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: 8 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. Utp14b Utp14a Utp11l Wdr36 Nop14 Utp20 Num ofGenesinQueryGeneset:8.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Rps7 Tbl3

Utp20 Nop14 Wdr36 Tbl3 Utp14a Rps7 Utp14b Utp11l Singletons CEM 1(242datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page1 Ebna1bp2 Mybbp1a Mrps18b Gemin5 Pdcd11 Ruvbl1 Atad3a Utp14a Polr1b Cirh1a Grwd1 Heatr1 Mak16 Nop16 Wdr46 Nop56 Wdr43 Nsun2 Wdr74 Wdr36 Nop14 Hspa4 Eif2b3 Ddx27 Ddx56 Ddx18 Rrp15 Rrp12 Pprc1 Utp20 Noc2l Noc4l Noc3l Nat10 Pwp2 Bop1 Nop2 Ppan Eif3b Ftsj3 Rrp9 Lyar Bysl Tsr1 Dis3 Gart Tbl3 Srm Aatf Nifk 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE44175 [18] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE33942 [12] GSE20954 [14] GSE13693 [9] GSE38031 [8] GSE27092 [6] GSE20987 [12] GSE30160 [6] GSE15155 [12] GSE12498 [12] GSE38335 [9] GSE51483 [45] GSE13408 [14] GSE46606 [30] GSE27114 [6] GSE12499 [10] GSE26568 [6] GSE44923 [16] GSE46150 [8] GSE4535 [6] GSE53951 [10] GSE10273 [9] GSE17886 [16] GSE6957 [12] GSE34126 [19] GSE30745 [12] GSE39886 [24] GSE26096 [10] GSE32386 [13] GSE46185 [6] GSE16691 [12] GSE33156 [18] GSE46091 [8] GSE7069 [8] GSE7342 [12] GSE6526 [16] GSE15267 [8] GSE27605 [8] GSE8621 [12] GSE32598 [11] GSE18042 [18] GSE10912 [6] GSE32986 [18] GSE9878 [6] GSE5976 [12] GSE7012 [13] GSE46090 [12] GSE8091 [16] GSE21861 [8] GSE44261 [12] GSE10113 [12] GSE9735 [9] GSE21063 [24] GSE12948 [9] GSE40282 [6] GSE6689 [12] GSE51804 [10] GSE13692 [8] GSE48203 [9] GSE46942 [7] GSE12464 [23] GSE28389 [20] GSE38304 [8] GSE7764 [10] GSE48382 [10] GSE31166 [6] GSE25423 [10] GSE46724 [6] GSE6933 [15] GSE21491 [9] GSE18993 [13] GSE36814 [20] GSE18395 [8] GSE18660 [10] GSE31598 [12] GSE42047 [24] GSE33199 [64] GSE30855 [6] GSE20100 [15] GSE51243 [7] GSE32214 [6] GSE11220 [44] GSE44355 [10] GSE5671 [18] GSE27546 [51] GSE14012 [24] GSE49128 [17] GSE15173 [6] GSE34324 [12] GSE48935 [12] GSE42877 [14] GSE18135 [18] GSE34902 [6] GSE2527 [6] GSE11222 [42] GSE56777 [8] GSE17513 [12] GSE32277 [33] GSE7503 [6] GSE21670 [16] GSE20302 [12] GSE12581 [16] GSE10871 [32] GSE41895 [12] GSE39984 [18] GSE55809 [8] GSE39897 [36] GSE39034 [9] GSE30962 [16] GSE29632 [42] GSE27378 [8] GSE17316 [12] GSE42021 [27] GSE51883 [30] GSE21842 [8] GSE12465 [14] GSE13874 [14] GSE15268 [16] GSE10806 [11] GSE13547 [12] GSE13493 [6] GSE23006 [48] GSE15808 [29] GSE4189 [14] GSE48790 [8] GSE37000 [47] GSE28593 [9] GSE16454 [24] GSE42883 [12] GSE10246 [182] GSE10913 [6] GSE34723 [101] GSE34114 [12] GSE7897 [60] GSE10627 [51] GSE34618 [7] GSE20391 [11] GSE51608 [6] GSE24289 [6] GSE21033 [12] GSE27786 [20] GSE6085 [43] GSE27563 [93] GSE31406 [12] GSE25825 [8] GSE4739 [19] GSE21309 [9] GSE25645 [17] GSE37907 [24] GSE13590 [12] GSE6065 [100] GSE9954 [70] CEM+ CEM GSE18115 [8] GSE15610 [12] GSE9533 [35] GSE43197 [27] GSE18136 [12] GSE52075 [9] 0.0 GSE49248 [12] GSE47959 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 205.97 207.00 208.24 209.93 210.30 212.24 212.63 213.00 214.55 214.60 214.88 215.48 215.61 216.13 217.67 218.68 219.99 220.33 223.06 223.74 226.02 226.38 227.05 227.43 227.67 233.73 233.87 235.00 237.62 238.02 241.15 241.30 241.39 241.52 244.09 246.38 246.80 247.30 247.65 248.62 251.48 256.17 258.02 261.11 264.20 1.0 Notes Mphosph10 Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page2 Fam203a Tomm40 Gpatch4 Dnajc11 Exosc2 Rbm19 Smyd5 Rsl1d1 Prpf31 C1qbp Polr1e Polr1a Wdr55 Nop58 Ddx51 Abce1 Ddx21 Ddx39 Znhit6 Pa2g4 Prmt5 Gspt1 Trmt6 Abcf2 Utp15 Yars2 Bms1 Cct6a Nol11 Elac2 Wdr4 Nhp2 Nob1 Pno1 Pop1 Dkc1 Rcc1 Pus7 Pes1 Imp4 Urb2 Rars Rrs1 Gnl3 Adsl Nip7 Nle1 Ltv1 Ncl 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 177.31 178.18 178.87 178.95 179.09 179.09 179.39 179.70 181.19 181.24 181.48 181.90 182.00 182.45 184.44 184.97 185.49 186.24 186.96 187.33 188.01 188.26 188.29 189.22 189.68 190.00 190.26 192.32 192.49 192.69 192.88 194.30 194.31 194.54 194.64 195.39 196.47 197.57 197.67 198.35 199.54 200.70 201.40 201.81 202.66 202.68 203.96 204.88 205.02 205.63 1.0 Notes Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page3 Zmynd19 Trmt61a Timm10 Sssca1 Mettl13 Dnttip2 Ruvbl2 Spata5 Mthfd1 Polr2h G3bp1 Heatr3 Wdr18 Aimp2 Bend3 Usp10 Apex1 Sdad1 Naa25 Naa15 Rrp1b Tex10 Gmps Dimt1 Nol10 Ptcd3 Sf3a3 Pwp1 Ttc27 Strap Gpn1 Wdr3 Nop9 Eif3g Eif3d Kti12 Xpo5 Pus1 Qtrt1 Lsg1 Rrp8 Gnl2 Utp6 Cct5 Ppat Tars Rcl1 Ipo5 Nkrf Atic 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 151.25 152.20 152.86 153.03 153.21 153.91 154.08 154.29 157.34 157.88 157.98 158.02 158.05 158.17 159.06 159.29 159.50 159.80 160.67 161.33 161.95 162.83 164.05 164.74 165.26 165.63 165.80 166.32 166.39 167.04 167.08 167.12 168.73 168.91 169.06 169.34 169.95 170.10 170.98 171.66 171.85 172.31 173.36 174.62 174.75 175.44 176.83 176.92 176.95 177.02 1.0 Notes Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page4 BC027231 Rps19bp1 Tomm70a Wbscr16 Snrnp40 Psmd12 Fastkd5 Ranbp1 Chchd4 Gtpbp4 Eef1e1 Lrpprc Nufip1 Kpnb1 Nup54 Nup93 Ncbp1 Rpp40 Nup43 Rpl7l1 Ddx31 Hspa9 Eif2b5 Eif2b1 Mettl1 Prmt3 Prmt1 Riok2 Sf3b3 Larp1 Pinx1 Cse1l Tcof1 Dph2 Shq1 Noa1 Ddx1 Diexf Ppa1 Mars Hars Dctd Ctu2 Ctps Ifrd2 Naf1 Pfas Tsr2 Mtrr Iars 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 130.36 130.46 130.54 130.81 131.01 131.62 131.77 132.98 133.43 133.60 134.54 135.50 135.96 136.17 136.95 137.21 137.56 137.63 138.59 139.72 140.13 140.71 140.73 141.06 141.17 141.84 142.78 142.93 143.18 143.40 143.58 143.63 144.18 144.66 144.97 145.05 145.63 145.89 146.42 146.57 146.94 147.75 148.52 148.85 148.95 149.73 150.25 150.30 151.04 151.11 1.0 Notes 3110082I17Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page5 Thumpd1 Wbscr22 Rsl24d1 Timm23 Ndufaf4 Enoph1 Nudcd1 Nup107 Cacybp Nup155 Otud6b Skiv2l2 Snrpa1 Rnmtl1 Ppm1g Dcaf13 Tcerg1 Mrpl12 Srfbp1 Polr3h Nup85 Shmt2 Dhx33 Usp39 Ddx20 Msto1 Tbrg4 Bccip Nif3l1 Dus1l Pcgf6 Pus7l Prpf3 Prpf4 Dohh Stip1 Phb2 Rae1 Tcp1 Orc2 Drg2 Rrn3 Yrdc Xpot Nol8 Cct2 Cct7 Lars Esf1 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 113.12 113.20 113.33 113.51 113.76 114.30 114.33 114.67 114.80 115.52 115.82 116.60 116.73 117.08 117.25 117.32 117.87 118.21 118.39 119.06 119.59 119.93 119.98 120.12 120.26 120.33 120.69 120.91 121.13 121.66 122.53 123.24 123.27 123.84 123.88 124.50 124.60 124.98 125.84 126.76 126.93 128.41 129.15 129.31 129.35 129.50 129.68 129.77 130.19 130.22 1.0 Notes 9130401M01Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page6 Hnrnpab Tamm41 L3mbtl2 Slc19a1 Syncrip Nup160 Nup133 Cd3eap Rbmxl1 Nup188 Mthfd1l Exosc3 Mrps22 Mrps27 Trmt11 Stoml2 Psmg1 Mrpl47 Rangrf Wdr89 Wdr77 Pdap1 Dhx29 Ddx46 Trip13 Ahsa1 Ddx10 Actl6a Tnpo3 Qtrtd1 Thoc5 Tsen2 Prmt6 Polr2f Phf5a Emg1 Nme1 Smn1 Surf6 Cstf2 Nudc Xpo4 Ece2 Taf5l Lap3 Cluh Krr1 Isy1 Aen 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 94.56 94.74 94.94 95.10 95.16 95.24 95.44 95.64 96.15 96.17 96.56 96.99 97.08 97.46 97.58 97.88 98.16 98.66 98.69 98.98 99.25 99.34 99.48 100.47 102.14 102.58 103.21 103.56 104.04 104.49 104.55 104.56 104.73 105.23 106.21 106.34 106.49 106.73 107.49 107.52 107.52 108.61 109.35 109.54 110.96 111.68 111.94 112.33 112.53 112.96 1.0 Notes D19Bwg1357e Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page7 Rnaseh1 Tmem97 Trmt10a Pabpc4 Hnrnpu Exosc7 Exosc1 Mrps10 Tada2a Metap2 Ppp1r8 Rbm8a Psmg3 Pgam5 Psmc4 Psmc5 Mrpl37 Ino80e Polr3g Ahctf1 Polr3a Nup35 Hspe1 Usp14 Dhx15 Eif1ad Cebpz Eif2s2 Gtf2f2 Pfdn4 Trmt1 Abcf1 Trmt5 Pold2 Eef1d U2af1 Wdr5 Coa7 Eif1a Eif3c Fpgs Gars Nars Clpp Yars Eif3l Parl Set Nvl 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 81.63 82.21 82.61 82.70 82.90 83.39 83.40 83.62 83.85 83.96 84.06 84.11 84.91 84.94 84.99 85.43 85.47 85.82 86.33 86.54 86.97 87.00 87.21 87.36 88.14 88.30 88.31 88.32 88.41 88.53 88.92 89.88 90.35 90.39 90.51 90.77 90.85 91.03 91.16 91.49 92.16 92.46 92.53 92.87 93.16 93.39 93.62 93.66 93.71 94.21 1.0 Notes 2410016O06Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page8 Mphosph6 BC003965 Hsp90aa1 Timm17a Tomm20 Rabggtb Sigmar1 Champ1 Trmt10c Ndufaf6 Nudcd2 Ccdc58 Mrps30 Snrpd3 Dctpp1 Rnf126 Rbm34 Cmss1 Psmd1 Zfp593 Adrm1 Myo19 Polr1c Wdr73 Rpp30 Rpap3 Ddx49 Naa50 Snrpb Prps1 Amd1 Trub1 Uchl5 Taf1d Snrpf Tyw3 Brix1 Rps9 Aven Eif5b Uba2 Exo1 Ppil1 Leo1 Orc1 Dbr1 Abt1 Taf9 Aqr 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 66.00 66.35 66.48 66.69 66.71 66.86 66.91 67.10 67.69 68.10 68.18 68.24 68.31 68.41 68.60 68.78 69.29 70.02 70.26 70.27 70.65 70.87 70.91 70.92 71.02 71.27 71.50 72.42 72.84 73.64 73.76 74.00 74.36 74.56 75.36 75.49 76.49 77.04 77.31 77.55 77.78 78.50 79.39 79.76 79.98 80.03 80.12 81.06 81.17 81.24 1.0 Notes 1110004E09Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page9 Xrcc6bp1 Suv39h2 Tmem11 Mmachc Magohb Pak1ip1 Fam98a Cops7a Kbtbd8 Ubqln4 Trim28 Hnrnpf Psme3 Mrpl16 Magoh Cwc22 Gtf2h2 Armc6 Pitrm1 Nubp1 Lrrc47 Polr2c Cand1 Nup62 Ppp5c Cdca7 Pbdc1 Znhit3 Mettl2 Mcm2 Hirip3 Ssrp1 Nol12 Larp4 Smu1 Tfdp1 Tars2 Mrpl3 Lsm2 Bzw1 Bzw2 Gps1 Odc1 Hus1 Iws1 Cct4 Alg3 Ppie Ung 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 52.18 52.20 52.24 52.51 52.72 52.85 52.87 53.55 53.59 53.66 53.81 54.17 54.45 54.72 55.03 56.23 56.24 56.32 56.67 57.27 57.29 57.93 58.87 59.87 59.95 60.43 60.92 61.15 61.37 61.38 61.57 61.58 61.63 61.94 62.00 62.14 62.21 62.24 62.45 62.59 62.70 62.74 63.12 63.71 63.85 63.94 63.99 64.92 65.44 65.59 1.0 Notes Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page10 D2Wsu81e Hsp90ab1 Tmem209 Fam185a Ube2cbp Psmd14 Fam60a Anp32b Exosc5 Exosc9 Zc3hc1 Prkrip1 Zc3h15 H2-Ke2 Isg20l2 Alkbh1 Rbmx2 Nap1l1 Psmd3 Psmd6 Grpel1 Gtf2e1 Knop1 Nubp2 Hsph1 Ddx54 Naa10 Eif4a1 Mrps7 Thoc3 Vprbp Gtf2f1 Tex30 Mcm5 Pfdn2 Setd6 Larp7 Rpl12 Sf3b4 Emc6 Crls1 Trnt1 Coa6 Eif3a Peo1 Mtx1 Vars Ydjc Ipo4 Gfer 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 38.55 38.91 39.42 39.61 39.71 40.18 40.29 40.47 41.12 41.91 41.96 42.25 43.14 43.47 43.58 43.60 43.77 43.83 43.97 45.15 45.23 45.84 46.04 46.36 46.38 46.67 46.74 46.99 47.04 47.05 47.12 47.49 47.58 47.94 48.46 48.75 48.87 49.05 49.10 49.26 50.13 50.41 51.35 51.41 51.43 51.45 51.56 51.74 51.95 52.13 1.0 Notes 2310057M21Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page11 Prpf40a Hspbp1 L2hgdh Cdc25a Exosc4 Tsen54 Metap1 Cnot11 Kansl2 Lmnb2 Psmc1 Psmc2 Mrpl11 Mrpl20 Zfp566 Slc7a5 Dhodh Dnph1 Lrrc59 Rqcd1 Cactin Ubap2 Cox10 Dhx37 Mrps2 Jagn1 Ctdp1 Banf1 Xrcc5 Rpl14 Mogs Cnbp Dph6 Cdk8 Tufm Eif4e Rcc2 Hells Tipin Mecr Ints2 Drg1 Hdgf Utp3 Api5 Hn1l Lig3 Ppif Etf1 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 29.10 29.20 29.51 29.70 29.76 30.48 31.48 31.53 31.56 31.75 31.89 32.00 32.17 32.40 32.61 32.61 32.63 32.70 32.75 32.85 33.02 33.05 33.57 33.77 33.81 33.87 33.88 33.98 34.18 34.39 35.02 35.03 35.19 35.20 35.40 35.60 35.90 35.95 36.01 36.07 36.49 36.53 36.82 37.50 37.52 37.72 37.86 38.05 38.34 38.43 1.0 Notes 2610318N02Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page12 Thumpd3 Anapc15 Ppp2r1b Timm13 Sac3d1 Spryd4 Ppp1r7 Gnb2l1 Nomo1 Txnrd1 Rbm14 Klhdc4 Pmpca Recql4 Mthfd2 Mrpl50 Mrpl22 Mrpl46 Mcph1 Prpf4b Carm1 Polr2b Ythdf2 Wdr12 Ube2k Eif2b4 Rps10 Cdc34 Slmo2 Usp36 Senp3 Thoc6 Alyref Mat2a Utp23 Pycr2 Trap1 Bola2 Pcid2 Mrpl2 Luc7l Ipo11 Mbd3 Gpn2 Sart3 Ecsit Mtap Coil Ak2 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 16.68 16.81 16.86 17.15 17.22 17.48 17.49 18.02 18.37 18.38 18.41 18.44 19.53 19.74 19.89 19.99 20.16 20.21 20.49 20.79 20.82 21.46 21.52 21.71 21.72 21.93 22.33 23.36 23.41 23.67 23.86 23.94 24.14 24.21 24.60 24.71 25.16 25.33 26.04 26.15 26.17 26.34 26.76 27.13 27.21 27.73 28.08 28.19 28.46 28.88 1.0 Notes 2410127L17Rik Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page13 Slc25a33 Samm50 Fastkd1 Timm44 Fam72a Ndufaf2 Prpf38a Prps1l3 Yae1d1 Mrps28 Mcmbp Psmd2 Smyd2 Psmb5 Psma4 Mrpl38 Mrpl40 Polr3d G3bp2 Pitpnb Phgdh Srsf10 Aimp1 Cpsf3l Shmt1 Kpna2 Cdc73 Pdcd2 Akap1 Zc3h8 Snrpc Cfdp1 Adat2 Nupl2 Uspl1 Telo2 Txlna Pycrl Adss Tefm Mtbp Fen1 Orc6 Prep Rtcb Eed Nln Ilf2 Mif 0.0 1.0

