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

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

Dataset: Num of genes in input gene set: 6 Total number of genes: 16493

CLIC PDF output has three sections:

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

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

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

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

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

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

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

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

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

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

Bottom panel shows the background distribution and the expression profile for CEM genes in this dataset. Ralbp1 Ccnb1 Ap2a2 Ap2a1 Numb Num ofGenesinQueryGeneset:6.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Epn1

Epn1 Ap2a1 Ralbp1 Ap2a2 Numb Ccnb1 CEM 1(13datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page1 Suv420h2 Tmem234 Atp6v0a1 Ranbp10 Smarcc2 Adipor1 Slc16a6 Fam76a Map2k2 Capn15 Ccdc97 Fbxo34 Ppp2r4 Ralbp1 Mknk1 Abhd4 Polr2a Atxn2l Wdr81 Ap1b1 Ccnb1 Gsk3a Pdpk1 Ap2a2 Ap2a1 Wdtc1 Mkrn1 Leng8 Tpcn1 Ncor1 Numb Cnot3 Actn4 Dctn1 Atg2a Tfdp2 Wbp2 Arrb1 Mavs Hagh Rgp1 Epg5 Epn1 Pcif1 Ssh1 Pef1 Slx4 Fzr1 Narf Cic 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE35825 [9] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE17509 [57] GSE30056 [24] GSE27786 [20] GSE14891 [8] GSE35763 [6] GSE2197 [6] GSE32214 [6] GSE14499 [26] GSE47196 [6] GSE33942 [12] GSE18115 [8] GSE23119 [9] GSE11723 [9] GSE22381 [12] GSE46600 [44] GSE32328 [24] GSE7348 [6] GSE24614 [6] GSE5861 [6] GSE28830 [9] GSE37975 [8] GSE18587 [9] GSE46606 [30] GSE21902 [31] GSE30980 [6] GSE18148 [6] GSE15326 [10] GSE39897 [36] GSE6837 [8] GSE30083 [12] GSE13408 [14] GSE27378 [8] GSE8065 [18] GSE31702 [10] GSE15772 [8] GSE13693 [9] GSE26568 [6] GSE32015 [51] GSE20726 [9] GSE36237 [64] GSE46871 [6] GSE42591 [26] GSE22086 [6] GSE27987 [31] GSE25423 [10] GSE9044 [6] GSE43779 [6] GSE22927 [38] GSE14004 [9] GSE5425 [6] GSE53916 [6] GSE38304 [8] GSE4230 [8] GSE27901 [23] GSE24705 [33] GSE42548 [29] GSE31013 [12] GSE34126 [19] GSE41307 [8] GSE9809 [10] GSE54785 [6] GSE22448 [6] GSE11680 [10] GSE25737 [6] GSE54976 [17] GSE20391 [11] GSE47414 [18] GSE47959 [8] GSE23178 [6] GSE8555 [8] GSE14843 [6] GSE8621 [12] GSE7424 [8] GSE18660 [10] GSE6998 [32] GSE22005 [23] GSE17097 [20] GSE15894 [8] GSE20954 [14] GSE38277 [18] GSE41925 [8] GSE46443 [12] GSE22418 [8] GSE30247 [16] GSE43373 [130] GSE25286 [10] GSE38257 [14] GSE20562 [20] GSE9509 [18] GSE33156 [18] GSE43635 [9] GSE13306 [17] GSE13635 [6] GSE12950 [6] GSE11679 [25] GSE17263 [6] GSE8322 [12] GSE33770 [8] GSE40282 [6] GSE35106 [9] GSE16707 [6] GSE28731 [10] GSE37431 [6] GSE26461 [6] GSE22527 [6] GSE16801 [9] GSE43928 [12] GSE17553 [16] GSE32354 [35] GSE6383 [6] GSE12499 [10] GSE20696 [8] GSE7258 [17] GSE10639 [8] GSE35219 [6] GSE31972 [6] GSE9441 [36] GSE25637 [9] GSE40795 [50] GSE13707 [20] GSE41095 [6] GSE26668 [6] GSE35260 [21] GSE3293 [8] GSE13106 [10] GSE6867 [6] GSE36810 [16] GSE4193 [8] GSE41759 [14] GSE16266 [6] GSE13611 [8] GSE7596 [6] GSE39233 [40] GSE9247 [15] GSE25767 [6] GSE18800 [25] GSE34215 [6] GSE53299 [6] GSE39449 [6] GSE7838 [9] GSE43775 [32] GSE31244 [6] GSE30160 [6] GSE30767 [8] GSE27195 [6] GSE17383 [6] GSE11221 [9] GSE32287 [16] GSE11358 [8] GSE20372 [6] GSE5841 [6] CEM+ CEM GSE42008 [6] GSE3962 [8] GSE3843 [8] GSE25645 [17] GSE31570 [6] GSE46185 [6] 0.0 GSE21594 [12] GSE33688 [12]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 5.34 5.36 5.38 5.45 5.46 5.53 5.54 5.57 5.66 5.71 5.71 5.75 5.80 5.83 5.86 5.88 5.89 5.89 6.06 6.09 6.14 6.15 6.17 6.22 6.34 6.39 6.40 6.46 6.47 6.50 6.53 6.79 6.84 6.88 7.16 7.20 7.20 7.22 7.38 7.97 8.19 8.95 9.54 9.69 1.0 Notes Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page2 Ppp1r16a Slc25a38 Fam104a Fam193a Fam134c Tbc1d17 R3hdm2 Ehbp1l1 Mospd1 Slc36a1 Gpcpd1 Vps13d Ccdc77 Zdhhc7 Tuba4a March2 Enthd2 Prkab1 Rnf167 Rnf123 Rbm38 Pxmp4 Kmt2b Ube3b Dedd2 Ubxn6 Ubac1 Vps11 Snx15 Lmtk2 Abtb1 Atg9a Dctn2 Dstyk Wbp1 Ypel3 Gps2 Dot1l Pnpo Bet1l Traf7 Pnkp Pdk2 Zfpl1 Tbx6 Gbf1 Ccnf Gclc Szt2 Gltp 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 3.96 3.97 4.00 4.01 4.01 4.02 4.03 4.06 4.08 4.08 4.13 4.14 4.15 4.18 4.23 4.24 4.24 4.28 4.28 4.29 4.30 4.33 4.33 4.35 4.35 4.40 4.41 4.42 4.44 4.51 4.52 4.57 4.58 4.68 4.70 4.70 4.72 4.79 4.88 4.89 4.90 5.02 5.05 5.08 5.08 5.09 5.15 5.27 5.27 5.28 1.0 Notes 8430419L09Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page3 Tbc1d10b Mad2l1bp Map1lc3b Fam210b Tubgcp6 Hmg20b Slc22a4 Man1b1 Golph3l Cdkn2c St3gal2 Mcoln1 Golga2 Ctdsp1 Numa1 Ap2m1 Hectd3 Tnrc6b Sh3gl1 Tmub2 Incenp Myo9b Pbrm1 Ap3d1 Kmt2c Spsb3 Ap5s1 Mroh1 Bcl2l1 Naa60 Taok2 Mcm2 Atp9b Atg14 Atg13 Tpra1 Lin37 Tbcel Gclm Ago2 Add1 Napa Xpo7 Plin3 Brap Nat6 Crat Cir1 Rb1 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 3.39 3.40 3.42 3.43 3.44 3.45 3.47 3.48 3.49 3.50 3.50 3.51 3.52 3.53 3.54 3.54 3.56 3.62 3.64 3.65 3.66 3.67 3.68 3.68 3.70 3.70 3.72 3.72 3.72 3.74 3.75 3.75 3.76 3.78 3.78 3.79 3.79 3.80 3.81 3.84 3.84 3.84 3.84 3.85 3.86 3.87 3.87 3.89 3.89 3.92 1.0 Notes Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page4 Fam214b Slc25a51 Ccndbp1 Abhd17a Tspan14 Ankrd54 Rmnd5a Dnajb12 Pip4k2c Fam63b Ranbp3 Serinc3 Slc35f6 March6 Rprd1b Arpc1a Katnb1 Rnf185 Ap1m1 Sppl2b Stxbp2 Zbtb22 Arrdc2 Fbxw5 Cdan1 Nfam1 Nelfcd Spsb2 Haus8 Ube2c Mtmr3 Cgrrf1 Cxxc1 Afmid Herc2 Hmbs Hyal2 Pias4 Tmc6 Cdipt Tprgl Yipf4 Sun1 Mafg Tsc2 Clpx Phf1 Lias Ccs Tst 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 2.84 2.85 2.86 2.87 2.89 2.90 2.94 2.95 2.95 2.98 2.98 3.00 3.03 3.04 3.05 3.06 3.06 3.06 3.09 3.09 3.12 3.12 3.13 3.13 3.15 3.17 3.17 3.20 3.21 3.21 3.21 3.22 3.24 3.24 3.24 3.26 3.26 3.27 3.29 3.30 3.31 3.32 3.33 3.33 3.33 3.35 3.35 3.38 3.38 3.38 1.0 Notes 2210018M11Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page5 Tmem203 Tbc1d22a Fam109b Fam134a Zkscan3 Mospd3 Fam63a Cercam Tubb4b Sec22b Ndufb9 Rmdn1 Nudt22 Cnnm2 Zfp830 Zfp414 Stradb Gucd1 Abhd5 Capn1 Ccna2 Hdac5 Vps18 Foxo1 Fkbp8 Chpf2 Cyth2 Pcgf1 Tom1 Scyl1 Etfdh Gab1 Apeh Tpp1 Ftsj1 Ints1 Sirt7 Gatc Get4 Rnf8 Vrk3 Nfe2 Bin3 Pigo Fxr2 Ulk1 E2f2 Gak Nit1 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 2.41 2.43 2.43 2.44 2.44 2.45 2.45 2.46 2.46 2.46 2.46 2.47 2.48 2.49 2.50 2.51 2.51 2.52 2.52 2.53 2.57 2.57 2.58 2.59 2.59 2.60 2.60 2.61 2.63 2.63 2.64 2.65 2.66 2.68 2.70 2.70 2.71 2.72 2.73 2.73 2.73 2.73 2.75 2.77 2.78 2.78 2.79 2.82 2.82 2.83 1.0 Notes Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page6 Arhgef11 Racgap1 Plekhm1 Zdhhc14 Ppip5k1 Lysmd3 Slc43a2 Slc27a4 Tcp11l2 Serinc5 Depdc5 Rab11b Ldlrap1 Cdc25b Ncapd2 Vps9d1 Cdc25c Rb1cc1 Dnttip1 Akirin2 Dhrs11 Chmp3 Kdm2a Dcaf11 Zfp335 Zfp524 Zfp276 Lrrc27 Lrrc57 Ncaph Ckap4 Casp9 Cdca8 Abca3 Vps52 Mcrs1 Mgst3 Aurka H2afx Hacl1 Nprl3 Prpf6 Ddb1 Cdc6 Snx3 Tbcd Aatk Klc4 Lig1 Arf2 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 2.04 2.04 2.05 2.05 2.06 2.06 2.06 2.08 2.09 2.09 2.09 2.11 2.11 2.11 2.12 2.12 2.13 2.13 2.13 2.13 2.14 2.15 2.16 2.16 2.16 2.17 2.17 2.18 2.19 2.20 2.21 2.21 2.23 2.23 2.23 2.24 2.24 2.25 2.25 2.25 2.26 2.27 2.28 2.29 2.31 2.32 2.37 2.40 2.40 2.40 1.0 Notes 1110034G24Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page7 Tmem189 Atp6v0d1 Calcoco1 Fam175b Gpatch2l Zkscan5 Sec14l1 Gnpda1 Capns1 Hexim1 Cep120 Eif2ak3 Sap130 Tbc1d2 Ndufv1 Ubald2 Rnf216 Fermt3 Pnpla6 Arid3b Ube2o Hmgcl Abcg2 Nucb1 Adck5 Wbp1l Sesn1 Foxo3 Fbxo5 Bpgm Akip1 Phf12 Tor1a Smg5 Stx5a Ipo13 Brpf1 Coq9 Spen Speg Urod Mia3 Snrk Slbp Ctc1 Cln8 Pigz Ttc4 Brf1 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 1.68 1.68 1.70 1.70 1.71 1.71 1.72 1.72 1.72 1.72 1.72 1.72 1.73 1.74 1.75 1.75 1.76 1.76 1.79 1.79 1.79 1.80 1.80 1.80 1.82 1.82 1.83 1.87 1.87 1.87 1.87 1.88 1.92 1.92 1.94 1.96 1.97 1.98 1.98 1.98 1.99 1.99 2.01 2.01 2.01 2.02 2.02 2.03 2.03 2.04 1.0 Notes 1600002H07Rik 1700037H04Rik 1700021K19Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page8 Eif4ebp2 Rps6kb2 Unc119b Tubgcp2 Ncaph2 Acad11 Thap11 Oraov1 Gpr146 Osgin1 Osbpl8 Prkag1 Dnajc5 Pcnxl3 Tmco6 Slc2a9 Mus81 Gtf3c1 Pram1 Dand5 Cactin Pfkfb1 Elovl1 Vps16 Wasf2 Dhrs1 Brca1 Gins4 Abcf3 Sppl3 Phf10 Cmc2 Mlst8 Isca1 Gen1 Gpx4 Ppox Bag6 Nelfa Aco2 Txn2 Nbr1 Sbf1 E4f1 Gsn Cat Cit 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 1.35 1.35 1.36 1.36 1.36 1.39 1.40 1.40 1.41 1.41 1.41 1.41 1.42 1.42 1.44 1.44 1.45 1.46 1.46 1.46 1.46 1.47 1.49 1.49 1.50 1.50 1.51 1.51 1.51 1.51 1.53 1.53 1.53 1.53 1.54 1.56 1.56 1.56 1.56 1.56 1.56 1.57 1.59 1.59 1.59 1.61 1.63 1.65 1.66 1.67 1.0 Notes Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page9 Fam114a2 Fam193b Slc25a11 Map3k11 Tmem65 Osgepl1 Scamp5 Slc46a3 Fam78a Pgrmc2 Snapc2 Cdc123 Mbtps1 Zc3h18 Golga4 Golga5 Pradc1 Rnf215 Prkaca Gas2l3 Stk17b Hs6st1 Gigyf1 Rtfdc1 Nup50 Cdkn3 Hif1an Pfkfb4 Acbd5 Eepd1 Bckdk Fcho2 Pacs2 Mcm5 Psrc1 Pms2 Pink1 Tonsl Tstd3 Prr11 Zzef1 Gde1 Chd3 Naga Cbr1 Pigq Iffo1 Ipo9 Cltc Ilk 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 0.99 1.00 1.01 1.01 1.04 1.05 1.06 1.06 1.06 1.07 1.08 1.09 1.10 1.11 1.11 1.11 1.11 1.12 1.14 1.15 1.15 1.16 1.16 1.16 1.17 1.17 1.18 1.19 1.19 1.20 1.21 1.21 1.23 1.24 1.24 1.25 1.25 1.25 1.26 1.26 1.26 1.26 1.27 1.29 1.29 1.30 1.31 1.31 1.32 1.33 1.0 Notes Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page10 Tmem150a Fam160a2 Trp53inp1 Trappc10 Dnase1l1 Slc25a40 Depdc1b Flywch1 Ppp1r3e Caskin2 Zfand2a Slc16a4 Fam45a Spata2l Pgm2l1 Ctdsp2 Rnf166 Cabin1 Steap3 Pnpla7 Fbxl20 Mapk3 Abcb6 Kifc5b Ncapg Ndc80 Hdac4 Top3b Fahd1 Lrwd1 Gm22 Smc4 Espl1 Sipa1 Ypel5 Mob2 Glrx5 Comt Chd2 Nanp Hbp1 Mtfr1 Dgkz Eya3 Grk6 Ctns Tcta Me2 Lbr Ell 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 0.78 0.80 0.80 0.80 0.81 0.81 0.81 0.81 0.81 0.81 0.81 0.83 0.85 0.86 0.86 0.86 0.87 0.87 0.87 0.87 0.87 0.88 0.88 0.89 0.89 0.89 0.89 0.90 0.90 0.91 0.91 0.91 0.91 0.92 0.92 0.92 0.93 0.94 0.94 0.95 0.95 0.96 0.96 0.96 0.96 0.98 0.98 0.99 0.99 0.99 1.0 Notes 2610507B11Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page11 Tmem14c Tmem115 Wbscr27 Ccdc125 Mcm3ap Rad23a Cep152 Rfxank Lmbr1l Smc1a Inpp5a Zfp426 Pik3c3 Lsm10 Fbxl19 G6pdx Mpv17 Arid3a Lrrc8a Cpeb2 Usp45 Acox1 Dhx32 Asna1 Exoc7 Coro7 Gmnn Tesk2 Rhot2 Ercc5 H2afv Mbd6 Prr13 Rrm2 Nelfb Chd8 Phkb Nagk Nrd1 Per1 Thra Frg1 Ifrd2 Nfyc Clk1 Helz Acd Pgp Tk1 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 0.46 0.48 0.48 0.48 0.48 0.49 0.49 0.51 0.54 0.55 0.56 0.56 0.57 0.57 0.58 0.58 0.61 0.62 0.63 0.63 0.65 0.65 0.66 0.66 0.66 0.67 0.67 0.67 0.67 0.68 0.68 0.68 0.70 0.70 0.70 0.72 0.72 0.72 0.74 0.74 0.75 0.75 0.75 0.76 0.76 0.76 0.77 0.77 0.77 0.77 1.0 Notes 2700097O09Rik 5430435G22Rik 1700017B05Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page12 Tmem150b Zdhhc24 Tbc1d25 Ankrd11 Cyp4f16 Arfgap3 Gpr162 Ctnna1 Acot13 Zranb1 Akt1s1 Epb4.1 Psmd4 Nbeal1 Wbp11 Eef1a2 Taldo1 Inpp5e Mpdu1 Myo9a Stard9 Chtf18 Rdh14 Pmm1 Ube3c Ncoa4 Spag5 Msrb1 Pex19 Tusc2 Dhrs3 Nsdhl Atad2 Adat3 Mrm1 Serf2 Ugp2 Aup1 Tlr13 Rev1 Xab2 Ska2 Tab1 Arsa Helb Atl2 Stil 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 0.24 0.25 0.25 0.25 0.26 0.26 0.26 0.26 0.27 0.27 0.28 0.28 0.28 0.29 0.29 0.29 0.29 0.30 0.30 0.31 0.32 0.32 0.32 0.33 0.33 0.33 0.33 0.33 0.34 0.34 0.34 0.35 0.35 0.35 0.35 0.36 0.36 0.38 0.38 0.39 0.39 0.40 0.41 0.42 0.42 0.42 0.43 0.45 0.45 0.46 1.0 Notes D230025D16Rik 9030624J02Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page13 Trp53bp2 Gm15800 Tgfbrap1 Gadd45a Rasgrp4 Dnajc16 Arhgef1 Zfyve21 Wrap53 Rab40c Tubb2a March8 Kdm5b Kctd20 Kctd21 Kdm3a Naprt1 Cenph Cenpq Ap5b1 Ccnb2 Acbd4 Rab43 Dhx16 Aaed1 Nipal3 Degs1 Josd2 Micu1 Agfg2 Prkd2 Rnf26 Clcn3 Wipf2 Stk25 Stk16 Fastk Osbp Sidt2 Dhx8 Ensa Pan2 Flot2 Lmf2 Mpst Cnst Prc1 Iscu 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE5236 [8] Scale ofaveragePearsoncorrelations GSE13692 [8] GSE13553 [10] GSE56777 [8] GSE13225 [6] GSE19668 [50] GSE11982 [6] 0.2 GSE57425 [6] GSE26496 [6] GSE13753 [10] GSE11149 [8] GSE35761 [6] GSE48203 [9] GSE39030 [6] GSE42601 [6] GSE6632 [6] 0.4 GSE43381 [26] GSE16684 [6] GSE11120 [10] GSE4029 [10] GSE27972 [6] GSE39458 [6] GSE42103 [9] GSE51243 [7] GSE45430 [9] 0.6 GSE27092 [6] GSE36415 [14] GSE15541 [12] GSE22774 [6] GSE56542 [8] GSE27605 [8] GSE9804 [9] GSE21716 [28] GSE17404 [9] 0.8 GSE29241 [6] GSE27881 [16] GSE38283 [7] GSE54581 [21] Score 0.05 0.06 0.06 0.06 0.06 0.06 0.06 0.07 0.07 0.08 0.08 0.08 0.09 0.09 0.10 0.10 0.10 0.11 0.11 0.11 0.11 0.12 0.12 0.12 0.12 0.12 0.13 0.13 0.13 0.13 0.14 0.14 0.15 0.15 0.15 0.16 0.17 0.17 0.17 0.18 0.18 0.19 0.19 0.19 0.20 0.20 0.21 0.22 0.22 0.23 1.0 Notes 2310067B10Rik Symbol Num ofCEMGenes:6.Predicted655.SelectedDatasets:13.Strength:0.0 CEM 1,Geneset"[C]RalBP1-CCNB1-AP2A-NUMB-EPN1complex",Page14 Aurkaip1 Zfand2b Lrrc20 Trip11 Abca7 Wwp2 Supt5 Hyls1 Nat8l Rtf1 0.0 1.0

