel1l3 Erbb2 Ovol1 Ovol2 Rnf43 Aim1l Bnipl Ano9 Pvrl4 Aim1 Ifnlr1 Itga3 Ptprf Urah Fzd6 Cobl Ntf5 Hpn Elf5 Sfn Frk 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 5.03 5.06 5.06 5.11 5.30 5.40 5.43 5.57 5.62 5.63 5.87 5.89 6.03 6.16 6.18 6.39 6.40 6.47 6.53 6.60 6.73 6.92 6.93 7.03 7.04 7.08 7.32 7.40 7.51 7.61 7.66 7.69 7.77 7.93 7.95 7.99 8.16 8.19 8.28 8.31 8.40 8.41 8.46 8.47 8.61 8.64 8.77 8.89 9.09 9.14 1.0 Notes D10Bwg1379e Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page5 St6galnac2 Rab11fip1 Epb4.1l4a Trp53bp2 Fam134b Shroom3 Tmem51 Tmem79 S100a14 Chmp2b Chmp4c Fam83h Slc37a1 Proser2 Cadps2 Gprc5a Mmp15 Mgat4a Coro2a Ctnnd1 Osbpl3 Atp8b1 Sptbn2 Ociad2 Zbtb42 Fnbp1l Zfp750 Arrdc1 Prom2 Cdk18 Pcdh1 Tpd52 Lmtk2 Numb Ptprk Gstt3 Gpx2 Lrrc1 Epn3 Cds1 Kazn Pak4 Misp Car2 Gjb2 Dlg3 Zfp7 Jup Clu 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 2.41 2.47 2.52 2.53 2.55 2.60 2.67 2.70 2.73 2.75 2.78 2.81 2.87 2.89 2.96 2.98 3.02 3.04 3.04 3.07 3.14 3.18 3.19 3.25 3.26 3.41 3.52 3.69 3.81 3.84 3.86 3.90 3.91 3.91 3.92 3.97 4.04 4.22 4.24 4.30 4.35 4.40 4.44 4.44 4.46 4.52 4.64 4.72 4.75 4.88 1.0 Notes 2200002D01Rik 2310007B03Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page6 Rab11fip4 Tmem102 Gramd1c Pdzk1ip1 Fam102a Tmprss4 Zdhhc13 Tmem40 Efcab4a Pip4k2c Slc52a3 Fam84a Chrnb1 Dnmbp Myl12b Cmtm6 Nudt14 Atp1a1 Stxbp2 Vamp8 Celsr2 Susd4 Kcnk5 Foxq1 Fhdc1 Erlin2 Gata3 Capsl Clcn3 Efna1 Plek2 Muc1 Dag1 Ssh3 Bex1 Bex4 Itgb6 Itgb4 Tox3 Mlph Arg2 Npnt Dcxr Dstn Fat1 Gca Shb Cd9 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 0.77 0.79 0.88 0.91 0.92 0.92 0.94 0.96 0.96 0.98 1.00 1.06 1.07 1.08 1.12 1.18 1.18 1.18 1.18 1.18 1.21 1.24 1.24 1.30 1.32 1.39 1.50 1.54 1.54 1.55 1.55 1.66 1.67 1.67 1.68 1.70 1.78 1.79 1.94 1.96 1.98 2.00 2.00 2.01 2.01 2.07 2.12 2.21 2.23 2.34 1.0 Notes Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page7 Slc15a2 Ppfibp2 Tspan8 Card10 Eps8l1 Rab20 Ston2 Plch2 Plch1 Rell1 0.0 1.0

GSE13259 [10] GSE21761 [43]

GSE6837 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE31313 [22] GSE35247 [15] GSE12618 [6] GSE12881 [6] GSE27675 [14] GSE17797 [19] GSE1983 [6] GSE34206 [8] GSE10659 [6] GSE20577 [12] GSE16380 [8] GSE10589 [6] GSE3501 [6] GSE31106 [18] GSE15794 [6] GSE51628 [15] GSE7069 [8] GSE3822 [16] GSE8024 [8] GSE26290 [12] GSE17263 [6] GSE29798 [6] GSE48884 [12] GSE22040 [9] GSE54349 [6] GSE34839 [6] GSE28593 [9] GSE11221 [9] GSE11382 [10] GSE6383 [6] GSE19979 [6] GSE51213 [16] GSE24295 [7] GSE9977 [24] GSE5309 [7] GSE16110 [16] GSE50813 [24] GSE15326 [10] GSE17796 [39] GSE23502 [8] GSE7810 [9] GSE34729 [6] GSE17096 [20] GSE17097 [20] GSE52474 [154] GSE31004 [8] GSE30684 [6] GSE15808 [29] GSE42565 [6] GSE8828 [6] GSE37658 [6] GSE14753 [6] GSE51080 [18] GSE25828 [8] GSE56755 [13] GSE55028 [6] GSE5671 [18] GSE11628 [12] GSE10290 [24] GSE27455 [12] GSE4189 [14] GSE18586 [9] GSE28664 [17] GSE41925 [8] GSE15069 [15] GSE2019 [12] GSE51483 [45] GSE50439 [15] GSE4816 [12] GSE12499 [10] GSE50603 [12] GSE16925 [15] GSE30488 [52] GSE24291 [6] GSE48790 [8] GSE56482 [8] GSE31940 [8] GSE12986 [10] GSE19616 [16] GSE31561 [36] GSE45143 [6] GSE27429 [8] GSE54774 [12] GSE7309 [12] GSE26771 [12] GSE17102 [9] GSE46211 [18] GSE40609 [28] GSE46209 [21] GSE15267 [8] GSE8488 [15] GSE17513 [12] GSE21247 [60] GSE26446 [8] GSE6290 [37] GSE18281 [33] GSE29632 [42] GSE26076 [12] GSE16364 [6] GSE38754 [40] GSE5976 [12] GSE13044 [59] GSE6933 [15] GSE13302 [30] GSE38831 [7] GSE55622 [22] GSE47872 [6] GSE30247 [16] GSE32095 [24] GSE42601 [6] GSE59437 [30] GSE14458 [12] GSE11259 [9] GSE35961 [12] GSE11186 [33] GSE45968 [6] GSE31359 [8] GSE23845 [15] GSE23408 [39] GSE9725 [16] GSE4002 [13] GSE39583 [21] GSE46169 [30] GSE13963 [15] GSE4734 [61] GSE16496 [102] GSE12078 [8] GSE18135 [18] GSE11274 [20] GSE19925 [6] GSE25737 [6] GSE22506 [12] GSE17266 [59] GSE27717 [11] GSE31598 [12] GSE24207 [73] GSE32223 [12] GSE37431 [6] GSE48382 [10] GSE49346 [6] GSE10776 [15] GSE38048 [20] GSE13235 [9] GSE13408 [14] GSE17297 [32] GSE30561 [6] GSE34351 [12] GSE35226 [12] GSE19091 [6] GSE39233 [40] GSE6589 [11] CEM+ CEM GSE20372 [6] GSE23200 [6] GSE10806 [11] GSE19076 [12] GSE6210 [12] GSE27848 [16] 0.0 GSE10989 [6] GSE13032 [18]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13259 Status: Public on Apr 01 2009 Title: Comparisons of epithelial and mesenchymal murine breast tumor cell lines Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19276366 Summary & Design: Summary: Epithelial tumor cells (E) underwent EMT in vivo in FVB/N mice generating mesenchymal tumors. Mesenchymal cell lines (M1-M4) were each derived from a different mouse. This study compares gene expression between these two different tumor types.

Keywords: cell type comparison

Overall design: Two replicates were prepared for each of five cell lines, one epithelial cell line (E) and 4 mesenchymal cell lines M1-M4.

Background corr dist: KL-Divergence = 0.0778, L1-Distance = 0.0460, L2-Distance = 0.0031, Normal std = 0.5332

0.799 Kernel fit Pairwise Correlations Normal fit

Density 0.400

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

SpontaneousSpontaneous epithelialRelapsed epithelialRelapsed mammary mesenchymalRelapsed mammary mesenchymal tumorRelapsed mammarymesenchymal cell tumor Relapsedline, mammarymesenchymal cell replicatetumor Relapsedline, mammarymesenchymal cell replicatetumor 1Relapsed line(0.212088) mammarymesenchymal cell 1,tumor 2 Relapsedreplicate line(0.204763) mammarymesenchymal cell 1,tumor replicate line 1 mammarymesenchymal (0.0723937) cell 2,tumor replicate line 2mammary (0.055373) cell 2,tumor replicate line 1mammary (0.0663564) cell 3,tumor replicate[ line 2min (0.0631136) cell 3,tumor replicate line 1 (0.0825773) cell ]4, replicate line 2 (0.0815633) 4, replicate 1[ (0.0837809) medium 2 (0.0779902) ] [ max ] CEM 1 Cldn7 3.1 17.9 11663.2 P ( S | Z, I ) = 1.00 Epcam 4.2 8.3 19025.7 Mean Corr = 0.84712Marveld2 2.3 16.4 988.6 Cldn3 2.5 11.0 10342.0 Cldn4 7.5 51.2 1060.4 Pard6b 36.8 59.7 560.0 Ocln 21.7 55.7 638.8 Tjp3 10.0 28.4 1047.9 Tjp2 192.1 333.3 3012.3 F11r 9.7 503.5 4015.7 Inadl 5.0 29.6 544.5 Cldn23 1.8 6.1 159.0 Prkcz 6.7 23.4 299.6 Shroom2 9.5 28.5 1278.4 Cldn8 1.8 2.8 74.4 Igsf5 3.0 25.2 652.8 Cldn6 10.7 28.6 48.4 Magi3 553.4 788.7 1276.7 Tjp1 1672.7 2141.7 4609.0 Esrp1 1.8 10.5 2788.0 Cdh1 2.8 90.5 6333.9 St14 21.0 54.2 4031.4 Cdcp1 5.5 59.1 5176.2 Prss8 1.8 5.4 735.6 CEM 1 + Spint1 24.9 60.2 3983.1 Top 10 Genes Ap1m2 6.8 15.2 5217.2 Irf6 2.0 14.9 1397.0 Erbb3 47.4 271.2 6443.9 Spint2 8.5 16.5 9314.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE21761" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 43 -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=GSE21761 Status: Public on Aug 09 2010 Title: A large intergenic non-coding RNA induced by p53 mediates global gene repression in the p53 transcriptional response Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20673990 Summary & Design: Summary: Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes.

Overall design: [4] RAS profiling: For p53 restoration, cultured tumor cell lines were incubated with 500nM 4-hydroxytamoxifen for the indicated times.

Background corr dist: KL-Divergence = 0.0959, L1-Distance = 0.0350, L2-Distance = 0.0024, Normal std = 0.4436

0.899 Kernel fit Pairwise Correlations Normal fit

Density 0.450

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

GFP0hrsGFP1hrs [MEF GFP3hrsprofiling] [MEF GFP6hrsprofiling] [MEF(0.0247423) GFP9hrsprofiling] [MEF(0.0173596) CRE0hrsprofiling] [MEF(0.018789) CRE1hrsprofiling] [MEF(0.024316) CRE3hrsprofiling] [MEF(0.0198001) CRE6hrsprofiling] [MEF(0.0219962) CRE9hrsprofiling] [MEF(0.0234049) siRNAprofiling] [MEF(0.0191316) hnRNPK siRNAprofiling] (0.015364) lincp21siRNA R1 (0.0180676) [hnRNPKKD p53R1siRNA [hnRNPKKDR1 control[hnRNPKKDsiRNA profiling] hnRNPKR1siRNA profiling] [hnRNPKKD (0.0195945)profiling] lincp21siRNA R2 (0.020213) [hnRNPKKD p53(0.0160575)R2siRNA profiling] [hnRNPKKDR2 control[hnRNPKKDsiRNA profiling] (0.0282287) hnRNPKR2siRNA profiling] [hnRNPKKD (0.0161941)profiling] lincp21siRNA R3 (0.0195131) [hnRNPKKD p53(0.0148312)R3siRNA profiling] [hnRNPKKDR3 control[hnRNPKKDsiP53_R1 profiling] (0.016336) R3siLincP21_R1 profiling] [lincP21KD[hnRNPKKD (0.0172229)profiling]siScramble_R1 (0.0273436) profiling][lincP21KD(0.022157)siP53_R2 profiling]siLincP21_R2 [lincP21KD (0.0197526) [lincP21KD (0.0184307)profiling]siScramble_R2 profiling] (0.017202) profiling][lincP21KDsiP53_R3 (0.0232608)siLincP21_R3 [lincP21KD (0.0232995) [lincP21KD profiling]R1 t=0 profiling] (0.01458) profiling][lincP21KD[RASR1 t=8 profiling] [RAS(0.0152858)R1 (0.0195434) t=16profiling] profiling] R1(0.0399708) [RAS t=24 (0.0180673)profiling] R1(0.0384373) [RAS t=40 profiling]R1 [RAS(0.0393858) t=48 profiling]R2 [RAS(0.0424531) t=0 profiling][RASR2 (0.0503649) t=8 profiling] [RASR2 (0.0531844) t=16 profiling] R2(0.0228825) [RAS t=24 profiling] R2(0.0201658) [RAS t=40 profiling]R2 [RAS(0.0188349) t=48 profiling]R3 [RAS(0.020076) t=0 profiling][RAS (0.0213213) profiling] (0.0245094) (0.0183287)[ min ] [ medium ] [ max ] CEM 1 Cldn7 24.4 35.3 8421.9 P ( S | Z, I ) = 1.00 Epcam 22.4 33.4 11455.8 Mean Corr = 0.83168Marveld2 13.3 20.1 663.9 Cldn3 18.4 28.3 7644.1 Cldn4 21.9 32.9 10709.6 Pard6b 50.0 159.9 3067.3 Ocln 23.5 34.7 410.9 Tjp3 21.0 32.8 153.2 Tjp2 343.9 1134.7 7511.0 F11r 303.3 997.9 6349.6 Inadl 19.6 33.9 474.8 Cldn23 16.1 23.6 1117.3 Prkcz 30.9 59.3 707.3 Shroom2 111.8 256.8 1328.6 Cldn8 15.0 22.3 118.4 Igsf5 19.8 31.4 1433.6 Cldn6 18.1 31.5 12144.0 Magi3 501.9 1599.4 2399.2 Tjp1 1349.9 2696.0 4128.7 Esrp1 17.0 23.7 2486.5 Cdh1 13.0 24.9 9190.2 St14 26.7 486.4 4561.9 Cdcp1 21.7 55.3 2167.2 Prss8 19.0 30.9 856.1 CEM 1 + Spint1 28.1 45.7 7171.7 Top 10 Genes Ap1m2 37.6 80.7 5764.4 Irf6 18.2 34.9 1673.0 Erbb3 27.5 40.3 1787.1 Spint2 74.3 204.6 9831.9

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE6837" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: comparative study

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

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

0.536 Kernel fit Pairwise Correlations Normal fit

Density 0.268

0.000 CEM 1

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

Pre-normalization Quantiles

unstimulatedunstimulated embryonicstimulated embryonicstimulated fibroblasts embryonicstimulated fibroblasts embryonic WT, stimulatedfibroblasts biologicalembryonic KO, stimulatedfibroblasts biologicalembryonicWT, rep1 stimulatedfibroblasts biological embryonicWT,(0.122602) rep1 fibroblasts biological embryonicrep1WT,(0.0899218) fibroblasts biological(0.0759351) rep2KO, fibroblasts biological (0.0638989) rep3KO,[ biological (0.0687685) min rep1KO, biological(0.226561) rep2] (0.0595155) rep3 (0.292797)[ medium ] [ max ] CEM 1 Cldn7 3.4 22.8 2660.0 P ( S | Z, I ) = 1.00 Epcam 3.7 27.5 2400.0 Mean Corr = 0.81944Marveld2 2.6 24.4 423.5 Cldn3 4.7 13.1 1760.0 Cldn4 13.1 42.3 217.1 Pard6b 60.8 253.7 1021.1 Ocln 7.0 30.1 642.5 Tjp3 18.9 87.7 373.1 Tjp2 766.3 1354.3 1874.3 F11r 104.6 1262.8 5204.9 Inadl 25.7 59.1 723.3 Cldn23 1.6 20.2 141.4 Prkcz 10.2 48.8 829.7 Shroom2 159.9 278.8 637.6 Cldn8 1.3 17.9 168.4 Igsf5 5.8 19.6 645.6 Cldn6 6.0 22.0 90.6 Magi3 1024.6 1310.1 3882.5 Tjp1 1674.7 3413.6 6848.6 Esrp1 2.5 32.8 898.1 Cdh1 1.6 22.8 8357.5 St14 15.4 63.2 1172.9 Cdcp1 10.1 47.2 817.7 Prss8 4.6 21.9 2169.1 CEM 1 + Spint1 25.4 134.9 1693.5 Top 10 Genes Ap1m2 10.3 37.6 1096.2 Irf6 2.8 22.4 594.9 Erbb3 28.9 39.8 2471.1 Spint2 20.1 33.2 5599.5

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE31313" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 22 -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=GSE31313 Status: Public on Aug 08 2012 Title: Expression data from anti-EpCAM treated and untreated SP cells compared to lung tissue Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Targeted therapies against cancer stem cells which are enriched in side populations (SP) involves interruption of Wnt-signalling. Furthermore, EpCAM is a SP marker and modulator of Wnt-signalling. Therefore, the effects of an anti-EpCAM treatment on SP-cells and WNT/Î²-catenin signalling was studied.

SP of the murine lung adenocarcinoma cell line A2C12 was obtained by fluorescence activated cell sorting and whole genome scans helped to define their molecular phenotype after anti-EpCAM antibody treatment.

Overall design: Anti-EpCAM treated and untreated A2C12 cells were subjected to Hoechst 33342 dye exclusion assay and sorted to SP fractions by FACS. Gene expression of SP cells was compared to non-transgenic lung tissue.

Background corr dist: KL-Divergence = 0.0208, L1-Distance = 0.0491, L2-Distance = 0.0029, Normal std = 0.7902

0.505 Kernel fit Pairwise Correlations Normal fit

Density 0.252

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

A2C12 SPA2C12 cells SPA2C12 biological cells SPA2C12 biological cells replicate anti-EpCAMA2C12 biological replicate 1 anti-EpCAM(0.080677)A2C12 replicate treated 2 anti-EpCAM(0.0886065)Male treatedSP lung,3 (0.0907954)Male cells biological treatedSPlung, biologicalMale cells biological SPlung, biologicalreplicateMale cells replicate biological lung, biologicalreplicateMale 1 replicate (0.0269979) biological1 (0.0827964)lung, replicateMale 2 replicate (0.0564472) biological2 (0.0888465)lung, replicateMale 3 (0.0371671) biological3 (0.0978943)lung, replicateMale 4 (0.0615085) biological lung, replicateFemale 5 (0.0173015) biological replicate Female lung,6 (0.0198036) biologicalreplicate Female lung,7 (0.0231248) biological Female lung,8 replicate (0.0177926) biological Femalelung, replicate 1 (0.0267634) biological Femalelung, replicate 2 (0.0275141) biological Femalelung, replicate 3 (0.0346809) biological Femalelung, replicate 4 (0.0268841) biological lung, replicate 5 (0.0250088) biological replicate 6 (0.0201249) replicate 7 (0.0222214)[ min8 (0.0270431) ] [ medium ] [ max ] CEM 1 Cldn7 2.4 2354.4 3555.2 P ( S | Z, I ) = 1.00 Epcam 2.4 1730.9 4037.0 Mean Corr = 0.80899Marveld2 2.4 430.3 663.2 Cldn3 2.4 2226.2 4515.7 Cldn4 36.5 178.0 470.4 Pard6b 91.6 980.1 1439.2 Ocln 2.4 568.3 681.5 Tjp3 2.5 399.7 481.0 Tjp2 338.3 2251.4 2518.5 F11r 1695.5 3571.6 4069.3 Inadl 52.7 664.1 840.3 Cldn23 2.5 81.7 129.6 Prkcz 9.0 706.4 846.0 Shroom2 52.8 541.4 665.7 Cldn8 2.5 142.9 189.7 Igsf5 2.5 684.6 1687.3 Cldn6 56.3 232.9 539.3 Magi3 1003.5 3389.6 4419.4 Tjp1 3078.2 8011.1 10949.0 Esrp1 2.4 837.7 1398.9 Cdh1 179.3 6651.7 9023.3 St14 2.5 674.1 1329.3 Cdcp1 40.7 580.1 1109.6 Prss8 2.4 1379.6 2394.0 CEM 1 + Spint1 44.9 1177.4 3705.7 Top 10 Genes Ap1m2 2.4 532.6 923.3 Irf6 2.4 609.0 767.4 Erbb3 58.1 1842.4 3378.9 Spint2 2.4 6171.8 10382.8

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE35247" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35247 Status: Public on Jan 21 2012 Title: Genome unstable murine prostate cancers acquire genomic aberrations and bone metastatic features of the human disease Organism: Mus musculus Experiment type: Genome variation profiling by genome tiling array Platform: GPL1261 Pubmed ID: 22341455 Summary & Design: Summary: Gene copy numbers of prostate tumors of G3 and G4 generations of LSL-mTert PB-Pten/p53 mouse model

Overall design: Prostate tumors were developed in G3 and G4 generations of LSL-mTert PB-Pten/p53 mice. These tumors were profiled with affy and aCGH. We used affy gene expression to correlate with the copy number alterations in the mouse prostate tumors.