GSE16874 [12] GSE6837 [8]

GSE4288 [36] Scale ofaveragePearsoncorrelations GSE7759 [112] GSE37676 [6] GSE7050 [18] GSE6674 [15] GSE7460 [52] GSE15871 [18] 0.2 GSE29241 [6] GSE42135 [42] GSE34863 [8] GSE39458 [6] GSE14406 [54] GSE27159 [8] GSE56345 [9] GSE16679 [8] GSE13611 [8] 0.4 GSE15121 [6] GSE58262 [18] GSE22841 [12] GSE34961 [9] GSE48932 [12] GSE5332 [12] GSE34279 [30] GSE38001 [12] GSE20604 [6] 0.6 GSE9760 [12] GSE31570 [6] GSE7404 [144] GSE31028 [6] GSE22989 [10] GSE30868 [8] GSE23495 [6] GSE48397 [10] GSE30176 [12] 0.8 GSE46600 [44] GSE29929 [14] GSE46854 [20] GSE43419 [20] Score 6.59 6.75 7.71 7.73 7.74 7.77 7.84 8.04 8.07 8.18 8.26 8.30 8.89 8.91 9.63 9.89 10.05 10.14 10.17 10.25 10.43 10.93 10.97 11.02 11.36 11.50 11.57 11.95 12.48 12.50 12.56 12.84 13.06 13.18 13.37 13.42 13.65 13.98 14.06 14.13 14.34 14.88 14.95 14.98 15.13 15.39 15.50 16.14 16.45 16.55 1.0 Notes E130012A19Rik C230052I12Rik Gadd45gip1 Symbol Num ofCEMGenes:5.Predicted683.SelectedDatasets:242.Strength:1.8 CEM 1,Geneset"[G]small-subunitprocessome",Page14 BC055324 Aasdhppt Ccdc137 Ccdc101 Hnrnpm Slc35a4 Slc29a2 Ranbp3 Aarsd1 Dnaaf2 Cbwd1 Slc7a6 Polr1d Med17 Polr2d Nsun5 Nop10 Kpna3 Naa16 Mybl2 Cpsf1 Xrcc6 Nme6 U2af2 Eme1 Prpf8 Btaf1 Cdc6 Ybx1 Fasn Dars Rfc5 Myc Ssb Tti2 0.0 1.0

GSE16874 [12] GSE6837 [8]

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

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

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

0.423 Kernel fit Pairwise Correlations Normal fit

Density 0.212

0.000 CEM 1

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

Pre-normalization Quantiles

BCells_WildType_day0_REP1BCells_WildType_day0_REP2BCells_WildType_day0_REP3BCells_Transgenic_day0_REP1 BCells_Transgenic_day0_REP2(0.0839984) BCells_Transgenic_day0_REP3(0.0619103) BCells_WildType_day2_REP1(0.06979)BCells_WildType_day2_REP2 (0.0921581)BCells_WildType_day2_REP3 (0.0693972)BCells_Transgenic_day2_REP1 (0.133935) BCells_Transgenic_day2_REP2(0.0992474) BCells_Transgenic_day2_REP3(0.075071) (0.15833) (0.0539631) (0.0413182)[ (0.0608806)min ] [ medium ] [ max ] CEM 1 Utp20 741.0 1878.5 2829.6 P ( S | Z, I ) = 1.00 Nop14 673.4 1632.8 2071.4 Mean Corr = 0.97265 Wdr36 840.6 1455.3 1803.2 Tbl3 449.7 1284.6 1526.9 Utp14a 54.4 124.2 160.5 Nop2 715.7 2309.1 3183.5 Rrp12 333.8 985.9 1240.2 Heatr1 1392.4 2693.7 3812.1 Mybbp1a 664.2 2587.0 3318.6 Grwd1 557.7 2440.8 3435.7 CEM 1 + Ftsj3 391.5 1469.4 1693.0 Top 10 Genes Nat10 593.6 1621.5 1880.7 Ddx18 1181.1 3380.8 4200.6 Cirh1a 997.9 4630.9 5504.4 Pwp2 524.0 1086.4 1424.6