GSE48338 [8] GSE18042 [18]

GSE35825 [9] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE17509 [57] GSE30056 [24] GSE27786 [20] GSE14891 [8] GSE35763 [6] GSE2197 [6] GSE32214 [6] GSE14499 [26] GSE47196 [6] GSE33942 [12] GSE18115 [8] GSE23119 [9] GSE11723 [9] GSE22381 [12] GSE46600 [44] GSE32328 [24] GSE7348 [6] GSE24614 [6] GSE5861 [6] GSE28830 [9] GSE37975 [8] GSE18587 [9] GSE46606 [30] GSE21902 [31] GSE30980 [6] GSE18148 [6] GSE15326 [10] GSE39897 [36] GSE6837 [8] GSE30083 [12] GSE13408 [14] GSE27378 [8] GSE8065 [18] GSE31702 [10] GSE15772 [8] GSE13693 [9] GSE26568 [6] GSE32015 [51] GSE20726 [9] GSE36237 [64] GSE46871 [6] GSE42591 [26] GSE22086 [6] GSE27987 [31] GSE25423 [10] GSE9044 [6] GSE43779 [6] GSE22927 [38] GSE14004 [9] GSE5425 [6] GSE53916 [6] GSE38304 [8] GSE4230 [8] GSE27901 [23] GSE24705 [33] GSE42548 [29] GSE31013 [12] GSE34126 [19] GSE41307 [8] GSE9809 [10] GSE54785 [6] GSE22448 [6] GSE11680 [10] GSE25737 [6] GSE54976 [17] GSE20391 [11] GSE47414 [18] GSE47959 [8] GSE23178 [6] GSE8555 [8] GSE14843 [6] GSE8621 [12] GSE7424 [8] GSE18660 [10] GSE6998 [32] GSE22005 [23] GSE17097 [20] GSE15894 [8] GSE20954 [14] GSE38277 [18] GSE41925 [8] GSE46443 [12] GSE22418 [8] GSE30247 [16] GSE43373 [130] GSE25286 [10] GSE38257 [14] GSE20562 [20] GSE9509 [18] GSE33156 [18] GSE43635 [9] GSE13306 [17] GSE13635 [6] GSE12950 [6] GSE11679 [25] GSE17263 [6] GSE8322 [12] GSE33770 [8] GSE40282 [6] GSE35106 [9] GSE16707 [6] GSE28731 [10] GSE37431 [6] GSE26461 [6] GSE22527 [6] GSE16801 [9] GSE43928 [12] GSE17553 [16] GSE32354 [35] GSE6383 [6] GSE12499 [10] GSE20696 [8] GSE7258 [17] GSE10639 [8] GSE35219 [6] GSE31972 [6] GSE9441 [36] GSE25637 [9] GSE40795 [50] GSE13707 [20] GSE41095 [6] GSE26668 [6] GSE35260 [21] GSE3293 [8] GSE13106 [10] GSE6867 [6] GSE36810 [16] GSE4193 [8] GSE41759 [14] GSE16266 [6] GSE13611 [8] GSE7596 [6] GSE39233 [40] GSE9247 [15] GSE25767 [6] GSE18800 [25] GSE34215 [6] GSE53299 [6] GSE39449 [6] GSE7838 [9] GSE43775 [32] GSE31244 [6] GSE30160 [6] GSE30767 [8] GSE27195 [6] GSE17383 [6] GSE11221 [9] GSE32287 [16] GSE11358 [8] GSE20372 [6] GSE5841 [6] CEM+ CEM GSE42008 [6] GSE3962 [8] GSE3843 [8] GSE25645 [17] GSE31570 [6] GSE46185 [6] 0.0 GSE21594 [12] GSE33688 [12]

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

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

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

0.493 Kernel fit Pairwise Correlations Normal fit

Density 0.246

0.000 CEM 1

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

Pre-normalization Quantiles

BMDM, BMDM,Tpl2 WT, BMDM,Tpl2 unstimulated, WT, BMDM,Tpl2 unstimulated, KO, BMDM,Tpl2 biologicalunstimulated, KO, BMDM,Tpl2 biologicalunstimulated, replicate WT, BMDM,Tpl2 biological LPS replicate WT, 1treated, BMDM, Tpl2(0.147088) biological LPS replicate KO, 2treated, biologicalTpl2(0.244956) LPS replicate KO, 1treated, biological(0.0936134) LPS replicate 2treated, biological(0.0587831) replicate 1 (0.115136) biological[ minreplicate 2 (0.112539) replicate ]1 (0.122088) 2 (0.105796)[ medium ] [ max ] CEM 1 Epn1 493.8 948.9 1022.1 P ( S | Z, I ) = 1.00 Ap2a1 906.9 1220.6 1412.9 Mean Corr = 0.67138 Ralbp1 788.1 1709.9 2089.8 Ap2a2 84.3 165.2 183.6 Numb 1376.4 3318.0 3581.7 Ccnb1 58.6 63.1 81.9 Wbp2 673.8 1072.0 1224.3 Smarcc2 734.6 1021.7 1194.5 Gsk3a 1556.7 2043.2 2207.5 Capn15 293.2 596.8 698.8 Atg2a 273.7 822.6 1035.4 CEM 1 + Atp6v0a1 1105.5 2869.9 3902.3 Top 10 Genes Rgp1 528.8 1090.3 1198.5 Polr2a 1406.8 3957.7 4584.6 Adipor1 129.3 433.6 548.9 Hagh 288.8 1123.1 1360.7

Null module GEO Series "GSE18042" 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=GSE18042 Status: Public on Sep 10 2009 Title: Erythroid differentiation: G1E model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19887574 Summary & Design: Summary: Analysis of erythroid differentiation using Gata1 gene-disrupted G1E ER4 clone cells. Estradiol addition activates an ectopically expressed Gata-1-estrogen receptor fusion protein, triggering synchronous differentiation. 30 hour time course corresponds roughly to late burst-forming unit-erythroid stage (t=0 hrs) through orthochromatic erythroblast stage (t=30 hrs).

Overall design: G1E ER4 cells cultured in G1E medium were treated at 6 time points with estradiol to initiate erythroid differentiation by activating Gata1 transcription factor and total RNAs from treated cells were extracted for microarray experiment. The erythroid differentiation status was confirmed by cell pellet color and expression of microRNA miR451. The design was similar to an earlier studies (Welch, J. J., Watts, J. A., Vakoc, C. R., Yao, Y., Wang, H., Hardison, R. C., Blobel, G. A., Chodosh, L. A., and Weiss, M. J. (2004)). Global regulation of erythroid gene expression by transcription factor GATA-1. Blood 104, 3136-3147), except that a more recent version of Affymetric chip was used to acheive greater transcriptome coverage.

Background corr dist: KL-Divergence = 0.0901, L1-Distance = 0.0663, L2-Distance = 0.0070, Normal std = 0.5071

0.884 Kernel fit Pairwise Correlations Normal fit

Density 0.442

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

pre-estradiol,pre-estradiol, biologicalpre-estradiol, biological3 hrep1 post-estradiol,biological biological(0.0413966)3 hrep2 post-estradiol,biological (0.0934478)3 hrep3 post-estradiol,biological (0.0606081)7 h post-estradiol,biological rep17 h post-estradiol,biological(0.0515643) rep27 h post-estradiol,biological(0.0375123) rep314 h (0.0476128) post-estradiol,biological rep114 h (0.0228147) post-estradiol,biological rep214 h (0.0113783) post-estradiol,biological rep321 h (0.0194627) post-estradiol,biological rep121 h post-estradiol,biological(0.00092721) rep221 h post-estradiol,biological(0.0112034) rep330 h post-estradiol,biological(0.0401894) rep130 h post-estradiol,biological(0.101687) rep230 h post-estradiol,biological(0.113433) rep3 (0.0639527) rep1 (0.111408) rep2 (0.0803057) rep3[ min (0.0910959) ] [ medium ] [ max ] CEM 1 Epn1 666.3 1370.4 2589.2 P ( S | Z, I ) = 1.00 Ap2a1 364.7 827.3 1606.6 Mean Corr = 0.64022 Ralbp1 395.6 483.8 683.6 Ap2a2 8.3 14.2 20.4 Numb 693.7 926.9 1288.4 Ccnb1 3463.7 4317.2 6288.5 Wbp2 1405.2 2777.2 5529.8 Smarcc2 455.2 573.4 744.9 Gsk3a 1459.4 2117.3 3147.3 Capn15 180.0 286.7 439.6 Atg2a 146.8 370.2 765.4 CEM 1 + Atp6v0a1 1073.7 2389.7 5159.6 Top 10 Genes Rgp1 442.0 658.9 930.2 Polr2a 2676.1 3158.0 3460.7 Adipor1 744.4 1414.7 1806.1 Hagh 417.9 1996.1 3746.3

Null module GEO Series "GSE35825" 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=GSE35825 Status: Public on Feb 15 2012 Title: Type I and II Interferon-Stimulated Genes in Murine Primary Bone Marrow Macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22371602 Summary & Design: Summary: We used microarrays to compare interferon-alpha (IFNa)- and interferon-gamma (IFNg)-stimulated genes under an equivalent biological input. The goal was to compare IFNa- and IFNg-stimulated genes, as well as to identify common and distinct sets of type I and II ISGs.

Overall design: Bone marrow macrophages derived from mouse bone marrow in M-CSF for 7 days. The cells were stimulated with 62U/mL IFNa and 1U/mL of IFNg for 2.5 hrs in culture. These concentrations induced equivalent STAT1 phosphorylation in BMMs.

Background corr dist: KL-Divergence = 0.0865, L1-Distance = 0.0224, L2-Distance = 0.0007, Normal std = 0.4706

0.848 Kernel fit Pairwise Correlations Normal fit

Density 0.424

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

Media rep1Media (0.184976) rep2Media (0.0391122) rep3IFNa (0.0331686) rep1IFNa (0.0990127) rep2IFNa (0.161189) rep3IFNg (0.150956) rep1IFNg (0.200827) rep2IFNg (0.0756779) rep3 (0.0550806) [ min ] [ medium ] [ max ] CEM 1 Epn1 1038.8 1320.8 1510.2 P ( S | Z, I ) = 1.00 Ap2a1 512.5 611.0 852.5 Mean Corr = 0.56655 Ralbp1 779.7 966.6 1306.2 Ap2a2 6.2 59.6 114.0 Numb 1362.0 1783.0 2148.1 Ccnb1 5.3 27.7 31.0 Wbp2 1565.2 1862.7 2253.0 Smarcc2 628.8 774.6 1194.4 Gsk3a 1190.7 1747.2 2104.7 Capn15 120.6 170.8 295.8 Atg2a 186.4 311.8 518.0 CEM 1 + Atp6v0a1 3378.2 4181.5 4845.8 Top 10 Genes Rgp1 470.5 561.4 671.9 Polr2a 1007.0 1361.2 1874.9 Adipor1 505.5 769.9 1166.7 Hagh 1051.1 1263.3 1481.2

Null module GEO Series "GSE17509" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 57 -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=GSE17509 Status: Public on Aug 20 2009 Title: Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19683682 Summary & Design: Summary: To gain insight into the changes in gene expression pattern upon Ebola infection, CD45+/+ (100% protein level) and CD45+/- (62% protein level) mice were challenged with mouse adapted Ebola virus. At time-points day 0, 1, 3, 5, 7, 9, 11 and 13, spleen tissue was harvested and splenocytes isolated. Total RNA was isolated for mRNA expression analysis. The mouse genome 430 2.0 array (Affymetrix, Inc.), which consists of over 39,000 genes in a single array, was used. Based on gene expression patterns, the variable genes were grouped into sixteen clusters. Each cluster contained genes associated with cellular immune processes, signaling, cell-cycle, complement coagulation cascade, biosynthesis/metabolism, ubiquitous genes involved in several cascades, and genes of unknown function. Interestingly, gene expression in clusters 2 and 3 were significantly downregulated by day 1 following EBOV challenge in CD45100% mice. In contrast, at day 1 following EBOV infection, the CD45 62% mice maintained gene expression patterns similar to day 0. The differences in gene expression patterns between the CD45 100% and CD45 62% splenocytes were less apparent at day 3 following infection and by days 5 and 7 they became very similar. At day 9, when wild-type mice had succumbed to the disease, the pattern in CD45 62% mice remained similar to the day 7 patterns of CD45 100% and CD45 62% mice. The pattern at days 11 and 13 in the CD45 62% mice had returned to that of day 0 CD45 100% or CD45 62% mice. These results suggested that in CD45 100% mice, subversion of the cell transcriptional machinery during the early stages of EBOV infection (day 1) might represent a major factor leading to death of the mice. In CD45 62% mice, early control of gene regulation likely provided the appropriate antiviral responses leading to regulated inflammation, immune co-stimulation, and survival.

Overall design: RNA expression in CD45 100% and 62% mice were compared at each time point: days 0, 1, 3, 5, and 7, using an empirical Bayes procedure. From 3 to 8 biological replicates were in each group. Samples for days 9, 11, and 13 (4 biological replicates each) were also available for only CD45 62%. Median expression values for highly variable genes within each group were clustered using agglomerative nesting over all available time points.

Background corr dist: KL-Divergence = 0.2878, L1-Distance = 0.0465, L2-Distance = 0.0049, Normal std = 0.2883

1.384 Kernel fit Pairwise Correlations Normal fit

Density 0.692

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

splenocytes_100%_d0_1splenocytes_100%_d0_2splenocytes_100%_d0_3splenocytes_100%_d1_1 (0.0778302)splenocytes_100%_d1_2 (0.058534)splenocytes_100%_d1_3 (0.00343526)splenocytes_100%_d1_4 (0.00361527)splenocytes_100%_d3_1 (0.00860425)splenocytes_100%_d3_2 (0.0183357)splenocytes_100%_d3_3 (0.0109544)splenocytes_100%_d3_4 (0.014854)splenocytes_100%_d5_1 (0.0194898)splenocytes_100%_d5_2 (0.0168656)splenocytes_100%_d5_3 (0.0141312)splenocytes_62%_d0_1 (0.0127261)splenocytes_62%_d0_2 (0.0100055)splenocytes_62%_d0_3 (0.00361003)splenocytes_62%_d0_4 (0.00805343)splenocytes_62%_d1_1 (0.0351368)splenocytes_62%_d1_2 (0.108272)splenocytes_62%_d1_3 (0.0214465)splenocytes_62%_d1_4 (0.0261635)splenocytes_62%_d3_1 (0.124082)splenocytes_62%_d3_2 (0.0478503)splenocytes_62%_d3_3 (0.0399716)splenocytes_62%_d3_4 (0.0114872)splenocytes_62%_d5_1 (0.00842494)splenocytes_62%_d5_2 (0.0137391)splenocytes_62%_d5_3 (0.00744087)splenocytes_62%_d5_4 (0.00473315)splenocytes_100%_d5_4 (0.00615675)splenocytes_100%_d7_1 (0.0047679)splenocytes_62%_d5_5 (0.0100522)splenocytes_62%_d9_1 (0.0129342)splenocytes_62%_d11_1 (0.0194884)splenocytes_62%_d13_1 (0.00504537)splenocytes_100%_d5_5 (0.00656096)splenocytes_100%_d7_2 (0.00311626)splenocytes_62%_d5_6 (0.0058802)splenocytes_62%_d7_1 (0.0157368)splenocytes_62%_d9_2 (0.0138716)splenocytes_62%_d11_2 (0.00934914)splenocytes_62%_d13_2 (0.00920904)splenocytes_100%_d5_6 (0.00436545)splenocytes_100%_d7_3 (0.00208805)splenocytes_62%_d5_7 (0.00932678)splenocytes_62%_d7_2 (0.0134357)splenocytes_62%_d9_3 (0.0158002)splenocytes_62%_d11_3 (0.00728542)splenocytes_62%_d13_3 (0.0134119)splenocytes_100%_d5_7 (0.00413123)splenocytes_100%_d7_4 (0.00914452)splenocytes_62%_d5_8 (0.00701467)splenocytes_62%_d7_3 (0.0202556)splenocytes_62%_d9_4 (0.00653899)splenocytes_62%_d11_4 (0.0101905)splenocytes_62%_d13_4 (0.00681011) (0.00617932) (0.00329314) (0.00876694)[ min ] [ medium ] [ max ] CEM 1 Epn1 368.9 609.4 2616.4 P ( S | Z, I ) = 1.00 Ap2a1 128.1 257.9 1047.3 Mean Corr = 0.29626 Ralbp1 818.5 1412.3 2582.2 Ap2a2 61.7 135.9 624.4 Numb 382.3 785.7 1259.0 Ccnb1 9.5 14.8 35.6 Wbp2 318.9 892.3 3194.5 Smarcc2 180.1 324.0 820.5 Gsk3a 1256.4 1768.8 2645.6 Capn15 42.1 82.8 249.4 Atg2a 53.0 114.6 237.4 CEM 1 + Atp6v0a1 66.5 161.3 1751.5 Top 10 Genes Rgp1 708.0 1021.3 1778.4 Polr2a 563.3 1142.8 7208.1 Adipor1 96.9 322.8 4606.2 Hagh 449.9 1749.0 11286.9

Null module GEO Series "GSE30056" 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=GSE30056 Status: Public on Aug 05 2011 Title: Reconstitution of the mouse germ-cell specification pathway in culture by pluripotent stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21820164 Summary & Design: Summary: The generation of properly functioning gametes in vitro, a key goal in developmental/reproductive biology, requires multi-step reconstitutions of complex germ cell development. Based on the logic of primordial germ cell (PGC)-specification, we demonstrate here the generation of PGC-like cells (PGCLCs) in mice with robust capacity for spermatogenesis from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pre-gastrulating epiblasts, but distinct from epiblast stem cells (EpiSCs). The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs are a meticulous capture of those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-beta 3 and SSEA1 as markers that purify PGCLCs with spermatogenic capacity free from tumorigenic undifferentiated cells. With the reconstitution of PGC specification pathway from the naive inner cell mass state, our study defines a paradigm for the essential step of in vitro gametogenesis.

Overall design: We performed this analysis to reveal the characters of the cells that we created in this study, epiblast-like cells (EpiLCs) and primordial germ cells-like cells (PGCLCs). Because EpiLCs were induced from embryonic stem cells (ESCs), and equivalent to pre-gastrulating epiblast (embryonic day [E] 5.5-6.0) in vivo (embryo), ESCs and epiblast were included in this analysis. Epiblast stem cells (EpiSCs) are a culture cell type derived from epiblast, and were also included. PGCLCs were supposed to be equivalent to E9.5 PGCs based on reporter fluorescent transgene expressions and epigenetic properties, and therefore E9.5 PGCs were also inckuded in this analysis. Because epiblast and E9.5 PGCs are of a small number of cells in embryos (a few hundred to thousand cells), cDNAs were amplified with a quantitative global PCR method (Kurimoto et al., 2006, Nucleic Acids Research) for microarray analyses. We took two biological replicate for each cell type.