Background corr dist: KL-Divergence = 0.2052, L1-Distance = 0.0483, L2-Distance = 0.0055, Normal std = 0.3318

1.202 Kernel fit Pairwise Correlations Normal fit

Density 0.601

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

G4 LSL-mTertG3 LSL-mTert PB-Pten/p53G3 LSL-mTert PB-Pten/p53G3 LSL-mTert 7106PT PB-Pten/p53G4 LSL-mTert 7523PTmRNA PB-Pten/p53G4 LSL-mTert 7526PT(0.0588817)mRNA PB-Pten/p53G4 LSL-mTert 8584PT(0.0378709)mRNA PB-Pten/p53G4 LSL-mTert 8589PT(0.0629354)mRNA PB-Pten/p53G4 LSL-mTert 8591PT(0.0429769)mRNA PB-Pten/p53G4 LSL-mTert 8781PT(0.0364821)mRNA PB-Pten/p53G3 LSL-mTert 9492PT(0.0651699)mRNA PB-Pten/p53G4 LSL-mTert 9493PT(0.0477715)mRNA PB-Pten/p53G3 LSL-mTert 10118PT(0.0697479)mRNA PB-Pten/p53G4 LSL-mTert 11563PT(0.0637421) mRNAPB-Pten/p53G4 LSL-mTert 11649PT (0.2584)mRNAPB-Pten/p53 11756PT (0.0465913)mRNAPB-Pten/p53 11819PM (0.0490781)mRNA 11959PT (0.0648926) mRNA[ min mRNA(0.0451853) ] (0.050274) [ medium ] [ max ] CEM 1 Cldn7 19.1 165.5 9845.7 P ( S | Z, I ) = 1.00 Epcam 7.6 268.6 22249.7 Mean Corr = 0.80075Marveld2 4.8 38.4 420.3 Cldn3 4.0 20.6 2240.1 Cldn4 38.7 143.5 1390.3 Pard6b 3.5 12.8 357.8 Ocln 38.6 85.8 271.0 Tjp3 7.9 50.6 1134.7 Tjp2 194.6 360.8 1391.8 F11r 369.2 640.0 4466.9 Inadl 3.0 47.2 399.0 Cldn23 3.6 29.7 444.4 Prkcz 6.8 18.8 238.0 Shroom2 203.6 277.6 802.9 Cldn8 4.1 43.8 1841.5 Igsf5 14.9 199.1 780.8 Cldn6 9.8 87.9 638.1 Magi3 485.8 704.0 1090.4 Tjp1 1177.9 1811.0 3568.6 Esrp1 3.0 13.1 1458.6 Cdh1 9.7 214.4 13748.5 St14 13.1 151.8 2001.7 Cdcp1 75.0 143.6 2382.8 Prss8 3.6 12.4 381.8 CEM 1 + Spint1 120.7 238.3 2972.8 Top 10 Genes Ap1m2 8.1 97.9 1991.0 Irf6 3.0 69.7 1032.1 Erbb3 118.1 196.6 1378.1 Spint2 55.6 346.6 11898.6

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE12618" 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=GSE12618 Status: Public on Jan 16 2009 Title: Gene expression profiles of E13 bladder compartments. (GUDMAP Series ID: 24) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of microdissected tissues and FACS sorted cells plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here delineates the gene expression profiles of the mesenchymal and epithelial compartments of the e13 mouse bladder.

Keywords: Mouse embryonic day 13 bladder mesenchyme and epithelium.

Overall design: FVB/N mice were time mated. At embryonic day 13 mice were euthanized by decapitation and the bladders were microdissected, cut just above the ureters, and treated with 20 ´M EDTA for 20 minutes. Mesenchymal and epithelial compartments were then separated by rimming the bladder with a needle and harvested in RLT. Total RNA was isolated for gene expression analysis using the Affymetrix MOE430 microarray chip

Background corr dist: KL-Divergence = 0.0343, L1-Distance = 0.0395, L2-Distance = 0.0022, Normal std = 0.6718

0.608 Kernel fit Pairwise Correlations Normal fit

Density 0.304

0.000 CEM 1

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

Pre-normalization Quantiles

mesenchyme1mesenchyme2 mesenchyme4(0.176734) urothelium5(0.172643) urothelium7(0.116267) (0.189304)urothelium8 (0.162944) (0.182107) [ min ] [ medium ] [ max ] CEM 1 Cldn7 138.8 7259.3 12623.5 P ( S | Z, I ) = 1.00 Epcam 348.5 15611.1 28437.6 Mean Corr = 0.78134Marveld2 37.7 4392.3 6423.2 Cldn3 5.6 54.7 270.6 Cldn4 13.7 217.9 612.7 Pard6b 135.2 2134.8 2912.9 Ocln 20.2 2225.6 4006.6 Tjp3 26.8 153.0 716.6 Tjp2 522.4 5288.3 7245.6 F11r 604.1 3454.2 3956.2 Inadl 286.9 2813.8 3409.6 Cldn23 14.9 3198.2 6597.3 Prkcz 175.7 652.8 1102.4 Shroom2 723.5 2386.9 3240.5 Cldn8 3.3 1832.0 2125.5 Igsf5 35.8 2257.2 4515.6 Cldn6 42.2 574.4 1412.0 Magi3 477.8 1693.1 2932.0 Tjp1 6272.9 10723.4 13847.7 Esrp1 29.1 9628.5 14057.8 Cdh1 36.0 9771.0 17058.1 St14 12.4 1231.1 3312.7 Cdcp1 62.7 2280.9 3250.5 Prss8 13.5 369.7 995.7 CEM 1 + Spint1 58.8 730.0 1521.8 Top 10 Genes Ap1m2 14.2 1730.6 2762.8 Irf6 443.6 10169.9 11049.8 Erbb3 160.0 6847.5 8689.5 Spint2 205.6 4191.2 6232.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE12881" 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=GSE12881 Status: Public on Jan 26 2009 Title: Loss of Caveolin-3 Induces the Development of a Lactogenic Microenvironment Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19164602 Summary & Design: Summary: Here, we show that functional loss of a single gene is sufficient to confer constitutive milk protein production and protection against mammary tumor formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly expressed in striated and smooth muscle cells. We demonstrate that Cav-3 is also expressed in myoepithelial cells within the mammary gland. To determine if genetic ablation of Cav-3 expression affects adult mammary gland development, we next studied the phenotype(s) of Cav-3 (-/-) null mice. Interestingly, detailed analysis of Cav-3 (-/-) virgin mammary glands shows dramatic increases in ductal thickness, side-branching, and the development of extensive lobulo-alveolar hyperplasia, akin to the changes normally observed during pregnancy and lactation. Analysis by genome-wide expression profiling reveals the upregulation of gene transcripts associated with pregnancy/lactation, mammary stem cells, and human breast cancers, consistent with a constitutive lactogenic phenotype. The expression levels of three key transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc are also significantly elevated. Experiments with pregnant mice directly show that Cav-3 (-/-) mice undergo precocious lactation. Finally, using orthotopic implantation of a transformed mammary cell line (known as Met-1), we demonstrate that virgin Cav-3 (-/-) mice are dramatically protected against mammary tumor formation. Interestingly, Cav-3 (+/-) mice also show similar protection, indicating that even reductions in Cav-3 levels are sufficient to render these mice resistant to tumorigenesis. Thus, Cav-3 (-/-) mice are a novel preclinical model to study the protective effects of a constitutive lactogenic microenviroment on mammary tumor onset and progression. Our current studies have broad implications for using the lactogenic micro-environment as a paradigm to discover new therapies for the prevention and/or treatment of human breast cancers. Most importantly, a lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anti-cancer therapies.

Overall design: All WT and Cav-3 knockout (KO) mice used in this study were in the FVB/N genetic background. 4-month old virgin female mice were utilized in a micro array study between 3 wildtype and 3 Caveolin-3 knock-out mammary glands.

Background corr dist: KL-Divergence = 0.0260, L1-Distance = 0.0141, L2-Distance = 0.0002, Normal std = 0.6931

0.576 Kernel fit Pairwise Correlations Normal fit

Density 0.288

0.000 CEM 1

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

Pre-normalization Quantiles

MammaryMammary Gland_WT_rep1Mammary Gland_WT_rep3Mammary Gland_WT_rep2 (0.108091)Mammary Gland_Cav-3KO_rep1 (0.159598)Mammary Gland_Cav-3KO_rep2 (0.196248) Gland_Cav-3KO_rep3 (0.157961) (0.183357)[ (0.194745)min ] [ medium ] [ max ] CEM 1 Cldn7 1406.3 5245.6 6330.1 P ( S | Z, I ) = 1.00 Epcam 1152.3 3481.6 4295.5 Mean Corr = 0.77157Marveld2 100.5 293.5 348.3 Cldn3 68.5 162.5 219.5 Cldn4 277.2 443.9 706.2 Pard6b 101.3 449.8 625.2 Ocln 137.6 361.6 488.4 Tjp3 258.3 1647.1 1951.5 Tjp2 716.7 1502.5 1556.3 F11r 1527.5 2495.6 2770.2 Inadl 170.6 389.9 512.9 Cldn23 45.0 81.6 122.3 Prkcz 333.4 553.5 669.6 Shroom2 230.2 465.6 620.2 Cldn8 366.5 2456.4 5342.6 Igsf5 106.3 403.1 826.9 Cldn6 109.6 181.4 192.9 Magi3 796.8 1536.7 2121.2 Tjp1 2260.5 3203.2 4077.5 Esrp1 603.8 2858.4 3410.7 Cdh1 620.8 1287.5 1740.8 St14 597.3 1974.2 2740.8 Cdcp1 988.8 2661.7 3090.4 Prss8 444.4 2036.8 2870.2 CEM 1 + Spint1 715.2 1509.6 2221.9 Top 10 Genes Ap1m2 771.1 3137.6 4704.9 Irf6 662.0 1769.5 1944.5 Erbb3 969.2 2284.4 4283.9 Spint2 500.8 1090.8 1210.7

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE27675" 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=GSE27675 Status: Public on Sep 15 2011 Title: Expression data from lung tumor and stromal cells of KrasTgfbr2 -/- mouse model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21911454 Summary & Design: Summary: Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse.

LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 ul of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally.

Overall design: We evaluated the tumor microenvironment response to Tgfbr2 deficient tumor cells. We compared lung tumor cell and stromal cell transcriptional profiles from five-week KrasTgfbr2 -/- and nine-week KrasTgfbr2 WT mice. We used mice at these time points to allow comparison of the stromal compartment of similarly advanced tumors.

Background corr dist: KL-Divergence = 0.0947, L1-Distance = 0.0412, L2-Distance = 0.0035, Normal std = 0.4458

0.895 Kernel fit Pairwise Correlations Normal fit

Density 0.447

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

KrasTgfbr2wtKrasTgfbr2wt stromaKrasTgfbr2wt stromaKrasTgfbr2-/-specimen stromaKrasTgfbr2-/-specimen 101 stroma(0.0381867)KrasTgfbr2-/-specimen 102 stroma(0.0579562)specimenKrasTgfbr2-/- 103 stroma(0.148893)specimenKrasTgfbr2wt 111 (0.0688315)stromaspecimenKrasTgfbr2wt 112 (0.0603941)specimenlungKrasTgfbr2wt 113 tumor (0.0569451) lungKrasTgfbr2-/- 114 specimen tumor (0.0639076) lungKrasTgfbr2-/- specimen tumor lung101KrasTgfbr2-/- (0.0690263)tumorspecimen lung102KrasTgfbr2-/- specimen (0.0699934)tumor lung103 specimen (0.0347378)tumor 111lung (0.0707694)specimen tumor 112 (0.0676801)specimen 113[ (0.0688313)min 114 (0.123847) ] [ medium ] [ max ] CEM 1 Cldn7 226.4 2273.8 4188.9 P ( S | Z, I ) = 1.00 Epcam 371.2 2455.0 7122.5 Mean Corr = 0.74172Marveld2 302.2 750.9 951.0 Cldn3 133.5 1676.2 2957.4 Cldn4 216.9 746.1 2803.6 Pard6b 77.4 1114.5 2352.3 Ocln 108.8 311.4 428.1 Tjp3 79.9 299.6 523.9 Tjp2 569.9 2815.6 3919.8 F11r 1012.5 3999.5 5012.6 Inadl 72.1 420.0 668.3 Cldn23 41.1 71.6 299.7 Prkcz 288.2 668.5 1402.5 Shroom2 176.6 649.2 837.1 Cldn8 74.9 125.9 272.9 Igsf5 148.3 1564.9 2708.4 Cldn6 50.7 60.0 96.2 Magi3 886.3 2609.2 5579.6 Tjp1 1978.5 4433.1 6546.4 Esrp1 113.9 1159.5 2676.1 Cdh1 697.6 5429.2 7601.8 St14 776.7 2419.5 3341.6 Cdcp1 459.5 3146.0 3854.3 Prss8 283.7 3865.7 5297.6 CEM 1 + Spint1 337.6 3208.3 4720.8 Top 10 Genes Ap1m2 141.2 863.8 1328.4 Irf6 97.5 717.0 1225.3 Erbb3 334.9 1745.7 2380.9 Spint2 1536.0 3599.1 6264.6

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE17797" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 19 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17797 Status: Public on Aug 29 2010 Title: UGE and UGM Reveal Novel Signaling Pathways and Ligand-Receptor Interactions in the Primitive Prostate Stem Cell Niche Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20941365 Summary & Design: Summary: We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their global gene expression profiles to define their differentially expressed regulators. To distinguish gene expression patterns that are shared by other developing epithelial/mesenchymal compartments in the embryo from those that pertain to the prostate stem cell niche, we also determine the global gene expression of epidermis and dermis of the same embryos. We identified a distinctive core of transcripts that were differentially regulated in the prostate stem cell niche. Our analysis indicates that several of the key transcriptional components that are likely to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Serbp1) and cell migration (e.g., Areb6 and Rreb1). Several of the promoter binding motifs that are enriched in the profiles are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. We also focused on defining ligand-receptor interactions that may be relevant in controlling signals in the stem cell niche and identified the Wnt/beta-catenin, ephrin, Notch, sonic hedgehog, FGF, TGF-beta and bone morphogenic signaling pathways as being of likely relevance in the prostate stem cell niches. Members of the integrins family including those that bind extracellular matrix proteins such as laminin and activate latent TGF-beta are also expressed in the prostate niche.development.

Keywords: Differential gene expression

Overall design: Six biological replicate experiments were performed for UGE. Five biological replicate experiments were performed for UGM. Four biological replicate experiments were performed for Epidermis. Four biological replicate experiments were performed for Dermis.

Background corr dist: KL-Divergence = 0.0825, L1-Distance = 0.0284, L2-Distance = 0.0013, Normal std = 0.4742

0.841 Kernel fit Pairwise Correlations Normal fit

Density 0.421

0.000 CEM 1

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

Pre-normalization Quantiles

mouse_urogenital_sinus_epithelium_rep1mouse_urogenital_sinus_epithelium_rep2mouse_urogenital_sinus_epithelium_rep3mouse_urogenital_sinus_epithelium_rep4mouse_urogenital_sinus_epithelium_rep5mouse_urogenital_sinus_epithelium_rep6 (0.0852679)mouse_urogenital_sinus_mesenchyme_rep1 (0.0737266)mouse_urogenital_sinus_mesenchyme_rep2 (0.0736353)mouse_urogenital_sinus_mesenchyme_rep3 (0.0460991)mouse_urogenital_sinus_mesenchyme_rep4 (0.0449857)mouse_urogenital_sinus_mesenchyme_rep5 (0.0478251)mouse_epidermis_rep1mouse_epidermis_rep2 (0.0457129)mouse_epidermis_rep3 (0.0462177)mouse_epidermis_rep4 (0.0409128) (0.070102)mouse_dermis_rep1 (0.0434684) (0.0506966)mouse_dermis_rep2 (0.0520947) (0.050139)mouse_dermis_rep3 (0.0543909) (0.0319279)mouse_dermis_rep4 (0.0448868) (0.0475513) (0.0503595)[ min ] [ medium ] [ max ] CEM 1 Cldn7 72.4 202.2 8535.1 P ( S | Z, I ) = 1.00 Epcam 92.1 615.3 5236.5 Mean Corr = 0.71517Marveld2 75.8 531.5 2320.1 Cldn3 66.4 172.6 570.5 Cldn4 184.0 975.1 2099.4 Pard6b 39.2 186.1 399.0 Ocln 46.9 372.4 1180.9 Tjp3 44.5 547.0 947.1 Tjp2 527.3 1976.4 2917.6 F11r 421.8 2134.7 5075.4 Inadl 68.4 246.5 1004.0 Cldn23 32.1 3207.2 5049.7 Prkcz 107.8 282.7 547.0 Shroom2 498.4 915.3 1370.9 Cldn8 43.6 158.4 1967.0 Igsf5 28.4 48.7 1087.4 Cldn6 75.0 131.6 2296.9 Magi3 727.8 1238.0 3673.5 Tjp1 3553.7 4732.2 7939.7 Esrp1 81.0 6295.0 11119.1 Cdh1 131.5 8415.3 11262.2 St14 141.5 1517.2 5073.6 Cdcp1 108.2 1867.5 3899.4 Prss8 83.6 821.6 3952.4 CEM 1 + Spint1 78.3 1925.9 4897.1 Top 10 Genes Ap1m2 61.1 1560.9 2801.3 Irf6 293.3 4224.7 9587.6 Erbb3 467.3 2515.1 4242.7 Spint2 350.3 2156.7 6119.5

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE1983" 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=GSE1983 Status: Public on Jul 01 2005 Title: Transcriptional Profiling of the Metanephric Kidney Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 15917337 Summary & Design: Summary: In this study we identify molecules with highly restricted expression patterns during the initial stages of metanephric development, when the ureteric bud has entered the metanephric mesenchyme and initiated branching morphogenesis. Using the Affymetrix Mouse Genome 430 2.0 Array, we compare gene expression patterns in ureteric bud tips, stalks and metanephric mesenchymes from mouse E12.5 embryos. To identify conserved molecular pathways, we also analyze transcriptional profiles in rat E13.5 ureteric buds and metanephric mesenchymes using the Affymetrix Rat Genome U34 Set. Taken together, these data sets help to identify conserved and highly localized transcripts in the metanephric kidney.

Keywords = Mus musculus

Keywords = Rattus norvegicus

Keywords = metanephric mesenchyme

Keywords = ureteric bud

Keywords = ureteric bud tips

Keywords = ureteric bud stalks

Keywords = molecular screen for spatially restricted transcripts

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0190, L1-Distance = 0.0266, L2-Distance = 0.0009, Normal std = 0.7646

0.528 Kernel fit Pairwise Correlations Normal fit

Density 0.264

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

UB tip 1UB (0.204913) tip 2UB (0.265981) stalkUB 1 (0.115644)stalkmetanephric 2 (0.071608)metanephric mesenchyme mesenchyme 1 (0.14329) 2 (0.198564)[ min ] [ medium ] [ max ] CEM 1 Cldn7 106.5 2820.2 5379.4 P ( S | Z, I ) = 1.00 Epcam 285.3 6342.2 12859.4 Mean Corr = 0.71051Marveld2 61.8 648.3 1179.3 Cldn3 95.2 1500.9 3354.6 Cldn4 124.7 4442.3 7425.8 Pard6b 81.1 529.2 1037.3 Ocln 108.1 1068.1 1777.9 Tjp3 91.3 213.2 381.2 Tjp2 1112.4 2178.1 2563.5 F11r 1465.8 2418.2 3483.1 Inadl 115.3 231.8 303.7 Cldn23 33.2 62.6 76.2 Prkcz 152.8 206.8 321.8 Shroom2 366.4 532.3 609.8 Cldn8 88.6 6390.4 6964.5 Igsf5 172.7 300.2 491.8 Cldn6 105.7 3209.2 6627.5 Magi3 886.4 1531.5 1803.9 Tjp1 3012.1 3278.2 3330.9 Esrp1 54.6 1719.7 4807.8 Cdh1 38.3 3567.2 5259.0 St14 118.1 525.8 1006.6 Cdcp1 149.1 554.0 1482.7 Prss8 76.2 885.1 1496.1 CEM 1 + Spint1 81.2 963.3 1352.2 Top 10 Genes Ap1m2 345.6 1416.8 3126.5 Irf6 48.8 542.0 579.2 Erbb3 103.4 1547.3 3288.6 Spint2 674.0 4208.1 7319.4

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE34206" 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=GSE34206 Status: Public on Dec 07 2011 Title: Gene regulation in macrophages from irradiated tumors Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22761754 Summary & Design: Summary: Tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression.

To investigate changes in the phenotype of tumor macrophages following radiation therapy, we FACS sorted tumor macrophages from Panc02 tumors. We have previously shown that we can distinguish mature tumor macrophages from immature myeloid and MDSC populations by expression of Gr1 and IA (MHC class II). To isolate these sub-populations, we first gated CD11b+ cells in the untreated or irradiated tumors, then sorted the CD11b+IA+ macrophage population and the CD11b+Gr1hi MDSC population. Cytospins of the sorted populations demonstrates that the CD11b+Gr1hi MDSC predominantly have a granulocyte morphology and the CD11b+IA+ cells have a macrophage morphology in both the untreated and irradiated tumors. RNA was purified from CD11b+IA+ macrophages from untreated or irradiated tumors 1 day or 7 days following radiation therapy and Gene Expression Microarray analysis was performed.