Null module Rps7 Utp14b Utp11l 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,(0.0674762) rep1 fibroblasts biological embryonicrep1WT,(0.0799557) fibroblasts biological(0.127571) rep2KO, fibroblasts biological (0.0206835) rep3KO,[ biological (0.0184851) min rep1KO, biological(0.348003) rep2] (0.0980361) rep3 (0.239789)[ medium ] [ max ] CEM 1 Utp20 500.8 2491.9 2831.5 P ( S | Z, I ) = 1.00 Nop14 336.8 1248.6 1798.2 Mean Corr = 0.96205 Wdr36 445.2 1665.5 1867.6 Tbl3 383.2 1559.0 2229.4 Utp14a 79.4 227.6 261.3 Nop2 419.7 3713.6 3967.7 Rrp12 136.3 1298.2 1327.3 Heatr1 776.1 2192.8 2506.0 Mybbp1a 500.1 5987.3 7573.2 Grwd1 374.8 2912.5 3392.2 CEM 1 + Ftsj3 269.5 2658.9 3528.5 Top 10 Genes Nat10 355.0 1024.8 1338.9 Ddx18 508.4 3064.4 3210.6 Cirh1a 683.3 4211.9 4740.7 Pwp2 325.0 983.9 1238.8

Null module Rps7 Utp14b Utp11l GEO Series "GSE44175" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44175 Status: Public on Feb 09 2013 Title: Expression data from mouse embyonic stem cell, neural progenitor and neuron Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23775126 Summary & Design: Summary: The effect of HMGN1 protein on gene expression of mouse ESC, NP and Neurons were investigated by comparing the transcriptome between Hmgn1+/+ and Hmgn1 -/- cells.

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

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

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

EmbyonicEmbyonic stemEmbyonic cell, stem Hmgn1+/+,Neural cell, stem Hmgn1+/+, progenitor,Neural cell, biological Hmgn1+/+, progenitor,Neural biological Hmgn1+/+, rep1 progenitor,Neuron, biological (0.0750005) Hmgn1+/+, rep2Neuron, biological Hmgn1+/+, (0.0630577) Hmgn1+/+, rep3Neuron, biological Hmgn1+/+, (0.0669086)rep1 biologicalEmbyonic biological(0.0246399)Hmgn1+/+, rep2 biologicalEmbyonic rep1(0.0141145) stem rep3 biological(0.0553953)Embyonic rep2cell,(0.0184564) stem (0.0855151)Hmgn1-/-,Neural rep3cell, stem (0.0679317)Hmgn1-/-, progenitor,Neural cell, biological Hmgn1-/-, progenitor,Neural biological Hmgn1-/-,rep1 progenitor,Neuron, biological(0.111889) Hmgn1-/-,rep2 biologicalNeuron, Hmgn1-/-, (0.0751291) Hmgn1-/-,rep3 biologicalNeuron, Hmgn1-/-, (0.0559269)rep1 biological biological(0.0253909) Hmgn1-/-, rep2 biological rep1(0.0296825) rep3 biological(0.0730467) rep2(0.0333318) (0.0580414) rep3[ min (0.0665423) ] [ medium ] [ max ] CEM 1 Utp20 297.8 1914.0 3998.9 P ( S | Z, I ) = 1.00 Nop14 451.5 1049.3 2017.4 Mean Corr = 0.96137 Wdr36 201.3 598.3 1990.8 Tbl3 163.2 529.5 1109.6 Utp14a 51.6 129.5 212.6 Nop2 195.3 869.3 2079.5 Rrp12 113.0 441.9 957.6 Heatr1 207.7 910.3 3179.8 Mybbp1a 110.1 797.6 2027.9 Grwd1 350.0 1770.7 2620.7 CEM 1 + Ftsj3 178.9 928.6 2046.1 Top 10 Genes Nat10 173.6 485.0 1627.3 Ddx18 661.6 2458.1 5481.7 Cirh1a 487.7 2068.2 6050.1 Pwp2 279.8 748.1 1641.6

Null module Rps7 Utp14b Utp11l 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 (0.12397)Wild-type_stimulated_sample 2 (0.0743637)PKD2-null_unstimulated_sample 3 (0.0985004) PKD2-null_unstimulated_sample1 (0.111598) PKD2-null_unstimulated_sample2 (0.0589169) PKD2-null_stimulated_sample3 (0.0801042)PKD2-null_stimulated_sample 1 (0.0701613)PKD2-null_stimulated_sample 2 (0.056172) 3 (0.0727353) 1 (0.121773) 2 (0.0503456)[ 3 (0.0813595)min ] [ medium ] [ max ] CEM 1 Utp20 799.7 3073.6 4173.3 P ( S | Z, I ) = 1.00 Nop14 931.5 2130.1 2554.7 Mean Corr = 0.95979 Wdr36 769.9 1837.0 2282.5 Tbl3 300.9 1206.6 1432.5 Utp14a 44.6 130.7 192.5 Nop2 510.9 2972.8 3533.2 Rrp12 288.4 1922.4 2376.3 Heatr1 1360.2 4760.0 5850.9 Mybbp1a 488.0 2262.6 2905.1 Grwd1 531.4 3673.2 5049.3 CEM 1 + Ftsj3 341.6 1504.8 1832.1 Top 10 Genes Nat10 280.8 1550.5 2052.4 Ddx18 1850.8 5411.1 6412.0 Cirh1a 1210.1 4137.7 5019.6 Pwp2 432.6 1959.9 2577.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE20954" 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=GSE20954 Status: Public on Aug 17 2010 Title: mRNA expression profile in mouse lung development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20520778 Summary & Design: Summary: We performed miRNA and mRNA profiling over a 7-point time course, encompassing all recognized stages of lung development and explore dynamically regulated miRNAs and potential miRNA-mRNA interaction networks specific to mouse lung development

Overall design: replicated time course of mouse lung development in 7 time points

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0372, L2-Distance = 0.0026, Normal std = 0.7245

0.551 Kernel fit Pairwise Correlations Normal fit

Density 0.275

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse lung-embryoMouse lung-embryoMouse day lung-embryoMouse 12-rep1 day lung-embryoMouse 12-rep2 (0.226373) day lung-embryoMouse 14-rep1 (0.150837) day lung-embryoMouse 14-rep2 (0.0767275) day lung-embryoMouse 16-rep1 (0.059441) day lung-embryoMouse 16-rep2 (0.0242288) day lung-postnatalMouse 18-rep1 (0.0167467) day lung-postnatalMouse 18-rep2 (0.0643654) lung-postnatalMouseday (0.0537562) 2-rep1 lung-postnatalMouseday (0.0197967)2-rep2 lung-postnatalMouseday (0.0186617)10-rep1 lung-postnatalday 10-rep2 (0.044707) day 30-rep1 (0.0652037) day 30-rep2 (0.0887385)[ min (0.090417) ] [ medium ] [ max ] CEM 1 Utp20 361.4 603.6 1321.4 P ( S | Z, I ) = 1.00 Nop14 254.6 320.6 653.1 Mean Corr = 0.95240 Wdr36 597.9 695.0 1198.4 Tbl3 271.4 342.7 1115.6 Utp14a 116.0 160.5 275.6 Nop2 432.8 524.7 1706.7 Rrp12 74.8 137.7 452.7 Heatr1 595.2 791.1 1885.5 Mybbp1a 360.9 428.6 1906.5 Grwd1 301.4 394.1 1613.8 CEM 1 + Ftsj3 178.5 255.8 834.6 Top 10 Genes Nat10 369.9 418.8 1069.5 Ddx18 835.1 1094.4 2984.6 Cirh1a 948.8 1249.8 3003.1 Pwp2 311.7 365.8 618.0

Null module Rps7 Utp14b Utp11l 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 (0.194703)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.19656)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.152169)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.15269) (0.145912)[ min(0.110731) (0.014419)] (0.00843323)[ (0.0243828) medium ] [ max ] CEM 1 Utp20 14.7 919.6 1962.4 P ( S | Z, I ) = 1.00 Nop14 21.4 398.3 833.9 Mean Corr = 0.94991 Wdr36 26.9 734.1 1044.4 Tbl3 87.7 686.0 1157.7 Utp14a 44.8 67.5 93.7 Nop2 129.4 754.3 1528.2 Rrp12 6.4 399.9 685.4 Heatr1 132.9 3444.5 5752.5 Mybbp1a 13.2 647.4 1512.2 Grwd1 528.0 748.8 1568.3 CEM 1 + Ftsj3 8.0 793.7 1972.7 Top 10 Genes Nat10 119.5 863.8 1781.5 Ddx18 68.3 1544.0 2204.4 Cirh1a 284.2 6101.1 6690.8 Pwp2 88.1 427.6 1209.9

Null module Rps7 Utp14b Utp11l GEO Series "GSE38031" 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=GSE38031 Status: Public on Jul 25 2013 Title: DNA damage-induced differentiation of NSC Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24052948 Summary & Design: Summary: Murine ES-derived neural stem cells (NSC) were not irradiated (ctrl) or irradiated with 10Gy and cultured for 7 days (irr).

The goal was to study the gene expression changes in NSC at d7 after irradiation.

Overall design: Total RNA was extracted from 4 ctrl and 4 irr samples (biological quadruplicates).

Background corr dist: KL-Divergence = 0.0114, L1-Distance = 0.0339, L2-Distance = 0.0011, Normal std = 0.9128

0.456 Kernel fit Pairwise Correlations Normal fit

Density 0.228

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_rep1ctrl_rep2 (0.149214)ctrl_rep3 (0.0890822)ctrl_rep4 (0.127975)irr_rep1 (0.106797)irr_rep2 (0.148988)irr_rep3 (0.143196)irr_rep4 (0.113321) (0.121427) [ min ] [ medium ] [ max ] CEM 1 Utp20 837.6 1164.6 1256.2 P ( S | Z, I ) = 1.00 Nop14 647.7 820.6 889.9 Mean Corr = 0.94891 Wdr36 443.7 772.6 824.6 Tbl3 459.6 880.5 974.0 Utp14a 70.7 95.8 111.0 Nop2 788.6 1307.6 1520.6 Rrp12 182.2 406.0 454.4 Heatr1 777.2 1655.9 1759.2 Mybbp1a 552.6 1196.7 1252.1 Grwd1 725.7 1971.8 2039.7 CEM 1 + Ftsj3 482.1 928.8 972.1 Top 10 Genes Nat10 342.6 549.5 607.8 Ddx18 1192.1 2408.1 2630.7 Cirh1a 1547.9 2251.5 2543.8 Pwp2 403.4 710.8 778.8

Null module Rps7 Utp14b Utp11l GEO Series "GSE27092" 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=GSE27092 Status: Public on Mar 13 2011 Title: Expression data from P14 TCR cytotoxic T cells overexpressing HDAC7 phosphorylation deficient mutant Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21399638 Summary & Design: Summary: The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile.