Background corr dist: KL-Divergence = 0.1263, L1-Distance = 0.0348, L2-Distance = 0.0025, Normal std = 0.4002

0.997 Kernel fit Pairwise Correlations Normal fit

Density 0.498

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

embryonicembryonic stemday cells stem1 epiblast (ESCs)day cells 1 epiblast like(ESCs)(2iLIF,day cells2 epiblast feederlike(2iLIF,day (EpiLCs), cells2 free),epiblast feederlikeday (EpiLCs), cellsbiological3biological free),epiblast likeday (EpiLCs), cellsbiological3biological epiblast rep1likerep1epiblast (EpiLCs), cells biological (0.0126036)(0.0430328) rep2likerep2epiblast stem(EpiLCs), cells biological (0.0148245)(0.0420612) cellsrep1primordial stem(EpiLCs), biological(EpiSCs),(0.0279399) cellsrep2primordial germ biological(EpiSCs),(0.0205042) rep1biologicalembryonic cell germ (0.0286517) (PGC) rep2biologicalembryonic cell rep1 stem (0.0265491)like (PGC) day(0.0532145) cellscells rep2 stem2 like epiblast (PGCLCs), (ESCs),day(0.0817975) cellscells 2 epiblast (PGCLCs),like(ESCs), epiblastPCR biological cells amplified, like epiblastPCR stem (EpiLCs), biological cells amplified, rep1cellsepiblast, biological stem (EpiLCs), (0.0941179) (EpiSCs),PCR rep2cellsepiblast, biological PCRamplified, (0.0613391)rep1 (EpiSCs),PCR amplified,PCRPGCLCs, (0.0410291) PCRamplified, rep2 amplified,biological amplified,PCRPGCLCs, (0.0300236) biologicalPCR amplified,biological amplified,PGCs biologicalrep1 biologicalPCR rep1(0.0400484) (E9.5), amplified,PGCs biologicalrep2 (0.0239268)biologicalrep1 rep2(0.0791211) PCR(E9.5), (0.0366922) (0.0267584)biologicalrep2amplified, PCRrep1 (0.0379023) amplified,(0.0505615) rep2biological (0.0387404) biological[ rep1min (0.0511737) rep2 ] (0.0373869)[ medium ] [ max ] CEM 1 Epn1 2.2 1100.7 1822.1 P ( S | Z, I ) = 1.00 Ap2a1 135.5 242.1 461.0 Mean Corr = 0.00926 Ralbp1 74.0 1090.2 2763.8 Ap2a2 9.0 57.2 188.1 Numb 30.3 342.8 815.3 Ccnb1 168.4 281.4 468.9 Wbp2 640.8 1393.3 3062.3 Smarcc2 100.7 215.7 707.2 Gsk3a 115.2 2545.4 3989.4 Capn15 101.2 419.8 1389.7 Atg2a 103.3 335.4 1106.2 CEM 1 + Atp6v0a1 33.6 187.3 367.3 Top 10 Genes Rgp1 240.5 547.7 1092.7 Polr2a 801.9 2471.1 6384.9 Adipor1 81.2 300.3 724.6 Hagh 900.3 1337.9 2374.1

Null module GEO Series "GSE27786" 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=GSE27786 Status: Public on May 19 2011 Title: Gene expression profile of mouse hematopoietic cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21540074 Summary & Design: Summary: Each fraction of mouse hematopoietic cells was purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and its gene expression was analyzed.

Overall design: Two biological replicates of each fraction were analyzed using a Mouse Genome 430 2.0 array (Affymetrix).

Background corr dist: KL-Divergence = 0.1762, L1-Distance = 0.0498, L2-Distance = 0.0060, Normal std = 0.3706

1.098 Kernel fit Pairwise Correlations Normal fit

Density 0.549

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

KSL cells,KSL biological cells,Lineage biological replicateLineage marker(-) replicate B220(+) 1marker(-) (0.0138931) cells, B220(+)2B biological(0.0270241) lymphocytes,cells,CD4(+) B biological lymphocytes, replicate TCD4(+) lymphocytes,biological replicate 1 TCD8(+) (0.0222864) lymphocytes,biological replicate 2 TCD8(+) (0.0200106)biological lymphocytes, replicate 1 TNK1.1+ biological(0.0336186) lymphocytes, replicate 2 NK1.1+NK biological(0.0251224) cells,replicate 1 CD3˛(+)NK1.1(+)(0.00630533)NK biological biological cells,replicate 2 CD3˛(+)NK1.1(+)(0.0183226) biological replicate replicate1 Ter119(+)(0.0125781) NKT replicate2 1cells,Ter119(+)(0.0131884) (0.00671031) NKTerythroblasts, biological 2cells,Gr-1(+) (0.0135786) erythroblasts, biological Gr-1(+)neutrophils, replicate biological Mac-1(+)neutrophils, replicate biological 1 (0.0119)replicatebiologicalMac-1(+) monocytes/macrophages, 2 (0.0181973)replicatebiological 1 replicate (0.23704)monocytes/macrophages, 2 replicate(0.236593) 1 (0.119699) 2 (0.110869) biological[ min biological replicate ] replicate 1 (0.0400205) [2 (0.0130435)medium ] [ max ] CEM 1 Epn1 458.1 675.4 1643.0 P ( S | Z, I ) = 0.99 Ap2a1 166.7 270.5 915.9 Mean Corr = 0.31532 Ralbp1 1671.0 3109.0 5662.6 Ap2a2 81.5 336.4 1004.7 Numb 518.3 1774.6 9840.0 Ccnb1 9.8 80.5 984.9 Wbp2 591.1 875.9 3577.1 Smarcc2 438.7 544.3 1149.6 Gsk3a 1258.4 1777.8 7004.8 Capn15 108.9 309.5 443.2 Atg2a 93.1 249.6 431.0 CEM 1 + Atp6v0a1 15.8 170.5 1570.9 Top 10 Genes Rgp1 783.7 1246.8 3587.8 Polr2a 545.1 907.9 2526.9 Adipor1 120.2 277.3 3697.6 Hagh 731.1 1042.5 37129.7

Null module GEO Series "GSE14891" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14891 Status: Public on Feb 19 2009 Title: Expression data of LPS-stimulated macrophages from wild-type and Zc3h12a-/- mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19322177 Summary & Design: Summary: Lipopolysaccharide (LPS), a Toll-like receptor (TLR) 4 ligand, induces the expression of various genes including proinflammatory cytokines, and the expression is modified by the presence of Zc3h12a.

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

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

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

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

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWild-type macrophagesWild-type macrophagesWild-type 0h macrophages (0.395575)Zc3h12aKO_macrophages_0h 1h macrophages (0.0684972)Zc3h12aKO_macrophages_1h 2h (0.0301007)Zc3h12aKO_macrophages_2h 4h (0.0925702)Zc3h12aKO_macrophages_4h (0.0963292) (0.0593392) (0.131992)[ (0.125596) min ] [ medium ] [ max ] CEM 1 Epn1 94.3 180.9 234.5 P ( S | Z, I ) = 0.95 Ap2a1 102.2 130.8 177.2 Mean Corr = 0.58774 Ralbp1 87.9 175.0 256.6 Ap2a2 44.7 58.3 72.0 Numb 1019.0 1702.1 2368.0 Ccnb1 55.0 75.0 124.5 Wbp2 3577.9 6013.6 7030.5 Smarcc2 206.8 328.7 444.3 Gsk3a 627.8 686.5 835.5 Capn15 36.9 50.1 97.5 Atg2a 38.0 71.3 107.3 CEM 1 + Atp6v0a1 1622.5 7365.1 9138.8 Top 10 Genes Rgp1 87.0 100.4 147.1 Polr2a 743.8 1964.1 2621.8 Adipor1 79.1 183.9 412.5 Hagh 63.4 101.2 136.1

Null module GEO Series "GSE35763" 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=GSE35763 Status: Public on Jun 01 2012 Title: Effect of fluoxetine treatment on translational profiles of Glt25d2 cortical pyramidal cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22632977 Summary & Design: Summary: Molecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment.

We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from S100a10-expressing corticostriatal projection neurons. We show that the S100a10 cells are a unique population of cortical cells that are strongly and specifically responsive to chronic SSRI administration and that this response requires p11 (the protein product of S100a10).

Our data demonstrate that the beneficial actions of antidepressant therapy can be mediated by a single cell type that is positioned to normalize activity between cortical and subcortical sites, and suggest that development of drugs that specifically target the activity of these cells may result in improved therapies to treat depression.

Overall design: Glt25d2 bacTRAP mice were administered either fluoxetine (FLX) or vehicle (VEH) in their drinking water for 15-18 days. Three independent TRAP replicates from cortex of each group were then collected. Total RNA from the immunoprecipitates was amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the S100a10 BAC labels some non-neuronal cells, we recommend only probe sets listed in Table S1 of the accompanying paper be included in the analysis.

Background corr dist: KL-Divergence = 0.0307, L1-Distance = 0.0183, L2-Distance = 0.0004, Normal std = 0.6655

0.599 Kernel fit Pairwise Correlations Normal fit

Density 0.300

0.000 CEM 1

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

Pre-normalization Quantiles

Glt25d2Glt25d2 cells, cortex,Glt25d2 cells, cortex,TRAPGlt25d2 cells, RNA, cortex,TRAPGlt25d2 cells, FLX RNA, cortex,TRAPGlt25d2 cells,treated, VEH RNA, cortex,TRAP cells, treated,biological FLX RNA, cortex,TRAP treated, biological VEH rep1 RNA, TRAP treated, biological(0.262142) FLX rep1RNA,[ treated, biological(0.196298)min VEH rep2 treated, biological(0.0917778) ]rep2 biological(0.141029) rep3 (0.135043)[ rep3medium (0.173711) ] [ max ] CEM 1 Epn1 395.5 1044.0 1139.8 P ( S | Z, I ) = 0.94 Ap2a1 374.0 1151.3 1319.5 Mean Corr = 0.52975 Ralbp1 1459.7 2393.7 3192.7 Ap2a2 10.6 12.2 13.1 Numb 1845.2 1997.9 2463.8 Ccnb1 5.7 5.9 6.0 Wbp2 3972.5 5516.5 5820.0 Smarcc2 453.2 685.1 1042.3 Gsk3a 2718.8 3519.5 3748.4 Capn15 298.4 364.7 369.1 Atg2a 124.0 184.3 243.1 CEM 1 + Atp6v0a1 3933.9 6977.6 7687.0 Top 10 Genes Rgp1 503.3 773.8 865.9 Polr2a 397.1 545.8 642.6 Adipor1 52.6 67.0 94.0 Hagh 6940.0 7970.2 7987.5

Null module GEO Series "GSE2197" 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=GSE2197 Status: Public on Mar 01 2005 Title: DC response to ISD vs CpG Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16413926 Summary & Design: Summary: Bone marrow-derived dendritic cells were left untreated or stimulated with lipid-transfected double-stranded DNA or CpG oligonucleotides for four hours before harvesting.

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0357, L1-Distance = 0.0292, L2-Distance = 0.0011, Normal std = 0.6498

0.625 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

ISD Exp.1CpG (0.144148) Exp.1Untreated (0.0733714)CpG Exp1 Exp2ISD (0.268313) (0.110379) Exp2Untreated (0.154893) Exp2 (0.248895) [ min ] [ medium ] [ max ] CEM 1 Epn1 717.4 835.0 1250.3 P ( S | Z, I ) = 0.90 Ap2a1 383.7 579.8 652.7 Mean Corr = 0.61699 Ralbp1 568.1 900.8 1441.6 Ap2a2 20.5 104.2 174.6 Numb 951.7 1251.9 1538.5 Ccnb1 15.6 51.2 91.1 Wbp2 1022.8 1203.9 1505.3 Smarcc2 629.0 838.0 867.4 Gsk3a 1218.0 1571.8 2847.6 Capn15 114.9 325.5 547.7 Atg2a 162.1 402.7 484.8 CEM 1 + Atp6v0a1 1405.5 1995.5 2443.6 Top 10 Genes Rgp1 355.3 607.5 798.8 Polr2a 543.5 806.8 1080.9 Adipor1 104.9 198.8 299.6 Hagh 652.3 715.6 1218.9

Null module GEO Series "GSE32214" 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=GSE32214 Status: Public on Oct 31 2011 Title: Expression profiling of erythroid developmental subsets isolated from mouse fetal liver. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22076376 Summary & Design: Summary: The S1 and S3 erythroid developmental subsets were isolated using flow cytometry and the cell surface markers CD71 and Ter119 as described by Pop et. al. 2010 (PMID: 20877475)

Expression profiles for S1 and S3 subsets were generated using Affymetrix GeneChips. Results were used to identify genes that are differentially expressed during erythropoiesis.

Overall design: Single cell suspensions were prepared by mechanically dissociating whole fetal livers obtained from E12.5 to E13.5 Balb/C mouse embryos. Cells were stained for CD71, Ter119, and a cocktail containing lineage-specific antibodies. S1 and S3 erythroid developmental subsets were identified and isolated using flow cytometric sorting as described by Pop et. al. 2010 (PMID: 20877475). S1 and S3 subsets were isolated on 3 seperate days to generate total RNA (biological replicates). 20 ng of total RNA from each biological replicate was converted to cDNA, linearly amplified and biotinylated using Ovation reagents (Nugen, San Carlos, CA). Samples were hybridized to Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA). Microarray suite 5 (MAS5) processed sample data were normalized to the average of 18SRNA (AFFX-18SRNAMur/X00686_M_at), GAPDH (AFFX-GapdhMur/M32599_3_at) and Î²-actin (1419734_at) expression values. These gene expression profiles were performed as part of the manuscript by Shearstone et. al. Global DNA Demethylation During Erythropoiesis In Vivo

Background corr dist: KL-Divergence = 0.0491, L1-Distance = 0.0863, L2-Distance = 0.0176, Normal std = 0.6771

0.820 Kernel fit Pairwise Correlations Normal fit

Density 0.410

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

S1 ReplicateS1 Replicate 1 (0.0831393)S1 Replicate 2 (0.276945)S3 Replicate 3 (0.075666)S3 Replicate 1 (0.202402)S3 Replicate 2 (0.175964) 3 (0.185883) [ min ] [ medium ] [ max ] CEM 1 Epn1 541.3 1070.0 1765.7 P ( S | Z, I ) = 0.88 Ap2a1 444.1 625.5 783.7 Mean Corr = 0.60350 Ralbp1 541.5 868.1 980.0 Ap2a2 82.9 300.0 1043.7 Numb 68.4 386.7 508.5 Ccnb1 2262.6 4333.0 5385.9 Wbp2 520.9 2073.7 2413.6 Smarcc2 715.0 1162.1 1749.1 Gsk3a 984.2 1782.1 1949.3 Capn15 45.4 230.2 348.9 Atg2a 81.9 304.3 394.2 CEM 1 + Atp6v0a1 429.4 1052.8 1628.9 Top 10 Genes Rgp1 247.7 711.1 1456.8 Polr2a 1330.4 2264.0 3013.8 Adipor1 476.3 1734.6 2951.4 Hagh 276.7 841.5 1412.2

Null module GEO Series "GSE14499" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 26 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14499 Status: Public on Jan 23 2009 Title: Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19198615 Summary & Design: Summary: We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/ˆ-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally.

Keywords: Treatment effect

Overall design: 26 Samples total: 4 biological replicates of APP transgenic mice BDNF treated, 4 biological replicates of APP transgenic mice GFP treated, 3 biological replicates of non-trangenic mice sham lesion and 2 biological replicates of non-transgenic mice GFP treated for both tissues: Entorhinal cortex and hippocampus.

Background corr dist: KL-Divergence = 0.1592, L1-Distance = 0.0299, L2-Distance = 0.0015, Normal std = 0.3705

1.077 Kernel fit Pairwise Correlations Normal fit

Density 0.538

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

EntorhinalEntorhinal cortex,Entorhinal cortex,APPEntorhinal transgenic cortex,APPEntorhinal transgenic cortex,APP animals,Entorhinal transgenic cortex,non-transgenic animals, BDNFEntorhinal cortex,APP animals,treated, BDNFEntorhinal transgenic cortex,non-transgenic animals, treated, biologicalBDNFEntorhinal cortex,non-transgenic animals,treated, GFPbiologicalEntorhinal rep1 treated,cortex,non-transgenic animals, biologicalGFP(0.0505866)Entorhinal rep2 cortex,non-transgenic treated,biologicalanimals, GFP (0.0319775)Entorhinal rep3 treated,cortex,APP animals,biological sham (0.0700619)rep1Entorhinal transgenic cortex,APP biologicalanimals,lesion,(0.0190046) sham Hippocampus,rep1 transgenic cortex,APP biological lesion,animals,(0.0269947) sham rep2Hippocampus, transgenic APP biologicallesion,(0.0133815)animals, GFP Hippocampus,rep1APP transgenic treated, biologicalanimals,(0.0179308)transgenic BDNF Hippocampus,rep2non-transgenic biological animals,(0.0245255)treated, GFP Hippocampus,rep3non-transgenic animals, treated, (0.0473354) biologicalGFP Hippocampus,rep2APP animals, GFP treated, biologicaltransgenic(0.0208643) Hippocampus,non-transgenictreated, animals,rep4 GFP biological (0.0806847) Hippocampus,treated,rep3APP biologicalanimals, sham transgenic(0.0378846) Hippocampus,rep4APP biologicalanimals,lesion, GFP rep1 transgenic(0.0532782) Hippocampus,APPtreated, biological animals,(0.0140707) GFP rep1 transgenic Hippocampus,treated,APP biological(0.0226211)animals, BDNF rep1 transgenic Hippocampus,APP biological animals,(0.0116457)treated, GFP rep2 transgenic Hippocampus,non-transgenictreated, animals,(0.0216374) biologicalBDNF rep2 non-transgenic biological (0.0141794)animals,treated, GFP rep1 APPtreated, animals, biologicalBDNF(0.0164251) rep3 transgenic animals, biological(0.229355)treated, sham rep2[ lesion,animals, sham biologicalmin(0.019781) rep4 biological lesion,(0.0182492) BDNF ] rep3 biological treated, (0.0511775) rep2 (0.0220098) biological[ rep3 medium (0.0330732) rep4 (0.0312646) ] [ max ] CEM 1 Epn1 741.7 956.1 1922.9 P ( S | Z, I ) = 0.68 Ap2a1 534.0 713.7 1810.7 Mean Corr = -0.02544 Ralbp1 591.8 1412.6 1782.9 Ap2a2 27.0 33.4 42.1 Numb 845.3 1051.9 1375.0 Ccnb1 23.0 33.4 40.7 Wbp2 3469.6 4191.3 6474.8 Smarcc2 1480.5 1658.6 2221.3 Gsk3a 1769.9 2007.2 2354.7 Capn15 419.2 664.7 891.5 Atg2a 296.2 366.2 436.2 CEM 1 + Atp6v0a1 2196.4 2817.8 6048.9 Top 10 Genes Rgp1 787.2 878.6 975.7 Polr2a 1383.3 1766.8 2111.9 Adipor1 166.5 227.7 280.6 Hagh 1798.7 2089.1 2661.5

Null module GEO Series "GSE47196" 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=GSE47196 Status: Public on May 23 2013 Title: Immunoglobulin-like domain receptor 1 mediates fat-stimulated cholecystokinin secretion. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23863714 Summary & Design: Summary: Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild type but not ILDR1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation is associated with increased [Ca2+]i consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.

Overall design: GFP positive cells from CCK-EGFP transgenic mice were isolated by FACS and the expression profile was compared with an equal number of non-fluorescent intestinal cells.

Background corr dist: KL-Divergence = 0.0167, L1-Distance = 0.0318, L2-Distance = 0.0015, Normal std = 0.7899

0.505 Kernel fit Pairwise Correlations Normal fit

Density 0.253

0.000 CEM 1

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

Pre-normalization Quantiles

IntestinalIntestinal CCK-EGFPIntestinal non-EGFP cellsIntestinal CCK-EGFP rep1 cellsIntestinal (0.20747)non-EGFP rep1 cellsIntestinal (0.207068) non-EGFP rep2 cells (0.0943165)CCK-EGFP rep2 cells (0.190554) rep3 cells (0.136776) rep3[ (0.163815)min ] [ medium ] [ max ] CEM 1 Epn1 623.6 1263.6 1297.7 P ( S | Z, I ) = 0.60 Ap2a1 414.7 629.6 698.8 Mean Corr = 0.61738 Ralbp1 741.3 951.7 1146.6 Ap2a2 129.4 532.1 841.5 Numb 1675.4 4047.8 4409.4 Ccnb1 15.6 87.4 666.8 Wbp2 1431.5 1744.3 1998.8 Smarcc2 1154.1 1513.8 1711.4 Gsk3a 1088.6 1632.1 2352.8 Capn15 313.2 1044.7 1167.7 Atg2a 900.8 1974.0 3174.6 CEM 1 + Atp6v0a1 1914.0 2660.6 2899.7 Top 10 Genes Rgp1 441.8 603.0 737.7 Polr2a 2653.7 3146.3 3313.3 Adipor1 351.6 807.0 1451.7 Hagh 565.9 1576.0 1997.4

Null module GEO Series "GSE33942" 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=GSE33942 Status: Public on Feb 29 2012 Title: Role of PKD2 in TCR-induced transcriptional reprogramming of naÃ¯ve T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23525088 Summary & Design: Summary: Comparison of transcriptional profile of TCR stimulated P14-TCR wild-type and P14-PKD2 null murine lymph node cells

Overall design: Lymph node cells from 3 biological replicates (3 wild-type and 3 PKD2 null mice) were isolated and left unstimulated or stimulated for 4 hours with antigenic peptide (gp33-41) prior to RNA extraction and hybridization to Affymetrix microarray.