Overall design: There are untreated and irradiated samples at time points 1 day and 7 days following radiation therapy. The experiment was repeated in entirety, generating a second gene array sample for each. For analysis, the untreated samples of 1 day and 7 days were grouped together.

Background corr dist: KL-Divergence = 0.0586, L1-Distance = 0.0288, L2-Distance = 0.0013, Normal std = 0.5440

0.756 Kernel fit Pairwise Correlations Normal fit

Density 0.378

0.000 CEM 1

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

Pre-normalization Quantiles

Tumor MacrophageTumor MacrophageTumor Untreated MacrophageTumor Untreated MacrophageTumor d1 rep1 Untreated MacrophageTumor d1 (0.263527) rep2 Untreated MacrophageTumor d7 (0.0987489) rep1 Irradiated MacrophageTumor d7 (0.0529741) rep2 Irradiated Macrophage d1 (0.098614) rep1 Irradiated d1 (0.172973) rep2 Irradiated d7 (0.0964024) rep1 [d7 (0.0968737) min rep2 (0.119887) ] [ medium ] [ max ] CEM 1 Cldn7 1028.1 2053.0 3744.7 P ( S | Z, I ) = 1.00 Epcam 1412.5 3025.9 5216.5 Mean Corr = 0.70967Marveld2 268.9 374.3 810.3 Cldn3 102.0 202.4 598.3 Cldn4 269.2 342.0 990.0 Pard6b 55.1 132.3 272.6 Ocln 89.1 226.3 733.4 Tjp3 206.3 476.4 801.1 Tjp2 804.3 1147.8 2007.8 F11r 2482.2 3147.5 3527.6 Inadl 58.6 126.9 336.5 Cldn23 69.4 157.3 405.7 Prkcz 30.8 129.7 317.8 Shroom2 134.7 280.7 764.0 Cldn8 1.4 4.4 9.4 Igsf5 60.4 146.3 429.3 Cldn6 328.1 581.5 1034.3 Magi3 198.8 378.3 856.5 Tjp1 898.5 2390.3 3820.1 Esrp1 808.9 2006.2 4284.2 Cdh1 2628.5 3863.4 5365.3 St14 348.1 590.5 1551.6 Cdcp1 298.5 660.9 1943.0 Prss8 47.0 125.6 307.1 CEM 1 + Spint1 4837.4 5927.3 6616.2 Top 10 Genes Ap1m2 84.8 209.2 661.5 Irf6 630.5 1732.4 3276.6 Erbb3 983.1 1677.7 3752.1 Spint2 690.7 1571.2 3325.9

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE10659" 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=GSE10659 Status: Public on Mar 17 2008 Title: AFFYMETRIX ANALYSIS OF E9.5 RFC MOUSE KO EMBRYOS REVEALS ALTERED EXPRN OF GENES IN THE CUBILIN-MEGALIN COMPLEX Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18400109 Summary & Design: Summary: The reduced folate carrier (RFC1) is an integral membrane protein and facilitative anion exchanger that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. Adequate maternal-fetal transport of folate is necessary for normal embryogenesis. Targeted inactivation of the murine RFC1 gene results in post-implantation embryo lethality, but daily folic acid supplementation of pregnant dams prolongs survival of homozygous embryos until mid-gestation. At E10.5 RFC1-/- embryos are developmentally delayed relative to wildtype littermates, have multiple malformations, including neural tube defects, and die due to failure of chorioallantoic fusion. The mesoderm is sparse and disorganized, and there is a marked absence of erythrocytes in yolk sac blood islands. Affymetrix microarray analysis and quantitative RT-PCR validation of the relative gene expression profiles in E9.5 RFC1-/- vs. RFC1+/+ embryos indicates a dramatic downregulation of multiple genes involved in erythropoiesis, and upregulation of several genes that form the cubilin-megalin multiligand endocytic receptor complex. Megalin protein expression disappears from the visceral yolk sac of RFC1-/- embryos, and cubilin protein is widely misexpressed. Inactivation of RFC1 impacts the expression of several ligands and interacting proteins in the cubilin-amnionless-megalin complex that are involved in the maternal-fetal transport of folate, vitamin B12, and other nutrients, lipids and morphogens required for normal embryogenesis.

Comparison of RFC KO, wildtype normal embryos vs. RFC KO, nullizygous affected embryos

Keywords: reduced folate carrier knockout, folate receptor, cubilin, megalin, embryos, gene expression, neural tube defect, chorioallantoic fusion

Overall design: 6 samples RFC KO mouse embryos, E9.5, folic acid treated: 3 Control, Wildtype, normal; 3 Affected, Nullizygous, CR/chorioallantoic defect; as paired-littermates with one normal and one affected embryo per set from each of three separate litters for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0372, L1-Distance = 0.0154, L2-Distance = 0.0002, Normal std = 0.6268

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

150 E2_WT_Normal_repl150 E9_Null_Affected_repl164 E11_Null_Affected_repl164 1 E8_WT_Normal_repl(0.231933)165 E11_Null_Affected_repl 1 (0.165279)165 E3_WT_Normal_repl 2 (0.128387) 2 (0.146382) 3 (0.176919) 3 (0.151101)[ min ] [ medium ] [ max ] CEM 1 Cldn7 246.1 566.7 948.2 P ( S | Z, I ) = 1.00 Epcam 1081.4 1721.6 2189.1 Mean Corr = 0.69921Marveld2 154.3 288.1 365.4 Cldn3 62.7 79.1 93.8 Cldn4 173.3 272.2 356.5 Pard6b 251.6 399.6 493.1 Ocln 90.5 118.0 205.9 Tjp3 71.0 114.0 116.7 Tjp2 1178.8 1355.2 1457.2 F11r 612.1 1481.4 2090.8 Inadl 86.4 143.9 200.3 Cldn23 41.9 48.5 75.9 Prkcz 167.9 192.4 198.8 Shroom2 754.2 978.2 1016.1 Cldn8 108.9 185.0 272.7 Igsf5 81.4 91.4 218.6 Cldn6 519.7 1220.2 1720.2 Magi3 1308.5 1875.0 2144.6 Tjp1 6609.3 7896.5 8396.2 Esrp1 644.2 978.6 1220.2 Cdh1 473.3 1092.5 1762.7 St14 240.0 350.5 460.3 Cdcp1 303.7 554.0 833.1 Prss8 288.9 589.0 939.6 CEM 1 + Spint1 208.2 389.9 514.5 Top 10 Genes Ap1m2 247.1 359.1 567.3 Irf6 70.3 183.8 462.8 Erbb3 494.5 540.9 663.5 Spint2 712.0 1056.0 1443.6

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE20577" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20577 Status: Public on Dec 01 2010 Title: Gestational taurine supplementation of mice: effect on offspring gene expression in liver and skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams.

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

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

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

0.543 Kernel fit Pairwise Correlations Normal fit

Density 0.271

0.000 CEM 1

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

Pre-normalization Quantiles

4 week 4liver, week untreated, 4liver, week untreated, 4liver, biologicalweek untreated, 4liver, biologicalweek replicate in 4liver,utero biologicalweek replicate in 1taurine 4liver,(0.0881365)utero week replicate in 2taurinesupplementation, 4skeletal(0.0507697)utero week 3taurinesupplementation, 4skeletal (0.0598135)muscle, week supplementation, 4skeletal muscle, weekuntreated,biological 4skeletal muscle, weekuntreated,biological biologicalreplicate 4skeletal muscle, weekuntreated,biological biologicalreplicate 1skeletal replicate muscle, (0.259768)in utero biologicalreplicate 2 replicate muscle, (0.0704024)in 1taurine (0.0683978)utero 3 replicate (0.0506041)in 2taurinesupplementation, (0.0611169)utero[ 3taurineminsupplementation, (0.0580763) supplementation, ] biological biological replicate[ mediumbiological replicate 1 (0.0596979) replicate 2 (0.0830214) ] 3 (0.0901954)[ max ] CEM 1 Cldn7 49.6 75.8 132.6 P ( S | Z, I ) = 1.00 Epcam 56.3 100.7 190.7 Mean Corr = 0.69235Marveld2 44.3 126.5 509.6 Cldn3 71.6 2303.7 3558.6 Cldn4 66.3 90.5 130.4 Pard6b 38.2 78.8 110.2 Ocln 63.4 145.9 205.0 Tjp3 102.6 394.3 1145.7 Tjp2 263.9 424.4 953.4 F11r 747.0 1636.9 5099.9 Inadl 47.1 75.8 100.9 Cldn23 37.1 49.0 87.6 Prkcz 85.9 205.0 460.1 Shroom2 134.3 321.6 754.1 Cldn8 38.4 45.5 53.6 Igsf5 48.2 844.7 1559.7 Cldn6 55.2 69.2 88.5 Magi3 169.7 868.1 1330.7 Tjp1 1535.7 2198.3 3669.2 Esrp1 48.0 59.9 95.7 Cdh1 39.3 556.2 5558.9 St14 78.2 125.7 546.2 Cdcp1 66.2 307.4 772.9 Prss8 55.0 153.5 436.7 CEM 1 + Spint1 57.7 75.3 146.6 Top 10 Genes Ap1m2 49.7 80.9 101.7 Irf6 48.4 187.8 1367.9 Erbb3 550.9 1817.2 3784.5 Spint2 354.4 3246.3 4878.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE16380" 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=GSE16380 Status: Public on Jan 28 2010 Title: Gene expression analyses of C/EBPb knockout in stem/progenitor cell populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20054865 Summary & Design: Summary: CCAAT/enhancer binding protein beta (C/EBPb) is a member of a family of highly conserved transcription factors that regulates numerous genes involved in proliferation and differentiation in a variety of tissues. C/EBPb is deregulated in human breast cancer and germline deletion of this gene results in multiple defects in mammary gland development. We hypothesized that C/EBPb regulates mammary stem cell self-renewal, maintenance and/or differentiation through the regulation of multiple target genes that coordinate mammary gland development. Utilizing both a germline knockout mouse model and a conditional knockout strategy, we demonstrated that mammosphere formation was significantly decreased in C/EBPb-deficient mammary epithelial cells (MECs). The ability of C/EBPb-deleted MECs to regenerate the mammary gland in vivo was severely impaired when transplanted at limiting dilution. Furthermore, serial transplantation of C/EBPb-null mammary tissue resulted in decreased outgrowth potential when compared to wildtype, and an early senescence phenotype. Flow cytometric analysis revealed that C/EBPb-null MECs contain a lower frequency of repopulating stem cells accompanied by an increase in committed, differentiated luminal cells as compared to wildtype. Microarray analysis of stem/progenitor cell populations was performed and revealed an alteration in cell fate specification in C/EBPb-null glands, exemplified by the aberrant expression of basal markers in the luminal cell compartment. Collectively, our studies demonstrate that C/EBPb is a critical regulator of mammary stem cell differentiation, and an important determinant of luminal cell fate specification.

Keywords: multiple group comparison

Overall design: To identify potential signaling pathways regulated by C/EBPb in stem/progenitor cells, microarray analysis was performed on two stem/progenitor cell subpopulations. For this analysis, subpopulations defined by LIN-CD24+CD29hi and LIN-CD24hiCD29lo were FACS sorted from wildtype and germline C/EBPb-/- glands, and RNA was isolated from each group.

Background corr dist: KL-Divergence = 0.0627, L1-Distance = 0.0241, L2-Distance = 0.0009, Normal std = 0.5244

0.761 Kernel fit Pairwise Correlations Normal fit

Density 0.380

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

CEBPb CEBPbknockout, CEBPbknockout, CD24+CD29hi CEBPbknockout, CD24+CD29hi CEBPbknockout, cells,CD24hiCD29lo CEBPbwildtype, biological cells,CD24hiCD29lo CEBPbwildtype, biological CD24+CD29hi cells, rep CEBPb wildtype,1 biologicalCD24+CD29hi(0.105727) cells, rep wildtype,2 biologicalcells,CD24hiCD29lo(0.102092) rep biological 1 cells,CD24hiCD29lo (0.178433) rep biological 2 cells,(0.153449)rep 1[ biological(0.097894) cells, minrep 2 biological(0.132191) rep] 1 (0.134605) rep 2 (0.0956093)[ medium ] [ max ] CEM 1 Cldn7 204.5 1969.8 2833.0 P ( S | Z, I ) = 1.00 Epcam 9849.3 12088.9 13523.5 Mean Corr = 0.67345Marveld2 473.2 1750.8 3334.3 Cldn3 10.5 59.5 253.9 Cldn4 151.8 1714.8 2953.3 Pard6b 327.6 823.7 1932.4 Ocln 107.3 1345.4 1738.0 Tjp3 49.4 551.1 658.9 Tjp2 768.6 1071.9 1444.3 F11r 1014.2 1172.9 1368.2 Inadl 683.2 911.1 1028.4 Cldn23 52.2 280.9 543.5 Prkcz 186.3 269.4 413.9 Shroom2 528.5 1071.9 1406.7 Cldn8 12.3 459.5 901.5 Igsf5 7.5 52.8 233.6 Cldn6 48.0 586.6 1107.6 Magi3 469.8 1622.3 2314.0 Tjp1 3340.4 3810.9 4984.3 Esrp1 1772.3 2969.1 3068.2 Cdh1 3605.9 7200.2 9301.1 St14 1375.6 2445.9 3512.0 Cdcp1 944.8 3294.4 3720.8 Prss8 166.7 521.4 677.4 CEM 1 + Spint1 1959.4 4135.4 5549.3 Top 10 Genes Ap1m2 223.1 403.4 566.5 Irf6 2928.9 4112.8 5580.4 Erbb3 386.9 3249.8 4748.3 Spint2 2872.5 3334.3 3580.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE10589" 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=GSE10589 Status: Public on Feb 19 2009 Title: Comparison of gene expression between the thyroid of mice lacking Slc26a4 and heterzygous controls. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19692489 Summary & Design: Summary: Determination of differential expression of genes in the thyroid of pendrin (Slc26a4) heterozygous and knockout mice at a time point corresponding to maximal thyroid gland activity, postnatal day 15 (P15).

Keywords: Differential expression under disease state

Overall design: A total of Six samples of thyroid RNA obtained from P15 mice were analyzed. Triplicates from pendrin (Slc26a4) heterozygous and knockout mice were run and analyzed.

Background corr dist: KL-Divergence = 0.0392, L1-Distance = 0.0183, L2-Distance = 0.0004, Normal std = 0.6178

0.653 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

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

Pre-normalization Quantiles

PostnatalPostnatal day 15Postnatal (P15)day 15Postnatal thyroid (P15)day 15Postnatal thyroidSlc26a4 (P15)day 15Postnatal thyroidSlc26a4 (heterozygous) (P15)day 15 thyroidSlc26a4 (knockout) (P15)day 15 thyroidSlc26a4 (heterozygous) (P15)mice mice (sample1)thyroidSlc26a4 (knockout) (sample2)[ Slc26a4 (heterozygous) micemin (0.15841) mice (0.169617) (sample3) (knockout) (sample4)] mice (0.122986) mice (0.140006) (sample5)[ (sample6) medium (0.145396) (0.263585) ] [ max ] CEM 1 Cldn7 2615.9 3394.2 3861.7 P ( S | Z, I ) = 1.00 Epcam 3544.6 4442.7 4866.1 Mean Corr = 0.67258Marveld2 657.5 980.7 996.1 Cldn3 587.5 687.3 867.5 Cldn4 75.9 102.0 131.4 Pard6b 278.0 413.9 506.8 Ocln 686.7 1172.0 1466.6 Tjp3 289.6 336.4 412.3 Tjp2 685.9 1546.4 1907.9 F11r 1093.0 1292.0 1518.7 Inadl 326.8 634.6 714.0 Cldn23 74.1 147.0 161.8 Prkcz 310.8 421.6 466.7 Shroom2 897.2 1161.7 1402.9 Cldn8 3033.6 3670.3 4509.3 Igsf5 515.1 645.3 728.7 Cldn6 230.9 629.4 775.8 Magi3 1041.9 1488.6 1700.3 Tjp1 4685.7 5095.7 5377.8 Esrp1 2421.4 3061.3 3757.8 Cdh1 4580.9 5958.0 6781.6 St14 407.8 551.9 613.4 Cdcp1 324.7 436.6 510.3 Prss8 867.2 1060.3 1384.0 CEM 1 + Spint1 1262.3 1847.5 2116.5 Top 10 Genes Ap1m2 506.4 702.6 914.4 Irf6 3736.0 4631.6 4919.5 Erbb3 1772.4 2144.4 2668.4 Spint2 2390.5 3191.0 3562.5

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE3501" 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=GSE3501 Status: Public on Jan 01 2006 Title: Comparative analysis of 10 week and 5 week Bitransgenic mice (LH mouse crossed with MMTV-neu mouse) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16434967 Summary & Design: Summary: To identify genes that may facilitate early steps of ErbB2/Neu-mediated mammary tumorigenesis, we performed comparative microarray analysis of 5- and 10-week bitransgenic mammary glands (LHxMMTV-neu) in triplicate.

Keywords: transgenic mouse, erbB2, MMTV-neu, HER2, mammary tumor, breast cancer

Overall design: We analyzed 3 pooled RNA samples that represented 3 animals for each time point so that a total of 9 bitransgenic mice were analyzed per time point.

Background corr dist: KL-Divergence = 0.0235, L1-Distance = 0.0195, L2-Distance = 0.0004, Normal std = 0.7222

0.562 Kernel fit Pairwise Correlations Normal fit

Density 0.281

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

10week10week bitransgenic10week bitransgenic Ker825 bitransgenic week (0.158341) Ker83 5bitransgenic week (0.183975) Ker4 5bitransgenic week (0.115837) Ker85 bitransgenic (0.136953) Ker86 (0.196966) Ker87 (0.207927)[ min ] [ medium ] [ max ] CEM 1 Cldn7 1907.8 4771.4 5916.3 P ( S | Z, I ) = 1.00 Epcam 4763.2 9134.0 11549.7 Mean Corr = 0.66350Marveld2 320.4 599.7 702.4 Cldn3 1329.1 3660.8 4522.4 Cldn4 459.1 1540.7 1815.0 Pard6b 107.9 579.3 662.5 Ocln 211.4 358.2 470.8 Tjp3 569.1 2125.7 2317.3 Tjp2 754.1 1143.4 1546.0 F11r 1599.2 2721.2 3053.9 Inadl 210.9 402.3 477.1 Cldn23 55.6 98.9 161.1 Prkcz 90.5 376.1 503.3 Shroom2 444.8 811.2 1067.3 Cldn8 664.9 4138.4 4760.6 Igsf5 223.6 869.7 994.6 Cldn6 55.9 215.1 374.0 Magi3 655.1 1227.1 1409.9 Tjp1 2514.7 3227.3 3329.5 Esrp1 1108.4 3055.2 3569.7 Cdh1 1603.4 3164.7 3485.4 St14 1123.0 3806.9 5058.1 Cdcp1 1031.1 2644.5 3037.6 Prss8 432.3 1365.2 1824.4 CEM 1 + Spint1 653.1 2429.2 2938.4 Top 10 Genes Ap1m2 1497.9 4363.5 4906.5 Irf6 692.5 1554.4 2272.1 Erbb3 1452.6 2954.2 3547.3 Spint2 2712.1 7360.7 8499.7

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE31106" 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=GSE31106 Status: Public on Aug 02 2012 Title: Expression data for the different phases of ulcerative colitis-associated carcinogenesis in a mouse model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22610167 Summary & Design: Summary: Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains inflammation-dysplasia-cancer sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC.

Overall design: 6-week-old male ICR mice were given a single intraperitoneal injection of AOM (10mg/kg) at Day 1, followed by three cycles of DSS administration (cycle 1: 2%, Day 8~14; cycle 2: 1.5%, Day 29~33; cycle 3: 1.5%, Day 50~54) in the drinking water. Instead, control group of mice were given a single intraperitoneal injection of saline (10mg/kg) at Day 1 and distilled water drinking from the beginning to the end without DSS. Colorectal tissues were collected at days 14, 28, 42, 56 and 140 (at the end of the 2nd, 4th, 6th, 8th and 20th week) from the AOM/DSS group and at day 14 from the control group. Pathological changes of each sample were identified under microscope. Samples collected at the end of the 2nd week were inflamed mucosae, the 4th week were low grade dysplasias, the 6th week were high grade dysplasias, the 8th week were high grade dysplasias with active inflammation, the 20th week were carcinomas, and the control sample were normal mucosae. Total RNA were extracted and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.