Overall design: In vitro generated P14 TCR cytotoxic T cells were retrovirally infected with a construct encoding GFP-HDAC7 phosphorylation deficient mutant, sorted in base of GFP expression (GFP positive and GFP negative) and processed for microarray analysis in three biological replicas.

Background corr dist: KL-Divergence = 0.0166, L1-Distance = 0.0217, L2-Distance = 0.0007, Normal std = 0.7816

0.510 Kernel fit Pairwise Correlations Normal fit

Density 0.255

0.000 CEM 1

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

Pre-normalization Quantiles

GFP negativeGFP negative 1GFP (biological negative 2GFP (biological replicapositive 3GFP (biological 1)replicapositive 1 (0.165049) GFP(biological 2)replicapositive 2 (0.120452) (biological replica3) 3 (0.137065) (biological 1)replica (0.16364) 2)replica (0.16164)[ min 3) (0.252153) ] [ medium ] [ max ] CEM 1 Utp20 819.6 1619.8 1726.9 P ( S | Z, I ) = 1.00 Nop14 742.9 1348.7 1493.0 Mean Corr = 0.94798 Wdr36 1102.4 1959.4 1976.5 Tbl3 470.7 643.7 788.0 Utp14a 42.2 59.9 63.9 Nop2 1286.8 2082.6 2508.9 Rrp12 572.6 1001.4 1043.9 Heatr1 1403.7 2991.8 3155.6 Mybbp1a 798.4 1798.4 1962.6 Grwd1 977.5 2108.1 2362.2 CEM 1 + Ftsj3 322.4 628.9 712.4 Top 10 Genes Nat10 637.6 1146.7 1227.7 Ddx18 2549.9 4323.8 4958.5 Cirh1a 1922.2 2902.4 3248.4 Pwp2 570.9 937.6 1051.0

Null module Rps7 Utp14b Utp11l GEO Series "GSE20987" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.748 Kernel fit Pairwise Correlations Normal fit

Density 0.374

0.000 CEM 1

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

Pre-normalization Quantiles

Bcl6 +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed +/+Bcl6 BCR-ABL1-transformed B +/+cellBcl6 BCR-ABL1-transformed precursors B +/+cellBcl6 BCR-ABL1-transformed precursors B -/-cell - untreatedBcl6BCR-ABL1-transformed precursors B -/-cell - untreatedBcl6BCR-ABL1-transformed precursors 1B (0.115211) -/-cell - untreatedBcl6BCR-ABL1-transformed precursors 2B (0.0864756) -/-cell - STI571Bcl6BCR-ABL1-transformed precursors B3 cell(0.114257) -/- - treatedSTI571Bcl6BCR-ABL1-transformed precursors B cell -/- - treatedSTI5711BCR-ABL1-transformed precursors (0.0729653)B cell - untreated treated2 precursors (0.0746003)B cell - untreated 3 precursors 1(0.0725968)B (0.075811) cell - untreated[ precursors 2B min(0.0510015) cell - STI571 precursors 3 (0.0306543) ]- treatedSTI571 - treatedSTI5711 (0.0680982)[ mediumtreated2 (0.091616) 3 (0.146713) ] [ max ] CEM 1 Utp20 283.6 1319.6 1661.1 P ( S | Z, I ) = 1.00 Nop14 305.8 991.0 1197.0 Mean Corr = 0.94007 Wdr36 466.2 1244.2 1410.7 Tbl3 424.5 1281.0 1541.3 Utp14a 94.5 109.6 142.0 Nop2 390.6 1642.3 1951.3 Rrp12 64.9 470.0 680.2 Heatr1 427.8 1676.5 2916.7 Mybbp1a 405.4 3116.8 3882.4 Grwd1 398.5 1878.0 2119.0 CEM 1 + Ftsj3 260.2 1109.9 1234.0 Top 10 Genes Nat10 182.8 896.8 1192.1 Ddx18 762.0 2657.9 2978.8 Cirh1a 720.8 3254.0 3642.0 Pwp2 202.9 622.2 738.7

Null module Rps7 Utp14b Utp11l GEO Series "GSE30160" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.522 Kernel fit Pairwise Correlations Normal fit

Density 0.261

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild replicate typewild replicate 1 type (0.376477)knockin replicate 2 (0.123274)knockin replicate 3 (0.12924)knock replicate 1 (0.167184) in replicate 2 (0.0774745) 3 (0.12635) [ min ] [ medium ] [ max ] CEM 1 Utp20 564.5 1098.7 1611.1 P ( S | Z, I ) = 1.00 Nop14 487.8 787.3 1205.4 Mean Corr = 0.93768 Wdr36 528.4 781.9 928.2 Tbl3 300.6 546.5 663.3 Utp14a 56.9 73.7 113.7 Nop2 590.5 1308.4 1651.2 Rrp12 174.7 446.8 730.5 Heatr1 977.0 1184.1 1590.5 Mybbp1a 540.5 1359.9 1620.6 Grwd1 650.0 1544.3 2265.1 CEM 1 + Ftsj3 376.8 729.2 965.5 Top 10 Genes Nat10 335.5 562.4 812.7 Ddx18 879.8 1390.0 1806.5 Cirh1a 783.2 1460.7 1989.7 Pwp2 355.9 564.2 803.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE15155" 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=GSE15155 Status: Public on Jan 04 2010 Title: Gene profiling of quiescent and activated skeletal muscle satellite cells by an in vivo approach Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19962952 Summary & Design: Summary: The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses by comparing satellite cells from adult skeletal muscles, where they are mainly quiescent, with cells from growing muscles, regenerating (mdx) muscles, or with cells in culture, where they are activated. Our study gives new insights into the satellite cell biology during activation and in respect with its niche.

We used microarrays to study the global programme of gene expression underlying adult satellite cell quiescence compared to activation states and to identify distinct classes of up-regulated genes in these two different states

Overall design: Skeletal muscle satellite cells were isolated by flow cytrometry using the GFP fluorescence marker from Pax3GFP/+ mice skeletal muscle. The transcriptome of quiescent satellite cells from adult Pax3GFP/+ muscle was compared to the transcriptome of activated satellite cells obtained from three different samples: 1) regenerating Pax3GFP/+:mdx/mdx muscle (Ad.mdx) , 2) growing 1 week old Pax3GFP/+ muscle (1wk), and 3) adult Pax3GFP/+ cells after 3 days in culture (Ad.cult).

Background corr dist: KL-Divergence = 0.0419, L1-Distance = 0.0196, L2-Distance = 0.0005, Normal std = 0.5936

0.672 Kernel fit Pairwise Correlations Normal fit

Density 0.336

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

quiescentquiescent satellitequiescent satellite cell_adultactivated satellite cell_adult muscle_rep1activated satellite cell_adult muscle_rep2activated satellite cell_adult (0.0751088) muscle_rep3activated satellite cell_adult (0.0856819) regeneratingactivated satellite cell_adult (0.0629036) regeneratingactivated satellite cell_1wk mdx regeneratingactivated muscle_rep1satellite cell_1wk mdxoldactivated growing muscle_rep2satellite cell_1wk mdxoldactivated (0.0171435) growing muscle_rep3 satellite muscle_rep1cell_cultured old (0.0154255) growing satellite muscle_rep2cell_cultured (0.0252573) (0.024731) 3days_rep1 muscle_rep3cell_cultured (0.0637953) 3days_rep2 (0.161052)[ (0.0242737) 3days_rep3min (0.268252) ] (0.176375) [ medium ] [ max ] CEM 1 Utp20 670.4 1452.7 3731.8 P ( S | Z, I ) = 1.00 Nop14 505.2 666.1 1373.4 Mean Corr = 0.92891 Wdr36 435.0 533.0 1546.2 Tbl3 297.1 622.6 1349.9 Utp14a 67.8 105.3 224.5 Nop2 491.1 991.3 3218.0 Rrp12 201.7 311.9 828.5 Heatr1 840.8 1187.8 2637.5 Mybbp1a 329.1 629.3 2036.4 Grwd1 1215.0 1588.2 4340.9 CEM 1 + Ftsj3 369.2 607.4 1819.9 Top 10 Genes Nat10 351.5 635.1 1140.5 Ddx18 717.4 1154.0 3474.2 Cirh1a 1459.3 2181.2 7447.2 Pwp2 727.9 909.1 2277.5

Null module Rps7 Utp14b Utp11l GEO Series "GSE12498" 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=GSE12498 Status: Public on Nov 21 2008 Title: Gene expression profiles regulated by Tead2 mutants, Yap, and cell density in NIH3T3 cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19004856 Summary & Design: Summary: Regulation of organ size is important for development and tissue homeostasis. In Drosophila, Hippo signaling controls organ size by regulating the activity of a TEAD transcription factor, Scalloped, through modulation of its coactivator protein Yki. The role of mammalian Tead proteins in growth regulation, however, remains unknown. Here we examined the role of mouse Tead proteins in growth regulation. In NIH3T3 cells, cell density and Hippo signaling regulated the activity of Tead proteins by modulating nuclear localization of a Yki homologue, Yap, and the resulting change in Tead activity altered cell proliferation. Tead2-VP16 mimicked Yap overexpression, including increased cell proliferation, reduced cell death, promotion of EMT, lack of cell contact inhibition, and promotion of tumor formation. Growth promoting activities of various Yap mutants correlated with their Tead-coactivator activities. Tead2-VP16 and Yap regulated largely overlapping sets of genes. However, only a few of the Tead/Yapregulated genes in NIH3T3 cells were affected in Tead1-/-;Tead2-/- or Yap-/- embryos. Most of the previously identified Yap-regulated genes were not affected in NIH3T3 cells or mutant mice. In embryos, levels of nuclear Yap and Tead1 varied depending on cell types. Strong nuclear accumulation of Yap and Tead1 were seen in myocardium, correlating with requirements of Tead1 for proliferation. However, their distribution did not always correlate with proliferation. Taken together, mammalian Tead proteins regulate cell proliferation and contact inhibition as a transcriptional mediator of Hippo signaling, but the mechanisms by which Tead/Yap regulate cell proliferation differ depending on cell types, and Tead, Yap and Hippo signaling may play multiple roles in mouse embryos.

We used microarrays to know the gene expression profiles regurated by Tead2-VP16, Tead2-EnR, Yap, and cell density in NIH3T3 cells.