Background corr dist: KL-Divergence = 0.0765, L1-Distance = 0.0838, L2-Distance = 0.0107, Normal std = 0.5803

0.807 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

Wild-type_unstimulated_sampleWild-type_unstimulated_sampleWild-type_unstimulated_sampleWild-type_stimulated_sampleWild-type_stimulated_sample 1 (0.0638523)Wild-type_stimulated_sample 2 (0.0921314)PKD2-null_unstimulated_sample 3 (0.0664544) PKD2-null_unstimulated_sample1 (0.102374) PKD2-null_unstimulated_sample2 (0.259508) PKD2-null_stimulated_sample3 (0.0957471)PKD2-null_stimulated_sample 1 (0.116989)PKD2-null_stimulated_sample 2 (0.0189171) 3 (0.0743727) 1 (0.0276492) 2 (0.0542021)[ 3 (0.027803)min ] [ medium ] [ max ] CEM 1 Epn1 314.7 403.9 442.2 P ( S | Z, I ) = 0.56 Ap2a1 196.7 225.2 323.7 Mean Corr = 0.27272 Ralbp1 1906.9 5192.8 6733.1 Ap2a2 65.1 156.0 223.0 Numb 958.3 1592.4 2015.4 Ccnb1 28.6 35.8 40.4 Wbp2 524.0 875.7 1193.7 Smarcc2 502.9 840.2 942.6 Gsk3a 1486.3 1655.2 1744.1 Capn15 331.2 394.0 447.5 Atg2a 452.0 1108.5 1390.1 CEM 1 + Atp6v0a1 72.5 95.3 121.0 Top 10 Genes Rgp1 926.2 1125.1 1215.3 Polr2a 1202.0 1926.6 2286.8 Adipor1 132.9 193.4 271.7 Hagh 645.2 861.6 1007.8

Null module GEO Series "GSE18115" 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=GSE18115 Status: Public on Dec 31 2010 Title: Dendritic cells and stress translation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (poly I:C), DCs mount a specific transcription program during which the growth arrest and DNA damage-inducible protein 34 (GADD34/MyD116), a phosphatase 1 (PP1) cofactor, is expressed. Together with its constitutively active counterpart CReP, GADD34 promotes an extensive dephosphorylation of the translation initiation factor eIF2-alfa in activated DCs. In turn, dephosphorylation of eIF2-alfa prevents the translation inhibition normally associated with cellular stress or detection of cytoplasmic double-stranded RNA. These observations have important implications in linking pathogen detection with the integrated stress responses molecular machinery. The importance of this regulation for DC function is exemplified by the alteration of IFN-beta production or the induction of caspase-3 cleavage upon inhibition of PP1 activity. #!#

Overall design: LPS-activated murine bone-marrow derived dendritic cells were transfected or pulsed with pIC and incubated for 4h or 16h. Cells were harvested, total RNA was extracted and analysed by Affymetrix microarrays analysis.

Background corr dist: KL-Divergence = 0.0630, L1-Distance = 0.0416, L2-Distance = 0.0028, Normal std = 0.5410

0.762 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

0h_no_LPS4h_LPS_pIC_soluble (0.339808)4h_LPS4h_LPS_pIC_lipofected (0.167198) (0.0666629)16h_LPS16h_LPS_pIC_soluble (0.0926988)16h_LPS_pIC_lipofected (0.115001)16h_LPS_ctrl_lipofected (0.12004) (0.0347039) (0.0638862)[ min ] [ medium ] [ max ] CEM 1 Epn1 366.4 638.1 1158.1 P ( S | Z, I ) = 0.44 Ap2a1 330.2 445.0 549.7 Mean Corr = 0.58541 Ralbp1 617.2 1120.0 1603.9 Ap2a2 11.1 120.2 199.1 Numb 1035.5 1286.5 1604.6 Ccnb1 9.8 39.2 141.5 Wbp2 770.7 1097.8 1778.5 Smarcc2 586.2 884.5 905.7 Gsk3a 904.0 1384.2 1771.1 Capn15 160.6 237.7 511.3 Atg2a 140.2 344.5 426.0 CEM 1 + Atp6v0a1 545.1 804.2 1004.3 Top 10 Genes Rgp1 410.0 833.6 1019.3 Polr2a 653.7 1452.1 1641.5 Adipor1 74.2 111.6 178.1 Hagh 273.2 434.2 1138.7

Null module GEO Series "GSE23119" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.576 Kernel fit Pairwise Correlations Normal fit

Density 0.288

0.000 CEM 1

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

Pre-normalization Quantiles

Normal Normalspermatogonia Normalspermatogonia VADspermatogonia control, spermatogoniaVAD control, rep1 spermatogonia (0.123075)VAD control, rep2 spermatogonia at (0.0694213)VAD 18 rep3 weeks, spermatogonia at (0.331905)VAD 18 weeks,rep1 spermatogonia atVAD 18(0.0333031) weeks,rep2 spermatogonia at 25(0.0248614) weeks,rep3 at 25(0.038533) weeks,rep1 at 25(0.0680078) weeks,rep2[ (0.0318046) min rep3 (0.279089) ] [ medium ] [ max ] CEM 1 Epn1 257.7 386.5 2890.5 P ( S | Z, I ) = 0.33 Ap2a1 243.1 385.6 1935.4 Mean Corr = 0.51622 Ralbp1 262.4 394.1 620.2 Ap2a2 5.5 9.8 86.1 Numb 447.1 893.7 1296.4 Ccnb1 142.3 200.5 1169.1 Wbp2 2334.9 4008.9 4959.9 Smarcc2 636.5 842.7 2702.2 Gsk3a 1424.7 1863.7 4359.2 Capn15 325.7 484.4 648.5 Atg2a 238.7 433.1 676.4 CEM 1 + Atp6v0a1 9.6 27.1 501.2 Top 10 Genes Rgp1 1813.5 2415.8 2796.9 Polr2a 736.6 944.3 2249.2 Adipor1 6.4 47.2 118.3 Hagh 8314.5 16332.1 21019.1

Null module GEO Series "GSE11723" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11723 Status: Public on Jun 02 2009 Title: Role of Notch signaling on hematopoietic stem cell differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18786418 Summary & Design: Summary: Although Notch signaling has been clearly implicated in lymphoid differentiation, its role in myeloid lineages differentiation is unclear.

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

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

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

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

0.637 Kernel fit Pairwise Correlations Normal fit

Density 0.319

0.000 CEM 1

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

Pre-normalization Quantiles

LSK_OP9-GFP_Rep1LSK_OP9-GFP_Rep2LSK_OP9-GFP_Rep3 (0.00976144)LSK_OP9-DL1_Rep1 (0.037651)LSK_OP9-DL1_Rep2 (0.102163)LSK_OP9-DL1_Rep3 (0.12695)LSK_OP9-DL1+CompoundE_Rep1 (0.199198)LSK_OP9-DL1+CompoundE_Rep2 (0.0923486)LSK_OP9-DL1+CompoundE_Rep3 (0.15679) (0.219228)[ min (0.0559088) ] [ medium ] [ max ] CEM 1 Epn1 197.5 259.1 378.4 P ( S | Z, I ) = 0.30 Ap2a1 288.5 335.6 492.5 Mean Corr = 0.56670 Ralbp1 782.8 872.8 902.8 Ap2a2 75.4 125.9 172.6 Numb 589.3 720.3 1037.3 Ccnb1 872.5 1038.9 1178.4 Wbp2 494.0 531.4 611.3 Smarcc2 1737.7 1800.8 1895.8 Gsk3a 407.8 458.9 496.5 Capn15 134.1 174.2 253.2 Atg2a 336.0 378.5 678.7 CEM 1 + Atp6v0a1 391.6 428.0 502.4 Top 10 Genes Rgp1 219.0 298.3 337.8 Polr2a 1825.7 2049.6 2264.6 Adipor1 681.1 1169.0 1461.6 Hagh 233.7 369.2 486.9

Null module GEO Series "GSE22381" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.449 Kernel fit Pairwise Correlations Normal fit

Density 0.224

0.000 CEM 1

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

Pre-normalization Quantiles

E10_otic_vesicle_wt_replicate1E10_otic_vesicle_wt_replicate2E10_otic_vesicle_mut_replicate1E10_otic_vesicle_mut_replicate2E10.5_otic_vesicle_wt_replicate1 (0.0730148)E10.5_otic_vesicle_wt_replicate2 (0.0729335)E10.5_otic_vesicle_mut_replicate1 (0.117665)E10.5_otic_vesicle_mut_replicate2 (0.0509456)2B1_Dlx5_replicate1 (0.0322081)2B1_Dlx5_replicate2 (0.0325706)2B1_empty_vector_replicate1 (0.0341986) (0.0888513)2B1_empty_vector_replicate2 (0.0699633) (0.125565) (0.156678) [(0.145406) min ] [ medium ] [ max ] CEM 1 Epn1 355.8 696.7 788.0 P ( S | Z, I ) = 0.19 Ap2a1 245.8 416.0 582.3 Mean Corr = 0.64789 Ralbp1 236.3 451.0 976.9 Ap2a2 31.9 46.2 104.4 Numb 4643.1 5882.0 6479.4 Ccnb1 52.0 173.0 488.5 Wbp2 869.9 1688.6 1758.9 Smarcc2 1199.8 2512.3 3162.5 Gsk3a 365.8 515.7 1233.6 Capn15 759.3 2054.8 2539.7 Atg2a 195.0 283.4 381.5 CEM 1 + Atp6v0a1 195.6 282.9 349.4 Top 10 Genes Rgp1 688.5 1004.1 1296.9 Polr2a 2516.8 4016.2 5031.8 Adipor1 85.3 117.6 203.9 Hagh 510.0 655.1 810.2

Null module GEO Series "GSE46600" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 44 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46600 Status: Public on Jun 20 2014 Title: Transcriptome and Molecular Pathways Analysis of CD4 T-Cells from Young NOD Mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24918037 Summary & Design: Summary: Type 1 diabetes is a multigenic disease caused by T-cell mediated destruction of the insulin producing Î²-cells. Although conventional (targeted) approaches of identifying causative genes have advanced our knowledge of this disease, many questions remain unanswered. Using a whole molecular systems study, we unraveled the genes/molecular pathways that are altered in CD4 T-cells from young NOD mice prior to insulitis (lymphocytic infiltration into the pancreas). Many of the CD4 T-cell altered genes lie within known diabetes susceptibility regions (Idd), including several genes in the diabetes resistance region Idd13 and two genes (Khdrbs1 and Ptp4a2) in the CD4 T-cell diabetogenic activity region Idd9/11. Alterations involved apoptosis/cell proliferation and metabolic pathways (predominant at 2 weeks), inflammation and cell signaling/activation (predominant at 3 weeks), and innate and adaptive immune responses (predominant at 4 weeks). We identified several factors that may regulate these abnormalities: IRF-1, HNF4A, TP53, BCL2L1 (lies within Idd13), IFNG, IL4, IL15, and prostaglandin E2, which were common to all 3 ages; AR and IL6 to 2 and 4 weeks; and Interferon (IFN-I) and IRF-7 to 3 and 4 weeks. Others were unique to the various ages (e. g. MYC, JUN, and APP to 2 weeks; TNF, TGFB1, NFKB, ERK, and p38MAPK to 3 weeks; and IL12 and STAT4 to 4 weeks). Our data suggest that diabetes resistance genes in Idd13 and Idd9/11, and BCL2L1, IL6-AR and IFNG-IRF-1-IFN-I/IRF-7-IL12 pathways play an important role in CD4 T-cells in the early pathogenesis of autoimmune diabetes. Thus, the alternative approach of investigation at the molecular systems level has captured new information, which combined with validation studies, offers the opportunity to test hypotheses on the role played by the genes/molecular pathways identified in this study, to understand better the mechanisms of autoimmune diabetes in CD4 T-cells, and to develop new therapeutic strategies for the disease.

Overall design: CD4 T-cells were purified from spleen leukocytes collected from 2-, 3- and 4-week old NOD mice and two age-matched control strains, NOR, and C57BL/6, (n=5 for each strain and each age group; except NOD2wk). NOR is an insulitis- and diabetes-free control strain that shares shares ~88% of its genome with NOD mice, including the diabetogenic H2g7 MHC haplotype and several important non-MHC T1D susceptibility loci. C57BL/6 is also a diabetes-resitant strain, but it is more genetically distantly related to NOD.

Background corr dist: KL-Divergence = 0.4129, L1-Distance = 0.0601, L2-Distance = 0.0093, Normal std = 0.2468

1.617 Kernel fit Pairwise Correlations Normal fit

Density 0.808

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

CD4T-cells_NODCD4T-cells_NODCD4T-cells_NOD mice_2wk_repCD4T-cells_NOD mice_2wk_repCD4T-cells_NOR mice_2wk_rep1 (0.0134572)CD4T-cells_NOR mice_2wk_rep2 (0.0241456)CD4T-cells_NOR mice_2wk_rep3 (0.0111149)CD4T-cells_NOR mice_2wk_rep4 (0.017511)CD4T-cells_NOR mice_2wk_rep1 (0.0616326)CD4T-cells_C57BL/6 mice_2wk_rep2 (0.0400317)CD4T-cells_C57BL/6 mice_2wk_rep3 (0.0171808)CD4T-cells_C57BL/6 4 (0.0411663) mice_2wk_repCD4T-cells_C57BL/6 5 (0.0278068) mice_2wk_repCD4T-cells_C57BL/6 mice_2wk_rep1 CD4T-cells_NOD(0.00308569) mice_2wk_rep2 CD4T-cells_NOD(0.00425506) mice_2wk_rep3 CD4T-cells_NOD(0.0161497) mice_3wk_rep 4 CD4T-cells_NOD(0.0088729) mice_3wk_rep 5 CD4T-cells_NOD(0.0188856) mice_3wk_rep1 (0.0210033)CD4T-cells_NOR mice_3wk_rep2 (0.0515473)CD4T-cells_NOR mice_3wk_rep3 (0.0160514)CD4T-cells_NOR mice_3wk_rep4 (0.0636498)CD4T-cells_NOR mice_3wk_rep5 (0.0138214)CD4T-cells_NOR mice_3wk_rep1 (0.00866896)CD4T-cells_C57BL/6 mice_3wk_rep2 (0.0885431)CD4T-cells_C57BL/6 mice_3wk_rep3 (0.0281619)CD4T-cells_C57BL/6 4 (0.0197133) mice_3wk_repCD4T-cells_C57BL/6 5 (0.00424093) mice_3wk_repCD4T-cells_C57BL/6 mice_3wk_rep1 CD4T-cells_NOD(0.00871482) mice_3wk_rep2 CD4T-cells_NOD(0.0323013) mice_3wk_rep3 CD4T-cells_NOD(0.0290021) mice_4wk_rep 4 CD4T-cells_NOD(0.0371873) mice_4wk_rep 5 CD4T-cells_NOD(0.0182623) mice_4wk_rep1 (0.0220271)CD4T-cells_NOR mice_4wk_rep2 (0.00991482)CD4T-cells_NOR mice_4wk_rep3 (0.0103427)CD4T-cells_NOR mice_4wk_rep4 (0.0130583)CD4T-cells_NOR mice_4wk_rep5 (0.0121628)CD4T-cells_NOR mice_4wk_rep1 (0.0108341)CD4T-cells_C57BL/6 mice_4wk_rep2 (0.0122431)CD4T-cells_C57BL/6 mice_4wk_rep3 (0.00375442)CD4T-cells_C57BL/6 4 (0.00844074) mice_4wk_repCD4T-cells_C57BL/6 5 (0.0147552) mice_4wk_repCD4T-cells_C57BL/6 mice_4wk_rep1 (0.0148944) mice_4wk_rep2 (0.0461054) mice_4wk_rep3 (0.024665) 4 [(0.0240071) min 5 (0.0266299) ] [ medium ] [ max ] CEM 1 Epn1 337.2 685.9 2660.9 P ( S | Z, I ) = 0.14 Ap2a1 160.3 344.8 1203.2 Mean Corr = 0.00120 Ralbp1 476.9 1039.5 1513.6 Ap2a2 37.7 226.2 402.4 Numb 801.6 1074.1 1623.8 Ccnb1 16.0 119.9 368.6 Wbp2 571.2 789.8 2160.7 Smarcc2 381.3 635.8 1490.2 Gsk3a 1169.6 1578.2 2370.4 Capn15 160.2 348.6 693.3 Atg2a 96.8 245.1 476.9 CEM 1 + Atp6v0a1 10.8 120.8 497.1 Top 10 Genes Rgp1 559.8 846.2 1530.7 Polr2a 782.8 1262.3 4486.2 Adipor1 71.7 255.9 546.6 Hagh 822.5 1320.0 2951.7

Null module GEO Series "GSE32328" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.856 Kernel fit Pairwise Correlations Normal fit

Density 0.428

0.000 CEM 1

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

Pre-normalization Quantiles

Human MouseLPS G (0.0355715)LPSCalf GLPS (0.0346377)No G Serum (0.0177219)Human LPS MouseControlG (0.0493938) ControlCalf G (0.0276629) Control NoG (0.024799) Serum G (0.143669)Mouse Control ControlHuman G (0.0424337) CalfControlH (0.015686) ControlNo H (0.0259728)Serum H (0.0778518)Mouse Control LPSHuman H H (0.0338355) (0.0371712) CalfLPS LPSH (0.0344544)No H Serum(0.0515135)Calf LPS LPS NoH I (0.0514684) (0.0419543)SerumHuman LPS MouseLPSI (0.054006) I (0.0274691) LPSNo Serum I (0.0276336)Calf Control ControlHuman I (0.0187382)I (0.0699212) MouseControl Control I (0.010063) I (0.0463708) [ min ] [ medium ] [ max ] CEM 1 Epn1 107.0 138.0 171.8 P ( S | Z, I ) = 0.09 Ap2a1 200.0 294.3 542.5 Mean Corr = 0.54697 Ralbp1 664.4 1069.8 2000.4 Ap2a2 50.6 96.8 139.5 Numb 1416.5 2032.5 3607.0 Ccnb1 59.2 159.6 290.9 Wbp2 430.1 696.7 1008.8 Smarcc2 719.8 1281.2 1894.8 Gsk3a 413.8 539.3 729.0 Capn15 62.6 103.6 140.5 Atg2a 123.8 304.7 530.3 CEM 1 + Atp6v0a1 808.2 1422.2 2039.5 Top 10 Genes Rgp1 497.5 1136.6 1556.2 Polr2a 1510.3 2989.2 4817.5 Adipor1 57.4 137.9 292.7 Hagh 90.2 224.9 332.1

Null module GEO Series "GSE7348" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: Treatment Comparison

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

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

0.647 Kernel fit Pairwise Correlations Normal fit

Density 0.323

0.000 CEM 1

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

Pre-normalization Quantiles

Naive-rep2N+L, (0.275568) rep2T+L, (0.150225) rep2Naive-rep1 (0.0801572)N+L, (0.147165) rep1T+L, (0.274227) rep1 (0.0726577) [ min ] [ medium ] [ max ] CEM 1 Epn1 658.7 1225.5 1307.6 P ( S | Z, I ) = 0.07 Ap2a1 289.6 505.6 677.2 Mean Corr = 0.49861 Ralbp1 552.4 994.5 1722.5 Ap2a2 7.9 64.4 212.0 Numb 967.6 2489.4 2663.4 Ccnb1 3.3 49.4 92.5 Wbp2 1010.4 1872.3 2287.2 Smarcc2 572.2 842.0 1015.1 Gsk3a 721.0 1143.7 1872.7 Capn15 46.6 218.7 281.9 Atg2a 37.2 257.2 317.4 CEM 1 + Atp6v0a1 622.9 1767.0 5126.1 Top 10 Genes Rgp1 389.3 594.3 620.7 Polr2a 364.0 1122.3 1339.5 Adipor1 12.6 79.6 245.2 Hagh 363.7 758.0 1112.1

Null module GEO Series "GSE24614" 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=GSE24614 Status: Public on Jun 15 2011 Title: Variegated gene expression caused by cell-specific long-range DNA interactions Organism: Mus musculus Experiment type: Other Platform: GPL1261 Pubmed ID: 21706023 Summary & Design: Summary: Mammalian genomes contain numerous DNA elements with potential transcription regulatory function but unknown target genes. We used transgenic, gain-of-function mice with an ectopic copy of the beta-globin locus control region (LCR) to better understand how regulatory elements dynamically search the genome for target genes. We find that the LCR samples a restricted nuclear sub-volume in which it forms preferential contacts with genes controlled by shared transcription factors. One contacted gene, betah1, located on another chromosome, is upregulated, providing genetic demonstration that mammalian enhancers can function between chromosomes. Upregulation is not pan-cellular but confined to selected jackpot cells significantly enriched for inter-chromosomal LCR-betah1 interactions. This implies that long-range DNA contacts are relatively stable and cell-specific and, when functional, cause variegated expression. We refer to this as spatial effect variegation (SEV). The data provide a dynamic and mechanistic framework for enhancer action, important for assigning function to the one- and three-dimensional structure of DNA.

Overall design: At the RNA level these mice were characterized with Affymetrix expression arrays. We analyzed three biological replicates for the WT and the knock-in.