Background corr dist: KL-Divergence = 0.1191, L1-Distance = 0.0266, L2-Distance = 0.0013, Normal std = 0.4164

0.958 Kernel fit Pairwise Correlations Normal fit

Density 0.479

0.000 CEM 1

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

Pre-normalization Quantiles

normal normalcolorectal normalcolorectal mucosa, inflamedcolorectal mucosa, biologicalinflamed colorectal mucosa, biological inflamedrep1 colorectal mucosa biological(0.0806353) lowrep colorectal grade 2mucosa at(0.0662005) low rep2wk, dysplasia grade 3mucosa at(0.0548486)biologicallow 2wk, dysplasia grade atatbiologicalhigh 4wk,2wk, rep dysplasia grade 1 atbiologicalbiological (0.0803132)high 4wk, rep dysplasia grade 2atbiological (0.149648)high 4wk, reprep dysplasia grade1 3biological at (0.0320206)(0.111754)high rep6wk, dysplasia grade2 atbiological(0.0352019)high rep6wk, dysplasia grade3 atbiological(0.0493858)high 6wk, rep dysplasia grade 1atbiological adenocarcinoma(0.0288974) 8wk, rep dysplasia 2atbiological adenocarcinoma(0.0324855) 8wk, rep 3atbiological adenocarcinoma(0.0234251) 8wk, repat 20wk, 1 biological (0.042803) repat biological 20wk, 2 (0.108254) repat biological 20wk, 3rep (0.0263) 1 biological (0.0352791) rep[ min2 (0.0244292) rep 3 ](0.0181197) [ medium ] [ max ] CEM 1 Cldn7 212.4 16306.6 20479.9 P ( S | Z, I ) = 1.00 Epcam 719.6 22091.2 25259.7 Mean Corr = 0.64926Marveld2 42.9 897.4 1333.7 Cldn3 118.3 2041.0 3457.2 Cldn4 211.6 1529.2 5040.6 Pard6b 36.6 291.5 354.4 Ocln 46.6 794.5 1567.3 Tjp3 91.3 1620.6 2063.8 Tjp2 863.8 3302.9 4570.1 F11r 1285.3 3838.7 4711.9 Inadl 58.0 615.6 871.4 Cldn23 35.2 1895.8 3398.5 Prkcz 130.4 362.4 582.3 Shroom2 193.7 675.1 834.6 Cldn8 25.9 1931.9 5346.7 Igsf5 52.9 1596.6 2062.9 Cldn6 65.4 101.5 401.7 Magi3 978.2 1892.3 3561.0 Tjp1 2897.6 4496.7 5335.9 Esrp1 39.5 3016.8 4200.1 Cdh1 211.0 11392.4 14541.3 St14 236.6 4857.2 6759.7 Cdcp1 87.5 1731.5 2105.8 Prss8 57.7 409.9 590.0 CEM 1 + Spint1 112.4 3096.5 3815.1 Top 10 Genes Ap1m2 76.3 1623.7 1992.0 Irf6 38.8 2784.2 4568.5 Erbb3 328.2 3866.6 6910.8 Spint2 1698.6 11718.2 16044.6

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE15794" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.597 Kernel fit Pairwise Correlations Normal fit

Density 0.298

0.000 CEM 1

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

Pre-normalization Quantiles

urothelium1_200209urothelium2_200209urothelium5_200209 (0.126334)mesenchyme1_200209 (0.171398)mesenchyme2_200209 (0.177247)mesenchyme3_200209 (0.264393) (0.117871) (0.142757)[ min ] [ medium ] [ max ] CEM 1 Cldn7 19.8 4594.7 6216.1 P ( S | Z, I ) = 1.00 Epcam 199.9 12079.4 13874.6 Mean Corr = 0.64779Marveld2 112.8 3510.8 4227.1 Cldn3 3.4 36.9 85.9 Cldn4 44.1 161.9 467.8 Pard6b 60.6 462.9 2000.4 Ocln 18.4 742.8 2257.3 Tjp3 17.0 98.3 173.2 Tjp2 1179.4 2668.2 3788.0 F11r 220.7 1613.0 2767.1 Inadl 643.8 1993.9 2277.2 Cldn23 6.6 3235.5 5873.7 Prkcz 192.1 440.0 514.7 Shroom2 1350.8 2080.3 2878.1 Cldn8 3.5 316.9 1142.0 Igsf5 25.3 332.6 893.9 Cldn6 40.0 549.7 948.9 Magi3 622.8 1108.5 2133.6 Tjp1 6556.5 8587.3 9130.1 Esrp1 33.5 5633.9 7960.6 Cdh1 9.5 3593.9 7284.9 St14 8.2 784.3 1230.1 Cdcp1 87.7 2405.8 2496.6 Prss8 1.4 222.6 362.9 CEM 1 + Spint1 73.6 569.4 1113.6 Top 10 Genes Ap1m2 6.7 1707.3 2763.3 Irf6 748.0 9823.8 13242.2 Erbb3 2198.0 5722.9 8602.8 Spint2 747.6 6200.7 6906.8

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE51628" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51628 Status: Public on Oct 24 2013 Title: Effects of acute Notch activation on the mammary epithelial compartment in vivo Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.

Overall design: Two timepoints (48h and 96h) of doxycycline induction in TetO-NICD1 (TICNX; control) and MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice with 3-4 replicates per timepoint

Background corr dist: KL-Divergence = 0.0788, L1-Distance = 0.0320, L2-Distance = 0.0014, Normal std = 0.4893

0.843 Kernel fit Pairwise Correlations Normal fit

Density 0.422

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

TICNX_48h_rep1TICNX_48h_rep2TICNX_48h_rep3 (0.06526)TICNX_48h_rep4 (0.0595084)TICNX_96h_rep1 (0.0682944)TICNX_96h_rep2 (0.040816)TICNX_96h_rep3 (0.0711752)MTB/TICNX_48h_rep1 (0.0654384)MTB/TICNX_48h_rep2 (0.0496672)MTB/TICNX_48h_rep3 MTB/TICNX_48h_rep4(0.0269715) MTB/TICNX_96h_rep1(0.0311443) MTB/TICNX_96h_rep2(0.0341981) MTB/TICNX_96h_rep3(0.070819) MTB/TICNX_96h_rep4(0.0360581) (0.141423) (0.119809) (0.119417)[ min ] [ medium ] [ max ] CEM 1 Cldn7 858.6 2133.6 6155.3 P ( S | Z, I ) = 1.00 Epcam 4677.0 7670.6 14818.3 Mean Corr = 0.63836Marveld2 133.6 290.2 803.6 Cldn3 380.0 703.4 2162.4 Cldn4 417.9 689.7 1086.2 Pard6b 36.1 66.8 282.6 Ocln 155.9 247.1 1116.0 Tjp3 220.2 432.5 1809.6 Tjp2 697.7 1027.2 2206.1 F11r 1518.4 1753.3 2695.3 Inadl 131.6 204.1 656.9 Cldn23 43.6 69.1 269.4 Prkcz 106.7 122.7 247.9 Shroom2 290.5 391.7 801.7 Cldn8 327.5 756.9 1473.2 Igsf5 55.9 82.4 183.8 Cldn6 85.4 118.3 197.4 Magi3 1175.4 1995.8 4030.3 Tjp1 2987.2 3519.0 4443.8 Esrp1 529.6 1479.0 4132.4 Cdh1 2108.7 3847.5 7346.5 St14 634.4 1043.2 1859.9 Cdcp1 578.8 1120.1 2232.2 Prss8 278.6 406.2 1102.3 CEM 1 + Spint1 223.2 380.6 1102.9 Top 10 Genes Ap1m2 367.7 904.8 2285.8 Irf6 330.4 541.9 1474.0 Erbb3 1045.6 1960.7 5065.5 Spint2 1900.5 3125.9 6009.5

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE7069" 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=GSE7069 Status: Public on Apr 20 2007 Title: Zfx controls the self-renewal of embryonic and hematopoietic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17448993 Summary & Design: Summary: Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult bone marrow HSC, but did not affect erythromyeloid progenitors or fetal HSC. In both ESC and HSC, Zfx activated a common set of direct target genes. In addition, the loss of Zfx resulted in the induction of immediate-early and/or stress-inducible genes in both SC types but not in their differentiated progeny. These studies identify the first shared transcriptional regulator of ESC and HSC, suggesting a common molecular basis of self-renewal in embryonic and adult SC.

Keywords: Global gene expression data analysis in Zfx-deficient murine ESC and HSC

Overall design: arrays (Affymetrix) at the Columbia University Microarray Project core facility according to the manufacturer's instructions. Samples were hybridized in duplicates, with the correlation between duplicate samples calculated at 0.995-0.997. Quality control and normalization were performed using positive and negative hybridization controls (Affymetrix) spiked into the RNA prior to labeling. Linear amplification of RNA was confirmed for every sample. Array scanning and raw data processing were done using GCOS 1.4 software (Affymetrix).

Background corr dist: KL-Divergence = 0.0096, L1-Distance = 0.0136, L2-Distance = 0.0002, Normal std = 0.8717

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

ESC_Zfx-flox_Replicate1ESC_Zfx-flox_Replicate2ESC_Zfx-null_Replicate1ESC_Zfx-null_Replicate2 (0.119907)HSC_Zfx-cko_Replicate1 (0.125244)HSC_Zfx-cko_Replicate2 (0.147989)HSC_Zfx-flox_Replicate1 (0.139792)HSC_Zfx-flox_Replicate2 (0.131525) (0.112507) (0.115236) (0.1078)[ min ] [ medium ] [ max ] CEM 1 Cldn7 18.4 215.0 483.9 P ( S | Z, I ) = 1.00 Epcam 9.6 2783.7 6188.2 Mean Corr = 0.63595Marveld2 82.9 162.2 224.6 Cldn3 2.5 3.7 28.0 Cldn4 7.1 423.7 935.3 Pard6b 106.0 268.0 329.5 Ocln 12.2 113.4 129.1 Tjp3 15.0 100.6 143.7 Tjp2 258.4 1615.6 1892.2 F11r 114.9 1889.3 2131.2 Inadl 66.3 111.1 157.6 Cldn23 10.3 20.9 38.4 Prkcz 5.9 269.6 354.4 Shroom2 33.3 1873.1 2066.2 Cldn8 2.2 3.0 16.4 Igsf5 33.3 59.5 100.9 Cldn6 54.7 659.2 1170.0 Magi3 181.7 378.6 696.2 Tjp1 928.4 3252.6 4354.0 Esrp1 2.0 276.4 471.0 Cdh1 52.8 6357.9 9704.7 St14 90.4 503.9 803.9 Cdcp1 73.0 118.8 258.0 Prss8 6.2 227.6 340.5 CEM 1 + Spint1 50.9 839.8 1647.7 Top 10 Genes Ap1m2 29.5 115.7 321.7 Irf6 63.4 108.1 187.4 Erbb3 481.0 868.4 1134.7 Spint2 1740.0 1942.3 3653.4

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE3822" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3822 Status: Public on May 01 2006 Title: Complete embryonic E11.5 metanephric kidney analysis of wild type and Hoxa11, Hoxd11 null targeted mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16581055 Summary & Design: Summary: E11.5 metanephric mesenchyme and ureteric bud were dissected from the E11.5 kidney rudiment using fine manual microdissection (ureteric bud only) or both fine manual microdissection and laser capture microdissection (metanephric mesenchyme) to define the gene expression profiles of these structures. Additionally, HoxA11, HoxD11 compound null E11.5 metanephric mesenchyme was obtained through laser capture microdissection allowing analysis of possible Hox targets in kidney development. Targets from multiple biological replicates of each were generated and the expression profiles were determined using Affymetrix MOE430_v2 arrays.

Keywords: embryonic metanephric kidney, kidney development, Hoxa11, Hoxd11, compound null targeted mice

Overall design: Using microdissection techniques, ureteric bud and metanephric mesenchyme were dissected from E11.5 kidney rudiments allowing the identificated genes specifically regulated in either structure. In addition, Hoxa11, Hoxd11 compound null E11.5 metanephric mesenchyme were normalized to wild type embryonic controls allowing the identification of potential Hox targets in normal kidney development. Each structure/genotype were represented in biological (seperate embryo) replicate.

Background corr dist: KL-Divergence = 0.1851, L1-Distance = 0.0434, L2-Distance = 0.0043, Normal std = 0.3462

1.152 Kernel fit Pairwise Correlations Normal fit

Density 0.576

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

HoxA11,Wild D11 type doubleWild embryonic type nullWild embryonicembryonic type E11.5Wildtype embryonic Metanephric E11.5E11.5Wild embryonic UreterictypeMetanephric E11.5Wildtype embryonicMesenchyme Ureteric E11.5BudWild embryonic replicateMesenchyme Metanephric type BudE11.5Wild replicateembryonic replicate Metanephrictype1 E11.5 (0.0710488)Wildtype replicateMesenchymeembryonic 5 Metanephric 2(0.0437826) E11.5(0.0885722)Wild embryonic Mesenchyme 1 Ureterictype (0.0974364)E11.5Wildtype replicate Mesenchymeembryonic Ureteric E11.5BudHoxA11, embryonicreplicate 1replicate Metanephric(0.0743383) BudE11.5HoxA11, replicateD11 replicate6 Metanephric3 (0.0522454)E11.5double (0.0741486)HoxA11, D11 Mesenchyme 2 Metanephric(0.0607153)4 doublenull (0.0643179)HoxA11, D11 embryonicMesenchyme doublenull replicateD11 Mesenchymeembryonic doublenull E11.5 replicate embryonic3 (0.0370638)Metanephric null E11.5 replicate embryonic 7 Metanephric(0.0380004) E11.5[ min 4Mesenchyme (0.0541824)Metanephric E11.5 Mesenchyme] Metanephric replicate Mesenchyme replicate [Mesenchyme 2 medium(0.071504) replicate 3 (0.0525372) replicate 4 (0.052273) ] 5 (0.0678336)[ max ] CEM 1 Cldn7 26.4 911.7 11400.5 P ( S | Z, I ) = 1.00 Epcam 376.2 2645.0 12854.9 Mean Corr = 0.62998Marveld2 108.5 303.2 3700.7 Cldn3 2.0 10.0 753.4 Cldn4 14.5 67.5 1797.6 Pard6b 69.9 184.5 1516.6 Ocln 6.6 87.4 2201.9 Tjp3 7.7 89.4 291.6 Tjp2 2061.3 3216.1 5942.1 F11r 359.7 1426.1 2770.6 Inadl 460.2 834.9 1751.0 Cldn23 5.4 23.1 528.2 Prkcz 3.7 183.3 512.5 Shroom2 394.6 709.8 1499.1 Cldn8 2.0 107.0 4304.4 Igsf5 52.3 161.6 1381.8 Cldn6 16.2 171.5 5822.4 Magi3 659.1 1800.7 3499.6 Tjp1 2304.7 4901.1 6938.1 Esrp1 2.4 546.8 9706.5 Cdh1 1.4 231.5 4297.7 St14 24.0 288.1 3373.8 Cdcp1 74.3 361.0 3856.9 Prss8 2.0 179.3 1704.0 CEM 1 + Spint1 39.0 198.9 2182.5 Top 10 Genes Ap1m2 26.7 273.6 4676.4 Irf6 3.0 303.9 1532.2 Erbb3 29.6 768.6 8403.1 Spint2 341.9 929.5 4527.0

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE8024" 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=GSE8024 Status: Public on Jun 25 2007 Title: Murine ES cells, neural precursor cells and embryonic fibroblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17603471 Summary & Design: Summary: Expression profiles for isogenic (129SvJae x C57BL/6) murine embryonic stem (ES) cells, neural precursors (NPC) obtained through in vitro differentiation of the ES cells, and embryonic fibroblasts (MEF) obtained at day 13.5.

Keywords: cell type comparison

Overall design: 3 replicates of wt ES cells, 3 replicates of wt NPCs obtained by in vitro differentiation, 2 replicated of primary MEFs

Background corr dist: KL-Divergence = 0.0402, L1-Distance = 0.0576, L2-Distance = 0.0045, Normal std = 0.7004

0.621 Kernel fit Pairwise Correlations Normal fit

Density 0.311

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

ES_wt_rep1ES_wt_rep2 (0.113798)ES_wt_rep3 (0.133188)NPC_wt_rep1 (0.155418)NPC_wt_rep2 (0.130787)NPC_wt_rep3 (0.118431)MEF_wt_rep1 (0.108386)MEF_wt_rep2 (0.122248) (0.117745) [ min ] [ medium ] [ max ] CEM 1 Cldn7 6.0 31.0 1962.9 P ( S | Z, I ) = 1.00 Epcam 3.8 8.5 5717.8 Mean Corr = 0.61990Marveld2 2.2 20.4 215.8 Cldn3 3.9 17.9 279.6 Cldn4 5.1 65.4 1458.3 Pard6b 3.9 75.5 579.4 Ocln 8.7 57.4 162.8 Tjp3 13.2 128.0 515.2 Tjp2 412.2 804.8 3004.3 F11r 8.9 349.3 1351.4 Inadl 27.0 55.1 82.6 Cldn23 2.9 11.8 29.9 Prkcz 23.9 48.0 872.0 Shroom2 341.8 618.8 1010.8 Cldn8 2.2 4.0 18.1 Igsf5 4.2 19.7 36.7 Cldn6 9.2 30.0 952.2 Magi3 307.0 494.2 1070.6 Tjp1 3153.1 3492.7 3973.5 Esrp1 2.7 11.9 1055.8 Cdh1 4.8 63.4 8008.5 St14 24.8 49.9 1274.9 Cdcp1 44.6 94.3 273.7 Prss8 4.0 7.9 387.9 CEM 1 + Spint1 23.9 69.3 1708.6 Top 10 Genes Ap1m2 3.4 41.0 1743.5 Irf6 4.0 38.5 357.0 Erbb3 38.8 138.1 725.7 Spint2 11.1 141.2 2900.1

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE26290" 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=GSE26290 Status: Public on Feb 01 2011 Title: Expression data from control and Phospholipid dependent kinase 1 (PDK1) null cytotoxic T-lymphocytes (CTL) and from control and Akt inhibitor treated CTL Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21295499 Summary & Design: Summary: In cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1).

The role of PDK1 and Akt in CTL has however not been fully defined.

In order to explore the relative roles of these kinases in CTL we used microarrays to profile the gene expression of control and PDK1 null CTL.

In separate experiments we compared the gene expression profiles of control and Akt inhibitor treated CTL.

Overall design: The gene expression patterns of the AktI treated and the untreated CTL were then compared by microarray.

Background corr dist: KL-Divergence = 0.0257, L1-Distance = 0.0736, L2-Distance = 0.0070, Normal std = 0.8329

0.479 Kernel fit Pairwise Correlations Normal fit

Density 0.239

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

TamoxifenTamoxifen Cre TamoxifenControl Cre PDK1Control CTL, Cre nullbiological PDK1Control CTL, CTL, nullbiologicalPDK1 biologicalCTL, replicate CTL, nullbiologicalwild biological replicate CTL, 1replicate type (0.086417)wild biological replicateCTL, 2replicate type (0.0988588)1 biological(0.0763663)wild CTL+AktI, 3replicate type (0.0756436)2 (0.0727338)wild CTL, replicate type biological3 biological(0.0809698)wild CTL+AktI, type1 (0.0781222)wild replicate CTL, replicate typebiological biological CTL+AktI,1 (0.0971236)2 (0.0858362) replicate replicate biological 2 (0.0898284)3 (0.0681363) [replicate min 3 (0.0899639)] [ medium ] [ max ] CEM 1 Cldn7 32.0 57.7 78.3 P ( S | Z, I ) = 1.00 Epcam 158.9 365.4 494.6 Mean Corr = 0.61849Marveld2 192.7 235.0 321.6 Cldn3 75.9 103.7 124.9 Cldn4 49.0 61.5 78.3 Pard6b 24.9 31.5 52.6 Ocln 36.1 54.5 72.2 Tjp3 116.0 171.0 222.0 Tjp2 292.8 428.5 573.5 F11r 52.8 105.6 125.0 Inadl 22.0 27.4 39.3 Cldn23 14.3 20.3 26.3 Prkcz 166.0 404.5 649.2 Shroom2 19.9 34.9 42.9 Cldn8 13.9 24.3 26.6 Igsf5 231.5 647.7 852.6 Cldn6 60.0 77.2 87.5 Magi3 183.1 247.8 290.1 Tjp1 905.7 2393.6 3122.5 Esrp1 26.6 31.9 34.5 Cdh1 769.1 3661.2 6259.4 St14 369.1 466.9 559.9 Cdcp1 49.7 69.9 83.3 Prss8 44.1 49.7 54.9 CEM 1 + Spint1 42.6 54.7 71.0 Top 10 Genes Ap1m2 159.7 215.2 278.1 Irf6 21.8 30.9 39.2 Erbb3 160.0 181.9 221.4 Spint2 1067.0 1665.4 1970.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE17263" 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=GSE17263 Status: Public on Apr 13 2010 Title: Gene expression profiling of constitutive activation of Smoothened in the mouse uterus Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20130264 Summary & Design: Summary: In order to gain a better understanding of Ihh action during embryo implantation, we constitutively activated Smo in the murine uterus using the PRcre mouse model (PRcre/+SmoM2+; SmoM2). Female SmoM2 mice were infertile. They exhibited normal serum progesterone levels and normal ovulation, but ova failed to be fertilized in vivo and the uterus failed to undergo the artificially induced decidual response. SmoM2 mice exhibited uterine hypertrophy. The endometrium had a reduced number of uterine glands and the endometrial stroma lost its normal morphologic characteristics. Microarray analysis of 3 month old SmoM2 uteri demonstrated a chondrocytic signature and confirmed that constitutive activation of SmoM2 increased extracellular matrix production. Thus, constitutive activation of Smo in the mouse uterus alters the extracellular matrix which interferes with early pregnancy.

Keywords: two group comparison

Overall design: We constitutively activated Hh signaling in the uterus by the expression of a mutant SmoM2 allele. We crossed these mice to the PRcre mouse model to constitutively activate Smo in the murine uterus (PRcre/+SmoM2+; SmoM2). High density DNA microarray analysis was performed on 3 month old control and SmoM2 uteri.