Keywords: Cell density, genetic modification

Overall design: Tead2-VP16-, Tead2-EnR-, Yap- and control vector-expressing cells were cultured at low or high density for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0711, L1-Distance = 0.0551, L2-Distance = 0.0045, Normal std = 0.5445

0.805 Kernel fit Pairwise Correlations Normal fit

Density 0.402

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-low-1ctrl-low-2 (0.266982)tead2VP16-conf-1 (0.308499)tead2VP16-conf-2yap-conf-1 (0.0254049)yap-conf-2 (0.0281056)(0.01966)tead2EnR-low-1 (0.0118512)tead2EnR-low-2ctrl-over-1 (0.0140755)ctrl-over-2 (0.0121027) (0.0618629)tead2VP16-over-1 (0.0635957)tead2VP16-over-2 (0.106004) (0.0818559) [ min ] [ medium ] [ max ] CEM 1 Utp20 628.8 926.7 1842.2 P ( S | Z, I ) = 1.00 Nop14 569.4 737.0 1262.3 Mean Corr = 0.92509 Wdr36 907.4 1229.2 2249.2 Tbl3 802.2 1130.5 1859.5 Utp14a 147.0 182.0 223.7 Nop2 896.6 1188.2 2832.9 Rrp12 275.5 543.6 1345.5 Heatr1 613.4 914.7 1486.9 Mybbp1a 1718.4 2810.8 6383.9 Grwd1 737.4 1212.0 2913.2 CEM 1 + Ftsj3 763.1 1124.1 2294.8 Top 10 Genes Nat10 560.0 713.5 1159.6 Ddx18 1776.6 2236.1 3795.4 Cirh1a 2099.8 2339.9 4470.0 Pwp2 356.4 500.4 863.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE38335" 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=GSE38335 Status: Public on May 31 2012 Title: JAK2 Naive and Persitent Murine BaF3 cells infected with MPLW515L Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22820254 Summary & Design: Summary: Transcriptional profiling of Murine BaF3 cells infected with MPLW515L grown under either normal conditions (Naive) or in 0.8 uM INCB18424 for 4-6 weeks (Persistent). Naive and Persistent cells were then treated with either DMSO (Control) or 0.8 uM INCB18424 for 4 hours. Goal was to determine transcriptional changes conditioned upon sensitivity/resistance of BaF3 MPLW515L mutants to JAK1/2 specific inhibitor.

Overall design: 3 condition experiment consiting of: 1) Naive cells treated with DMSO (Control) , 2) NaÃ¯ve cells treated with 0.8 uM INCB18424 for 4 hours (Acute) and 3) Persistent cells treated with 0.8 uM INCB18424 for 4 hours (Persistent). Biological replicates: 3 DMSO control replicates, 3 Acute replicates, 3 Persistent replicates.

Background corr dist: KL-Divergence = 0.0258, L1-Distance = 0.0561, L2-Distance = 0.0057, Normal std = 0.7359

0.542 Kernel fit Pairwise Correlations Normal fit

Density 0.271

0.000 CEM 1

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

Pre-normalization Quantiles

DMSO ControlDMSO Control DMSO1 (0.148161) Control INCB184242 (0.186062) INCB184243 (0.141643) AcuteINCB18424 1 Acute (0.0394805)INCB18424 2 Acute (0.0644006)INCB18424 3 Persistent (0.0174953)INCB18424 Persistent 1 (0.101306) Persistent 2 (0.139784) 3 (0.161668)[ min ] [ medium ] [ max ] CEM 1 Utp20 832.0 1742.0 2395.2 P ( S | Z, I ) = 1.00 Nop14 684.6 748.4 1266.5 Mean Corr = 0.92215 Wdr36 329.6 492.2 821.3 Tbl3 91.3 161.6 260.6 Utp14a 40.8 94.7 234.5 Nop2 704.4 1031.0 2719.3 Rrp12 384.0 751.9 1557.6 Heatr1 775.8 1276.9 2430.9 Mybbp1a 763.4 1211.8 3064.6 Grwd1 352.6 811.4 2001.2 CEM 1 + Ftsj3 1740.8 2646.1 4260.8 Top 10 Genes Nat10 306.1 345.3 583.2 Ddx18 2796.2 3659.8 5825.2 Cirh1a 2669.8 3442.0 6765.7 Pwp2 215.7 457.0 1002.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE51483" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 45 -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=GSE51483 Status: Public on May 19 2014 Title: Transcriptional Atlas of Cardiogenesis Maps Congenital Heart Disease Interactome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24803680 Summary & Design: Summary: Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, the transcriptional landscape of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide expression profile of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, prioritized stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling the bioinformatics of the congenital heart disease interactome, we deconstructed disease-centric regulatory networks encoded within this cardiogenic atlas to reveal stage-specific developmental disturbances clustered on epithelial-to-mesenchymal transition (EMT), BMP regulation, NF-AT signaling, TGFb-dependent induction, and Notch signaling. Therefore, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease.

Overall design: To interrogate the temporal and spatial expression profiles across the entire genome during mammalian heart development, we designed a time-course microarray experiment using the mouse model at defined stages of cardiogenesis, starting with embryonic stem cells (ESC, R1 stem cell line), early embryonic developmental stages: E7.5 whole embryos, E8.5 heart tubes, left and right ventricle tissues at E9.5, E12.5, E14.5, E18.5 to 3 days after birth (D3) and adult heart (Figure 1A). At each time point, microarray experiments were performed on triplicate biological samples. Starting at E9.5, tissue samples from left ventricles (LV) and right ventricles (RV) were microdissected for RNA purification and microarray analysis to determine spatially differential gene expression between LV and RV during heart development.

Background corr dist: KL-Divergence = 0.0679, L1-Distance = 0.0271, L2-Distance = 0.0013, Normal std = 0.5057

0.789 Kernel fit Pairwise Correlations Normal fit

Density 0.394

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse R1Mouse Stem R1Mouse Cells Stem R1.1R1Mouse Cells Stem (0.131065) R1.2E7.5Mouse Cells (0.105897)whole R1.3E7.5Mouse embryo (0.13285)whole E7.5Mouse embryo tissuewhole E8.5Mouse E7.1embryo tissuewhole E8.5Mouse (0.0546606) E7.2heart tissuewhole E8.5Mouse (0.0656802) tissue E7.3heart whole E9.5Mouse (0.0787997)(heart tissue heart left E9.5Mousetube) ventricle(heart tissue left E8.1 E9.5Mousetube) ventricle(heart tissue (0.00472982) left E8.2 E9.5Mousetube) ventricle E9L.1 tissue (0.0110397) right E8.3 E9.5Mouse (0.0047475) E9L.2ventricletissue (0.00585524) right E9.5Mouse (0.00262732) E9L.3ventricle tissueright E12.5Mouse (0.00978905) ventricle E9R.1 tissue left E12.5Mouse ventricle(0.0123764) E9R.2 tissue left E12.5Mouse ventricle(0.00236553) E9R.3tissue left E12.5Mouse ventricle(0.0049268) E12L.1 tissue right E12.5Mouse (0.00391605)E12L.2ventricletissue right E12.5Mouse (0.00634095)E12L.3ventricle tissueright E14.5Mouse (0.00752342)ventricle E12R.1 tissueleft E14.5Mouse ventricle E12R.2(0.0059618) tissueleft E14.5Mouse ventricle tissue E12R.3(0.00479053) left E14.5Mouse ventricle E14L.1 tissue (0.00710407) right E14.5Mouse (0.00937064)E14L.2ventricletissue right E14.5Mouse (0.00647807)E14L.3ventricle tissueright E18.5Mouse (0.0108551)ventricle E14R.1 tissueleft E18.5Mouse ventricle E14R.2(0.0154292) tissueleft E18.5Mouse ventricle tissue E14R.3(0.0149588) left E18.5Mouse ventricle E18L.1 tissue (0.00773073) right E18.5Mouse (0.0131873)E18L.2ventricletissue right E18.5Mouse (0.0137658)E18L.3ventricle tissueright leftMouse (0.00614284)ventricle E18R.1 tissue leftMouse ventricle E18R.2 (0.0066585)tissue leftMouse ventricle atE18R.3 (0.00730699)tissue 3rightMouse days at (0.00600246)ventricletissue after3rightMouse days birth atventricle aftertissue3rightAdult days D3L.1 birth ventricle mouseat aftertissueAdult 3(0.0107238) D3L.2 days birth leftmouseat tissueAdult after3(0.00859946) ventricleD3L.3 days leftbirthmouseatAdult after3(0.00960363) ventricle days D3R.1tissue leftbirthmouseAdult after ventricle (0.0132988) AdltL.1D3R.2tissue rightbirthmouseAdult (0.00897455) AdltL.2(0.0303148)ventricleD3R.3tissue rightmouse (0.0100836) AdltL.3(0.0309506)ventricle tissueright (0.0274792)ventricle AdltR.1 tissue AdltR.2(0.0259932)tissue[ min AdltR.3(0.027704) ] (0.0153418) [ medium ] [ max ] CEM 1 Utp20 444.8 950.3 4858.6 P ( S | Z, I ) = 1.00 Nop14 364.2 509.9 1900.2 Mean Corr = 0.91810 Wdr36 337.3 420.7 1547.5 Tbl3 182.3 263.4 805.0 Utp14a 38.5 80.4 281.3 Nop2 378.5 772.2 2514.3 Rrp12 160.9 308.7 1273.8 Heatr1 231.2 546.0 4043.4 Mybbp1a 263.1 465.2 2823.6 Grwd1 455.6 811.8 2817.4 CEM 1 + Ftsj3 131.1 248.2 1497.1 Top 10 Genes Nat10 202.3 291.3 1295.2 Ddx18 661.7 1240.8 4987.0 Cirh1a 740.1 1012.1 4785.1 Pwp2 267.9 439.5 1492.9

Null module Rps7 Utp14b Utp11l 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) (0.0715574) EB (B21)WT (0.0396675) ESC (0.0804758)WT (B21) EB (0.0851459)(J1)WT ESC(0.0740969)WT (J1) EB (0.0670557) (R1)WT ESC (0.0913948)TKO (R1) EB (0.0509399)TKO (7-4-1) ESC TKO(0.0704793) (7-4-1) EBTKO (Dutch) (0.050314) ESCTKO (0.0205507) (Dutch) EBTKO (Ta1-12) (0.0743168) ESC (0.0895578)(Ta1-12) (0.134447) [ min ] [ medium ] [ max ] CEM 1 Utp20 643.8 2029.3 3393.2 P ( S | Z, I ) = 1.00 Nop14 676.8 1450.3 1983.5 Mean Corr = 0.91597 Wdr36 438.7 1302.1 2286.4 Tbl3 325.1 789.7 1709.0 Utp14a 42.8 102.0 252.1 Nop2 785.5 1684.2 3380.4 Rrp12 100.4 312.2 1089.4 Heatr1 698.9 2266.4 6051.7 Mybbp1a 1003.7 3173.2 5427.2 Grwd1 434.9 1165.9 2247.3 CEM 1 + Ftsj3 750.9 2386.9 4010.2 Top 10 Genes Nat10 260.4 614.6 1756.8 Ddx18 1236.8 2886.2 6490.0 Cirh1a 1830.9 4981.1 8027.0 Pwp2 246.0 577.3 1179.3