Background corr dist: KL-Divergence = 0.0272, L1-Distance = 0.0584, L2-Distance = 0.0041, Normal std = 0.8832

0.499 Kernel fit Pairwise Correlations Normal fit

Density 0.250

0.000 CEM 1

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

Pre-normalization Quantiles

WT fetalWT liver fetal expressionWT liver fetal expressionhLCR liver replicate knock-inexpressionhLCR replicate 1 knock-in(0.0859658) hLCRfetal replicate 2 liver knock-in(0.16028) fetal expression 3 liver (0.491865) fetal expression liver replicate expression replicate[ 1 min(0.0730657) replicate 2 (0.054426) ] 3 (0.134398)[ medium ] [ max ] CEM 1 Epn1 855.4 1141.6 3552.5 P ( S | Z, I ) = 0.05 Ap2a1 383.2 545.2 1518.5 Mean Corr = 0.51106 Ralbp1 410.6 479.1 812.5 Ap2a2 131.1 138.3 141.6 Numb 773.5 1013.0 1380.3 Ccnb1 109.8 154.6 251.0 Wbp2 1162.1 1529.1 2465.1 Smarcc2 451.8 630.0 1349.2 Gsk3a 1405.8 1930.0 2595.0 Capn15 302.2 401.9 1142.9 Atg2a 198.4 240.3 344.7 CEM 1 + Atp6v0a1 679.7 953.5 1760.3 Top 10 Genes Rgp1 623.7 740.4 1705.2 Polr2a 1184.9 1687.9 7605.9 Adipor1 1410.8 1749.7 2300.4 Hagh 2262.6 2776.9 3115.7

Null module GEO Series "GSE5861" 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=GSE5861 Status: Public on Sep 19 2006 Title: Searching for Brca1 regulated X-linked genes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17350580 Summary & Design: Summary: We compared the expression levels of X-linked genes in the mammary glands of Brca1 D11/D11;p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle: virgin, pregnant day 16.5, and lactation day 1, using a cDNA microarray. In about 690 X-linked genes that are expressed at these three stages of mammary cycle of development, we found 16 X-linked genes showed altered expression levels in Brca1 D11/D11;p53+/- mammary glands in comparison with controls at all three time points. Among them, 9 genes were up-regulated and 7 were down-regulated. This result indicates that mutation of Brca1 could affect expression of a few X-linked genes in mammary tissues. However, this was unlikely caused by failure of X chromosome inactivation, as seven of them were down-regulated, and Xist RNA was expressed in all the Brca1 mutant mammary tissues.

Keywords: BRCA1 mutation analysis

Overall design: Mutations in breast cancer associated gene-1 (BRCA1) are associated with hereditary breast and ovarian cancers. BRCA1 encodes a tumor suppressor protein that functions in DNA repair, transcriptional regulation, chromatin remodeling, centrosome duplication and checkpoint control, etc.. We were interested in fishing out the genes regulated by Brca1. Three pairs of mammary glands from Brca1 D11/D11;p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle were analyzed by microarray for gene expression levels.

Background corr dist: KL-Divergence = 0.0156, L1-Distance = 0.0313, L2-Distance = 0.0012, Normal std = 0.8049

0.496 Kernel fit Pairwise Correlations Normal fit

Density 0.248

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

02-07-05_Deng_Mouse430_2_79602-07-05_Deng_Mouse430_2_80102-07-05_Deng_Mouse430_2_I44202-07-05_Deng_Mouse430_2_I44305-24-04_Deng_Mouse430_2_1548 (0.082458)05-24-04_Deng_Mouse430_2_T744 (0.0338876) (0.15864) (0.262933) (0.185087)[ min (0.276994) ] [ medium ] [ max ] CEM 1 Epn1 465.9 838.0 1732.0 P ( S | Z, I ) = 0.05 Ap2a1 205.1 394.1 652.2 Mean Corr = 0.48920 Ralbp1 465.6 1457.8 2051.2 Ap2a2 81.9 204.5 363.0 Numb 1253.5 1943.8 2302.4 Ccnb1 13.1 94.5 157.8 Wbp2 619.3 1182.1 1478.4 Smarcc2 947.9 1790.6 2260.7 Gsk3a 1015.8 2172.4 3884.6 Capn15 340.7 470.6 1135.1 Atg2a 172.6 277.2 656.0 CEM 1 + Atp6v0a1 272.7 337.6 1551.9 Top 10 Genes Rgp1 774.2 1035.4 1332.4 Polr2a 361.2 1209.8 2032.7 Adipor1 175.5 312.6 399.8 Hagh 1635.7 1891.0 2489.9

Null module GEO Series "GSE28830" 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=GSE28830 Status: Public on Dec 01 2013 Title: Differential gene expression in CD11b+ splenocytes from mice subject to social threat vs. control (II) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Gene expression profiling was carried out on splenocyte mRNA samples collected from 6 animals subject to repeated social threat and 6 animals subject to non-threatening control conditions (pooled into 3 groups of 2). The primary research question is whether gene expression differs in CD11b+ splenocytes from animals exposed to social threat vs non-threatening control conditions.

Keywords: Risk prediction

Overall design: This study provides an additional body of data from the same general protocol used in Series GSE16661, and will support more extensive analyses than the original study.

Background corr dist: KL-Divergence = 0.0554, L1-Distance = 0.0377, L2-Distance = 0.0018, Normal std = 0.5796

0.732 Kernel fit Pairwise Correlations Normal fit

Density 0.366

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 pool 1-2Control pool (0.111653) 3-4Threat pool (0.236757) 5-6 1Threat (0.135351)(0.107743) 2Threat (0.137813) 3Threat (0.115422) 4Threat (0.0837008) 5Threat (0.0259023) 6 (0.0456579) [ min ] [ medium ] [ max ] CEM 1 Epn1 1242.6 1359.0 1524.4 P ( S | Z, I ) = 0.05 Ap2a1 536.7 637.0 671.7 Mean Corr = 0.49589 Ralbp1 1559.7 1777.0 1972.8 Ap2a2 74.5 94.2 117.2 Numb 1571.6 2047.4 2278.7 Ccnb1 40.1 46.4 56.5 Wbp2 1393.1 1550.6 1728.1 Smarcc2 591.8 711.2 754.6 Gsk3a 2177.7 2250.8 2406.9 Capn15 234.5 254.5 280.8 Atg2a 646.4 676.6 738.3 CEM 1 + Atp6v0a1 697.0 936.6 1097.5 Top 10 Genes Rgp1 482.7 622.2 775.9 Polr2a 773.0 922.0 1252.9 Adipor1 581.9 664.9 703.4 Hagh 474.8 543.1 564.0

Null module GEO Series "GSE37975" 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=GSE37975 Status: Public on Jul 18 2012 Title: Comparison of matched primary and metastasis 4T1.2 syngeneic mammary tumor model of spontaneous bone metastasis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22820642 Summary & Design: Summary: Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2rÎ³-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.

Overall design: Microarrays were used to profile transcriptional alterations inherent in tumor cells growing in bone when compared to matched primary tumor cells in the 4T1.2 murine mammary tumor model. Primary and metastasized tumor were isolated from the same mouse with 4 independent biological replicates.

Background corr dist: KL-Divergence = 0.0268, L1-Distance = 0.0775, L2-Distance = 0.0083, Normal std = 0.8403

0.475 Kernel fit Pairwise Correlations Normal fit

Density 0.237

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

4T1.2_Primary_Rep-014T1.2_BoneMetastases_Rep-014T1.2_Primary_Rep-024T1.2_BoneMetastases_Rep-02 (0.0860424)4T1.2_Primary_Rep-034T1.2_BoneMetastases_Rep-03 (0.0963035) (0.0364069)4T1.2_Primary_Rep-044T1.2_BoneMetastases_Rep-04 (0.0313759) (0.0379742) (0.0610401) (0.156114) [ (0.494743)min ] [ medium ] [ max ] CEM 1 Epn1 559.0 722.9 1782.2 P ( S | Z, I ) = 0.05 Ap2a1 270.0 343.3 473.7 Mean Corr = 0.32100 Ralbp1 1910.3 2658.3 11762.1 Ap2a2 38.1 99.7 290.8 Numb 516.8 2075.0 2946.9 Ccnb1 49.1 64.3 160.4 Wbp2 837.7 1175.4 1785.2 Smarcc2 260.8 379.6 507.9 Gsk3a 2433.5 3807.7 9095.3 Capn15 350.8 579.5 725.7 Atg2a 239.4 371.0 496.7 CEM 1 + Atp6v0a1 349.5 635.0 1716.9 Top 10 Genes Rgp1 545.8 855.5 1341.7 Polr2a 1422.9 2635.7 3658.0 Adipor1 109.0 346.3 526.4 Hagh 542.8 1082.3 1578.8

Null module GEO Series "GSE18587" 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=GSE18587 Status: Public on Sep 21 2011 Title: Specific modulation of mucosal immune response, tolerance and proliferation in mice colonized with A. muciniphila Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21904534 Summary & Design: Summary: Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.

Keywords: Analysis of target gene regulation by using microarrays

Overall design: Adult germ-free female NMRI-KI mice (45 65 days) were used for bacterial mono-association. Two bacterial strains were used in this study, A. muciniphila MucT (ATTC BAA-835) and L. plantarum WCFS1 (NCIMB 8826). A. muciniphila was grown anaerobically in a basal mucin based medium and L. plantarum was grown anaerobically at 37´C in Man-Rogosa-Sharpe broth (MRS; Le Pont de Claix, France). After 7 days of colonization, mice were killed by cervical dislocation and terminal ileum, cecum and ascending colon specimens were sampled.

Background corr dist: KL-Divergence = 0.0560, L1-Distance = 0.0627, L2-Distance = 0.0089, Normal std = 0.5753

0.855 Kernel fit Pairwise Correlations Normal fit

Density 0.427

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

ileum_germ_free_non_inoculated_(pool)ileum_germ_free_inoculated_A.muciniphila_(pool)ileum_germ_free_inoculated_L.plantarum_(pool)caecum_germ_free_non_inoculated_(pool)caecum_germ_free_inoculated_A.muciniphila_(pool)caecum_germ_free_inoculated_L.plantarum_(pool) (0.041221)colon_germ_free_non_inoculated_(pool)colon_germ_free_inoculated_A.muciniphila_(pool) (0.129158)colon_germ_free_inoculated_L.plantarum_(pool) (0.398114) (0.0212069) (0.136724) (0.106035) (0.0590306)[ min ] (0.0634329) (0.0450765)[ medium ] [ max ] CEM 1 Epn1 1210.4 1302.9 1551.6 P ( S | Z, I ) = 0.04 Ap2a1 99.7 136.5 186.5 Mean Corr = 0.50495 Ralbp1 824.7 987.4 1094.1 Ap2a2 4.6 39.7 249.2 Numb 1603.4 1911.9 2854.7 Ccnb1 7.0 18.7 47.3 Wbp2 915.2 1044.9 1309.5 Smarcc2 781.2 820.6 899.4 Gsk3a 1106.9 1276.2 1402.2 Capn15 37.5 106.4 208.8 Atg2a 153.4 213.8 261.6 CEM 1 + Atp6v0a1 158.2 262.4 373.5 Top 10 Genes Rgp1 577.7 1123.0 1248.0 Polr2a 664.9 858.6 979.7 Adipor1 106.2 154.1 195.1 Hagh 2733.2 3818.2 4293.2

Null module GEO Series "GSE46606" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 30 -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=GSE46606 Status: Public on May 04 2013 Title: Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4 (expression) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23684984 Summary & Design: Summary: Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.

Overall design: Resting mature peripheral primary B cells were enriched from the spleens of Irf4+/+ or Irf4-inducible mice on the Irf4-/- background. We sought to compare gene expression profiles of wild type and Irf4 mutant B cells in response to mitogens that promote the differentiation of the B cells into plasma cells and cells that have undergone class switch recombination. Day 0 samples represent RNA analysis of unstimulated cells, whereas Day 1 and Day 3 samples represent analysis of stimulated cells in culture. For stimulation, cells were cultured with insect cell purified CD40L and IL-2/4/5 cytokines for the indicated days. In the case of doxycycline-mediated rescue of IRF4 expression, doxycycline was added at predefined low and high concentrations that yield low or high numbers of plasma cells, respectively (see Molecular Systems Biology 7:495). Each replicate represents analysis of B cells from an individual mouse. Of the three replicates in each group, two were performed in parallel and one was performed at a different time. All cells were lysed using Trizol and total RNA was purified according to manufacturer's suggestions. The high quality of the RNA was confirmed using Agilent Bioanalyzer 2100 system. 250ng of RNA was then processed into biotinylated cRNA according to standard procedures and used to hybridize to Affymetrix 430 2.0 arrays. Signal intensities were normalized using the D-Chip algorithm (PM-only model) and the output was used to quantify differential gene expression between groups.

Background corr dist: KL-Divergence = 0.0934, L1-Distance = 0.0402, L2-Distance = 0.0024, Normal std = 0.4712

0.897 Kernel fit Pairwise Correlations Normal fit

Density 0.448

0.000 CEM 1

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

Pre-normalization Quantiles

4KO-hiD14KO-hiD3 rep1 4KO-loD1(0.0289355) rep1 4KO-loD3(0.0251444) rep1 4KO-zeroD0(0.0213024) rep1 4KO-zeroD1(0.0147087) rep14KO-zeroD3 (0.119323) rep14KO-hiD1 (0.0207745) rep14KO-hiD3 rep2(0.0155712) 4KO-loD1(0.0250192) rep2 4KO-loD3(0.0378106) rep2 4KO-zeroD0(0.0196572) rep2 4KO-zeroD1(0.0188545) rep24KO-zeroD3 (0.0803411) rep24KO-hiD1 (0.0258223) rep24KO-hiD3 rep3(0.0153323) 4KO-loD1(0.0101907) rep3 4KO-loD3(0.0266056) rep3 4KO-zeroD0(0.00964397) rep3 4KO-zeroD1(0.0105147) rep34KO-zeroD3 (0.110771) rep3WT-D0 (0.0061933) rep3 rep1WT-D1 (0.0120853) (0.0931873) rep1WT-D3 (0.0262908) rep1WT-D0 (0.00711761) rep2WT-D1 (0.0974434) rep2WT-D3 (0.0311336) rep2WT-D0 (0.00712431) rep3WT-D1 (0.0535731) rep3WT-D3 (0.0230298) rep3 (0.00649866) [ min ] [ medium ] [ max ] CEM 1 Epn1 1524.6 2140.5 3490.2 P ( S | Z, I ) = 0.03 Ap2a1 317.2 480.6 797.3 Mean Corr = 0.23993 Ralbp1 1765.2 1950.0 2235.6 Ap2a2 141.8 167.4 381.4 Numb 527.3 607.1 778.4 Ccnb1 93.1 143.0 190.2 Wbp2 651.6 972.9 2155.0 Smarcc2 445.8 593.5 869.3 Gsk3a 2488.9 2668.6 3331.6 Capn15 291.9 329.5 380.6 Atg2a 306.2 394.3 1017.6 CEM 1 + Atp6v0a1 195.9 432.3 708.9 Top 10 Genes Rgp1 779.8 991.4 1204.7 Polr2a 2473.6 3038.7 4069.9 Adipor1 102.0 139.4 395.4 Hagh 462.3 662.6 852.0

Null module GEO Series "GSE21902" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 31 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21902 Status: Public on Jun 16 2010 Title: Expression Data from chemical induced tumors obtained from NDR1+/+, NDR1+/- and NDR1-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20551432 Summary & Design: Summary: Loss and heterozygosity for NDR1 predisposes mice to T-cell lymphoma development. To analyze mechanisms of tumor development in these mice chemically (ENU)-induced tumors were collected and RNA was extracted.

Overall design: Tumors were collected from mice upon tumor development or 9 months after ENU treatment. Tumors were flash frozen and parts of the tumors were analyzed for RNA, proteins and histology.

Background corr dist: KL-Divergence = 0.2115, L1-Distance = 0.0483, L2-Distance = 0.0061, Normal std = 0.3362

1.199 Kernel fit Pairwise Correlations Normal fit

Density 0.600

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

NDR1WT_Thymocytes_F_01NDR1WT_Thymocytes_F_02NDR1WT_Thymocytes_M_01NDR1WT_Thymocytes_M_02 (0.00927888)NDR1HT_Thymocytes_F_01 (0.00484141)NDR1HT_Thymocytes_F_02 (0.0412934)NDR1HT_Thymocytes_M_01 (0.0130465)NDR1HT_Thymocytes_M_02 (0.008727)NDR1KO_Thymocytes_F_01 (0.0103711)NDR1KO_Thymocytes_F_02 (0.0273036)NDR1KO_Thymocytes_M_01 (0.013741)NDR1KO_Thymocytes_M_02 (0.00841984)NDR1WT_Tumorcells_01 (0.0073414)NDR1WT_Tumorcells_02 (0.0361098)NDR1WT_Tumorcells_03 (0.010959)NDR1WT_Tumorcells_04 (0.00849685)NDR1WT_Tumorcells_05 (0.0290486)NDR1HT_Tumorcells_01 (0.0080877)NDR1HT_Tumorcells_02 (0.0374649)NDR1HT_Tumorcells_03 (0.0736717)NDR1HT_Tumorcells_04 (0.0124386)NDR1HT_Tumorcells_05 (0.0145785)NDR1HT_Tumorcells_06 (0.0165974)NDR1HT_Tumorcells_07 (0.0421433)NDR1KO_Tumorcells_01 (0.140877)NDR1KO_Tumorcells_02 (0.00627598)NDR1KO_Tumorcells_03 (0.0828101)NDR1KO_Tumorcells_04 (0.0225024)NDR1KO_Tumorcells_05 (0.00787077)NDR1KO_Tumorcells_06 (0.174471)NDR1KO_Tumorcells_07 (0.0273891) (0.0211701) (0.0465126) (0.0361594)[ min ] [ medium ] [ max ] CEM 1 Epn1 143.7 228.3 1682.1 P ( S | Z, I ) = 0.02 Ap2a1 34.7 83.0 596.3 Mean Corr = 0.07234 Ralbp1 581.9 1075.3 4403.8 Ap2a2 61.0 182.7 608.9 Numb 492.6 768.4 1343.8 Ccnb1 8.4 20.3 36.7 Wbp2 236.2 540.6 741.9 Smarcc2 468.9 966.0 1777.3 Gsk3a 623.9 933.0 2361.6 Capn15 140.5 244.2 1535.7 Atg2a 57.5 184.9 675.0 CEM 1 + Atp6v0a1 9.4 21.4 887.3 Top 10 Genes Rgp1 537.5 1343.9 1732.4 Polr2a 927.0 1708.2 4340.1 Adipor1 60.0 163.1 619.8 Hagh 128.0 270.7 465.8

Null module GEO Series "GSE30980" 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=GSE30980 Status: Public on May 21 2014 Title: Gene profiling on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24705356 Summary & Design: Summary: Velo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos.

Overall design: To obtain enough RNA for microarray hybridization experiments, dissected mandibular arches from three Tbx1+/+ and three Tbx1-/- E10.5 embryos were pooled according to genotype, with three microarrays performed in total per genotype. The tissue was homogenized in Buffer RLT (QIAGEN). Total RNA was isolated with the RNeasy Micro Kit according to the manufacturers protocol. Quality and quantity of total RNA was determined using an Agilent 2100 Bioanalyzer (Agilent) and an ND-1000 Spectrophotometer (NanoDrop), respectively. Biotinylated single-stranded cDNA targets were amplified from 100 nanograms (ng) starting total RNA using the Ovation RNA Amplification System V2 and FL- Ovation cDNA Biotin Module V2 (NuGEN). A total of 3.75 Î¼g of cDNA from the last step was hybridized to the GeneChip Test3 array (Affymetrix) to test the quality of the labeled target. Nucleic acid samples that passed quality control were then hybridized to the GeneChip Mouse Genome 430 2.0 Arrays (Affymetrix). Hybridization, washing, staining and scanning were performed in the Genomics Core at Einstein (http://www.einstein.yu.edu/genetics/CoreFacilities.aspx?id=23934) according to the Affymetrix manual.