Background corr dist: KL-Divergence = 0.0278, L1-Distance = 0.0182, L2-Distance = 0.0003, Normal std = 0.6861

0.590 Kernel fit Pairwise Correlations Normal fit

Density 0.295

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,Control, replicateControl, replicate 1 (0.151125)SmoM2, replicate 2 (0.145809)SmoM2, replicate 3 (0.1917)SmoM2, replicate 1 (0.179293) replicate 2 (0.150962) 3 (0.181112)[ min ] [ medium ] [ max ] CEM 1 Cldn7 3363.8 4766.7 10584.0 P ( S | Z, I ) = 1.00 Epcam 3671.4 9085.1 13620.9 Mean Corr = 0.61615Marveld2 307.8 665.1 990.9 Cldn3 919.1 2293.6 3575.9 Cldn4 153.6 487.5 983.2 Pard6b 99.9 292.7 357.2 Ocln 143.8 318.5 366.2 Tjp3 350.1 1653.1 2573.2 Tjp2 1389.4 1700.8 1949.3 F11r 2181.2 3088.6 3561.7 Inadl 465.0 729.0 887.1 Cldn23 500.7 1723.2 2280.9 Prkcz 145.7 302.9 332.0 Shroom2 868.6 996.3 1218.1 Cldn8 66.2 301.1 572.5 Igsf5 212.4 509.2 719.8 Cldn6 36.6 86.1 131.0 Magi3 579.8 755.4 850.9 Tjp1 4326.6 4700.8 5431.4 Esrp1 994.8 2302.2 3073.5 Cdh1 4464.6 9087.0 13069.3 St14 1141.1 2529.0 4051.2 Cdcp1 344.5 993.1 1782.8 Prss8 323.8 773.5 1024.5 CEM 1 + Spint1 583.5 1275.9 1817.1 Top 10 Genes Ap1m2 561.2 1222.3 1970.1 Irf6 1224.6 1979.3 2401.4 Erbb3 707.2 2511.0 2685.1 Spint2 6508.7 13648.5 15003.7

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE29798" 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=GSE29798 Status: Public on Feb 15 2012 Title: A combined RNAi and localization approach for dissecting long noncoding RNAs reveals a function of Panct1 in ES cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22327834 Summary & Design: Summary: Long non-coding RNAs (lncRNAs) regulate diverse biological pathways. Unlike protein coding genes, where methods to comprehensibly study their functional roles in cellular systems are available, techniques to systematically investigate lncRNAs have largely remained unexplored. Here, we report a technology for combined Knockdown and Localization Analysis of Non-coding RNAs (c-KLAN) that merges phenotypic characterization and localization approaches to study lncRNAs. Using a library of endoribonuclease prepared short interfering RNAs (esiRNAs) coupled with a pipeline for synthesizing labeled riboprobes for RNA fluorescence in situ hybridization (FISH), we demonstrate the utility of c-KLAN by identifying a novel transcript Panct1 (Pluripotency associated non-coding transcript 1) that regulates embryonic stem cell identity. We postulate that c-KLAN should be generally useful in the discovery of lncRNAs implicated in various biological processes.

Overall design: In this experiment, the levels of Panct1(AK156552) have been depleted by RNAi and the expression levels of all genes have been monitored 72 hours post transfection with esiRNAs against Panct1. An esiRNA against non-targeting Luciferase was used as a negative control.

Background corr dist: KL-Divergence = 0.0258, L1-Distance = 0.0248, L2-Distance = 0.0006, Normal std = 0.7131

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.290

0.000 CEM 1

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

Pre-normalization Quantiles

Oct4GipES_Panct1_esiRNA_72h_rep1Oct4GipES_Panct1_esiRNA_72h_rep2Oct4GipES_Panct1_esiRNA_72h_rep3Oct4GipES_Luc_esiRNA_72h_rep1Oct4GipES_Luc_esiRNA_72h_rep2Oct4GipES_Luc_esiRNA_72h_rep3 (0.162872) (0.145087) (0.17587) (0.17718) (0.150946)[ min (0.188045) ] [ medium ] [ max ] CEM 1 Cldn7 1074.1 3367.6 4030.8 P ( S | Z, I ) = 1.00 Epcam 6504.2 8764.8 9856.5 Mean Corr = 0.61203Marveld2 144.7 310.3 400.0 Cldn3 113.5 199.1 253.7 Cldn4 780.6 1803.8 2058.7 Pard6b 304.2 382.0 459.5 Ocln 128.8 167.4 215.8 Tjp3 164.2 220.9 264.5 Tjp2 2792.1 3429.7 4060.7 F11r 1671.8 2175.1 2482.4 Inadl 42.1 170.9 209.0 Cldn23 22.4 24.7 28.2 Prkcz 304.1 358.9 398.1 Shroom2 684.5 1190.6 1308.6 Cldn8 13.4 14.2 15.9 Igsf5 50.8 67.1 82.6 Cldn6 1000.9 2431.3 2653.8 Magi3 295.9 370.6 421.0 Tjp1 2318.4 3391.0 3501.7 Esrp1 707.8 1021.8 1131.4 Cdh1 8415.9 9720.8 10469.2 St14 595.2 1412.3 1538.7 Cdcp1 191.2 528.9 607.8 Prss8 264.5 323.3 441.9 CEM 1 + Spint1 487.4 579.0 619.0 Top 10 Genes Ap1m2 967.7 2140.7 2380.2 Irf6 112.0 228.6 266.4 Erbb3 518.8 651.2 953.8 Spint2 4603.1 4930.5 5137.5

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE48884" 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=GSE48884 Status: Public on Jul 16 2013 Title: Cyclin D1 determines estrogen depependent signaling in mouse mammary gland. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23864650 Summary & Design: Summary: Ovariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays.

Overall design: Six separate control Ccnd1+/+ C57BL/6 were compared to six Ccnd1-/- C57BL/6 mice. 3 mice in each group treated with placebo and three mice treated with E2

Background corr dist: KL-Divergence = 0.0851, L1-Distance = 0.0269, L2-Distance = 0.0012, Normal std = 0.4687

0.851 Kernel fit Pairwise Correlations Normal fit

Density 0.426

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse mammaryMouse mammaryMouse gland mammaryMouse Ccnd1+/+ gland mammaryMouse Ccnd1+/+ gland Vehicle mammaryMouse Ccnd1+/+ gland VehicleRep1 mammaryMouse Ccnd1+/+ gland(0.0796149) VehicleRep2 mammaryMouse Ccnd1+/+ gland(0.0546134) E2Rep3 mammaryRep1Mouse Ccnd1+/+ gland(0.117482) E2 (0.0820709) mammaryRep2Mouse Ccnd1-/- gland E2 (0.195501) mammaryRep3Mouse Ccnd1-/- glandVehicle (0.0560998) mammaryMouse Ccnd1-/- gland VehicleRep1 mammary Ccnd1-/-(0.0505646) gland VehicleRep2 Ccnd1-/-(0.112281) gland E2Rep3 Rep1 Ccnd1-/-(0.0602502) E2 (0.0674752) Rep2[ minE2 (0.0439241) Rep3 ](0.0801231) [ medium ] [ max ] CEM 1 Cldn7 45.2 161.1 2242.6 P ( S | Z, I ) = 1.00 Epcam 65.8 252.0 2700.8 Mean Corr = 0.60694Marveld2 39.4 82.2 210.7 Cldn3 51.8 63.7 124.6 Cldn4 52.6 101.0 642.1 Pard6b 34.3 42.3 110.5 Ocln 59.7 107.1 204.4 Tjp3 56.1 121.2 406.2 Tjp2 414.0 777.2 1234.4 F11r 987.6 1375.2 2038.8 Inadl 24.6 100.8 251.2 Cldn23 15.2 16.7 40.8 Prkcz 109.3 184.6 231.2 Shroom2 204.5 307.8 552.6 Cldn8 18.6 29.9 435.4 Igsf5 23.4 29.1 46.9 Cldn6 78.5 84.3 138.8 Magi3 435.4 483.4 747.4 Tjp1 1217.1 1759.0 2221.3 Esrp1 28.3 84.2 1105.2 Cdh1 27.5 154.7 1045.7 St14 82.7 219.6 1338.6 Cdcp1 88.5 239.4 1520.0 Prss8 45.5 87.3 348.3 CEM 1 + Spint1 103.4 160.2 898.2 Top 10 Genes Ap1m2 216.3 420.1 2390.1 Irf6 48.8 213.5 963.8 Erbb3 219.5 474.8 2965.1 Spint2 284.3 368.1 688.3

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE22040" 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=GSE22040 Status: Public on Dec 01 2010 Title: Gene expression data from somites of E9.5 mouse embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We used microarrays to identify Pax3 targets during myogenesis in the mouse embryo

Overall design: Mouse embryos were genotyped Pax3GFP/+ or Pax3PAX3-FKHR/GFP and dissected at E9.5 under a fluorescent binocular. Somites were dissected from the interlimb region and the more hypaxial domain separated from the neural tube and the epaxial extremity of the somites. GFP positive cells were then sorted by flow cytometry before RNA extraction and hybridization on Affymetrix microarrays. We also sorted GFP negative cells.

Background corr dist: KL-Divergence = 0.0785, L1-Distance = 0.0184, L2-Distance = 0.0003, Normal std = 0.4841

0.824 Kernel fit Pairwise Correlations Normal fit

Density 0.412

0.000 CEM 1

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

Pre-normalization Quantiles

somite ofsomite PAX3FKHR ofsomite PAX3FKHR repofsomite PAX3FKHR 1 (0.1179) repofsomite GFP+ 2 (0.097) repofsomite rep GFP+ 3 1(0.138465) (0.110913)ofsomite rep GFP+ 2 (0.0728548)ofsomite rep GFP- 3 (0.0722817)ofsomite rep GFP- 1 (0.12322) of rep GFP- 2 (0.114301) rep 3 (0.153065)[ min ] [ medium ] [ max ] CEM 1 Cldn7 47.5 69.0 391.2 P ( S | Z, I ) = 1.00 Epcam 48.1 60.8 1043.7 Mean Corr = 0.60204Marveld2 32.7 42.2 199.6 Cldn3 80.8 105.6 129.8 Cldn4 43.6 58.4 122.1 Pard6b 83.3 106.9 198.4 Ocln 48.1 60.4 76.1 Tjp3 60.6 70.0 102.7 Tjp2 1598.4 1665.8 2312.8 F11r 503.8 677.0 2995.2 Inadl 57.8 78.8 237.6 Cldn23 28.0 30.7 39.7 Prkcz 80.5 129.0 152.5 Shroom2 484.3 527.4 794.7 Cldn8 22.8 31.0 72.3 Igsf5 144.3 172.4 196.8 Cldn6 48.5 61.3 479.0 Magi3 663.5 741.1 1597.5 Tjp1 3795.5 4677.4 5688.1 Esrp1 38.9 48.4 627.3 Cdh1 29.1 40.0 654.2 St14 60.3 87.2 311.6 Cdcp1 44.5 47.3 289.8 Prss8 36.2 49.3 286.8 CEM 1 + Spint1 44.0 54.1 300.3 Top 10 Genes Ap1m2 32.6 40.9 146.5 Irf6 40.1 48.1 162.9 Erbb3 207.1 1069.3 1548.1 Spint2 449.5 494.6 1066.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE54349" 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=GSE54349 Status: Public on Jan 24 2014 Title: Expression data from colon and livers of mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARs role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research.

Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARs role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research.

Overall design: Total hepatic and colonic RNA from each respective group were pooled (n=7). The microarray analysis was carried as out as described by Jia et al. 8 Mouse Genome 430 2.0 Array GeneChips (Affymetrix, Santa Clara, CA) containing over 30,000 gene probe sets were used for genome-wide expression profiling.

Background corr dist: KL-Divergence = 0.0145, L1-Distance = 0.0248, L2-Distance = 0.0008, Normal std = 0.8186

0.487 Kernel fit Pairwise Correlations Normal fit

Density 0.244

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

CON ColonDSS (0.201596)ColonDSSPAR (0.134773)CON Colon LiverDSS (0.12604) (0.204781) LiverDSSPAR (0.181611) Liver (0.151199) [ min ] [ medium ] [ max ] CEM 1 Cldn7 12.8 18463.3 19696.2 P ( S | Z, I ) = 1.00 Epcam 29.5 25924.1 28100.4 Mean Corr = 0.60172Marveld2 266.9 678.5 932.3 Cldn3 937.2 2996.4 3685.2 Cldn4 26.1 727.6 864.8 Pard6b 3.5 246.0 391.0 Ocln 236.2 995.8 1649.2 Tjp3 195.2 1399.9 1549.3 Tjp2 226.1 1980.3 2472.7 F11r 998.0 2433.3 3000.8 Inadl 221.0 768.1 1228.5 Cldn23 5.8 1063.5 1805.0 Prkcz 302.0 593.6 915.0 Shroom2 736.3 1010.9 1188.8 Cldn8 10.0 3830.2 4848.4 Igsf5 1041.1 1738.6 2914.8 Cldn6 4.5 51.7 82.0 Magi3 1181.7 2273.2 2419.7 Tjp1 1702.6 5146.3 5281.0 Esrp1 10.3 4947.6 5241.1 Cdh1 1671.8 19212.4 24674.8 St14 10.7 3882.3 4757.8 Cdcp1 91.7 1817.5 2034.3 Prss8 284.8 531.6 697.9 CEM 1 + Spint1 105.9 3653.0 4245.7 Top 10 Genes Ap1m2 23.3 2445.5 3363.4 Irf6 1388.8 2525.5 4084.1 Erbb3 3222.2 5664.4 8320.5 Spint2 1347.2 12088.6 14048.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE34839" 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=GSE34839 Status: Public on Feb 28 2012 Title: Pten loss and RAS/MAPK activation cooperate to promote EMT and prostate cancer metastasis initiated from stem/progenitor cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22350410 Summary & Design: Summary: PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.

Overall design: Murine mutants with prostate specific loss of Pten and K-ras activation (K-rasG12D) under regulation of the probasin promoter developed high grade, invasive prostate cancer. RNA was extracted from dissected prostate lobes from individual mutants with pathology thought to closely mimic human disease. Prostate tissue was subject to RNA extraction and hybridization on Affymetrix cDNA microarrays.

Background corr dist: KL-Divergence = 0.0408, L1-Distance = 0.0392, L2-Distance = 0.0022, Normal std = 0.6408

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

Pb-Cre+;PtenL/W;K-rasG12D/W,Pb-Cre+;PtenL/W;K-rasG12D/W,Pb-Cre+;PtenL/W;K-rasG12D/W,Pten null,Pten biological null,Pten biological null,rep1 biological(0.130289)(0.1284) rep2 (0.187306)(0.269276) rep3 (0.150674)(0.134053)[ min ] [ medium ] [ max ] CEM 1 Cldn7 692.6 8830.2 10517.9 P ( S | Z, I ) = 1.00 Epcam 2993.9 20449.4 23337.4 Mean Corr = 0.59829Marveld2 144.0 1008.6 1467.2 Cldn3 1037.4 2685.4 4033.1 Cldn4 1340.0 6478.1 10023.8 Pard6b 65.3 601.2 759.1 Ocln 107.2 885.6 1519.6 Tjp3 106.1 1307.0 1897.3 Tjp2 1651.9 2419.6 2733.0 F11r 2646.8 4520.3 5606.5 Inadl 214.5 910.4 1341.3 Cldn23 145.3 1239.2 1987.8 Prkcz 63.7 372.6 458.9 Shroom2 347.2 1023.4 1151.8 Cldn8 41.1 1995.7 5030.0 Igsf5 815.5 1631.3 1858.2 Cldn6 56.9 67.3 105.6 Magi3 1811.7 2752.9 4012.7 Tjp1 2872.0 3540.4 3745.4 Esrp1 224.6 2892.4 4242.1 Cdh1 3273.2 12708.6 14552.6 St14 283.1 3916.0 5315.8 Cdcp1 851.1 2050.9 2982.6 Prss8 68.1 1387.1 1575.1 CEM 1 + Spint1 456.3 3041.2 4134.3 Top 10 Genes Ap1m2 247.1 2203.0 3166.6 Irf6 620.6 4469.4 5078.0 Erbb3 161.3 2439.4 2774.6 Spint2 2096.1 14469.6 16013.9

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE28593" 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=GSE28593 Status: Public on Apr 15 2011 Title: KMT1E Mediated H3K9 Methylation Is Required for the Maintenance of Embryonic Stem Cells by Repressing Trophectoderm Differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20014010 Summary & Design: Summary: Dynamic regulation of histone methylation by methyltransferases and demethylases plays a central role in regulating the fate of embryonic stem (ES) cells. The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene results in peri-implantation lethality and prevents the propagation of ES cells. However, Setdb1- null blastocysts do not display global changes in H3K9 methylation or DNA methylation, arguing against a genome- wide defect. Here we show that conditional deletion of the Setdb1 gene in ES cells results in the upregulation of lineage differentiation markers, especially trophectoderm-specific factors, similar to effects observed upon loss of Oct3/4 expression in ES cells. We demonstrate that KMT1E deficiency in ES cells leads to a decrease in histone H3K9 methylation at and derepression of trophoblast-associated genes such as Cdx2. Furthermore, we find genes that are derepressed upon Setdb1 deletion to overlap with known targets of polycomb mediated repression, suggesting that KMT1E mediated H3K9 methylation acts in concert with polycomb controlled H3K27 methylation. Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells.

Overall design: Analysis of KMT1E-deficiency in mouse embryonic stem cells using a Setdb1 conditional allele and tamoxifen-inducible Cre/loxP recombination

Background corr dist: KL-Divergence = 0.0295, L1-Distance = 0.0506, L2-Distance = 0.0029, Normal std = 0.7544

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.291

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

Setdb1 Setdb12lox/1lox Setdb12lox/1lox plus tamoxifenSetdb12lox/1lox plus tamoxifenSetdb12lox/1lox/Cre plus1 (0.110671) tamoxifenSetdb12lox/1lox/Cre 2 (0.0785791) minus Setdb12lox/1lox/Cre 3 (0.0951077) tamoxifen minus Setdb12lox/1lox/Cre tamoxifen minus Setdb12lox/1lox/Cre 1 (0.10158) tamoxifen plus 2lox/1lox/Cre 2 (0.102446) tamoxifen plus 3 (0.115135) tamoxifen plus1 (0.114393) tamoxifen 2[ (0.152273) min 3 (0.129816) ] [ medium ] [ max ] CEM 1 Cldn7 1279.9 2964.8 7842.1 P ( S | Z, I ) = 1.00 Epcam 8912.1 11511.4 14361.3 Mean Corr = 0.59795Marveld2 64.3 138.2 524.7 Cldn3 357.0 456.9 2556.8 Cldn4 4552.0 8529.7 19285.1 Pard6b 725.1 861.5 2735.5 Ocln 89.7 212.6 254.9 Tjp3 195.1 425.1 587.9 Tjp2 3191.3 4303.0 6523.7 F11r 1597.5 1900.8 4052.0 Inadl 27.9 38.3 301.5 Cldn23 18.4 21.4 93.5 Prkcz 352.6 537.6 874.9 Shroom2 736.4 1020.6 1159.7 Cldn8 12.0 14.3 16.3 Igsf5 21.8 29.3 35.1 Cldn6 1685.2 1839.6 4393.0 Magi3 360.6 514.7 996.6 Tjp1 2942.3 3225.5 5266.4 Esrp1 703.8 1160.8 1535.3 Cdh1 8802.1 11110.6 14794.3 St14 1803.6 1984.7 4598.2 Cdcp1 379.1 613.9 4390.4 Prss8 426.8 621.8 3176.4 CEM 1 + Spint1 1274.9 1592.6 3601.5 Top 10 Genes Ap1m2 1442.6 1669.0 2283.3 Irf6 170.5 288.5 589.0 Erbb3 723.2 1379.9 2015.1 Spint2 4949.5 5433.9 8389.3

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE11221" 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=GSE11221 Status: Public on Apr 22 2008 Title: Gene expression profiles of detrusor, stroma and urothelium isolated from SMGA (Actg2) transgenic neonatal bladders using LCM. (GUDMAP Series ID: 20) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of compartmental bladder tissues collected through laser capture microscopy.

Keywords: Gene expression comparison from developing regions of the mouse postnatal day 1 and postnatal day 2 urogenital system.

Overall design: Bladders were isolated from newborn SMGA/EGFP transgenic mice, embedded in OCT, frozen and sectioned (8 microns). Detrusor, stroma and urothelium were isloated using laser capture microscopy. The caps were frozen on dry ice and stored at -80 degrees C until RNA was extracted for gene expression analysis. Laser captured and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.