Null module Rps7 Utp14b Utp11l 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(0.0364414) rep1 4KO-loD3(0.0221336) rep1 4KO-zeroD0(0.0359077) rep1 4KO-zeroD1(0.0262801) rep14KO-zeroD3 (0.0255069) rep14KO-hiD1 (0.0261005) rep14KO-hiD3 rep2(0.0209923) 4KO-loD1(0.0276067) rep2 4KO-loD3(0.0249344) rep2 4KO-zeroD0(0.0130043) rep2 4KO-zeroD1(0.0166153) rep24KO-zeroD3 (0.0423304) rep24KO-hiD1 (0.0184801) rep24KO-hiD3 rep3(0.0288213) 4KO-loD1(0.0303452) rep3 4KO-loD3(0.0137675) rep3 4KO-zeroD0(0.0330428) rep3 4KO-zeroD1(0.00616344) rep34KO-zeroD3 (0.0420592) rep3WT-D0 (0.0340256) rep3 rep1WT-D1 (0.0155493) (0.0484126) rep1WT-D3 (0.090543) rep1WT-D0 (0.0100781) rep2WT-D1 (0.0446145) rep2WT-D3 (0.0894003) rep2WT-D0 (0.0129001) rep3WT-D1 (0.0743982) rep3WT-D3 (0.0707894) rep3 (0.0187557) [ min ] [ medium ] [ max ] CEM 1 Utp20 682.3 1158.7 2672.5 P ( S | Z, I ) = 1.00 Nop14 1250.8 1428.2 1997.2 Mean Corr = 0.91080 Wdr36 530.9 784.9 1416.1 Tbl3 230.5 366.7 977.6 Utp14a 113.2 148.0 252.6 Nop2 789.2 1627.9 3037.7 Rrp12 371.8 585.2 1561.9 Heatr1 1638.9 2464.9 3885.8 Mybbp1a 763.1 1208.0 2856.0 Grwd1 523.6 937.1 2437.7 CEM 1 + Ftsj3 847.9 1796.0 3582.4 Top 10 Genes Nat10 592.9 792.0 1591.4 Ddx18 1432.4 2017.9 3855.5 Cirh1a 1226.2 1930.8 4083.5 Pwp2 366.8 502.1 1229.0

Null module Rps7 Utp14b Utp11l GEO Series "GSE27114" 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=GSE27114 Status: Public on Sep 04 2012 Title: Expression data from REST knock-out versus REST wild type cells during in vitro neurogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22964890 Summary & Design: Summary: While changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. We developed a computational model on the premise that transcription factors (TFs) direct dynamic chromatin changes during cell fate decisions. When applied to a neurogenesis paradigm, this approach predicted the TF REST as a determinant of gain of Polycomb-mediated H3K27me3 in neuronal progenitor cells. We prove this prediction experimentally by showing that the absence of REST causes loss of H3K27me3 at target promoters in trans at the same cellular state. Moreover, promoter fragments containing a REST binding site are sufficient to recruit H3K27me3 in cis, while deletion of their REST site results in loss of H3K27me3. These findings illustrate that computational modeling can systematically identify TFs that regulate chromatin dynamics genome-wide. Local determination of Polycomb activity by REST exemplifies such TF based regulation of chromatin.

Overall design: Expression profiling of REST knock-out (RESTko) versus REST wildtype (RESTwt) or REST heterozygous knock-out (RESThet) cells at three stages of in vitro neuronal differentiation. RESTko and RESTwt/RESThet embryonic stem (ES) cells were differentiated to terminal neurons (TN) via a defined neuronal progenitor (NP) state. Three biological replicates (suffixes a to c).

Background corr dist: KL-Divergence = 0.0155, L1-Distance = 0.0419, L2-Distance = 0.0020, Normal std = 0.8997

0.478 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

2_ESwt_a2_ESwt_b (0.264107)2_NPwt_a (0.208867)2_NPwt_b (0.0739075)2_TNwt_a (0.0597577)2_TNwt_b (0.24602) (0.147341) [ min ] [ medium ] [ max ] CEM 1 Utp20 584.1 1306.4 2798.9 P ( S | Z, I ) = 1.00 Nop14 695.4 1410.7 2531.4 Mean Corr = 0.90831 Wdr36 499.4 1536.8 2838.0 Tbl3 427.9 1438.9 2559.6 Utp14a 69.4 86.9 106.2 Nop2 773.2 1340.8 3103.4 Rrp12 299.3 409.1 1170.1 Heatr1 585.3 1747.3 4639.9 Mybbp1a 548.4 2305.1 4186.5 Grwd1 579.1 1200.6 2255.4 CEM 1 + Ftsj3 243.8 727.4 2097.9 Top 10 Genes Nat10 398.3 716.5 2689.7 Ddx18 525.4 2504.2 3889.0 Cirh1a 889.5 3092.7 4741.6 Pwp2 304.9 448.6 813.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE12499" 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=GSE12499 Status: Public on Feb 01 2009 Title: Oct4-Induced Pluripotency in Adult Neural Stem Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19203577 Summary & Design: Summary: The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.

Overall design: - NSC_4

Background corr dist: KL-Divergence = 0.0125, L1-Distance = 0.0370, L2-Distance = 0.0023, Normal std = 0.8572

0.465 Kernel fit Pairwise Correlations Normal fit

Density 0.233

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

NSCs-derivedNSCs-derived iPSNSCs-derived cells iPSOne-factor by cells one-factor iPSOne-factor by cells (Oct4)one-factor One-factor(Oct4) by iPS (Oct4)one-factor cell-derivedsample_1 Neural(Oct4) iPS (Oct4) cell-derivedsample_2stem Neural(Oct4) (0.0313994) iPS NSCs cell cell-derivedsample_3stemNeural sample_1(0.0259082) sample_1 NSCs cell stemNeural sample_2(0.0555788) sample_2 NSCs(0.0869875) cell (0.234988) stem sample_3 sample_3 (0.0499885) cell (0.173147) sample_4 (0.101808) (0.199945) (0.0402492)[ min ] [ medium ] [ max ] CEM 1 Utp20 1521.4 1694.9 3478.9 P ( S | Z, I ) = 1.00 Nop14 853.3 996.0 2772.0 Mean Corr = 0.90774 Wdr36 846.3 933.8 2125.9 Tbl3 687.1 1193.2 1716.5 Utp14a 63.3 79.8 209.4 Nop2 839.7 1500.3 3300.2 Rrp12 363.2 472.5 1706.9 Heatr1 1218.2 1397.9 3730.0 Mybbp1a 1283.0 2462.0 4605.9 Grwd1 1195.5 1906.7 3645.5 CEM 1 + Ftsj3 759.2 872.3 2257.1 Top 10 Genes Nat10 408.7 614.5 1250.9 Ddx18 2146.2 2442.6 7143.0 Cirh1a 2133.6 3363.9 11577.2 Pwp2 606.1 879.0 1437.5

Null module Rps7 Utp14b Utp11l 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(0.241378) rep. CTL, 2 transduced(0.161378) rep. biological CTL, 3 (0.0905794) biological CTL, rep. 1biological (0.191081)[ rep. min 2 (0.0691554) rep. ] 3 (0.246428)[ medium ] [ max ] CEM 1 Utp20 1073.8 1684.8 2431.0 P ( S | Z, I ) = 1.00 Nop14 930.4 1179.4 1486.5 Mean Corr = 0.90309 Wdr36 1123.3 1433.7 1559.4 Tbl3 509.7 711.0 879.9 Utp14a 105.1 140.8 172.6 Nop2 1367.8 1752.2 2467.1 Rrp12 614.5 802.1 1019.0 Heatr1 2069.4 2829.9 3467.0 Mybbp1a 1352.1 1801.2 2438.2 Grwd1 1362.2 1867.9 2444.2 CEM 1 + Ftsj3 514.0 675.5 861.0 Top 10 Genes Nat10 789.9 1018.5 1208.9 Ddx18 2045.4 2935.1 3376.5 Cirh1a 2759.4 3389.3 3808.4 Pwp2 686.9 797.7 1024.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE44923" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44923 Status: Public on Mar 06 2013 Title: An Epigenetic Component of Hematopoietic Stem Cell Aging Amenable to Reprogramming Into a Young State Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23476050 Summary & Design: Summary: Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden.

Overall design: Hematopoietic stem cells (HSC) have been sorted out from young and aged steady-state mice, and from recipients transplanted with young and aged bone marrow. Generated iPS and commercially available ES cells were also sorted and analyzed.

Background corr dist: KL-Divergence = 0.0286, L1-Distance = 0.0494, L2-Distance = 0.0038, Normal std = 0.7036

0.567 Kernel fit Pairwise Correlations Normal fit

Density 0.284

0.000 CEM 1

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

Pre-normalization Quantiles

Young transplantedYoung transplantedAged HSC,transplantedAged biological HSC,transplantedES cells biologicalHSC, replicateES from biological cells HSC, OpenreplicateAged 1from biological(0.0537401) Biosystems replicatesteady-state PrimogenixAged 2 (0.0594557) replicatesteady-state 1Aged (0.103313) (0.0805833) (0.0761924)male steady-state 2Young (0.06237)HSC, male steady-statebiologicalYoung HSC, male steady-statebiologicalYoung HSC, replicate male steady-statebiologicaliPS replicateHSC, cells 1male (0.059351)iPS biologicalof replicateHSC, cells a 2male aged(0.0502773)iPS biologicalof HSC, cells hematopoieticreplicatea3 aged(0.064362)iPS biologicalof cellshematopoieticreplicatea 1young (0.0452863) of origin,replicatea hematopoietic2young (0.0472777) biologicalorigin, hematopoietic3 (0.0472779) biological origin, replicate[ min biologicalorigin, replicate 1 (0.0569762) ]biological replicate2 (0.0703454) replicate 1[ (0.0600862) medium 2 (0.063105) ] [ max ] CEM 1 Utp20 610.6 1944.0 4838.3 P ( S | Z, I ) = 1.00 Nop14 630.1 977.5 1610.8 Mean Corr = 0.90008 Wdr36 654.1 878.5 1951.6 Tbl3 258.1 561.6 2317.1 Utp14a 73.3 156.1 265.3 Nop2 382.0 754.5 2897.7 Rrp12 109.5 395.2 1291.4 Heatr1 855.8 2232.7 4469.4 Mybbp1a 365.2 945.0 2590.5 Grwd1 268.7 919.8 3021.7 CEM 1 + Ftsj3 295.7 775.5 1706.1 Top 10 Genes Nat10 406.3 938.7 3017.8 Ddx18 472.3 1230.9 4122.3 Cirh1a 786.3 2243.1 6745.9 Pwp2 213.5 1431.9 1906.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE46150" 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=GSE46150 Status: Public on Oct 01 2013 Title: Gene expression profiling of primary mouse embryonic palatal mesenchymal cells in Tgfbr2 mutant mouse models Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23975680 Summary & Design: Summary: The overall goal of this project is to investigate the role of TGF-beta signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.

Overall design: To investigate the adverse effects of dysfunctional TGF-Beta signaling on the cellular metabolism of palatal mesenchyme during palatogenesis, we analyzed mice with a neural crest cell-specific conditional inactivation of Tgfbr2 (Tgfbr2fl/fl;Wnt1-Cre). We performed microarray analyses of primary mouse embryonic palatal mesenchymal cells of Tgfbr2fl/fl;Wnt1-Cre mutant mice and Tgfbr2fl/fl control mice, collected at embryonic day 13.5 (n=4 per genotype) and cultured with standard media (DMEM with supplements). Cells were collected after 2 passages.