Background corr dist: KL-Divergence = 0.0413, L1-Distance = 0.0184, L2-Distance = 0.0004, Normal std = 0.6119

0.659 Kernel fit Pairwise Correlations Normal fit

Density 0.330

0.000 CEM 1

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

Pre-normalization Quantiles

Tbx1+/+,Tbx1-/-, replicaTbx1+/+, replica 1 (0.120715) Tbx1-/-,1 replica (0.318204)Tbx1+/+, replica 2 (0.173515) Tbx1-/-,2 replica (0.129564) replica 3 (0.0664625) 3 (0.19154) [ min ] [ medium ] [ max ] CEM 1 Epn1 294.4 338.0 396.0 P ( S | Z, I ) = 0.01 Ap2a1 392.6 436.5 450.3 Mean Corr = 0.53765 Ralbp1 314.2 355.8 395.6 Ap2a2 103.3 140.6 155.3 Numb 839.4 882.1 968.6 Ccnb1 2389.6 2676.9 2710.0 Wbp2 220.7 303.7 320.3 Smarcc2 630.9 806.5 887.1 Gsk3a 561.0 675.6 700.3 Capn15 241.9 336.3 381.6 Atg2a 163.2 194.4 209.3 CEM 1 + Atp6v0a1 292.5 363.7 430.2 Top 10 Genes Rgp1 428.5 466.6 527.4 Polr2a 1622.4 1806.8 1942.0 Adipor1 495.7 594.7 704.2 Hagh 134.6 149.2 208.1

Null module GEO Series "GSE18148" 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=GSE18148 Status: Public on Sep 19 2009 Title: Microarray analysis of Cbfb-deficient regulatory T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19800266 Summary & Design: Summary: Gene expression profiles of Cbfb-deficient and control Treg cells were compared.

Abstract: Naturally arising regulatory T (Treg) cells express the transcription factor FoxP3, which critically controls the development and function of Treg cells. FoxP3 interacts with another transcription factor Runx1 (also known as AML1). Here we showed that Treg cell-specific deficiency of CbfÎ², a cofactor for all Runx proteins, or that of Runx1, but not Runx3, induced lymphoproliferation, autoimmune disease, and hyper-production of IgE. Cbfb-deleted Treg cells exhibited impaired suppressive function in vitro and in vivo, with altered gene expression profiles including attenuated expression of FoxP3 and high expression of interleukin-4. The Runx complex bound to more than 3000 gene loci in Treg cells, including the Foxp3 regulatory regions and the Il4 silencer. In addition, knockdown of RUNX1 showed that RUNX1 is required for the optimal regulation of FoxP3 expression in human T cells. Taken together, our results indicate that the Runx1-CbfÎ² heterodimer is indispensable for in vivo Treg cell function, in particular, suppressive activity and optimal expression of FoxP3.

Overall design: CD4+CD25hi cells, most of which were Foxp3+ Treg cells, were isolated from Cbfb-flox/flox: Foxp3-ires-Cre (n = 3) and control Cbfb-flox/wt: Foxp3-ires-Cre (n = 3) mice. Total RNA was extracted from those purified Cbfb-deficient or control Treg cells.

Background corr dist: KL-Divergence = 0.0242, L1-Distance = 0.0115, L2-Distance = 0.0001, Normal std = 0.7004

0.570 Kernel fit Pairwise Correlations Normal fit

Density 0.285

0.000 CEM 1

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

Pre-normalization Quantiles

Cbfb-deficientControl Treg_rep1Control Treg_rep1Control Treg_rep2 (0.18959) (0.275024)Cbfb-deficient Treg_rep3 (0.128079)Cbfb-deficient (0.132504) Treg_rep2 Treg_rep3 (0.0796074) (0.195196)[ min ] [ medium ] [ max ] CEM 1 Epn1 543.7 616.6 992.3 P ( S | Z, I ) = 0.01 Ap2a1 388.0 441.6 592.5 Mean Corr = 0.40511 Ralbp1 1055.6 1851.8 2150.6 Ap2a2 187.0 255.7 484.6 Numb 1897.5 2226.5 2547.2 Ccnb1 41.3 46.7 54.3 Wbp2 1110.2 1476.7 2097.9 Smarcc2 365.5 436.0 696.8 Gsk3a 1422.1 1499.1 1846.5 Capn15 586.8 791.4 1031.5 Atg2a 353.1 404.0 798.2 CEM 1 + Atp6v0a1 206.5 285.4 365.7 Top 10 Genes Rgp1 1052.7 1229.5 1687.4 Polr2a 1360.5 1818.1 3592.0 Adipor1 213.3 270.6 363.2 Hagh 841.4 893.8 909.0

Null module 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 (0.0806881) sh-2LKR13_Wt1 (0.064979) sh-1LKR13_Control-1 (0.0708018) sh-2LKR13_Control-2 (0.0629114)LKR13_Control-3 (0.0482904)LKR13_Control-4 (0.051657)LKR13_Kras (0.0996972)LKR13_Kras (0.0540553) sh-3 (0.185582) sh-4 (0.281338) [ min ] [ medium ] [ max ] CEM 1 Epn1 685.1 882.7 1738.5 P ( S | Z, I ) = 0.00 Ap2a1 429.1 520.0 981.6 Mean Corr = 0.31299 Ralbp1 1003.0 1857.0 2650.5 Ap2a2 44.6 61.1 82.1 Numb 863.5 937.1 1263.9 Ccnb1 64.2 80.3 114.8 Wbp2 1766.6 2546.4 3400.6 Smarcc2 359.0 514.1 619.5 Gsk3a 1169.2 1328.9 1831.1 Capn15 201.7 282.4 410.7 Atg2a 506.2 754.9 1027.3 CEM 1 + Atp6v0a1 729.9 1413.8 2249.1 Top 10 Genes Rgp1 635.9 726.2 918.3 Polr2a 487.7 793.4 1792.4 Adipor1 227.4 434.0 656.4 Hagh 1134.7 1442.4 1779.5

Null module GEO Series "GSE39897" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.878 Kernel fit Pairwise Correlations Normal fit

Density 0.439

0.000 CEM 1

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

Pre-normalization Quantiles

embryoembryo at Egg,embryo atbiological Egg,embryo atbiological Egg, rep1embryo at biological(0.061502) TS01, rep2embryo at (0.0437332)biological TS01, rep3embryo at (0.0518037)biological TS01, rep1embryo at biological(0.0647907) TS09, rep2embryo at biological(0.042871) TS09, rep3embryo at biological(0.0411186) TS09, rep1embryo at biological(0.0264765) TS11, rep2embryo at biological(0.0213035) TS11, rep3embryo at biological(0.0225017) TS11, rep1embryo at biological(0.0260437) TS13, rep2embryo at biological(0.0430249) TS13, rep3embryo at biological(0.0491584) TS13, rep1embryo at biological(0.019456) TS16, rep2embryo at biological(0.0124547) TS16, rep3embryo at biological(0.00836294) TS16, rep1embryo at biological(0.00743334) TS19, rep2embryo at biological(0.0131429) TS19, rep3embryo at biological(0.00638518) TS19, rep1embryo at biological(0.0120428) TS21, rep2embryo at biological(0.00975813) TS21, rep3embryo at biological(0.0144765) TS21, rep1embryo at biological(0.016819) TS22, rep2embryo at biological(0.0107311) TS22, rep3embryo at biological(0.0166804) TS22, rep1embryo at biological(0.0186196) TS23, rep2embryo at biological(0.0122871) TS23, rep3embryo at biological(0.0117641) TS23, rep1embryo at biological(0.0459557) TS25, rep2embryo at biological(0.0651397) TS25, rep3embryo at biological(0.0712879) TS25, rep1embryo at biological(0.0440526) TS27, rep2embryo at biological(0.0101085) TS27, rep3 at biological(0.0143198) TS27, rep1 biological(0.0124939) rep2 (0.0141634) rep3[ (0.0377371)min ] [ medium ] [ max ] CEM 1 Epn1 188.7 484.1 1070.5 P ( S | Z, I ) = 0.00 Ap2a1 90.4 419.9 922.4 Mean Corr = -0.11053 Ralbp1 387.7 777.0 5368.6 Ap2a2 5.5 95.3 262.5 Numb 1036.8 1388.6 2372.6 Ccnb1 36.2 78.5 224.9 Wbp2 466.4 661.7 1536.2 Smarcc2 242.7 775.2 1739.1 Gsk3a 910.7 1205.3 2474.8 Capn15 219.7 413.6 822.1 Atg2a 88.4 196.5 500.1 CEM 1 + Atp6v0a1 107.4 265.2 811.8 Top 10 Genes Rgp1 600.0 767.9 1446.0 Polr2a 662.5 1544.0 2375.6 Adipor1 180.0 350.0 738.0 Hagh 466.4 1025.8 2233.3

Null module GEO Series "GSE6837" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: comparative study

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

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

0.536 Kernel fit Pairwise Correlations Normal fit

Density 0.268

0.000 CEM 1

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

Pre-normalization Quantiles

unstimulatedunstimulated embryonicstimulated embryonicstimulated fibroblasts embryonicstimulated fibroblasts embryonic WT, stimulatedfibroblasts biologicalembryonic KO, stimulatedfibroblasts biologicalembryonicWT, rep1 stimulatedfibroblasts biological embryonicWT,(0.0705785) rep1 fibroblasts biological embryonicrep1WT,(0.0978708) fibroblasts biological(0.0530693) rep2KO, fibroblasts biological (0.0675372) rep3KO,[ biological (0.0978738) min rep1KO, biological(0.327963) rep2] (0.0493396) rep3 (0.235768)[ medium ] [ max ] CEM 1 Epn1 472.4 670.2 1632.6 P ( S | Z, I ) = 0.00 Ap2a1 197.8 290.9 405.8 Mean Corr = 0.28741 Ralbp1 700.3 1118.4 1402.3 Ap2a2 4.5 14.6 177.6 Numb 477.9 638.6 2933.4 Ccnb1 18.1 70.5 79.9 Wbp2 399.6 649.6 1988.4 Smarcc2 210.9 393.3 1366.6 Gsk3a 976.4 1383.8 2031.0 Capn15 74.8 224.8 489.9 Atg2a 128.0 209.6 508.3 CEM 1 + Atp6v0a1 59.4 149.9 759.9 Top 10 Genes Rgp1 365.7 488.9 1144.5 Polr2a 787.7 821.9 1593.0 Adipor1 299.7 439.2 566.4 Hagh 483.4 550.3 2732.9

Null module GEO Series "GSE30083" 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=GSE30083 Status: Public on Feb 13 2012 Title: Expression data from CD4 single positive thymocyte subsets from C57BL/6 mice of 6-8 wks of age Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22022412 Summary & Design: Summary: After positive selection in the thymus, the newly generated single positive (SP) thymocytes are phenotypically and functionally immature and undergo apoptosis upon antigen stimulation. In the thymic medullary microenvironment, SP cells progressively acquire immunocompetence. Negative selection to remove autoreactive T cells also occur at this stage. We have defined four subsets of CD4 SP, namely, SP1, SP2, SP3, and SP4 that follow a functional maturation program and a sequential emergence during mouse ontogeny.

We used microarray to detail the global programm of gene expression during the maturation of murine CD4 single positive thymocytes

Overall design: Four subsets of CD4+CD8-CD25-NK1.1- thymocytes from C57BL/6 mice of 6-8 wks of age were purified for RNA extraction and hybridization on Affymetrix microarrays, namely, SP1 (Qa-2-6C10+CD69+), SP2 (Qa-2-6C10-CD69+), SP3 (Qa-2-6C10-CD69-), SP4 (Qa-2+6C10-CD69-).

Background corr dist: KL-Divergence = 0.0812, L1-Distance = 0.0208, L2-Distance = 0.0005, Normal std = 0.4748

0.840 Kernel fit Pairwise Correlations Normal fit

Density 0.420

0.000 CEM 1

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

Pre-normalization Quantiles

SP1, biologicalSP2, biologicalSP3, rep1 biological(0.0603105)SP4, rep1 biological(0.0392055)SP1, rep1 biological(0.139336)SP2, rep1 biological(0.021527)SP3, rep2 biological(0.0336271)SP4, rep2 biological(0.0710312)SP1, rep2 biological(0.0334304)SP2, rep2 biological(0.0680781)SP3, rep3 biological(0.137647)SP4, rep3 biological(0.14472) rep3 (0.0903867) rep3 (0.1607) [ min ] [ medium ] [ max ] CEM 1 Epn1 428.5 534.8 596.6 P ( S | Z, I ) = 0.00 Ap2a1 348.5 503.1 585.8 Mean Corr = -0.02785 Ralbp1 618.1 1157.3 2548.8 Ap2a2 376.2 517.1 677.5 Numb 563.3 899.5 1420.0 Ccnb1 73.3 218.1 464.3 Wbp2 263.5 531.5 762.0 Smarcc2 583.6 789.8 1010.6 Gsk3a 1143.4 1566.7 1695.6 Capn15 348.8 430.6 822.4 Atg2a 356.3 550.2 622.0 CEM 1 + Atp6v0a1 138.9 172.8 208.3 Top 10 Genes Rgp1 757.0 1144.9 1511.9 Polr2a 748.8 1132.2 3555.8 Adipor1 269.4 333.4 451.6 Hagh 411.0 580.2 825.2

Null module GEO Series "GSE13408" 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=GSE13408 Status: Public on Sep 01 2009 Title: Cell cycle exit and terminal differentiation independent of the Rb gene family during embryonic development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21059851 Summary & Design: Summary: The retinoblastoma cell cycle regulator pRb and the two related proteins p107 and p130 are thought to suppress cancer development both by inhibiting the G1/S transition of the cell cycle in response to growth-arrest signals and by promoting cellular differentiation. Here, we investigated the phenotype of Rb family triple knock-out (TKO) embryonic stem cells as they differentiate in vivo and in culture. Confirming the central role of the Rb gene family in cell cycle progression, TKO mouse embryos did not survive past mid-gestation and differentiating TKO cells displayed increased proliferation and cell death. However, patterning and cell fate determination were largely unaffected in these TKO embryos. Furthermore, a number of TKO cells, including in the neural lineage, were able to exit the cell cycle in G1 and terminally differentiate. This ability of Rb family TKO cells to undergo cell cycle arrest was associated with the repression of target genes for the E2F6 transcription factor, uncovering a pRb-independent control of the G1/S transition of the cell cycle. These results show that the Rb gene family is required for proper embryonic development but is not absolutely essential to induce G1 arrest and differentiation in certain lineages.

Overall design: Genome-wide gene expression was analyzed for wild-type and TKO ESC and EB cells. Three biological replicates were isolated for wild-type ESCs, TKO ESCs, and wild-type EBs, while five biological replicates were isolated for TKO EBs.

Background corr dist: KL-Divergence = 0.0569, L1-Distance = 0.0273, L2-Distance = 0.0013, Normal std = 0.5413

0.737 Kernel fit Pairwise Correlations Normal fit

Density 0.368

0.000 CEM 1

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

Pre-normalization Quantiles

TKO EBTKO (2-55-2) EBWT (14-14-4) (0.108844) EB (B21)WT (0.0732508) ESC (0.0622832)WT (B21) EB (0.0919815)(J1)WT ESC(0.0593796)WT (J1) EB (0.057086) (R1)WT ESC (0.076282)TKO (R1) EB (0.0684384)TKO (7-4-1) ESC TKO(0.0657326) (7-4-1) EBTKO (Dutch) (0.0452685) ESCTKO (0.0605843) (Dutch) EBTKO (Ta1-12) (0.0446178) ESC (0.0670713)(Ta1-12) (0.11918) [ min ] [ medium ] [ max ] CEM 1 Epn1 667.8 887.4 991.5 P ( S | Z, I ) = 0.00 Ap2a1 301.9 480.4 700.1 Mean Corr = 0.30241 Ralbp1 710.5 1398.0 2002.9 Ap2a2 29.1 49.2 81.9 Numb 549.7 770.2 1306.8 Ccnb1 23.1 133.9 277.9 Wbp2 1012.1 1580.0 2341.2 Smarcc2 142.4 393.7 826.9 Gsk3a 1864.9 2384.6 2788.6 Capn15 114.7 177.4 261.6 Atg2a 81.1 194.3 267.7 CEM 1 + Atp6v0a1 136.9 279.0 1081.2 Top 10 Genes Rgp1 322.4 532.2 850.0 Polr2a 1788.4 2373.7 3534.0 Adipor1 166.1 342.0 982.1 Hagh 412.0 1321.1 1645.7

Null module GEO Series "GSE27378" 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=GSE27378 Status: Public on Dec 01 2011 Title: Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22144105 Summary & Design: Summary: Dorsomorphin is a small molecule inhibitor of type I bone morphogenic protein receptors (BMPRs). We have found that dorsomorphin affects a wide range of T cell function. In order to obtain the bigger picture of the effects of DM in T cell activation. transcriptomic analysis was performed using mouse primary CD25-CD4+ T cells with either DM (4 Î¼M) or vehicle in the presence or absence of stimulation by anti-CD3 and -CD28 antibodies.

Overall design: Mouse CD4+ T cells were prepared and cultured with or without stimulation by plate bound anti-CD3 mAb and soluble anti-CD28 mAb for 1 hour. Subsequently, 4 Î¼M DM or DMSO was added and cells were incubated for 6 hours. Total RNA was isolated using Qiagen RNeasy mini kits.

Background corr dist: KL-Divergence = 0.0595, L1-Distance = 0.0472, L2-Distance = 0.0033, Normal std = 0.5727

0.736 Kernel fit Pairwise Correlations Normal fit

Density 0.368

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl CD4+ TDorsomorphin-treated CD4+cells-replicate1 TDorsomorphin-treated cells-replicate2Control (0.0506979) ControlCD4+stimulated (0.0233684) T Dorsomorphin-treated CD4+stimulatedcells-replicate1 CD4+ TDorsomorphin-treated cells-replicate2 T CD4+cells-replicate1 (0.160864) T cells-replicate2 stimulated (0.162022) (0.167794) stimulated CD4+ (0.293607)[ Tmin CD4+cells-replicate1 T cells-replicate2] (0.0961646)[ (0.0454825)medium ] [ max ] CEM 1 Epn1 206.9 412.4 506.9 P ( S | Z, I ) = 0.00 Ap2a1 142.3 203.1 257.9 Mean Corr = 0.42676 Ralbp1 835.8 2599.4 4273.5 Ap2a2 152.1 714.3 2252.1 Numb 678.5 2477.5 3451.4 Ccnb1 6.4 36.2 60.0 Wbp2 395.3 1177.3 1563.8 Smarcc2 166.6 608.1 1182.8 Gsk3a 1580.6 2245.9 3864.5 Capn15 340.8 787.7 1053.8 Atg2a 144.6 897.1 1379.2 CEM 1 + Atp6v0a1 17.2 37.9 123.6 Top 10 Genes Rgp1 469.3 1199.5 1601.4 Polr2a 1117.5 1605.3 3688.8 Adipor1 149.4 507.4 742.3 Hagh 704.6 917.4 1230.7

Null module GEO Series "GSE8065" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8065 Status: Public on Jun 12 2007 Title: Gene expression during early postnatal development of the small intestine Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18388184 Summary & Design: Summary: It was the purpose to analyse the changes in gene expression which occur in the mouse small intestine from the pre-weaning to the post-weaning stage. The gene expression was accordingly followed from postnatal day 4 to postnatal day 32.

Keywords: Time-course

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

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

0.782 Kernel fit Pairwise Correlations Normal fit

Density 0.391

0.000 CEM 1

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

Pre-normalization Quantiles

476_4d 478_4d(0.0321925) 480_4d(0.112067) 481_7d(0.026995) 484_7d(0.0112694) 488_7d(0.0189786) 486_9d(0.0148303) 488_9d(0.0167503) 490_9d(0.0292875) 496_11d(0.03742)497_11d (0.0384127)498_11d (0.0762849)1143_24d (0.0174885)1146_24d (0.119288)1279_32d (0.0690829)1281_32d (0.0316875)1285_32d (0.0435175)1148_24d (0.076538) (0.22791) [ min ] [ medium ] [ max ] CEM 1 Epn1 937.5 1760.6 2553.0 P ( S | Z, I ) = 0.00 Ap2a1 307.2 377.7 513.9 Mean Corr = 0.30776 Ralbp1 764.8 1177.4 2385.7 Ap2a2 64.8 177.2 454.2 Numb 1716.9 2161.5 3260.8 Ccnb1 42.2 52.9 110.3 Wbp2 817.6 1685.5 2324.2 Smarcc2 529.6 1138.1 1638.9 Gsk3a 1088.4 1360.1 1582.4 Capn15 329.4 1236.3 1541.9 Atg2a 268.3 362.9 509.1 CEM 1 + Atp6v0a1 640.3 2096.1 2538.1 Top 10 Genes Rgp1 1022.9 1323.2 1655.2 Polr2a 718.8 1279.6 1655.4 Adipor1 187.7 345.1 604.8 Hagh 1292.0 1651.7 3281.4

Null module GEO Series "GSE31702" 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=GSE31702 Status: Public on Aug 30 2011 Title: CD4+ T cell gene expression in B6 vs B6.Sle1c2 mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22711888 Summary & Design: Summary: Sle1c is a sublocus of the NZM2410-derived Sle1 major susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring CD4+ T cell-intrinsic hyperactivation and increased susceptibility to chronic graft-versus-host disease (cGVHD) that mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Recombinant congenic strains expressing Sle1c2 exhibited a T cell-intrinsic CD4+ T cell hyperactivation and cGVHD susceptibility, similar to mice with the parental Sle1c.