Background corr dist: KL-Divergence = 0.0937, L1-Distance = 0.0479, L2-Distance = 0.0047, Normal std = 0.4656

0.857 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

2801_Detrusor1848_Detrusor 2715_Detrusor(0.0623733) 2299_Urothelium(0.0657279) 2951_Urothelium(0.097464)2291_Urothelium (0.089794)2833_Stroma (0.158141)2865_Stroma (0.0847047) (0.113585)2295_Stroma (0.164546) (0.163665) [ min ] [ medium ] [ max ] CEM 1 Cldn7 60.2 734.3 9094.4 P ( S | Z, I ) = 1.00 Epcam 6.9 2998.7 14021.3 Mean Corr = 0.59495Marveld2 5.4 767.0 3095.5 Cldn3 2.1 6.0 31.9 Cldn4 3.2 179.3 1391.1 Pard6b 8.0 705.7 2093.8 Ocln 17.9 379.6 1264.7 Tjp3 36.2 85.5 328.1 Tjp2 482.6 1985.2 4442.5 F11r 424.5 2710.7 5382.0 Inadl 170.1 544.5 2360.5 Cldn23 2.6 257.8 8904.8 Prkcz 19.8 399.4 1382.3 Shroom2 348.8 1009.2 1565.8 Cldn8 2.5 155.4 6651.2 Igsf5 18.4 514.3 4219.6 Cldn6 7.3 48.6 323.8 Magi3 520.2 724.2 1149.5 Tjp1 4227.9 4651.2 7153.7 Esrp1 7.2 1835.4 7346.1 Cdh1 16.8 590.2 11491.9 St14 9.5 144.6 2813.3 Cdcp1 65.2 785.1 3516.7 Prss8 5.0 208.0 2212.0 CEM 1 + Spint1 78.7 380.2 2146.7 Top 10 Genes Ap1m2 6.5 543.2 2866.0 Irf6 460.9 1057.2 6999.5 Erbb3 336.1 497.5 7118.9 Spint2 2497.3 5737.5 12334.7

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE11382" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: Tumor co-promotion study

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

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

0.624 Kernel fit Pairwise Correlations Normal fit

Density 0.312

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl liver, biologicalAFB1 liver, liver,biologicalAFB1 rep biological 1liver, (0.092497)AFB1+H. rep biological 2 rep(0.0691191)AFB1+H. hepaticus 1 (0.0797571) repControl hepaticus 2 liver,(0.0811127)Control cecum, biological liver,AFB1+H. cecum,biological biological repAFB1+H. biological hepaticus1 rep(0.0794427) rep 1 hepaticus(0.167285)2 rep(0.0899403) cecum, 2 (0.122066) cecum,biological biological[ rep min 1 (0.123683) rep ]2 (0.0950968)[ medium ] [ max ] CEM 1 Cldn7 4.6 50.2 18060.5 P ( S | Z, I ) = 1.00 Epcam 10.1 90.0 26393.7 Mean Corr = 0.58920Marveld2 340.6 482.0 1128.6 Cldn3 1728.8 2803.3 4473.7 Cldn4 13.0 102.5 1429.2 Pard6b 79.7 144.0 650.7 Ocln 443.1 674.3 992.2 Tjp3 520.4 887.4 3036.1 Tjp2 552.1 710.9 1780.1 F11r 2624.0 3314.4 4916.1 Inadl 241.4 279.5 785.1 Cldn23 6.0 51.1 3835.7 Prkcz 426.6 692.2 1054.8 Shroom2 641.7 865.2 1170.8 Cldn8 1.5 21.1 356.7 Igsf5 709.1 982.5 2045.2 Cldn6 11.3 46.6 72.7 Magi3 978.5 1238.0 1435.2 Tjp1 1602.2 2361.0 3661.9 Esrp1 5.6 54.7 5569.9 Cdh1 277.3 1287.9 19515.0 St14 17.5 72.9 8749.9 Cdcp1 53.4 148.9 2099.0 Prss8 44.3 202.3 530.0 CEM 1 + Spint1 39.4 119.6 8169.8 Top 10 Genes Ap1m2 27.9 111.3 4909.0 Irf6 1108.4 2063.0 4505.6 Erbb3 4511.4 5421.5 8623.8 Spint2 2158.8 2556.9 12675.0

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam 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(0.15476) Epi intestineB small Mes(0.17478) Epi A intestineC (0.18758) Mes(0.162134) B (0.168225) Mes C (0.152522)[ min ] [ medium ] [ max ] CEM 1 Cldn7 374.0 10213.6 10697.5 P ( S | Z, I ) = 1.00 Epcam 410.7 13477.0 15917.4 Mean Corr = 0.57997Marveld2 93.5 703.5 967.6 Cldn3 117.9 823.1 1142.8 Cldn4 214.8 785.9 928.2 Pard6b 83.4 145.5 241.9 Ocln 349.0 1086.1 1191.2 Tjp3 110.0 768.0 928.2 Tjp2 440.2 1142.8 1684.6 F11r 1334.4 1646.3 2222.9 Inadl 47.0 328.2 483.8 Cldn23 38.0 623.8 842.3 Prkcz 349.0 1224.8 1276.7 Shroom2 464.1 651.2 716.6 Cldn8 40.7 1013.4 1935.1 Igsf5 145.2 1536.0 1935.1 Cldn6 77.8 124.1 145.5 Magi3 654.8 1732.1 1935.1 Tjp1 2026.8 2807.3 3437.2 Esrp1 95.8 543.1 733.3 Cdh1 77.8 7222.1 8689.1 St14 493.5 1805.5 2172.3 Cdcp1 283.5 967.6 1164.1 Prss8 107.4 2222.9 2866.3 CEM 1 + Spint1 698.0 3464.2 3870.2 Top 10 Genes Ap1m2 191.6 4764.8 5250.8 Irf6 305.5 2449.6 3143.6 Erbb3 566.9 2813.8 2933.1 Spint2 1496.1 7740.5 9981.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE19979" 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=GSE19979 Status: Public on Jan 22 2010 Title: Gene expression profiles of P7 bladder epithelium compartments isolated from Upk1b mice. (GUDMAP Series ID: 34) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing genitourinary tract The central thesis is straightforward. The combination of microdissected tissues and FACS sorted cells plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here delineates the gene expression profiles of the epithelial compartments of the P7 mouse bladder.

Overall design: At postnatal day 7 mice were euthanized by CO2 asphyxiation and the bladders were removed and cut at the bladder neck. The bladder was cut into rings and treated with 1 mg/ml trypsin in Tyrode’s solution for 30 minutes at 37 Ć. The layers were separated by gentle microdissection and the epithelial layer was further digested in a mixture of Blendzymes 1 & 4 at 37 Ć until a single cell suspension was obtained. The samples were placed in RLT and stored at -80 Ć.RNA was prepared and the Epicentre 2-round amplification scheme described under the Lessard Group Protocols on the GUDMAP pages were performed. The Affymetrix GeneChip Mouse Genome 430 2.0 Array was used to interrogate the amplified RNA.

Background corr dist: KL-Divergence = 0.0264, L1-Distance = 0.0357, L2-Distance = 0.0018, Normal std = 0.7181

0.556 Kernel fit Pairwise Correlations Normal fit

Density 0.278

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

uroplakin1-veuroplakin2-ve (0.134228)uroplakin5-ve (0.225709)uroplakin1+ve (0.22523)uroplakin2+ve (0.141792)uroplakin5+ve (0.134422) (0.138619) [ min ] [ medium ] [ max ] CEM 1 Cldn7 282.2 8480.2 9784.9 P ( S | Z, I ) = 1.00 Epcam 1033.7 11812.9 14149.6 Mean Corr = 0.57266Marveld2 31.2 2305.0 4036.5 Cldn3 2.6 19.3 37.6 Cldn4 139.5 1911.9 2015.1 Pard6b 94.1 3146.4 4395.8 Ocln 40.9 927.2 1851.7 Tjp3 167.0 472.1 616.1 Tjp2 769.3 7511.9 9223.5 F11r 809.6 2346.3 4975.7 Inadl 41.0 1918.1 3641.5 Cldn23 287.9 10707.4 15290.3 Prkcz 16.9 1176.9 1236.8 Shroom2 292.4 1529.3 2705.6 Cldn8 6.1 1799.8 2581.8 Igsf5 45.6 3927.1 4305.3 Cldn6 8.9 83.3 165.7 Magi3 474.2 1431.2 1821.3 Tjp1 3034.4 8696.7 11017.2 Esrp1 195.1 6400.7 7702.2 Cdh1 501.6 13633.1 18011.9 St14 153.2 2026.4 2655.5 Cdcp1 202.1 2722.6 3613.2 Prss8 32.2 1112.4 1481.2 CEM 1 + Spint1 370.9 2761.2 4835.0 Top 10 Genes Ap1m2 24.3 1748.2 2591.6 Irf6 74.2 6595.9 9105.7 Erbb3 96.9 5543.5 7091.8 Spint2 438.4 6249.3 8208.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE51213" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51213 Status: Public on Sep 26 2013 Title: Effect of chronic glucocorticoid (GC) treatment on neonatal mouse whole cerebellum and whole lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Dexamethasone (1ug/g, Dex) or vehicle (saline) injected into postnatal days 0-7 (P0 to P7) of C57BL6J mouse pups every day. Whole organ were harvested at P7.

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

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

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.290

0.000 CEM 1

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

Pre-normalization Quantiles

whole cerebellumwhole cerebellumwhole with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone replicate with cerebellumwhole dexamethasone replicate with B39 cerebellumwhole vehicle(0.0782113) replicate with B49 cerebellumwhole vehiclereplicate(0.0410437) replicate with B50 lungwhole vehiclereplicate(0.0543355) B78with B52with lung (0.0449507)whole vehicle replicate(0.0591145)dexamethasone B79 with lung (0.0518848)whole replicatedexamethasone B80 with lung (0.0483412)whole dexamethasone B81replicate with lung (0.047006)whole dexamethasone replicate with B28 lungwhole vehicle(0.062166) replicate with B31 lungwhole vehiclereplicate(0.0847757) replicate with B40 lung vehiclereplicate(0.0816668) B12with B46 (0.0497513) vehiclereplicate(0.123442) B14 (0.0619658) replicate B19 [(0.0623748) min B22 (0.0489704) ] [ medium ] [ max ] CEM 1 Cldn7 35.8 1310.2 2847.2 P ( S | Z, I ) = 1.00 Epcam 46.9 920.1 1698.8 Mean Corr = 0.57151Marveld2 41.5 184.5 392.2 Cldn3 56.5 662.9 3880.5 Cldn4 43.5 88.9 969.4 Pard6b 65.4 985.4 3331.7 Ocln 86.1 569.7 1067.0 Tjp3 35.6 118.0 338.3 Tjp2 764.9 1799.1 2386.4 F11r 275.2 5953.1 8685.1 Inadl 185.1 400.4 795.7 Cldn23 35.4 75.6 467.3 Prkcz 419.5 1138.6 1862.9 Shroom2 826.9 1083.2 3402.4 Cldn8 27.9 84.0 188.2 Igsf5 31.7 354.5 1464.6 Cldn6 34.4 55.0 87.9 Magi3 436.9 1898.5 2516.7 Tjp1 1673.1 6469.0 7838.8 Esrp1 25.0 657.9 1050.8 Cdh1 136.7 4782.8 8978.8 St14 57.6 517.6 1360.9 Cdcp1 42.9 558.6 1371.0 Prss8 43.4 1289.5 3993.1 CEM 1 + Spint1 53.5 746.2 1883.3 Top 10 Genes Ap1m2 64.5 430.3 849.8 Irf6 25.3 457.2 1066.3 Erbb3 72.0 950.5 2916.5 Spint2 511.8 2332.1 4818.3

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE24295" 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=GSE24295 Status: Public on Sep 23 2010 Title: Gene expression in epithelial and non-epithelial cells of renal origin Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20978075 Summary & Design: Summary: We aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.

Overall design: Affymetrix Mouse Genome 430 2.0 microarrays from mouse E12.5 ureteric bud tips, ureteric bus stalks, and metanephric mesenchymes had previously been published (GEO deposition: GDS1583) (Schmidt-Ott, K. M., Yang, J., Chen, X., Wang, H., Paragas, N., Mori, K., Li, J. Y., Lu, B., Costantini, F., Schiffer, M. et al. (2005). Novel regulators of kidney development from the tips of the ureteric bud. J Am Soc Nephrol 16, 1993-2002.). We added a new microarray analysis from a subclone of mIMCD-3 cells and recalculated expression values in the complete dataset by robust multichip analysis.

Background corr dist: KL-Divergence = 0.0216, L1-Distance = 0.0311, L2-Distance = 0.0012, Normal std = 0.7597

0.525 Kernel fit Pairwise Correlations Normal fit

Density 0.263

0.000 CEM 1

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

Pre-normalization Quantiles

mouse E12.5mouse metanephric E12.5mouse metanephric E12.5mouse mesenchyme_biological ureteric E12.5mouse mesenchyme_biological ureteric budE12.5mouse stalk_biological ureteric budE12.5mouse stalk_biological ureteric replicatebudinner tip_biological replicatemedullary replicatebud 1 (0.0994899) tip_biological replicate 1 2collecting(0.0793957) (0.139035)replicate 2[ (0.0539419) minreplicate duct 1 (0.0985682) cell ]2 line (0.164203) (mIMCD-3)[ medium (0.365367) ] [ max ] CEM 1 Cldn7 96.9 2921.8 5689.8 P ( S | Z, I ) = 1.00 Epcam 284.3 6901.2 14224.9 Mean Corr = 0.56445Marveld2 59.6 657.1 1238.2 Cldn3 76.1 1262.9 2844.8 Cldn4 120.6 4660.0 7808.8 Pard6b 78.2 487.3 1717.9 Ocln 96.2 864.9 1495.3 Tjp3 84.1 202.0 425.0 Tjp2 1145.1 2307.6 2768.6 F11r 1429.4 2406.6 3641.5 Inadl 106.7 222.4 394.6 Cldn23 36.3 75.7 80.2 Prkcz 148.7 193.5 414.3 Shroom2 360.2 583.7 1126.1 Cldn8 88.1 7448.2 8110.6 Igsf5 155.5 261.0 2038.9 Cldn6 61.7 3686.7 7664.9 Magi3 845.4 1538.4 2577.7 Tjp1 3110.8 3315.8 4807.2 Esrp1 49.4 1646.5 4523.0 Cdh1 33.9 3637.7 5390.3 St14 110.0 520.3 2241.9 Cdcp1 143.5 527.3 2076.2 Prss8 73.8 827.7 1455.2 CEM 1 + Spint1 74.2 971.1 2312.1 Top 10 Genes Ap1m2 300.0 1378.1 3093.6 Irf6 41.7 525.1 1142.7 Erbb3 93.6 1395.6 3324.7 Spint2 664.8 4525.1 8000.1

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE9977" 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=GSE9977 Status: Public on Sep 30 2009 Title: Expression data from NIH-3T3 cells treated with mock, 100 U/ml IFN alpha or 100 U/ml gamma for 1or 3h Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18658122 Summary & Design: Summary: Differential gene expression caused by 1h and 3h of IFN alpha or gamma treatment was analyzed in total cellular RNA of NIH-3T3 cells compared to mock

We used microarrays to analyze the effects of 1 and 3h of IFNalpha and gamma treatment in total cellular RNA

Keywords: time course in total cellular RNA (tc-RNA)

Overall design: NIH-3T3 cells ( 5th to 15th passage after thawing) were split from confluent plates 24h before start of the experiment. At the begin of the experiment about 80% confluency was reached. The experiment was started by applying fresh, prewarmed, CO2-equilibrated medium containing either mock, 100U/ml IFN alpha or 100 U/ml IFN gamma. Labeling was either started together with addition of IFN for 60 minutes or for 30 minutes starting 150 minutes after begin of treatment.

Background corr dist: KL-Divergence = 0.0343, L1-Distance = 0.0629, L2-Distance = 0.0042, Normal std = 0.7786

0.512 Kernel fit Pairwise Correlations Normal fit

Density 0.256

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

1h mock1h tc-RNA mock1h tc-RNARep.1 mock1h (0.0190525) tc-RNARep.2 mock1h (0.0263939) 200´MRep.3 mock1h (0.0758471) 4sU200´M mock tc-RNA1h 4sU200´M mock tc-RNARep.11h 4sU200´M 100U/ml (0.0169594) tc-RNARep.21h 4sU 100U/ml IFNalpha (0.114795) tc-RNARep.31h 100U/ml IFNalpha (0.0278152) Rep.4+1h 200´M 100U/ml IFNalpha (0.0310653) + 1h 4sU200´M 100U/ml IFNalphatc-RNA + 1h 4sU200´M 100U/ml IFN tc-RNARep.1 200´M 1h 4sUgamma 100U/ml (0.0225006) IFN tc-RNARep.2 4sU1h gamma+ tc-RNA100U/ml200´M (0.0931146)IFN Rep.33h gamma+ 4sUmock,200´MRep.4 (0.0126921)IFN tc-RNA3h gamma,+ (0.0390447) 150-180 4sUmock,200´M tc-RNA3hRep.1 200´M 150-180 4sUmock,min (0.0190089) tc-RNA3h500´MRep.2 4sU 150-180 100U/mlmin tc-RNA(0.133102) 4sU3h500´MRep.3 100U/mlmin tc-RNAIFNalpha, Rep.4(0.0258057) 4sU3h500´M 100U/ml tc-RNAIFNalpha,Rep.1 (0.0346319) 150-1804sU3h 100U/ml(0.0259075) tc-RNAIFNalpha,Rep.2 150-180 3hmin 100U/ml(0.0259993) IFNgamma,Rep.3500´M 150-180 3hmin 100U/ml(0.0504389) IFNgamma,4sU500´M min 150-180tc-RNA IFNgamma,4sU500´M 150-180tc-RNA Rep.1min 4sU 500´M (0.0250045) 150-180tc-RNA Rep.2min 4sU500´M [(0.0241782) Rep.3min mintc-RNA 4sU500´M (0.0513408) tc-RNA Rep.1] 4sU (0.0309688) tc-RNARep.2 (0.0443207) [Rep.3 medium (0.0300122) ] [ max ] CEM 1 Cldn7 25.9 27.3 33.5 P ( S | Z, I ) = 1.00 Epcam 20.9 21.9 26.9 Mean Corr = 0.58217Marveld2 24.2 25.3 29.4 Cldn3 19.6 21.1 25.1 Cldn4 17.2 17.6 19.6 Pard6b 34.6 49.9 217.1 Ocln 21.1 22.2 30.0 Tjp3 19.8 22.9 28.3 Tjp2 750.3 1912.6 4050.4 F11r 21.1 21.9 25.7 Inadl 31.9 39.0 73.4 Cldn23 25.0 26.6 34.5 Prkcz 23.2 25.0 30.5 Shroom2 23.8 24.8 27.6 Cldn8 21.2 22.2 27.0 Igsf5 20.9 21.8 24.4 Cldn6 18.8 19.3 21.8 Magi3 823.1 1473.8 2567.4 Tjp1 2289.3 2742.7 4754.9 Esrp1 21.2 21.8 24.8 Cdh1 29.7 32.5 39.0 St14 22.9 23.6 37.7 Cdcp1 22.7 23.4 26.3 Prss8 18.9 19.4 21.5 CEM 1 + Spint1 21.7 22.6 26.1 Top 10 Genes Ap1m2 24.3 25.2 29.6 Irf6 21.0 21.8 24.5 Erbb3 24.8 26.0 31.7 Spint2 18.5 19.1 21.8

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE5309" 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=GSE5309 Status: Public on Jul 15 2006 Title: Transcriptional Profiling of Mammary Gland Side Population Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16282442 Summary & Design: Summary: Similar to the bone marrow, the mammary gland contains a distinct population of Hoechst-effluxing side population cells, MG-SPs. To better characterize MG-SPs, their microarray gene profiles were compared to the remaining cells, which retain Hoechst dye (MG-NSPs). For analysis, gene ontology (GO) that describes genes in terms of biological processes and ontology traverser (OT) that performs enrichment analysis were utilized. OT showed that MG-SP specific genes were enriched in the GO categories of cell cycle regulation and checkpoints, multi-drug resistant transporters, organogenesis, and vasculogenesis. The MG-NSP upregulated genes were enriched in the GO category of cellular organization and biogenesis which includes basal epithelial markers, p63, smooth muscle actin (SMA), myosin, alpha-6 integrin, cytokeratin (CK) 14, as well as luminal markers, CK8 and CD24. Additional studies showed that a higher percentage of MG-SPs exist in the G1 phase of the cell cycle compared to the MG-NSPs. G1 cell cycle block of MG-SPs may be explained by higher expression of cell cycle negative regulatory genes such as TGF-beta2 (transforming growth factor-beta2), IGFBP-5 (insulin like growth factor binding protein-5), P18 INK4C and Wnt-5a (wingless-5a). Accordingly, a smaller percentage of MG-SPs expressed nuclear b-catenin, possibly as a consequence of the higher expression of Wnt-5a. In conclusion, microarray gene profiling suggests that MG-SPs are a lineage deficient mammary gland sub-population expressing key genes involved in cell cycle regulation, development and angiogenesis.

Supplemental File Descriptions:

Table 1 is a list of 1632 Genes differentially expressed by MG-SP and MG-NSP; Criteria for comparison included 1.2-fold difference in expression levels, false discovery rate (FDR) 9.4%, P value less than 0.05.

Table 2 is a list of 771 Genes differentially expressed by MG-SP and MG-NSP; Criteria for comparison included 1.5-fold difference in expression levels, FDR 3.4%, P value less than 0.05.

Table 3 is a list of 335 Genes differentially expressed by MG-SP and MG-NSP; Criteria for comparison included 2-fold difference in expression levels, FDR 0%, P value less than 0.05.

Table 4 is a list of 90 Genes differentially expressed by MG-SP and MG-NSP; Criteria for comparison included 2-fold difference in expression levels, FDR 0%, P value less than 0.01.