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0160, L2-Distance = 0.0003, Normal std = 0.5769

0.692 Kernel fit Pairwise Correlations Normal fit

Density 0.346

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

Wnt1-Cre;Tgfbr2Wnt1-Cre;Tgfbr2Wnt1-Cre;Tgfbr2 ConditionalWnt1-Cre;Tgfbr2 Conditional KnockoutTgfbr2 Conditional KnockoutWildtypeTgfbr2 ConditionalMouse KnockoutWildtypeTgfbr2 Mouse ModelMouse KnockoutWildtypeTgfbr2 ModelMEPMMouse ModelMouse Wildtype MEPM 1ModelMEPMMouse ModelMouse(0.0922888) 1MEPM 2 ModelMEPMMouse (0.095901) Model(0.0773104) 2MEPM 3 ModelMEPM(0.0523857) (0.17181) 3[MEPM4 (0.075845) (0.0858133)min 4 (0.348646) ] [ medium ] [ max ] CEM 1 Utp20 430.4 596.1 845.9 P ( S | Z, I ) = 1.00 Nop14 317.2 377.9 513.8 Mean Corr = 0.89311 Wdr36 469.4 623.1 937.1 Tbl3 152.5 242.0 361.4 Utp14a 97.3 127.5 187.6 Nop2 411.0 502.5 914.6 Rrp12 139.9 191.7 351.1 Heatr1 576.6 625.3 779.0 Mybbp1a 202.7 328.1 636.0 Grwd1 496.5 599.2 1108.8 CEM 1 + Ftsj3 206.3 293.1 428.5 Top 10 Genes Nat10 346.9 360.6 418.5 Ddx18 902.1 1105.7 1565.1 Cirh1a 545.8 796.5 1317.4 Pwp2 369.2 418.1 547.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE4535" 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=GSE4535 Status: Public on Oct 04 2006 Title: primary FDC Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17015706 Summary & Design: Summary: expression profiles of FDC and BMDC are compared

Keywords: cell type comparison

Overall design: expression profiles of FDC and BMDC are compared

Background corr dist: KL-Divergence = 0.0390, L1-Distance = 0.0480, L2-Distance = 0.0034, Normal std = 0.6676

0.620 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

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

Pre-normalization Quantiles

Bone marrowBone marrow derivedFollicular derived dendriticFollicular dendritic dendriticSV40 cell dendritic cell transformed(0.187983)Activated 1 cell (0.112942) cell 2 (0.093369) 2 SV40(0.0390648) FDC-like transformed cell line FL-YFDC-like[ min (0.140028) cell ]line FL-Y (0.426613)[ medium ] [ max ] CEM 1 Utp20 482.6 773.6 2469.5 P ( S | Z, I ) = 1.00 Nop14 446.1 1429.0 2778.0 Mean Corr = 0.88941 Wdr36 549.6 1337.9 2680.5 Tbl3 554.9 1119.2 2422.9 Utp14a 9.7 68.1 179.4 Nop2 740.9 1925.7 4742.2 Rrp12 194.4 340.8 1371.0 Heatr1 538.8 1276.6 2422.6 Mybbp1a 1109.0 1865.7 4144.8 Grwd1 382.5 494.6 2391.1 CEM 1 + Ftsj3 449.9 827.0 1975.4 Top 10 Genes Nat10 374.8 575.6 1137.2 Ddx18 607.9 1129.1 3620.0 Cirh1a 819.0 1986.8 5393.5 Pwp2 235.5 278.4 665.3

Null module Rps7 Utp14b Utp11l GEO Series "GSE53951" 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=GSE53951 Status: Public on Jan 10 2014 Title: Gene expression after type-I interferon treatment in primary neurons, primary fibroblasts and L929 cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24453359 Summary & Design: Summary: Microarray expression profilling of mouse primary mixed cortical/hippocampal neurons, primary fibroblasts and L929 cells to compare ISGs signature in disctinct cell types

Overall design: Primary mixed cortical/hippocampal neurons, primary fibroblasts (MEFs) and L929 cells were mock-treated or treated with 5U/mL of IFN-beta and RNA was harvested after 24 hours. For neurons and fibroblast, 2 samples were analyzed for each condition.

Background corr dist: KL-Divergence = 0.0405, L1-Distance = 0.0863, L2-Distance = 0.0101, Normal std = 0.7845

0.611 Kernel fit Pairwise Correlations Normal fit

Density 0.305

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

neurons_mock_sample1neurons_IFNb_sample1neurons_mock_sample2neurons_IFNb_sample2 (0.149174)MEFs_mock_sample1 (0.102816)MEFs_IFNb_sample1 (0.0971035)MEFs_mock_sample2 (0.0954933) MEFs_IFNb_sample2(0.0553061) (0.156459)L929_mock L929_IFNb(0.0601608) (0.0462474) (0.145095) (0.0921447) [ min ] [ medium ] [ max ] CEM 1 Utp20 390.1 1771.5 2053.5 P ( S | Z, I ) = 1.00 Nop14 508.6 946.3 1165.8 Mean Corr = 0.88814 Wdr36 247.0 595.5 945.7 Tbl3 394.7 561.8 827.1 Utp14a 66.3 117.1 224.6 Nop2 593.5 1182.0 1665.3 Rrp12 298.2 418.2 579.4 Heatr1 452.4 1232.4 1471.0 Mybbp1a 355.6 1621.4 1907.2 Grwd1 505.1 1023.8 1335.3 CEM 1 + Ftsj3 310.8 1170.4 1475.2 Top 10 Genes Nat10 371.6 603.1 721.5 Ddx18 719.0 2016.7 2593.4 Cirh1a 884.2 2365.0 2890.8 Pwp2 316.3 497.5 638.3

Null module Rps7 Utp14b Utp11l GEO Series "GSE10273" 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=GSE10273 Status: Public on Jan 26 2008 Title: Convergent molecular pathways that induce immunoglobulin light-chain recombination Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18280186 Summary & Design: Summary: Productive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa (Îº) or lambda (Î») light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the ˛” 3† and ˛» enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the Îº intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells.

We used microarrys to identify the changes in gene expression under different levels of the cytokine IL-7 and after rescue of genetic defect.

Keywords: growth conditions and rescue

Overall design: IRF4,8 null pre-B cells were cultures in the indicated conditions prior to RNA isolation and hybridization to Affymetrix arrays.

Background corr dist: KL-Divergence = 0.0485, L1-Distance = 0.0228, L2-Distance = 0.0005, Normal std = 0.5808

0.703 Kernel fit Pairwise Correlations Normal fit

Density 0.351

0.000 CEM 1

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

Pre-normalization Quantiles

IRF4,8 null_IL7hi_rep1IRF4,8 null_IL7lo_rep1IRF4,8 null_+IRF4_rep1IRF4,8 (0.165052) null_IL7hi_rep2IRF4,8 (0.178296) null_IL7lo_rep2IRF4,8 (0.0106472) null_+IRF4_rep2IRF4,8 (0.0770946) null_IL7hi_rep3IRF4,8 (0.143968) null_IL7lo_rep3IRF4,8 (0.0351103) null_+IRF4_rep3 (0.0876503) (0.178161) (0.124021)[ min ] [ medium ] [ max ] CEM 1 Utp20 682.5 1769.9 2131.8 P ( S | Z, I ) = 1.00 Nop14 1507.9 2068.9 2295.2 Mean Corr = 0.88621 Wdr36 591.2 1330.1 1788.9 Tbl3 385.6 793.3 1145.4 Utp14a 121.4 187.4 222.4 Nop2 1167.2 2563.9 3038.8 Rrp12 157.3 537.2 731.4 Heatr1 1605.4 3346.7 4156.4 Mybbp1a 523.2 1939.6 3312.9 Grwd1 784.0 1271.7 1668.0 CEM 1 + Ftsj3 483.1 1287.2 1739.4 Top 10 Genes Nat10 320.8 1015.3 1318.0 Ddx18 1323.2 3258.9 3759.6 Cirh1a 1113.1 2896.5 3375.5 Pwp2 470.3 846.3 1031.3

Null module Rps7 Utp14b Utp11l GEO Series "GSE17886" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17886 Status: Public on Mar 22 2010 Title: Gene expression data of BBB and BCB two-cell embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20107036 Summary & Design: Summary: We constructed one-cell stage embryos by maternal pronuclear (mPN) transfer having B6 ooplasm, B6 paternal PN (pPN), and either B6 or C3H mPN (BBB and BCB, respectively). We collected embryos of each type that were either treated (BBB+a, BCB+a) or untreated with Î±-amanitin (BBB, BCB) at the two-cell stage for microarray analysis.

Comparison of the transcriptomes of these different kinds of embryos revealed genes for which expression differs according to maternal PN strain of origin, and the Î±-amanitin data revealed which of these differences is due to gene transcription, as opposed to any transcription-independent differences attributable to ooplasm-derived maternal mRNA pools.

Overall design: There are 4 replicates for each kind/treatment two-cell embryos (BBB, BCB, BBB+a, BCB+a).

Background corr dist: KL-Divergence = 0.0287, L1-Distance = 0.0723, L2-Distance = 0.0067, Normal std = 0.7860

0.588 Kernel fit Pairwise Correlations Normal fit

Density 0.294

0.000 CEM 1

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

Pre-normalization Quantiles

BBB two-cellBBB two-cell embryos,BBB two-cell embryos,BBB Sample1 two-cell embryos,BCB Sample2 (0.108575) two-cell embryos,BCB Sample3 (0.0640438) two-cell embryos,BCB Sample4 (0.030001) two-cell embryos,BCB Sample1 (0.0368135) two-cell embryos,Î±-amantin-treated Sample2 (0.0541354) embryos,Î±-amantin-treated Sample3 (0.0883516)Î±-amantin-treated Sample4 (0.0727676) BBBÎ±-amantin-treated two-cell (0.0569512) BBBÎ±-amantin-treated two-cell embryos, BBBÎ±-amantin-treated two-cell embryos, BBB Sample1Î±-amantin-treated two-cell embryos, BCB Sample2 (0.0456426)Î±-amantin-treated two-cell embryos, BCB Sample3 (0.0966195) two-cell embryos, BCB Sample4 (0.0577191) two-cell embryos, BCB Sample1 (0.0563962) two-cell embryos, Sample2 (0.0513563)[ embryos,min Sample3 (0.0644078) ] Sample4 (0.0610078) (0.0552118)[ medium ] [ max ] CEM 1 Utp20 1046.1 1866.5 2536.2 P ( S | Z, I ) = 1.00 Nop14 109.7 528.1 1110.9 Mean Corr = 0.88012 Wdr36 274.6 1325.0 1699.2 Tbl3 34.6 583.1 1168.6 Utp14a 54.5 546.7 738.9 Nop2 93.8 2128.4 2692.9 Rrp12 4.0 827.8 1263.9 Heatr1 408.3 1388.7 2170.9 Mybbp1a 5.0 532.4 775.2 Grwd1 100.2 1979.7 3315.0 CEM 1 + Ftsj3 25.2 288.4 570.4 Top 10 Genes Nat10 158.4 1129.1 1530.7 Ddx18 326.9 3004.8 3726.5 Cirh1a 422.1 3000.3 3581.1 Pwp2 105.6 852.6 1195.9

Null module Rps7 Utp14b Utp11l GEO Series "GSE6957" 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=GSE6957 Status: Public on Jul 19 2007 Title: Transcriptional profiling of bipotential embryonic liver cells to identify liver progenitor cell surface markers (430) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17641245 Summary & Design: Summary: The ability to purify to homogeneity a population of hepatic progenitor cells from adult liver is critical for their characterization prior to any therapeutic application. As a step in this direction, we have utilized gene profiling of a bipotential liver cell line from dpc 14 mouse embryonic liver to catalog genes expressed by liver progenitor cells. These cells, known as Bipotential Mouse Embryonic Liver (BMEL) cells, proliferate in an undifferentiated state and are capable of differentiating into hepatocyte-like and cholangiocyte-like cells in vitro. Upon transplantation, BMEL cells are capable of differentiating into hepatocytes and cholangiocytes in vivo. Microarray analysis of gene expression in the 9A1 and 14B3 BMEL cell lines grown under proliferating and differentiating conditions was used to identify cell surface markers preferentially expressed in the bipotential undifferentiated state. This analysis revealed that proliferating BMEL cells express many genes involved in cell cycle regulation whereas differentiation of BMEL cells by cell aggregation causes a switch in gene expression to functions characteristic of mature hepatocytes. In addition, microarray data and protein analysis indicated that the Notch signaling pathway could be involved in maintaining BMEL cells in an undifferentiated stem cell state. Using GO annotation, a list of cell surface markers preferentially expressed on undifferentiated BMEL cells was generated. One marker, Cd24a, is specifically expressed on progenitor oval cells in livers of DDC treated animals. We therefore consider Cd24a expression a candidate molecule for purification of hepatic progenitor cells.