We performed a microarray analysis on CD4+ T cells to gain insights into the transcriptional programs that regulate the hyperactivation conferred by Sle1c2.

Overall design: CD4+ T cell cDNA was prepared from spenocytes from 5 mice from each strain and B6.Sle1c2 gene expression was compared to B6 gene expresion.

Background corr dist: KL-Divergence = 0.0810, L1-Distance = 0.0213, L2-Distance = 0.0006, Normal std = 0.4784

0.834 Kernel fit Pairwise Correlations Normal fit

Density 0.417

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

B6-1 (0.036614)B6-2 (0.0620963)B6-3 (0.107671)B6-4 (0.217358)B6-5 (0.0953166)REC5-1REC5-2 (0.144486)REC5-3 (0.0412261)REC5-4 (0.0430892)REC5-5 (0.210961) (0.0411815) [ min ] [ medium ] [ max ] CEM 1 Epn1 125.0 256.2 346.0 P ( S | Z, I ) = 0.00 Ap2a1 88.8 172.9 205.7 Mean Corr = 0.29153 Ralbp1 1040.7 1346.0 1428.6 Ap2a2 42.1 101.4 151.3 Numb 705.2 764.4 960.2 Ccnb1 504.5 1009.9 1234.2 Wbp2 2049.3 2969.0 3052.5 Smarcc2 523.2 648.6 691.8 Gsk3a 3456.8 4031.6 4145.0 Capn15 242.4 298.5 331.3 Atg2a 234.2 293.0 305.1 CEM 1 + Atp6v0a1 204.0 552.8 787.7 Top 10 Genes Rgp1 536.5 683.7 732.3 Polr2a 3208.0 3546.5 3752.3 Adipor1 875.1 1110.4 1437.0 Hagh 168.8 374.3 548.8

Null module GEO Series "GSE15772" 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=GSE15772 Status: Public on May 20 2009 Title: WT Dorsal Skin Time Course Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19494835 Summary & Design: Summary: Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.

Overall design: To gain insights into common and unique transcriptional regulatory programs during epidermal differentiation, we profiled global gene expression in mouse dorsal skin at E14.5, E16.5, and E18.5.

Background corr dist: KL-Divergence = 0.0139, L1-Distance = 0.0232, L2-Distance = 0.0006, Normal std = 0.8175

0.488 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

E14.5 WTE14.5 Dorsal WTE16.5 SkinDorsal WT 1-2E16.5 SkinDorsal (0.29335) WT 1-3E16.5 SkinDorsal (0.265487) WT 6E18.5 (0.0659713) SkinDorsal WT 7E18.5 (0.104269) SkinDorsal WT 8E18.5 (0.116361) SkinDorsal WT 5-5 SkinDorsal (0.0313506) 6-4 Skin (0.110007) 1-4 (0.0132044)[ min ] [ medium ] [ max ] CEM 1 Epn1 139.9 1079.1 1260.3 P ( S | Z, I ) = 0.00 Ap2a1 77.3 519.5 945.0 Mean Corr = 0.21903 Ralbp1 973.5 1604.1 2050.9 Ap2a2 78.8 224.9 420.1 Numb 704.4 1509.3 2042.6 Ccnb1 19.3 82.7 924.9 Wbp2 614.0 882.8 1721.3 Smarcc2 585.2 1198.0 1414.4 Gsk3a 600.5 2034.5 3037.0 Capn15 87.4 853.8 1874.3 Atg2a 53.1 411.4 567.3 CEM 1 + Atp6v0a1 341.0 739.1 1431.9 Top 10 Genes Rgp1 268.9 989.9 1285.4 Polr2a 820.2 1686.9 3179.2 Adipor1 394.4 567.6 763.4 Hagh 89.2 910.7 1141.8

Null module GEO Series "GSE13693" 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=GSE13693 Status: Public on Feb 06 2009 Title: Gene expression profiling of normal mouse myeloid cell populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7RÎ±), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.

Overall design: See summary.

Background corr dist: KL-Divergence = 0.0176, L1-Distance = 0.0380, L2-Distance = 0.0018, Normal std = 0.8108

0.500 Kernel fit Pairwise Correlations Normal fit

Density 0.250

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

NORMALNORMAL BM NEUTROPHILS_2NORMAL BM NEUTROPHILS_1NORMAL BM NEUTROPHILS_3NORMAL (0.197983)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.412553)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.0777032)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.0637242) (0.0727651)[ min(0.091555) (0.0253827)] (0.0442876)[ (0.0140456) medium ] [ max ] CEM 1 Epn1 1479.5 2102.1 4287.8 P ( S | Z, I ) = 0.00 Ap2a1 211.4 253.2 306.4 Mean Corr = 0.35616 Ralbp1 848.1 1184.6 4159.4 Ap2a2 25.2 42.9 129.6 Numb 1051.7 2537.5 7232.9 Ccnb1 16.2 50.0 382.1 Wbp2 1223.6 2807.5 3884.8 Smarcc2 608.1 696.7 866.3 Gsk3a 2713.7 3115.8 5944.2 Capn15 33.0 423.9 589.0 Atg2a 206.3 315.2 1924.1 CEM 1 + Atp6v0a1 219.1 304.6 2871.2 Top 10 Genes Rgp1 1067.1 1900.9 4406.1 Polr2a 1928.3 2333.1 3092.7 Adipor1 263.3 360.6 1466.8 Hagh 877.1 1514.7 1818.2

Null module GEO Series "GSE26568" 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=GSE26568 Status: Public on May 31 2013 Title: Impact of KLF2 expression on T cell genetic program Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24155966 Summary & Design: Summary: On triggering of the T cell receptor CD8 T lymphocytes downregulate expression of the transcription factor KLF2. KLF2 expression remains low as these cells differentiate to Cytotoxic T lymphocytes (CTL) but may be re-expressed depending on the local environmental signals.

We used retroviral transduction to enforce KLF2 expression in CTL to determine the impact of it re-expression on the CTL genetic program.

Overall design: T lymphocytes with a transgenic T cell receptor (P14 LCMV) isolated from murine spleens were activated with gp33-41 peptide for 2 days and transduced with empty vector (evGFP) or GFP-KLF2. After differentiation to CTL in culture with Interleukin-2 for 2 further days, cells positive for GFP were isolated by Fluorescence Activated Cell Sorting and the RNA extracted for microarray analysis.

Background corr dist: KL-Divergence = 0.0293, L1-Distance = 0.0215, L2-Distance = 0.0005, Normal std = 0.6816

0.600 Kernel fit Pairwise Correlations Normal fit

Density 0.300

0.000 CEM 1

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

Pre-normalization Quantiles

evGFP transducedevGFP transducedevGFP CTL, transducedGFP-KLF2 biological CTL,GFP-KLF2 biological transduced CTL, rep.GFP-KLF2 1biological transduced(0.170665) rep. CTL, 2 transduced(0.0435419) rep. biological CTL, 3 (0.402536) biological CTL, rep. 1biological (0.105199)[ rep. min 2 (0.214516) rep. ] 3 (0.0635425)[ medium ] [ max ] CEM 1 Epn1 361.0 397.1 425.2 P ( S | Z, I ) = 0.00 Ap2a1 200.9 231.3 254.8 Mean Corr = 0.49903 Ralbp1 2007.0 2355.4 2475.4 Ap2a2 87.9 97.5 108.1 Numb 547.9 635.0 680.2 Ccnb1 128.5 167.9 204.3 Wbp2 326.7 654.5 857.3 Smarcc2 705.1 775.5 794.5 Gsk3a 1243.2 1421.7 1442.0 Capn15 266.2 320.8 352.2 Atg2a 399.9 550.5 640.4 CEM 1 + Atp6v0a1 65.8 97.6 106.7 Top 10 Genes Rgp1 966.3 1057.3 1309.1 Polr2a 1542.7 1941.0 2306.3 Adipor1 105.5 127.0 145.3 Hagh 485.5 623.9 668.3

Null module GEO Series "GSE32015" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32015 Status: Public on Dec 03 2012 Title: Expression data from inducible ES stable cell lines Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23180766 Summary & Design: Summary: In order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the different inducible cell lines

Transcriptome analysis of the inducible transgenic mouse ES cell lines

Overall design: For the analysis on the different inducible cell lines, total RNA was extracted from three biological replicates grown in medium deprived of Tetracycline for 17 and 24 hours; RNA extracted from un-induced clones was used as control. Total RNA extracted from parental cell line EBRTcH3 (EB3) was used as additional control.

Background corr dist: KL-Divergence = 0.3818, L1-Distance = 0.0747, L2-Distance = 0.0167, Normal std = 0.2525

1.580 Kernel fit Pairwise Correlations Normal fit

Density 0.790

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

CTRL, biologicalCTRL, biologicalCTRL, replicate biologicalinducible replicate 1 (0.0218502)inducible replicateclone 2 (0.0278403)inducible of clone AIRE3 (0.0175823)induced of deleted clone AIREinduced of clone deletedisoform, AIRE ofinduced clone deleted isoform,AIRE biological ofinducible deleted clone isoform,AIRE biological replicate1 ofinducible deletedisoform, cloneAIRE biological replicate2inducible deletedofisoform, (0.0079505)clonebiological BRWD1, replicate3induced ofisoform, (0.0137593)clonebiological BRWD1, biologicalreplicate1induced ofclone (0.00554975)biological BRWD1, biologicalreplicate2 of induced replicate1 (0.0171375)clone BRWD1, biologicalreplicate3 of inducible replicate2 (0.0459433)clone BRWD1, (0.0236948)biological of inducible replicate3(0.008504) cloneBRWD1, (0.0106066)biological replicate1inducible of clone (0.0166189)GTF2I,biological replicate2induced of (0.0337363)clone biologicalGTF2I, replicate3induced ofclone (0.0148389) biologicalGTF2I, replicate1 ofinduced clone (0.00506314)GTF2I, biological replicate2 ofinducible clone (0.0132801) biologicalGTF2I, replicate3 ofinducible (0.0208971) biologicalcloneGTF2I, replicate1inducible of (0.016955) biologicalclone GTF2IRD1, replicate2induced (0.0147494)of clone GTF2IRD1, replicate3 induced biological (0.0167298) ofclone GTF2IRD1, ofinduced biological(0.108679) clone GTF2IRD1, replicate1 ofinduciblebiological clone GTF2IRD1, replicate2 (0.0169887)biological ofinducible cloneGTF2IRD1, replicate3 (0.0147264)biologicalinducible of replicate1clone GTF2IRD2, (0.0272345)biologicalinduced of replicate2clone GTF2IRD2, (0.0275757) inducedbiological ofclone replicate3 GTF2IRD2, (0.0254321) ofinducedbiological clone GTF2IRD2, replicate1 (0.0243911) ofinduciblebiological clone GTF2IRD2, replicate2 (0.0311846)biological ofinducible cloneGTF2IRD2, replicate3 (0.0224868)biologicalinducible of replicate1clone MYC, (0.0149077)biologicalinduced of replicate2biologicalclone MYC, (0.0352432)induced ofclone replicate3biological MYC, (0.0243758)replicate1 ofinduced clone biologicalMYC, (0.0196677)replicate2 of inducible (0.013396) biologicalclone MYC, replicate3 of inducible (0.0212407)biological cloneMYC, replicate1 inducible (0.0323977)biologicalof clone SUMF1,replicate2 (0.0174369)induced of clone SUMF1,replicate3 biological (0.0240656)induced ofclone SUMF1, biological (0.0279123) ofreplicate1induced clone SUMF1, biological ofreplicate2inducible clone SUMF1, (0.0036644)biological ofreplicate3inducible cloneSUMF1, (0.00566371)biological replicate1inducible of clone (0.00876456) biologicalWBSCR1, replicate2induced of (0.0086949) clone WBSCR1, replicate3biologicalinduced of clone(0.0096647) WBSCR1, biological ofinduced clone (0.0160905) replicate1WBSCR1, biological of clone replicate2WBSCR1, (0.0120891)biological of replicate3WBSCR1, (0.00618752)biological replicate1 (0.00965296)biological[ replicate2 min (0.0108869) replicate3 (0.0119821)] (0.0140287)[ medium ] [ max ] CEM 1 Epn1 387.1 794.3 1271.9 P ( S | Z, I ) = 0.00 Ap2a1 397.5 834.5 1323.0 Mean Corr = -0.04026 Ralbp1 633.3 1172.6 2586.9 Ap2a2 39.7 49.9 72.7 Numb 358.7 511.7 710.5 Ccnb1 105.6 143.0 281.6 Wbp2 688.4 1337.8 2441.2 Smarcc2 129.8 173.0 245.8 Gsk3a 1123.8 1369.8 1779.4 Capn15 348.1 506.4 695.5 Atg2a 345.6 541.7 743.0 CEM 1 + Atp6v0a1 232.8 440.9 624.3 Top 10 Genes Rgp1 399.9 505.9 661.0 Polr2a 1243.9 3294.3 6459.6 Adipor1 333.8 512.8 830.9 Hagh 998.0 1215.9 1627.4

Null module GEO Series "GSE20726" 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=GSE20726 Status: Public on Mar 10 2011 Title: Gene expression analysis of mouse ear samples treated with chemical allergen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22974541 Summary & Design: Summary: Identification of chemical allergen inducible genes in mouse skin.

Ear samples were isolated from CL57BL/6 mice 6 hours after topical application of a prototypic chemical allergen, a skin irritant or vehicle alone.

Overall design: Total RNA were extracted from ear skin samples treated with a chemical allergen, a skin irritant, or vehicle alone for 6 hours.

Background corr dist: KL-Divergence = 0.0921, L1-Distance = 0.0243, L2-Distance = 0.0009, Normal std = 0.4511

0.884 Kernel fit Pairwise Correlations Normal fit

Density 0.442

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

vehicle,vehicle, rep1 (0.121399)vehicle, rep2 (0.0996303)DNFB, rep3 (0.2513) rep1DNFB, (0.081323) rep2DNFB, (0.190585) rep3BAC, (0.0694979) rep1BAC, (0.0404851) rep2BAC, (0.0893447) rep3 (0.0564357) [ min ] [ medium ] [ max ] CEM 1 Epn1 690.2 981.3 1548.4 P ( S | Z, I ) = 0.00 Ap2a1 529.7 627.2 1148.1 Mean Corr = 0.35662 Ralbp1 617.6 927.9 1571.2 Ap2a2 76.9 137.3 326.6 Numb 1304.9 1471.0 1577.3 Ccnb1 15.8 55.0 201.7 Wbp2 1420.4 1758.1 2454.4 Smarcc2 1118.5 1450.8 1645.3 Gsk3a 1788.0 1995.3 4107.5 Capn15 347.6 469.0 602.5 Atg2a 234.6 383.0 485.0 CEM 1 + Atp6v0a1 776.9 969.5 1855.5 Top 10 Genes Rgp1 638.8 911.8 1058.2 Polr2a 699.3 1322.7 1983.5 Adipor1 889.4 1590.5 2171.9 Hagh 1666.1 1762.5 2267.1

Null module GEO Series "GSE36237" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 64 -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=GSE36237 Status: Public on Mar 09 2012 Title: Tg2576 and wild-type mice treated with PDE9A-inhibitor Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Many forms of synaptic plasticity are critically dependent upon production of cGMP to trigger activity-dependent increases in synaptic size and strength. Phosphodiesterase 9A (PDE9A) is a high affinity, cGMP-specific phosphodiesterase with widespread distribution in the central nervous system. Inhibition of PDE9A results in significant accumulation of cGMP in brain tissue and cerebrospinal fluid (CSF) of rodents, and increases CSF cGMP in human volunteers. We hypothesized that chronic exposure to a PDE9A inhibitor, and the associated elevations in brain cGMP could provide a therapeutic benefit to vulnerable synapses chronically exposed to AÎ² in transgenic mice over-expressing human mutant amyloid precursor protein (Tg2576 mice). A total of N=20 animals per group of 4 month old Tg2576 mice and non-transgenic littermates (WT) were implanted with Alzet osmotic minipumps to deliver vehicle or the PDE9A inhibitor PF-04447943. Neurobehavioral outcomes were measured as conditioned fear response after 28 days of treatment and subsequently brains were harvested for measurement of AÎ², gene expression profiling or synaptic density as assessed by Golgi staining of dendrites. Dendritic spine density on apical dendrites of CA1 neurons exhibited a small but significant deficit in the density of dendritic spines in vehicle treated Tg2576 mice as compared to WT mice. This deficit was ameliorated by 30 days of exposure to PF-04447943. No significant drug effect was observed in WT mice. No significant effects of drug treatment were observed on AÎ² levels in Tg2576 mice. Behavioral analysis of Tg2576 mice showed deficits in fear conditioning as early as 2 months old, and therefore were considered unlikely to be due to the accumulation of oligomeric AÎ². These deficits were not affected by drug treatment. Transcriptional profiles of Tg2576 mice treated with drug compared to vehicle showed evidence of regulation of pathways related to synaptic plasticity and remodeling of the dendritic cytoskeleton, consistent with stabilization of vulnerable spine structure. These data supports the hypothesis that PDE9A inhibition can stabilize vulnerable synapses early in the Alzheimers disease process.

Overall design: 4-month old Tg2576 mice and non-transgenic (WT) littermates were implanted with minipumps to deliver vehicle or the PDE9A-inhibitor, PF-04447943, for 28 days. At the end of the study, hippocampus and frontal cortex were dissected from n=8 mice per group, RNA was isolated, and hybridized to Affymetrix 430 2.0 mouse whole genome microarray.

Background corr dist: KL-Divergence = 0.1705, L1-Distance = 0.0379, L2-Distance = 0.0029, Normal std = 0.3549

1.124 Kernel fit Pairwise Correlations Normal fit

Density 0.562

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

Hipp PDE9Hipp Tg+, PDE9Hipp rep1 Tg+, PDE9 (0.0287789)Hipp rep2 Tg+, PDE9 (0.00737377)Hipp rep3 Tg+, PDE9 (0.00570723)Hipp rep4 Tg+, PDE9 (0.0157478)Hipp rep5 Tg+, PDE9 (0.00776866)Hipp rep6 Tg+, PDE9 (0.0266249)Hipp rep7 Tg+, PDE9 (0.0112487)Hipp rep8 Tg-, PDE9 (0.00462074)Hipp rep1 Tg-, PDE9 (0.00605026)Hipp rep2 Tg-, PDE9 (0.0139295)Hipp rep3 Tg-, PDE9 (0.00666311)Hipp rep4 Tg-, PDE9 (0.00640964)Hipp rep5 Tg-, PDE9 (0.00609437)Hipp rep6 Tg-, PDE9 (0.00738602)Hipp rep7 Tg-, Veh (0.0113252)Hipp rep8 Tg+, Veh (0.0207639) rep1Hipp Tg+, (0.0294973)Veh rep2Hipp Tg+, (0.0662695)Veh rep3Hipp Tg+, (0.0382459)Veh rep4Hipp Tg+, (0.0220514)Veh rep5Hipp Tg+, (0.00785487)Veh rep6Hipp Tg+, (0.0105493)Veh rep7Hipp Tg+, (0.0117672)Veh rep8Hipp Tg-, (0.0190655)Veh rep1Hipp Tg-, (0.0198115) Veh rep2Hipp Tg-, (0.0171254) Veh rep3Hipp Tg-, (0.0159637) Veh rep4Hipp Tg-, (0.0160937) Veh rep5Hipp Tg-, (0.00696797) Veh rep6Hipp Tg-, (0.0242564) Veh rep7PfC Tg-, PDE9(0.0107397) rep8PfC Tg+, PDE9(0.0152323) PfCrep1 Tg+, PDE9 (0.00602945) PfCrep2 Tg+, PDE9 (0.0462351) PfCrep3 Tg+, PDE9 (0.0121891) PfCrep4 Tg+, PDE9 (0.0366764) PfCrep5 Tg+, PDE9 (0.0112157) PfCrep6 Tg+, PDE9 (0.0112103) PfCrep7 Tg+, PDE9 (0.0123928) PfCrep8 Tg-, PDE9 (0.0108677) rep1PfC Tg-, PDE9 (0.0173786) rep2PfC Tg-, PDE9 (0.010665) rep3PfC Tg-, PDE9 (0.0127553) rep4PfC Tg-, PDE9 (0.0101816) rep5PfC Tg-, PDE9 (0.00858406) rep6PfC Tg-, PDE9 (0.00796857) rep7PfC Tg-, Veh (0.00970668) rep8PfC Tg+, Veh (0.0256799) rep1PfC Tg+, (0.0230852)Veh rep2PfC Tg+, (0.0126103)Veh rep3PfC Tg+, (0.0143524)Veh rep4PfC Tg+, (0.0141846)Veh rep5PfC Tg+, (0.0150429)Veh rep6PfC Tg+, (0.0229771)Veh rep7PfC Tg+, (0.0142872)Veh rep8PfC Tg-, (0.00514835)Veh rep1PfC Tg-, (0.0170203) Veh rep2PfC Tg-, (0.0166968) Veh rep3PfC Tg-, (0.00922548) Veh rep4PfC Tg-, (0.0220666) Veh rep5PfC Tg-, (0.0116058) Veh rep6PfC Tg-, (0.0135855) Veh rep7 Tg-, (0.00728528) rep8 (0.0131055) [ min ] [ medium ] [ max ] CEM 1 Epn1 1602.7 2674.7 3723.3 P ( S | Z, I ) = 0.00 Ap2a1 1205.4 1780.8 2523.3 Mean Corr = 0.00409 Ralbp1 1473.8 1718.6 2396.2 Ap2a2 55.1 115.8 179.9 Numb 667.2 1323.8 2075.0 Ccnb1 25.4 39.7 65.1 Wbp2 3857.5 5115.7 6641.3 Smarcc2 1457.4 2025.9 2627.9 Gsk3a 1765.7 2401.2 3733.5 Capn15 475.1 702.8 971.8 Atg2a 331.3 412.2 524.7 CEM 1 + Atp6v0a1 4198.8 5030.1 6628.9 Top 10 Genes Rgp1 437.1 572.8 733.8 Polr2a 291.9 607.4 1026.2 Adipor1 123.2 203.7 306.4 Hagh 2248.3 2541.5 4012.3