Keywords: Normal C57BL/6 Mammary Gland Epithelial Cells

Overall design: Gene expression profiles were obtained by hybridizing amplified RNA from four replicate MG-SP and MG-NSP samples to Affymetrix 430 2.0 microarray chips. To isolate MG-SP and MG-NSPs, mammary gland cells were stained using the Hoechst dye 33342 and fluorescence displayed at two wavelength emissions, blue and red. The MG-SP and MG-NSP regions were indicated by trapezoids on the left (R1) and right (R2), respectively. We and others have previously shown that the R1 region is composed of side population cells since verapamil blocks their appearance. The cells in each region (R1 and R2) were sorted, their RNA isolated and amplified by two rounds of in vitro amplification and applied to Affymetrix chips. Hybridization, scanning, and production of raw data files were performed according to the Affymetrix standard protocols. Normalization and model-based expression measurements were performed with dChip. Two of the chips were eliminated from further analysis due to the high percentage of probe sets called an array outlier after model based expression analysis by dChip (Not included). The genes were filtered to eliminate those with very low expression values in most samples. From 45,000 probe sets, 16,744 probe sets were retained and used for further analysis. For normalization purposes and to allow for data comparison with other centers, universal mouse reference RNA (Stratagene) was hybridized to two chips. All other arrays were normalized to one of the universal mouse reference RNA arrays expressing average intensity closest to the median intensity of all chips (Stratagene Ref 2).

Background corr dist: KL-Divergence = 0.0531, L1-Distance = 0.0342, L2-Distance = 0.0017, Normal std = 0.5752

0.715 Kernel fit Pairwise Correlations Normal fit

Density 0.357

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

SP3 5-24-04NSP3 hnl_JR_865_MA2_3855.txt 5-24-06SP4 6-14-04 hnl_JR_865_MA2_3856.txtNSP4 hnl_JR_865_MA2_4113.txt 6-14-04Strategene hnl_JR_865_MA2_4114.txtSP2 (0.113648) Ref5-17-04 NSP22 hnl_JR_865_MA2_4355.txt (0.164007) hnl_JR_865_MA2_3764.txt 5-17-04 (0.0973805) hnl_JR_865_MA2_3765.txt (0.117977) (0.298598)[ (0.120373)min (0.0880173)] [ medium ] [ max ] CEM 1 Cldn7 145.9 933.4 1929.7 P ( S | Z, I ) = 1.00 Epcam 1415.4 3207.7 5900.4 Mean Corr = 0.55920Marveld2 57.5 417.9 777.4 Cldn3 7.3 110.3 321.4 Cldn4 86.0 1083.6 3268.8 Pard6b 86.0 150.5 241.4 Ocln 34.7 167.0 266.3 Tjp3 55.5 94.4 146.0 Tjp2 930.6 1826.3 3071.8 F11r 631.2 1082.5 1393.1 Inadl 102.2 215.9 579.9 Cldn23 1.0 70.1 177.2 Prkcz 94.2 130.2 166.3 Shroom2 203.8 622.6 688.5 Cldn8 9.3 47.6 82.7 Igsf5 7.3 136.2 205.7 Cldn6 7.6 96.8 240.1 Magi3 967.4 1253.0 2247.7 Tjp1 5910.2 6037.2 7425.5 Esrp1 15.1 1067.7 2023.8 Cdh1 71.0 3057.7 7252.3 St14 306.3 489.7 1563.3 Cdcp1 42.1 2247.8 4490.6 Prss8 3.9 20.3 59.1 CEM 1 + Spint1 36.3 257.5 472.2 Top 10 Genes Ap1m2 37.0 172.0 568.2 Irf6 98.1 616.3 1529.5 Erbb3 380.2 2032.4 2808.6 Spint2 563.6 914.1 1845.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE16110" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16110 Status: Public on Jul 01 2009 Title: Altered mouse mammary gland gene expression and tumor growth following chronic social isolation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Clinical studies have revealed that social support improves the outcome of cancer patients while epidemiological studies suggest that social isolation increases the risk of death associated with several chronic diseases. However, the precise biological consequences of an unfavorable social environment have not been defined. To do so, robust, reproducible pre-clinical models are needed to study the mechanisms whereby an adverse environment impacts on gene expression and cancer biology. Because random assignment of inbred laboratory mice to well-defined social environments allows accurate and repeated measurements of behavioral and endocrine parameters, transgenic mice provide a pre-clinical framework with which to begin to determine gene-environment mechanisms. In this study, we found that female C3(1)/SV40 T-antigen mice deprived of social interaction from weaning exhibited increased expression of genes encoding key metabolic pathway enzymes in the pre-malignant mammary gland. Chronic social isolation was associated with upregulated fatty acid synthesis and glycolytic pathway gene expression - both pathways known to contribute to increased breast cancer growth. Consistent with the expression of metabolic genes, isolated mice subsequently developed significantly larger mammary gland tumors compared to group-housed mice. Endocrine evaluation confirmed that isolated mice developed a heightened corticosterone stress response compared to group-housed mice. Together, these transdisciplinary studies show for the first time that an adverse social environment is associated with altered mammary gland gene expression and tumor growth. Moreover, the identification of specific alterations in metabolic pathways favoring tumor growth suggests potential molecular biomarkers and/or targets (e.g. fatty acid synthesis) for preventive intervention in breast cancer.

Overall design: SV40 Tag mice we isolated or grouped at weaning. Mouse mammary glands were rapidly excised at necropsy and immediatley flash frozen to detect difference in gene expression between thoraci MG from isolated versus group-housed female mice.

Background corr dist: KL-Divergence = 0.0385, L1-Distance = 0.0261, L2-Distance = 0.0009, Normal std = 0.6020

0.663 Kernel fit Pairwise Correlations Normal fit

Density 0.331

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse_Group_15w_Rep1Mouse_Group_15w_Rep2Mouse_Group_15w_Rep3Mouse_Group_15w_Rep4 (0.054876)Mouse_Iso_15w_Rep1 (0.0500062)Mouse_Iso_15w_Rep2 (0.0903673)Mouse_Iso_15w_Rep3 (0.0580128)Mouse_Iso_15w_Rep4 (0.042436)Mouse_Group_20w_Rep1 (0.0479115)Mouse_Group_20w_Rep2 (0.0540936)Mouse_Group_20w_Rep3 (0.0615478)Mouse_Group_20w_Rep4 (0.0743161)Mouse_Iso_20w_Rep1 (0.0753121)Mouse_Iso_20w_Rep2 (0.025337)Mouse_Iso_20w_Rep3 (0.0662609)Mouse_Iso_20w_Rep4 (0.12405) (0.0679775) (0.0562107) (0.0512844)[ min ] [ medium ] [ max ] CEM 1 Cldn7 1217.2 2715.9 3642.9 P ( S | Z, I ) = 1.00 Epcam 6773.4 10512.1 12449.7 Mean Corr = 0.54952Marveld2 440.6 723.2 1055.9 Cldn3 1868.8 2358.5 2876.4 Cldn4 1607.1 2956.8 3633.1 Pard6b 119.7 225.4 414.1 Ocln 318.1 419.3 561.5 Tjp3 270.8 402.8 548.2 Tjp2 833.0 1264.9 1711.7 F11r 1509.0 1858.1 2314.7 Inadl 244.2 327.1 547.0 Cldn23 287.8 401.3 513.4 Prkcz 318.4 445.9 507.8 Shroom2 498.4 711.9 922.4 Cldn8 616.4 1022.8 1400.0 Igsf5 244.6 273.1 343.5 Cldn6 180.0 223.4 346.0 Magi3 840.6 962.7 1115.8 Tjp1 1767.6 2556.3 3109.0 Esrp1 1051.9 1923.6 2726.6 Cdh1 3483.3 5524.1 7177.4 St14 1408.7 2931.9 4213.3 Cdcp1 791.7 1205.2 1794.2 Prss8 396.5 485.5 557.6 CEM 1 + Spint1 637.7 919.9 1171.1 Top 10 Genes Ap1m2 755.5 1034.3 1469.5 Irf6 730.8 1066.4 1415.2 Erbb3 1101.1 1499.5 1845.7 Spint2 4547.4 5285.9 6065.1

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE50813" 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=GSE50813 Status: Public on Dec 31 2013 Title: Prevention of mammary tumor progression by silencing HoxA1 via intraductal injection of nanoparticle-formulated siRNA Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24382894 Summary & Design: Summary: Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.

Overall design: 8 week wild type FVB mouse whole mammary gland and 8week to 20 week transgenic FVB C3(1)-SV40Tag mouse whole mammary gland

Background corr dist: KL-Divergence = 0.1026, L1-Distance = 0.0245, L2-Distance = 0.0008, Normal std = 0.4380

0.911 Kernel fit Pairwise Correlations Normal fit

Density 0.455

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 weeks8 wildweeks type8 wildweeks Mammary33 type8 wildweeks Mammary34 type8 wild(0.036306)weeks Mammary35 type8 wild(0.0276224)weeks Mammary36 type8 tumor(0.058679)weeks Mammary37 8Mammary1 tumor(0.0437347)weeks 8Mammary2 tumor(0.0314262)weeks (0.0290082) 8Mammary3 tumorweeks (0.0194315) 12Mammary4 tumor weeks (0.0222995) 12Mammary5 tumorweeks (0.0245142)12 Mammary6 tumorweeks (0.0231647)12 Mammary7 tumorweeks (0.0309803)12 Mammary8 tumorweeks (0.013376)16 Mammary9 tumorweeks (0.0195387)16 Mammary10 tumorweeks (0.0197099)16 Mammary11 tumorweeks (0.0202125)16 Mammary13 tumorweeks (0.0177102)16 Mammary14 tumorweeks (0.0200869)20 Mammary15 tumorweeks (0.0243016)20 Mammary32 tumorweeks (0.04083)20 Mammary22 tumorweeks (0.0191431)20 Mammary23 tumorweeks (0.0775084) Mammary24 tumor (0.11187) Mammary31 (0.125376) (0.14317)[ min ] [ medium ] [ max ] CEM 1 Cldn7 793.9 2207.9 6945.4 P ( S | Z, I ) = 1.00 Epcam 7319.3 12877.6 35582.6 Mean Corr = 0.54226Marveld2 139.1 393.1 1654.5 Cldn3 428.5 1029.8 2128.2 Cldn4 619.5 1061.4 6256.4 Pard6b 77.4 163.4 1416.5 Ocln 108.0 235.2 759.0 Tjp3 258.7 457.6 852.6 Tjp2 724.5 1713.3 4406.9 F11r 1662.1 1996.2 4115.0 Inadl 178.5 334.5 941.9 Cldn23 66.3 177.0 1382.4 Prkcz 96.4 148.4 286.9 Shroom2 258.6 427.3 1147.9 Cldn8 295.2 755.5 1564.5 Igsf5 75.0 245.3 602.9 Cldn6 76.3 134.9 245.4 Magi3 1080.9 1503.1 2231.6 Tjp1 2286.4 2988.3 5462.5 Esrp1 908.9 1927.0 4428.3 Cdh1 1584.9 4655.9 13315.7 St14 942.2 1755.8 6202.8 Cdcp1 928.5 1328.8 4686.0 Prss8 399.0 521.6 706.1 CEM 1 + Spint1 251.0 366.9 1451.4 Top 10 Genes Ap1m2 602.3 825.8 1497.8 Irf6 612.0 977.3 3254.9 Erbb3 1224.9 1993.2 4322.5 Spint2 2798.7 4490.9 17721.9

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE15326" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15326 Status: Public on Mar 01 2010 Title: LKR13-Kras-WT1-KO Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: K-ras is one of the most frequently mutated human oncogenes. However, activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we describe a novel loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor and at physiological levels, but had no effect on cells expressing wild-type K-ras. Furthermore, loss of Wt1 in lung cancer cell lines that harbor mutant K-ras leads to apoptosis. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras.

We compare the expression profiles of K-ras mutant mouse cell line (LKR13) upon shRNA knockdown of K-ras itself or Wt1. The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras.

Overall design: LKR13 cells were infected with plko.1s vectors carrying one of two shRNAs against K-ras or Wt1. Control cells were infected with an shRNA against GFP. 48 hours after infection, cells were selected with puromycin for 3 days. RNA was isolated using Trizol 7 days after infection. RNA was further prepared by passage over an RNeasy column. cDNA synthesis, biotinylation of cRNA and hybridization to mouse Genechip 430A v2 containing 39,000 probes was performed according to the manufacturers instructions (Affymetrix, Santa Clara). Microarray data was normalized with Expression Console software (Affymetrix, Santa Clara), using RMA algorithms.

Background corr dist: KL-Divergence = 0.0699, L1-Distance = 0.0280, L2-Distance = 0.0013, Normal std = 0.4948

0.806 Kernel fit Pairwise Correlations Normal fit

Density 0.403

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

LKR13_KrasLKR13_Kras sh-1LKR13_Wt1 (0.119906) sh-2LKR13_Wt1 (0.0717079) sh-1LKR13_Control-1 (0.0840157) sh-2LKR13_Control-2 (0.0783632)LKR13_Control-3 (0.0800032)LKR13_Control-4 (0.0762089)LKR13_Kras (0.119035)LKR13_Kras (0.118966) sh-3 (0.100834) sh-4 (0.150961) [ min ] [ medium ] [ max ] CEM 1 Cldn7 70.8 210.5 401.8 P ( S | Z, I ) = 1.00 Epcam 358.4 1253.2 2547.6 Mean Corr = 0.54209Marveld2 426.5 629.8 1068.3 Cldn3 136.6 276.8 914.3 Cldn4 95.3 375.0 624.2 Pard6b 259.8 384.1 760.9 Ocln 262.4 609.7 956.0 Tjp3 365.0 794.8 2037.1 Tjp2 2582.8 3658.7 5342.7 F11r 2533.3 4888.9 5808.5 Inadl 320.3 711.3 1222.4 Cldn23 56.3 191.1 594.3 Prkcz 112.2 179.8 275.6 Shroom2 378.9 450.6 593.5 Cldn8 17.8 20.8 23.4 Igsf5 209.5 405.7 704.5 Cldn6 581.9 2967.5 5756.5 Magi3 1204.7 1513.0 3008.3 Tjp1 4163.2 4968.7 7044.4 Esrp1 24.0 28.4 34.5 Cdh1 7537.1 11695.7 14535.8 St14 139.4 333.4 654.8 Cdcp1 779.4 1200.1 1702.8 Prss8 42.6 105.0 128.3 CEM 1 + Spint1 181.3 571.3 1464.3 Top 10 Genes Ap1m2 79.4 96.6 124.7 Irf6 173.8 543.0 1194.3 Erbb3 1384.4 2444.1 4072.1 Spint2 4743.0 9297.2 13273.4

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE17796" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 39 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17796 Status: Public on Jan 11 2010 Title: Expression data from B6C3F1 mice treated with reduced oxygen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice received decreasing oxygen concentrations from 21% to 6% O2 for ~ 30 minutes. Then, the mice remained an additional 120 minutes at 6% O2, control mice were placed insimilarchambers but recieved normal (21%) oxygen.

Overall design: Mice were euthanased by cervical dislocation under ketamine / acepromazine (100 mg/kg / 5 mg/kg, I.P) anesthesia. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 39 arrays.

Background corr dist: KL-Divergence = 0.0270, L1-Distance = 0.0739, L2-Distance = 0.0083, Normal std = 0.7950

0.502 Kernel fit Pairwise Correlations Normal fit

Density 0.251

0.000 CEM 1

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

Pre-normalization Quantiles

liver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-rep 1 (0.0298847)liver-hypoxia-2hours-rep 2 (0.0284749)liver-hypoxia-2hours-rep 3 (0.0329682)liver-hypoxia-2hours-rep 4 (0.0287041)liver-hypoxia-2hours-rep 1 (0.0225734)liver-hypoxia-2hours-rep 2 (0.0233177)liver-hypoxia-2hours-rep 3 (0.0320838)liver-hypoxia-2hours-rep 4 (0.0244826)liver-hypoxia-2hours-rep 5 (0.0382413)liver-vehicle-2hours-rep 6 (0.0318269)liver-vehicle-2hours-rep 7 (0.0371076)liver-vehicle-2hours-rep 8 (0.0340198)liver-vehicle-2hours-rep 5 (0.0321043)bone 6 (0.0319328) marrow-vehicle-2hours-repbone 7 (0.0323274) marrow-vehicle-2hours-repbone 8 (0.0307773) marrow-vehicle-2hours-repbone marrow-hypoxia-2hours-repbone 1 (0.0355067)marrow-hypoxia-2hours-repbone 2 (0.030069)marrow-hypoxia-2hours-repbone 3 (0.0268613)marrow-hypoxia-2hours-repspleen-vehicle-2hours-rep 1 (0.0275533)spleen-vehicle-2hours-rep 2 (0.0244188)spleen-vehicle-2hours-rep 3 (0.0288031)spleen-vehicle-2hours-rep 41 (0.0323395)(0.0199553)spleen-hypoxia-2hours-rep 2 (0.0182035)spleen-hypoxia-2hours-rep 3 (0.0177537)spleen-hypoxia-2hours-rep 4 (0.0177714)spleen-hypoxia-2hours-rep 1 (0.0249485)spleen-vehicle-2hours-rep 2 (0.0216884)spleen-hypoxia-2hours-rep 3 (0.0186774)spleen-hypoxia-2hours-rep 4 (0.0251735)spleen-vehicle-2hours-rep 5 (0.0172211)spleen-vehicle-2hours-rep 7 (0.0136387)spleen-vehicle-2hours-rep 8 (0.0157628)spleen-hypoxia-2hours-rep 6 (0.0213105)spleen-hypoxia-2hours-rep 7 (0.0207481) 8 (0.0216775) 5 (0.0145679) 6 (0.0145232)[ min ] [ medium ] [ max ] CEM 1 Cldn7 48.9 62.7 84.4 P ( S | Z, I ) = 1.00 Epcam 44.8 86.6 370.3 Mean Corr = 0.54146Marveld2 43.2 185.5 522.0 Cldn3 45.2 64.2 3010.7 Cldn4 59.5 90.3 143.1 Pard6b 21.2 47.9 120.1 Ocln 61.1 85.1 743.8 Tjp3 96.9 170.0 848.6 Tjp2 174.5 247.5 818.3 F11r 612.8 980.9 3037.3 Inadl 34.7 74.0 98.8 Cldn23 17.5 26.2 39.8 Prkcz 55.3 142.0 891.9 Shroom2 75.7 210.1 982.8 Cldn8 17.1 23.2 31.2 Igsf5 31.4 48.3 1459.1 Cldn6 52.5 94.3 125.9 Magi3 290.0 496.5 1181.4 Tjp1 365.1 845.3 1578.6 Esrp1 22.0 35.6 61.9 Cdh1 35.5 156.3 3344.2 St14 109.6 170.4 524.5 Cdcp1 44.4 89.9 187.1 Prss8 38.9 56.1 310.5 CEM 1 + Spint1 62.3 126.5 186.3 Top 10 Genes Ap1m2 53.8 139.7 251.8 Irf6 22.3 72.6 1677.6 Erbb3 192.5 293.7 6251.0 Spint2 843.1 1648.2 4264.4

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE23502" 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=GSE23502 Status: Public on Dec 15 2010 Title: Differentially expressed genes of CD11b+Gr-1+ myeloid cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21170045 Summary & Design: Summary: Differentially expressed genes of CD11b+Gr-1+ immature myeloid cells (IMCs) in the bone marrow and colonic tumor setting of histidine decarboxylase (HDC)-KO mice were examined by microarray (Affymetrix Mouse 430.2 array). Myeloid differentiation-related candidate genes were sought to be isolated and functionally studied.

Overall design: Four sets of comparisons were performed to screen for upregulated or downregulated genes in the HDC-KO CD11b+Gr-1+ IMCs or MDSCs (experiment group) compared to the WT group: (1) HDC-expressing CD11b+Gr-1+ IMCs of bone marrow of HDC KO mice compared to bone marrow IMCs of WT mice; (2) CD11b+Gr-1+ MDSCs in tumors of HDC-KO mice compared to WT mice; (3) CD11b+Gr-1+ MDSCs of WT colon tumors compared to IMCs in the WT bone marrow; and (4) CD11b+Gr-1+ MDSCs of colon tumors of HDC-KO mice compared to IMCs in the bone marrow of HDC-KO mice.

Background corr dist: KL-Divergence = 0.0311, L1-Distance = 0.0412, L2-Distance = 0.0020, Normal std = 0.7230

0.594 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWild-type myeloid-derivedHistidine myeloid-derivedHistidine decarboxylase suppressorWild-type decarboxylase suppressorWild-type cell nullmyeloid-derived from myeloid-derivedHistidine cell nullmyeloid-derived bone from myeloid-derivedHistidine marrow,decarboxylase bone suppressor suppressor marrow,decarboxylase rep1 suppressor (0.11196) suppressorcell null rep2 cellfrom myeloid-derived (0.0845869) cell fromnull colon cellfrom myeloid-derived [bone tumor,frommin colon marrow, bone suppressor rep1tumor, ] marrow, (0.0733945)rep1 suppressor rep2 (0.0898383) cell (0.0845794)rep2 from[ (0.104791) cellmedium colon from tumor, colon rep1tumor, ] (0.204578) rep2 (0.246272)[ max ] CEM 1 Cldn7 14.8 370.7 4002.1 P ( S | Z, I ) = 1.00 Epcam 13.4 1929.4 8425.3 Mean Corr = 0.53652Marveld2 10.5 16.0 62.4 Cldn3 14.3 24.3 226.2 Cldn4 10.8 38.8 176.9 Pard6b 9.1 12.9 38.4 Ocln 10.2 13.0 32.0 Tjp3 68.3 91.1 449.4 Tjp2 16.7 48.1 159.8 F11r 8.3 38.7 150.2 Inadl 10.1 12.4 46.2 Cldn23 9.1 29.5 720.0 Prkcz 12.7 16.1 26.5 Shroom2 13.9 17.7 23.3 Cldn8 9.1 18.1 29.4 Igsf5 11.2 22.3 347.6 Cldn6 7.4 8.7 9.7 Magi3 402.2 1073.4 1207.8 Tjp1 12.4 114.4 656.4 Esrp1 9.9 29.1 217.5 Cdh1 12.9 1648.6 3888.7 St14 26.9 46.3 573.8 Cdcp1 11.1 13.1 52.9 Prss8 8.6 10.6 14.3 CEM 1 + Spint1 12.2 32.4 597.7 Top 10 Genes Ap1m2 12.0 14.1 38.2 Irf6 8.6 24.6 237.8 Erbb3 18.2 152.2 934.6 Spint2 231.9 469.0 2599.1

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE7810" 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=GSE7810 Status: Public on May 18 2007 Title: Comparative analysis of gene expression WT and Nrf2-/- mice Type II cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17895394 Summary & Design: Summary: We hypothesize that gene expression in the Type II cells of Nrf2+/+ and Nrf2-/- mice are divergent thus contributing the cell growth. More specifically, type II cells from Nrf2-/- mice have increased reactive oxygen species that cause the impaired cell growth. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Nrf2+/+ and Nrf2-/- cells.

Keywords: comparative expression profiling

Overall design: . This study utilizes microarray analysis to test these hypotheses. Three sets of type II cells were isolated from lungs from both Nrf2+/+ and Nrf2-/- mice and grown for 5 days. RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430 2.0 array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05. Further, Absolute | FC - FC SEM | >= 1.5.

Background corr dist: KL-Divergence = 0.0624, L1-Distance = 0.0171, L2-Distance = 0.0003, Normal std = 0.5241

0.761 Kernel fit Pairwise Correlations Normal fit

Density 0.381

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

MNR 1-2MNR WT 2-23 (0.0937372)MNR WT 5-24 (0.0799738)MNR KO 26-2 (0.108403)MNR KO 37-2 (0.118627)MNR KO Treated8-2MNR KO Treated1-3 2 MNR(0.128089) WT 2-35 3 (0.107519) MNR(0.111549) KO 43-3 (0.124785) KO Treated 4 (0.127318)[ min ] [ medium ] [ max ] CEM 1 Cldn7 546.7 1642.1 3289.2 P ( S | Z, I ) = 1.00 Epcam 1317.5 2345.8 4519.5 Mean Corr = 0.53279Marveld2 114.0 252.3 464.3 Cldn3 121.2 479.5 1299.5 Cldn4 621.9 2746.4 6274.3 Pard6b 124.7 699.7 1027.0 Ocln 146.6 239.7 291.1 Tjp3 64.9 133.0 184.3 Tjp2 495.3 1503.8 2602.9 F11r 2310.4 3332.9 3903.5 Inadl 73.7 188.5 293.9 Cldn23 82.6 101.1 181.6 Prkcz 79.8 192.4 318.7 Shroom2 383.8 558.4 981.9 Cldn8 2.0 7.2 28.7 Igsf5 42.9 322.4 581.2 Cldn6 374.3 678.2 1633.6 Magi3 574.9 694.6 720.7 Tjp1 1804.1 2703.1 3587.1 Esrp1 71.5 400.1 876.2 Cdh1 2001.8 5284.1 12027.8 St14 365.2 1080.3 1580.5 Cdcp1 325.1 1073.5 1790.4 Prss8 38.6 99.5 149.4 CEM 1 + Spint1 522.8 1088.3 1720.1 Top 10 Genes Ap1m2 130.2 399.8 656.3 Irf6 177.6 392.5 619.1 Erbb3 282.1 393.1 873.6 Spint2 1369.2 3176.6 5268.7

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE34729" 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=GSE34729 Status: Public on Jan 09 2013 Title: Gene expression changes induced by overexpression of EVI1 in Lin- hematopoietic cells [Lin] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23212151 Summary & Design: Summary: The transcription factor Evi1 is essential for the formation and maintenance of hematopoietic stem cells, and induces clonal dominance with malignant progression upon constitutive activation by chromosomal rearrangements or transgene integration events. To understand the immediate and adaptive response of primary murine hematopoietic cells to the transcriptional upregulation of Evi1, we developed an inducible lentiviral vector system with a robust expression switch. We found that Evi1 delays differentiation and promotes survival in myeloid culture conditions, orchestrating a battery of genes involved in stemness (Aldh1a1, Ly6a [Sca1], Abca1, Epcam, among others). Importantly, Evi1 suppresses Cyclins and Cyclin-dependent kinases (Cdk), while it upregulates Cdk inhibitors, inducing quiescence in various proliferation-inducing cytokine conditions and operating in a strictly dose-dependent manner. Hematopoietic cells with persisting Evi1-induction tend to adopt a relatively low expression level. We thus classify Evi1 as a dormancy-inducing oncogene, likely requiring epigenetic and genetic compensation for cell expansion and malignant progression.

Overall design: Lin- Rosa26rtTA cells were isolated, transduced in S3F11 cytokines, induced the next day with DOX [1 Î¼g/ml] and 20 hours later sorted for negative/low or highly EGFP expressing cells, from which total RNA was extraced and subjected to Microarray Analysis

Background corr dist: KL-Divergence = 0.0204, L1-Distance = 0.0378, L2-Distance = 0.0015, Normal std = 0.8069

0.530 Kernel fit Pairwise Correlations Normal fit

Density 0.265

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

EVI_GFPEVI_GFP negativeEVI_GFP negative Lin-EVI_GFP cells negative Lin- replicateEVI_GFP cells positive Lin- replicate EVI_GFP 1cells positive(0.143338) Lin- replicate cells2 positive(0.128181) Lin- replicate cells3 (0.158741) Lin- replicate 1cells (0.183723) replicate 2[ (0.166869) min 3 (0.219148) ] [ medium ] [ max ] CEM 1 Cldn7 29.8 904.3 941.6 P ( S | Z, I ) = 1.00 Epcam 144.9 3467.6 3707.6 Mean Corr = 0.52840Marveld2 235.0 918.1 967.8 Cldn3 9.5 13.9 18.5 Cldn4 7.6 78.1 130.9 Pard6b 39.8 144.7 175.1 Ocln 31.0 230.7 376.8 Tjp3 234.5 378.5 867.1 Tjp2 303.5 520.7 670.7 F11r 313.2 1208.2 1250.5 Inadl 7.9 11.3 25.2 Cldn23 9.6 14.1 25.7 Prkcz 18.5 26.0 31.7 Shroom2 10.9 19.3 25.0 Cldn8 4.3 5.2 5.9 Igsf5 12.7 14.1 22.4 Cldn6 9.0 34.6 65.7 Magi3 86.4 114.3 170.5 Tjp1 1895.4 2108.7 2214.3 Esrp1 14.7 1357.4 1858.9 Cdh1 5989.6 8680.6 8826.4 St14 106.8 251.6 342.3 Cdcp1 155.8 1105.8 1175.6 Prss8 9.4 22.3 39.4 CEM 1 + Spint1 241.3 389.4 498.1 Top 10 Genes Ap1m2 49.8 58.7 66.5 Irf6 841.5 3279.7 4240.2 Erbb3 559.3 3940.1 4458.7 Spint2 1154.5 2671.3 2906.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE17096" 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=GSE17096 Status: Public on Dec 09 2011 Title: mRNA composition of IRP1 mRNPs in mouse tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21940823 Summary & Design: Summary: Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP1 (iron regulatory protein 1).

Overall design: All the microarray procedures were conducted at the EMBL Genomics Core Facility using standard Affymetrix protocols. In brief, approximately 120ng of immunoprecipitated RNA was used as input to a two-step amplification procedure to generate biotin-labeled RNA fragments for hybridization to the Affymetrix GeneChip Mouse Genome 430 2.0 array (Eukaryotic Sample and Array Processing manual 701024 Rev.3). Intensity values for the hybridizations were obtained either using RMA, calculations done in bioconductor (www.bioconductor.org) or MAS5, calculated using Affymetrix GCOS package. MAS5 calculated intensities were further quantile normalized using bioconductor.

Background corr dist: KL-Divergence = 0.0791, L1-Distance = 0.0942, L2-Distance = 0.0182, Normal std = 0.5457

0.753 Kernel fit Pairwise Correlations Normal fit

Density 0.377

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

IRP1 immunoprecipitationIRP1 controlIRP1 immunoprecipitationimmunoprecipitationIRP1 duodenum controlIRP1 immunoprecipitationimmunoprecipitationIRP1 replica duodenumduodenum controlIRP1 1 (0.055724) immunoprecipitationimmunoprecipitationIRP1 replicareplica liverduodenum controlIRP1 21 replica (0.0633967)(0.0582879) immunoprecipitationimmunoprecipitationIRP1 replica 1 (0.0949914) liverliver controlIRP1 2 replicareplica (0.068956) immunoprecipitationimmunoprecipitationIRP1 21 (0.0553958) (0.0241231) spleenliver controlIRP1 replica replica immunoprecipitationimmunoprecipitationIRP1 2 (0.044001) 1spleenspleen control(0.037855)IRP1 replicareplica immunoprecipitationimmunoprecipitationIRP1 2bone1spleen control (0.0297173)(0.0208425)IRP1 marrow replica immunoprecipitationimmunoprecipitationIRP1 replica bone2bone control (0.0330613)IRP1 marrow marrow1 (0.0299547) immunoprecipitationimmunoprecipitationIRP1 replicareplica brainbone control replicamarrow 21 (0.0362048) (0.0373021)immunoprecipitation 1 replica (0.0589605)brainbrain replica replica2 (0.0302336)[ 21min (0.0546506)(0.0797945)brain replica ] 2 (0.0865471)[ medium ] [ max ] CEM 1 Cldn7 65.8 132.5 28278.8 P ( S | Z, I ) = 1.00 Epcam 71.0 171.9 30604.5 Mean Corr = 0.52570Marveld2 99.0 401.2 1448.2 Cldn3 58.8 84.2 1178.9 Cldn4 121.4 198.5 1606.8 Pard6b 23.6 53.2 608.5 Ocln 80.9 255.9 2202.7 Tjp3 57.4 93.0 1060.9 Tjp2 214.9 862.9 4470.0 F11r 421.5 1116.7 9200.9 Inadl 42.4 126.2 1055.8 Cldn23 25.9 40.1 341.7 Prkcz 86.5 355.6 2184.7 Shroom2 50.2 805.1 2773.9 Cldn8 25.3 38.4 62.8 Igsf5 36.1 49.9 1863.3 Cldn6 51.3 68.5 136.1 Magi3 179.9 966.0 2728.9 Tjp1 263.7 2855.6 6017.5 Esrp1 31.9 50.4 1059.1 Cdh1 42.2 67.2 5516.6 St14 135.0 375.4 8502.6 Cdcp1 130.4 341.1 4282.3 Prss8 44.9 97.2 478.5 CEM 1 + Spint1 60.6 113.5 3442.2 Top 10 Genes Ap1m2 219.9 305.6 4966.1 Irf6 43.0 80.6 5102.3 Erbb3 177.0 682.0 11503.9 Spint2 971.6 2130.6 17420.3

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE17097" 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=GSE17097 Status: Public on Dec 09 2011 Title: mRNA composition of IRP2 mRNPs in mouse tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21940823 Summary & Design: Summary: Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP2 (iron regulatory protein 2).

Background corr dist: KL-Divergence = 0.0612, L1-Distance = 0.0894, L2-Distance = 0.0146, Normal std = 0.5980

0.686 Kernel fit Pairwise Correlations Normal fit

Density 0.343

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

IRP2 immunoprecipitationIRP2 controlIRP2 immunoprecipitationimmunoprecipitationIRP2 duodenum controlIRP2 immunoprecipitationimmunoprecipitationIRP2 replica duodenumduodenum controlIRP2 1 (0.0500704) immunoprecipitationimmunoprecipitationIRP2 replicareplica liverduodenum controlIRP2 21 replica (0.0703369)(0.0475346) immunoprecipitationimmunoprecipitationIRP2 replica 1 (0.0254266) liverliver controlIRP2 2 replicareplica (0.0672858) immunoprecipitationimmunoprecipitationIRP2 21 (0.0190977) (0.0224562) spleenliver controlIRP2 replica replica immunoprecipitationimmunoprecipitationIRP2 2 (0.0230985) 1spleenspleen control(0.0398036)IRP2 replicareplica immunoprecipitationimmunoprecipitationIRP2 2bone1spleen control (0.0340695)(0.0366949)IRP2 marrow replica immunoprecipitationimmunoprecipitationIRP2 replica bone2bone control (0.0397542)IRP2 marrow marrow1 (0.0607572) immunoprecipitationimmunoprecipitationIRP2 replicareplica brainbone control replicamarrow 21 (0.0837504) (0.0309563)immunoprecipitation 1 replica (0.0454862)brainbrain replica replica2 (0.0918425)[ 21min (0.0811916)(0.0504177)brain replica ] 2 (0.0799692)[ medium ] [ max ] CEM 1 Cldn7 30.7 69.1 16239.5 P ( S | Z, I ) = 1.00 Epcam 53.2 140.5 19806.1 Mean Corr = 0.52425Marveld2 83.4 321.5 779.6 Cldn3 48.3 109.5 212.6 Cldn4 118.1 353.6 1241.6 Pard6b 29.6 77.1 813.0 Ocln 52.7 295.7 2079.4 Tjp3 32.7 105.8 447.4 Tjp2 185.6 577.0 2649.0 F11r 469.1 1449.9 8006.6 Inadl 116.5 239.8 1904.1 Cldn23 16.7 31.1 330.2 Prkcz 92.6 215.4 1364.9 Shroom2 132.8 654.8 3221.7 Cldn8 24.0 55.7 115.1 Igsf5 29.6 85.6 2547.5 Cldn6 81.7 120.3 230.2 Magi3 215.4 1011.5 1665.4 Tjp1 166.3 1314.7 2271.2 Esrp1 16.4 45.1 1811.1 Cdh1 42.1 109.7 10622.8 St14 115.9 585.2 6410.9 Cdcp1 121.6 335.9 2928.6 Prss8 33.3 104.9 292.2 CEM 1 + Spint1 81.0 136.1 2195.0 Top 10 Genes Ap1m2 88.1 333.7 1888.5 Irf6 34.0 105.3 2702.3 Erbb3 232.4 683.8 7031.0 Spint2 1208.6 1774.3 7830.8

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE52474" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 154 -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=GSE52474

Background corr dist: KL-Divergence = 0.1954, L1-Distance = 0.0793, L2-Distance = 0.0167, Normal std = 0.3721 GEO Series "GSE31004" 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=GSE31004 Status: Public on Dec 15 2011 Title: Effects of Nicotine on the Fetal Mouse Palate Development and Transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus. To demonstrate the effect of nicotine on craniofacial development, particularly palatogenesis, we delivered three different doses of nicotine (1.5, 3.0 and 4.5 mg/kg/day) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous osmotic mini-pump. We assessed the pups for morphological anomalies, as well as genome-wide mRNA (transcriptome) microarray analysis. Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality in the pups. However, it did not cause obvious cleft palate. The microarray data analysis using IPA identified differential expression of genes involved in various biological pathways, particularly cancer, genetic diseases, and tissue development in response to consistent nicotine exposure. 6232 up-regulated and 6310 down-regulated genes were detected in nicotine-treated groups compared to the control. Moreover, 45% of the genes associated with cleft palate were found to be affected by nicotine. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and RT-PCR. We concluded that consistent nicotine exposure during pregnancy interferes with normal growth and development of the fetus including palatogenesis; however, this interference does not result in cleft palate, rather smaller palate size with persistent MES. To our knowledge, this is the first experiment revealing the impact of nicotine on the fetal palate transcriptome in mice.

Overall design: Total 8 samples were analyzed. Using an osmotic minipump, duplicate samples from palates of either sterile physiological saline or nicotine (1.5 mg/kg/day, 3.0 mg/kg/day, or 4.5 mg/kg/day)-treated newborn pups.

Background corr dist: KL-Divergence = 0.0673, L1-Distance = 0.0308, L2-Distance = 0.0016, Normal std = 0.5256

0.759 Kernel fit Pairwise Correlations Normal fit

Density 0.379

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

Saline control,Saline control, Nicbiological 1.5mg/kg/day, Nicbiological rep1 1.5mg/kg/day,Nic (0.224456) rep2 biological3.0mg/kg/day,Nic (0.232904) biological3.0mg/kg/day, rep1Nic biological4.5mg/kg/day,(0.117317) rep2Nic biological4.5mg/kg/day,(0.0831909) rep1 biological(0.0853903) rep2 biological(0.0743029) rep1 (0.0790184) rep2[ min (0.103421) ] [ medium ] [ max ] CEM 1 Cldn7 50.3 334.8 3327.6 P ( S | Z, I ) = 1.00 Epcam 76.5 280.7 5484.8 Mean Corr = 0.51673Marveld2 112.1 285.8 1200.9 Cldn3 124.7 215.5 430.3 Cldn4 56.9 143.1 296.1 Pard6b 79.0 321.3 656.7 Ocln 43.9 143.7 472.0 Tjp3 39.9 122.2 440.4 Tjp2 377.5 606.4 915.5 F11r 683.7 1632.7 2457.1 Inadl 102.9 256.3 553.7 Cldn23 33.3 115.8 402.6 Prkcz 228.3 300.3 544.6 Shroom2 512.3 820.2 1500.5 Cldn8 32.1 68.6 2351.4 Igsf5 45.6 160.4 1477.8 Cldn6 16.7 51.7 421.3 Magi3 449.8 669.1 842.9 Tjp1 2947.9 3869.0 4846.9 Esrp1 104.2 466.9 1658.3 Cdh1 587.0 2648.3 7791.9 St14 69.5 173.3 638.7 Cdcp1 53.6 199.3 316.1 Prss8 36.8 296.0 1163.6 CEM 1 + Spint1 149.2 425.0 1826.4 Top 10 Genes Ap1m2 53.0 158.8 1261.7 Irf6 294.9 614.8 2305.2 Erbb3 985.6 1917.1 3116.7 Spint2 494.3 1437.0 5904.2

Null module Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam GEO Series "GSE30684" 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=GSE30684 Status: Public on Feb 16 2012 Title: Stem Cell Antigen-1 (Sca-1) Regulates Mammary Tumor Development and Cell Migration Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22140470 Summary & Design: Summary: Stem cell antigen-1 (Sca-1 or Ly6A) is a member of the Ly6 family of glycosyl phostidylinositol (GPI)-anchored cell surface proteins. To determine the potential mechanisms by which Sca-1 regulates cell migration, adhesion, and tumor development; we performed an Affymetrix mouse genome 430A 2.0 array on cDNA comparing shLuc and shSca-1 from cells grown in vitro.

Overall design: We performed an Affymetrix mouse genome 430A 2.0 array on cDNA comparing shLuc and shSca-1 from cells grown in vitro. Experimental groups were profiled in biological triplicate.

Background corr dist: KL-Divergence = 0.0380, L1-Distance = 0.0371, L2-Distance = 0.0017, Normal std = 0.6765

0.628 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

shLuc-treatedshLuc-treated Wnt1-YLshLuc-treated Wnt1-YLshSca-1-treated cells, Wnt1-YLbiologicalshSca-1-treated cells, biologicalshSca-1-treated cells,Wnt1-YL rep 1 biological (0.108424) Wnt1-YL repcells, 2 (0.148405) Wnt1-YLbiological repcells, 3 (0.388384) biological cells, rep[ 1 biological (0.107868)min rep 2 (0.139052) rep] 3 (0.107868)[ medium ] [ max ] CEM 1 Cldn7 40.5 46.8 4841.4 P ( S | Z, I ) = 1.00 Epcam 15.7 30.7 11636.8 Mean Corr = 0.51648Marveld2 2.9 17.8 512.6 Cldn3 19.7 79.0 1960.2 Cldn4 54.8 102.8 2722.4 Pard6b 79.8 94.9 450.3 Ocln 20.4 37.2 239.1 Tjp3 21.3 36.9 132.7 Tjp2 799.2 980.6 1125.3 F11r 3638.4 4688.1 5475.5 Inadl 27.9 45.3 409.2 Cldn23 8.3 36.0 182.7 Prkcz 114.8 145.1 350.8 Shroom2 18.4 24.8 738.3 Cldn8 4.1 21.4 50.1 Igsf5 18.9 41.9 56.4 Cldn6 16.7 33.4 36.5 Magi3 190.2 263.9 802.7 Tjp1 2668.3 3115.9 3395.8 Esrp1 10.2 20.5 4020.9 Cdh1 49.9 91.9 9328.4 St14 12.4 25.1 1317.6 Cdcp1 1511.9 1912.5 2886.4 Prss8 8.3 22.4 213.9 CEM 1 + Spint1 87.8 134.1 2147.4 Top 10 Genes Ap1m2 5.2 30.1 1282.2 Irf6 2549.5 6049.0 6632.5 Erbb3 47.6 60.8 1385.0 Spint2 3788.5 4424.9 10085.7