Null module GEO Series "GSE46871" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.592 Kernel fit Pairwise Correlations Normal fit

Density 0.296

0.000 CEM 1

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

Pre-normalization Quantiles

Hippocampus,Hippocampus, Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe mice, Hippocampus,Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe with18 mice, month-old, high with18 mice,Abeta month-old, high [ ACE12 plaque mice,Abetamin month-old, inhibitor-treated-rep1 ACE12 load-rep1plaque month-old,] inhibitor-treated-rep2 with load-rep2 (0.254313) low with Abeta[ (0.280004) (0.0332076)lowmedium plaque Abeta (0.0909621) load-rep1plaque load-rep2] (0.155784) (0.18573)[ max ] CEM 1 Epn1 954.9 1584.1 1965.8 P ( S | Z, I ) = 0.00 Ap2a1 571.1 757.1 1083.4 Mean Corr = 0.13984 Ralbp1 718.9 1185.8 1276.9 Ap2a2 8.0 18.8 26.8 Numb 833.8 896.2 1035.3 Ccnb1 3.5 6.3 22.3 Wbp2 3336.6 3823.7 4475.4 Smarcc2 1410.5 2106.1 2611.2 Gsk3a 1976.5 2168.1 2583.8 Capn15 520.3 719.7 794.5 Atg2a 187.9 330.3 425.4 CEM 1 + Atp6v0a1 2408.5 2821.5 3207.6 Top 10 Genes Rgp1 622.8 719.9 1033.3 Polr2a 621.9 923.3 1350.9 Adipor1 205.3 265.6 317.9 Hagh 2788.7 3099.9 3310.9

Null module GEO Series "GSE42591" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 26 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42591 Status: Public on Jul 01 2013 Title: Expression data from fresh and cultured islets at different glucose concentrations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23685457 Summary & Design: Summary: Î²-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring ˛†-cell adaptation to the organisms insulin demands. We have observed in pancreatic islets that stimulatory glucose concentrations induced a gene profile that was similar to that of freshly isolated islets, indicating that glucose-elicited cues are involved in maintaining Î²-cell identity. Low glucose induces the expression of ubiquitous genes involved in stress responses, nutrient sensing, and organelle biogenesis. By contrast, stimulatory glucose concentrations activate genes with a more restricted expression pattern (Î²- and neuronal- cell identity). Consistently, glucose-induced genes are globally reduced in islets deficient with Hnf1a (MODY3), characterized by a deficient glucose metabolism. Of interest, a cell cycle gene module was the most enriched among the variable genes between intermediate and stimulatory glucose concentrations. Glucose regulation of the islet transcriptome was unexpectedly broadly maintained in islets from aged mice. However, the cell cycle gene module is selectively lost in old islets and the glucose activation of this module is not recovered even in the absence of the cell cycle inhibitor p16.

We used microarrays to detail the global programme of gene expression regulated by glucose in young and aged pancreatic islets as well as freshly-isolated islets.

Overall design: Pancreatic islets from young and old mice were isolated and cultured at different glucose concentrations for RNA extraction and hybridization on Affymetrix microarrays. Islets were cultured at 3mM (G3), 5.5mM (G5), 11mM (G11) and 16mM (G16). Freshly-isolated islets (F) were also processed for RNA extraction . We also assessed the dynamic glucose regulation of gene expression at different time-points after an overnight at 3mM (T0): after 1h at 11mM (T1) and after 4h (T4).

Background corr dist: KL-Divergence = 0.1425, L1-Distance = 0.0297, L2-Distance = 0.0013, Normal std = 0.3825

1.043 Kernel fit Pairwise Correlations Normal fit

Density 0.522

0.000 CEM 1

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

Pre-normalization Quantiles

old isletsold at islets G3,old biological at islets G3,old biological at islets rep1G5,old biological (0.0674971)at islets rep2G5,old biological (0.0424767)at islets rep1G11,fresh (0.0371818)atbiological rep2G11, oldfresh (0.0286754) islets,biological rep1oldyoung biological islets, (0.0224549) rep2 isletsyoung biological (0.0164363) rep1 at islets youngG3, (0.0545773) rep2biological at islets youngG3, (0.0118937) biological at islets rep1youngG5, biological (0.0212588)at islets rep2youngG5, biological (0.0115811)at islets rep1youngG11, (0.0287492)atbiological islets rep2youngG11, (0.033759)atbiological islets youngG11, rep1 at biological(0.022485) islets youngG11, rep2 at biological(0.0362966) islets freshG16, rep3 at biologicalyoung(0.0967378) freshG16, rep4 islets, biologicalyoung(0.080002)young rep1 biological islets, (0.0224252) isletsyoung rep2 biological at (0.0520529) isletsrep1 youngT0, biological (0.0735698)at isletsrep2 youngT0, biological (0.0275662)at isletsrep1 youngT1, biological(0.0279425) at isletsrep2 youngT1, biological(0.0172988) at isletsrep1 T4, biological(0.0485802) at rep2 T4, biological(0.0399389) rep1 (0.0279567) rep2[ min (0.0506061) ] [ medium ] [ max ] CEM 1 Epn1 314.7 893.1 1138.8 P ( S | Z, I ) = 0.00 Ap2a1 197.7 388.1 578.8 Mean Corr = -0.02288 Ralbp1 1276.1 1703.6 2253.5 Ap2a2 23.4 150.8 277.9 Numb 753.8 1364.8 1796.5 Ccnb1 3.3 33.5 134.0 Wbp2 646.6 2375.5 4298.9 Smarcc2 535.4 893.9 1932.6 Gsk3a 1107.5 1362.7 1833.8 Capn15 147.4 489.0 722.8 Atg2a 16.8 170.7 231.0 CEM 1 + Atp6v0a1 274.7 1673.0 2254.8 Top 10 Genes Rgp1 941.4 1301.7 1712.6 Polr2a 1175.9 2198.2 3518.3 Adipor1 63.7 130.5 217.6 Hagh 2411.9 2995.5 3600.7

Null module GEO Series "GSE22086" 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=GSE22086 Status: Public on Sep 19 2011 Title: Expression data from quadriceps muscle of WT and ERRgamma transgenic mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21356518 Summary & Design: Summary: We show that the orphan nuclear receptor ERRg is expressed at high levels in type I muscle and when transgenically expressed in anaerobic type II muscles (ERRGO mice) or cultured cells, powerfully regulates VEGF expression, angiogenesis and vascular supply in absence of exercise. ERRGO mice show increased expression of genes promoting fat metabolism, mitochondrial respiration and type I fiber specification. In parallel, the type II muscle in ERRGO mice display an activated angiogenic program marked by myofibrillar induction and secretion of pro-angiogenic factors, frank neo-vascularization and a 100% increase in running endurance. Surprisingly, the induction of VEGF and type I muscle properties by ERRg does not involve the transcriptional co-activator PGC1a. Instead, ERRg genetically activates the energy sensor AMPK which is typically inactive in absence of exercise. Therefore, ERRg and AMPK, known regulators of mitochondrial function and metabolism, together control a novel angiogenic pathway that anatomically synchronizes vascular arborization to oxidative metabolism revealing an exercise-independent mechanism for matching supply and demand.

Keywords: ERRgamma overexpression compared to wild-type

Overall design: Comparison of gene expression from quadriceps muscles isolated from wild type and alpha-skeletal actin-ERRgamma-transgenic mice.

Background corr dist: KL-Divergence = 0.0412, L1-Distance = 0.0214, L2-Distance = 0.0005, Normal std = 0.6143

0.659 Kernel fit Pairwise Correlations Normal fit

Density 0.329

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 quadriceps,wild-type quadriceps, biologicalERRgamma quadriceps, biologicalERRgamma rep1 transgenic biologicalERRgamma(0.097975) rep2 transgenic (0.108538) quadriceps, rep3 transgenic (0.388781) quadriceps, biological quadriceps, biological[ rep1min biological(0.118679) rep2 ] (0.19023) rep3 (0.0957968)[ medium ] [ max ] CEM 1 Epn1 1359.5 1811.4 1887.7 P ( S | Z, I ) = 0.00 Ap2a1 445.2 688.4 758.9 Mean Corr = 0.28021 Ralbp1 1001.6 1146.4 1276.5 Ap2a2 13.1 74.7 114.9 Numb 678.9 854.6 877.8 Ccnb1 9.3 76.4 103.6 Wbp2 989.2 1458.5 1640.9 Smarcc2 738.7 813.0 881.6 Gsk3a 2385.0 2882.5 4527.0 Capn15 152.7 190.5 409.2 Atg2a 308.9 804.6 1086.5 CEM 1 + Atp6v0a1 623.8 787.8 899.3 Top 10 Genes Rgp1 520.9 707.8 806.9 Polr2a 567.7 863.2 903.6 Adipor1 846.6 1102.9 1681.9 Hagh 1997.6 2342.6 3005.6

Null module GEO Series "GSE27987" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 31 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27987 Status: Public on Aug 25 2011 Title: Differential pre-mRNA processing in Crebbp+/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21901164 Summary & Design: Summary: The presence of unspliced transcripts in hematopoietic stem cells (HSCs) and the proposed association of CREBBP with the constitutive production of unspliced RNA and with pre-mRNA processing prompted us to examine more closely an anomaly we had noted in microarray-based gene expression studies but had previously attributed to experimental noise. We noticed that more than half of the probe sets down-regulated in Crebbp+/- fetal liver HSCs (FLHSCs) relative to wild-type (WT) mapped entirely within introns, rather than detecting exonic or spliced sequences. We therefore set out to test whether this might be evidence that reduced CREBBP levels selectively alter the generation of full-length, unspliced pre-mRNA. We also asked whether this process might be associated with differentiation since self-renewal and lineage commitment are the both responses for which HSCs are primed.

Overall design: cell type comparison

Background corr dist: KL-Divergence = 0.0422, L1-Distance = 0.0924, L2-Distance = 0.0091, Normal std = 0.9341

0.496 Kernel fit Pairwise Correlations Normal fit

Density 0.248

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

Crebbp CrebbpwtHSC CrebbpsamplewtHSC Crebbp samplewtHSC1 replicate Crebbp samplewtHSC1 replicate 1 (0.0116192) Crebbp samplehetHSC2 replicate 2 (0.020922) Crebbp hetHSC 2sample replicate 1 (0.0214496) CrebbphetHSC sample1 replicate 2 (0.0176853) Ep300hetHSC sample1 replicate 1 wtHSC(0.0221804)Ep300 sample2 replicate 2 samplewtHSC(0.0166531)Ep300 2 replicate 1 samplewtHSC(0.0233175)1Ep300 replicate 2 samplewtHSC(0.0175882)1Ep300 replicate 1 (0.02078) samplehetHSC2Ep300 replicate 2 (0.103311) hetHSC 2Ep300sample replicate 1 (0.0131706) hetHSC Ep300sample1 replicate 2 (0.0112901) hetHSC Cdkn1asample1 replicate 1 (0.0147071) Cdkn1asample2wtHSC replicate 2 (0.0164812) Cdkn1a21wtHSC replicate(0.00911336) 1 (0.0172137)Cdkn1a 2wtHSC (0.0156448) 2 (0.010505)Cdkn1a 3nullHSC (0.0196631)Cdkn1a nullHSC 1 (0.0216484)Cdkn1a nullHSC 2 (0.015679)Crebbp nullHSC 3 (0.00278934) CrebbpwtMEF 4 (0.0309974) Crebbp1wtMEF (0.0887113) Crebbp2wtMEF (0.0573955) Crebbp3wtMEF (0.0643034) Crebbp4hetMEF (0.0638422) CrebbphetMEF 1 (0.0623543) CrebbphetMEF 2 (0.0592541) hetMEF 3 (0.0567533) 4 (0.0729763) [ min ] [ medium ] [ max ] CEM 1 Epn1 78.9 202.7 1127.4 P ( S | Z, I ) = 0.00 Ap2a1 131.5 253.2 1786.7 Mean Corr = 0.22893 Ralbp1 193.5 447.4 1023.2 Ap2a2 35.7 81.2 208.3 Numb 103.6 310.2 1085.5 Ccnb1 8.9 948.7 2207.1 Wbp2 207.7 484.4 1019.1 Smarcc2 833.6 1571.8 2009.9 Gsk3a 351.9 745.4 4193.8 Capn15 32.5 163.1 526.0 Atg2a 29.3 63.8 243.7 CEM 1 + Atp6v0a1 5.4 13.3 1118.2 Top 10 Genes Rgp1 311.6 610.2 1127.5 Polr2a 1247.7 2425.5 3521.1 Adipor1 73.5 400.3 1090.9 Hagh 32.2 65.0 597.6

Null module GEO Series "GSE25423" 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=GSE25423 Status: Public on Dec 31 2013 Title: LSD1 knockdown in 3T3-L1 preadipocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23595969 Summary & Design: Summary: Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells.

Overall design: The 24h sample groups (siC.24h and siLsd1.24h) consist of two biological replicate samples; the 48h sample groups (siC.48h and siLsd1.48h) consist of three biological replicate samples. Each sample was hybridized to a separate array, for a total of ten arrays.

Background corr dist: KL-Divergence = 0.0685, L1-Distance = 0.0356, L2-Distance = 0.0017, Normal std = 0.5250

0.795 Kernel fit Pairwise Correlations Normal fit

Density 0.397

0.000 CEM 1

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

Pre-normalization Quantiles

3T3-L1 siControl3T3-L1 siControl3T3-L1 24h, biologicalsiLSD13T3-L1 24h, biologicalsiLSD13T3-L124h, rep biological 1 siControl3T3-L124h, (0.084001) rep biological 2 siControl 3T3-L1 rep(0.0393025) 48h, 1 (0.120623) biologicalsiControl 3T3-L1rep 48h, 2 (0.100275) biologicalsiLSD13T3-L1 48h,rep 1 biologicalsiLSD13T3-L148h, (0.154188) rep biological 2 siLSD148h, (0.178877) rep biological 3 48h, rep(0.0874664) 1 biological (0.0267279) rep 2 (0.0279084) [rep min 3 (0.18063) ] [ medium ] [ max ] CEM 1 Epn1 1210.8 1630.8 2082.9 P ( S | Z, I ) = 0.00 Ap2a1 202.8 218.8 260.3 Mean Corr = 0.17503 Ralbp1 623.3 1237.6 1873.9 Ap2a2 28.1 70.1 117.9 Numb 635.0 780.5 941.0 Ccnb1 26.3 42.6 54.0 Wbp2 911.3 1106.3 1189.7 Smarcc2 322.8 585.9 979.5 Gsk3a 2146.3 2412.1 2777.8 Capn15 115.8 187.7 228.1 Atg2a 239.3 294.9 393.6 CEM 1 + Atp6v0a1 181.4 285.8 468.1 Top 10 Genes Rgp1 578.1 754.3 1034.9 Polr2a 2298.4 2793.9 3228.0 Adipor1 43.2 100.5 131.3 Hagh 931.3 1124.3 1307.3

Null module GEO Series "GSE9044" 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=GSE9044 Status: Public on Sep 19 2007 Title: HOXB4 target genes in ES cell-derived embryoid bodies (EBs) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17940039 Summary & Design: Summary: To unravel the molecular mechanism by which HOXB4 promotes the expansion of early hematopoietic progenitors within differentiating ES cells, we analzed the gene expression profiles of embryoid bodies (EBs) in which transcription of HOXB4 had been induced or not induced. A substantial number of the identified HOXB4 target genes are involved in signaling pathways important for controlling self-renewal, maintenance and differentiation of stem cells. Furthermore, we demonstrate that HOXB4 activity and FGF-signaling are intertwined. HOXB4-mediated expansion of ES cell-derived early progenitors was enhanced by specific and complete inhibition of FGF-receptors. In contrast, the expanding activity of HOXB4 on hematopoietic progenitors in day4-6 embryoid bodies was blunted in the presence of basic FGF (FGF2) indicating a dominant negative effect of FGF-signaling on the earliest hematopoietic cells. Taken together, we show that modulation of FGF signaling is an essential feature of HOXB4 activity in the context of embryonic hematopoiesis.

Keywords: plus/minus induction of HOXB4 gene expression by treatment with doxycycline (Dox)

Overall design: Biological replicates: 3

Background corr dist: KL-Divergence = 0.0351, L1-Distance = 0.0254, L2-Distance = 0.0008, Normal std = 0.6458

0.625 Kernel fit Pairwise Correlations Normal fit

Density 0.313

0.000 CEM 1

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

Pre-normalization Quantiles

EBs w/oEBs doxy with replicaEBs doxy w/o A EBsreplica doxy(0.257382) with replica EBsA doxy(0.0349164) w/o B EBsreplica doxy(0.214295) with replica B doxy(0.0638926) C replica (0.163479) C (0.266035)[ min ] [ medium ] [ max ] CEM 1 Epn1 404.4 544.8 942.3 P ( S | Z, I ) = 0.00 Ap2a1 225.7 424.2 829.4 Mean Corr = 0.26766 Ralbp1 393.0 567.7 779.3 Ap2a2 144.6 227.1 377.9 Numb 1038.9 1988.1 2239.6 Ccnb1 75.2 146.2 154.3 Wbp2 571.9 814.9 1302.9 Smarcc2 373.5 487.1 637.5 Gsk3a 756.4 1044.2 1773.1 Capn15 279.4 549.1 703.9 Atg2a 70.7 98.4 204.0 CEM 1 + Atp6v0a1 310.2 420.1 657.8 Top 10 Genes Rgp1 899.9 1017.9 1780.6 Polr2a 592.6 1194.8 2047.1 Adipor1 163.0 307.7 385.7 Hagh 414.0 459.7 765.9

Null module GEO Series "GSE43779" 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=GSE43779 Status: Public on Jan 28 2013 Title: Expression data from 2-amino acetophenone (2-AA) treated mouse Skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Metabolic responses begin promptly upon the initiation of infection, and progress as a series of coordinated events. Mitochondria may play a key role in the development of insulin resistance. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections.

We have used mouse skeletal muscle transcriptome data which have led to the hypothesis that 2-AA causes harm to the host by triggering mitochondrial dysfunction in skeletal muscle.

Overall design: The gastrocnemius muscles were isolated from control and 4days 2-AA treated mouse for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0223, L1-Distance = 0.0276, L2-Distance = 0.0011, Normal std = 0.7411

0.538 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

control controlbiological controlbiological rep1 2-AA biological(0.110696) rep2 treatment2-AA (0.195949) rep3 treatment2-AA biological(0.0736275) treatment biological rep1 biological(0.325749) rep2 (0.0802851) rep3[ (0.213693) min ] [ medium ] [ max ] CEM 1 Epn1 489.4 746.8 1298.0 P ( S | Z, I ) = 0.00 Ap2a1 275.6 548.0 587.5 Mean Corr = 0.29916 Ralbp1 985.7 1208.3 1849.8 Ap2a2 12.6 37.6 241.8 Numb 824.8 984.6 1337.6 Ccnb1 4.4 13.5 20.6 Wbp2 524.8 745.4 846.6 Smarcc2 415.3 1414.1 2813.5 Gsk3a 876.1 2139.9 3035.9 Capn15 63.0 122.2 191.0 Atg2a 117.0 169.1 232.1 CEM 1 + Atp6v0a1 263.9 355.5 807.9 Top 10 Genes Rgp1 374.5 493.1 706.7 Polr2a 541.6 646.0 930.0 Adipor1 203.8 403.9 679.2 Hagh 861.1 1543.4 3432.5

Null module