Keywords: cell type comparison

Overall design: RNA was extracted from two independently isolated BMEL cell lines (9A1 and 14B3) after culture under three conditions (basal, aggregate 1 day, and aggregate 5 days). Duplicate biological replicates were collected for each cell line:culture condition combination for a total of 12 samples. Samples were biotin-labeled, hybridized to mouse 430 2.0 chips, and scanned according to established Affymetrix protocols.

Background corr dist: KL-Divergence = 0.0532, L1-Distance = 0.0670, L2-Distance = 0.0087, Normal std = 0.5905

0.722 Kernel fit Pairwise Correlations Normal fit

Density 0.361

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

basal culture,basal culture, 9A1,basal rep culture, 9A1,basal 1 (430) rep culture, 14B3, D1(0.0496414)2 (430) aggregate rep 14B3, D1(0.0978755) 1 aggregate(430) rep culture,D1 (0.189752)2 aggregate(430) culture, 9A1,D1 (0.146919) aggregate rep culture, 9A1,D5 1 (430)aggregate rep culture, 14B3,D5 (0.0248724)2 (430)aggregate repculture, 14B3,D5 (0.0718887) 1 aggregate (430) repculture, 9A1,D5 (0.0201223)2 aggregate (430) rep culture, 9A1, 1 (0.0919007) (430) rep culture, 14B3, (0.0824873)2 (430) rep 14B3, (0.0803661) 1 (430) rep[ (0.0819169)2min (430) (0.0622573) ] [ medium ] [ max ] CEM 1 Utp20 250.7 603.6 1535.7 P ( S | Z, I ) = 1.00 Nop14 590.0 881.1 1924.5 Mean Corr = 0.87506 Wdr36 765.8 1162.0 1848.6 Tbl3 349.8 470.4 1074.1 Utp14a 51.8 65.2 97.8 Nop2 511.0 838.8 2422.2 Rrp12 138.1 171.5 648.3 Heatr1 221.1 546.2 1554.3 Mybbp1a 293.2 1174.5 3842.5 Grwd1 292.7 670.7 1759.5 CEM 1 + Ftsj3 157.6 500.1 1590.3 Top 10 Genes Nat10 320.1 572.7 1090.3 Ddx18 988.8 1273.4 3270.0 Cirh1a 942.7 1914.1 3987.9 Pwp2 290.7 464.1 982.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE34126" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 19 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34126 Status: Public on Dec 05 2011 Title: An Animal Model of Myc-driven medulloblastoma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22340590 Summary & Design: Summary: Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB, and identify a novel model that can be used to test therapies for this devastating disease.

To gain insight into the pathways that control growth of MYC-driven MB, we compared gene expression profiles of murine Myc/DNp53 (MP) tumor cells to those of freshly isolated cerebellar stem cells (Prom1+Lin- cells) and of tumors from Ptch1 mutant mice (a model for Sonic Hedgehog-associated MB). RNA was isolated from stem cells and tumor cells using the RNAqueous kit (Ambion). RNA was labeled and hybridized to Affymetrix Mouse Genome 430 2.0 arrays.

Overall design: 19 mouse cell samples (stem cells and tumor cells) were analyzed. There are four groups of samples, three with five biological replicates and the last with four (one outlier was removed). To gain insight into the mechanisms of transformation into tumors, we compared the gene expression profiles of MP tumor cells derived from stem cells (Myc/DNp53-infected Prom1+Lin- cells, designated MP-pl) or progenitors (Myc/DNp53-infected Prom1+ cells, designated MP-p) to gene expression profiles of uninfected stem cells (designated NSC) and profiles from a distinct model of medulloblastoma, the patched mutant mouse (designated ptch1).

Background corr dist: KL-Divergence = 0.1063, L1-Distance = 0.0311, L2-Distance = 0.0018, Normal std = 0.4292

0.929 Kernel fit Pairwise Correlations Normal fit

Density 0.465

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 normalstem cells normalstem rep1 cells normalstem (0.0477985) rep2 cells normalstem (0.0566163) rep3 cells stem (0.0535911) rep4 cell-derivedcellsstem (0.0299144) rep5 cell-derivedstem (0.0445569) tumors cell-derivedstem tumorsrep1 cell-derivedstem (0.038227) tumorsrep2 cell-derivedpatched (0.0671313) tumorsrep3patched (0.094744)tumors tumorsrep4patched (0.0441678) tumorsrep1 rep5 (0.0413182)patched (0.0237556) tumorsrep2 (0.0415376)progenitor-derived tumorsrep3 (0.0401554)progenitor-derived rep4 (0.145037)progenitor-derived tumorsprogenitor-derived tumorsrep1progenitor-derived (0.031734) tumorsrep2 (0.0116002) tumorsrep3 (0.0100075) tumorsrep4 (0.057386) rep5[ (0.120721)min ] [ medium ] [ max ] CEM 1 Utp20 477.4 1530.0 2797.1 P ( S | Z, I ) = 1.00 Nop14 465.8 1412.7 2247.6 Mean Corr = 0.87474 Wdr36 387.1 956.0 1397.5 Tbl3 781.3 1163.0 1665.5 Utp14a 73.5 149.6 312.2 Nop2 605.5 2088.2 3967.4 Rrp12 208.2 425.4 1202.1 Heatr1 648.7 2807.7 3963.5 Mybbp1a 847.7 2200.4 4345.2 Grwd1 667.3 1676.8 2586.3 CEM 1 + Ftsj3 335.7 1496.6 1976.8 Top 10 Genes Nat10 375.9 1183.5 1703.7 Ddx18 1329.0 2886.8 3836.7 Cirh1a 1313.7 5393.3 7078.8 Pwp2 530.2 1058.5 1666.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE30745" 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=GSE30745 Status: Public on Aug 05 2011 Title: Expression data from murine acute myeloid leukemia (AML) cells following shRNA-mediated suppression of Myb Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21828272 Summary & Design: Summary: Using an integrative approach combining a Tet-off conditional AML mouse model, global expression profiling following suppression of the driving MLL-AF9 oncogene, and a new Tet-on conditional shRNA expression system we have identified Myb as critical mediator of addiction to MLL-AF9. Suppression of Myb in established AML in vivo terminates aberrant self-renewal and triggers a terminal myeloid differentiation program that precisely phenocopies the effects of suppressing MLL-AF9. Remarkably, suppressing Myb effectively eradicates aggressive and chemotherapy resistant AML.

To further investigate Myb dependent transcriptional programs involved in mediating aberrant self-renewal in leukemia, we globally surveyed gene expression changes following acute shRNA-induced suppression of Myb in an established Tet-on competent model of MLL-AF9;NrasG12D-induced AML.

Overall design: To enable regulatable suppression of Myb in AML, we retrovirally transduced established Tet-on competent MLL-AF9;NrasG12D induced AML cells with TRMPV-Neo vectors (Zuber et al., Nature Biotech, 2010) harboring shRNAs targeting Myb (shMyb.2572 and shMyb.2652), a control shRNA targeting Renilla Luciferase (shRen.713), or an empty miR30 cassette of the recipient cloning vector (Rec). Following drug selection, shRNA expression was induced by doxycycline treatment and total RNA was isolated from sorted shRNA expressing (Venus+/dsRed+) leukemia cells after 3 days of dox treatment, and subjected to Affymetrix microarray expression analysis. Expression profiles following expression of two independent Myb shRNAs were compared to those observed after induction in shRen.713- and Rec-expressing control samples (each in 3 biological replicates).

Background corr dist: KL-Divergence = 0.0709, L1-Distance = 0.0225, L2-Distance = 0.0008, Normal std = 0.5020

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

shMyb.2572shMyb.2572 biolshMyb.2572 repl biol 1,shMyb.2652 3 repl d dox,biol 2,shMyb.2652 3 replsorted d dox,biol 3,shMyb.2652 3 repl(0.0894601)sorted d dox,biol 1,Rec 3 repl(0.0307239)sorted d vectordox,biol 2,Rec 3 repl(0.125577)sorted d biol vectordox, 3,Rec repl3 (0.138454)sorted d biol vector dox,1, shRen.7133 repl d(0.0353955)sorted dox,biol 2, shRen.7133 replsorted d(0.0993548) bioldox, 3, shRen.7133repl (0.0387261)sorted d bioldox, 1, 3 repl (0.0718009) sortedd dox,biol 2, 3 repl(0.121951)sorted d dox, 3, 3 (0.041244)sorted d dox, [ (0.0883707)sorted min (0.118942) ] [ medium ] [ max ] CEM 1 Utp20 161.7 646.2 1016.5 P ( S | Z, I ) = 1.00 Nop14 290.5 624.1 862.6 Mean Corr = 0.87154 Wdr36 433.7 926.4 1307.6 Tbl3 283.1 665.7 1219.1 Utp14a 83.2 119.6 142.2 Nop2 484.7 863.2 1886.1 Rrp12 214.2 544.9 1026.8 Heatr1 864.1 1954.0 2915.1 Mybbp1a 304.5 1313.2 1987.2 Grwd1 421.7 884.5 1470.9 CEM 1 + Ftsj3 210.0 540.9 821.5 Top 10 Genes Nat10 246.5 708.1 1766.8 Ddx18 795.3 1549.9 2422.1 Cirh1a 794.1 1670.3 2038.5 Pwp2 298.6 639.9 897.8

Null module Rps7 Utp14b Utp11l GEO Series "GSE39886" 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=GSE39886 Status: Public on Aug 04 2012 Title: Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22912406 Summary & Design: Summary: Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to BRD4 and other proteins of the BET (bromodomain and extra-terminal domain) family, was previously shown to suppress the production of pro-inflammatory proteins by macrophages and block acute inflammation in mice. Here we investigate the effect of I-BET-762 on T cell function. We show that treatment of naÃ¯ve CD4+ T cells with I-BET-762 during early differentiation modulates subsequent cytokine production, and inhibits the ability of Th1-skewed cells to induce autoimmune pathogenesis in a model of experimental autoimmune encephalomyelitis (EAE) in vivo. The suppressive effects of I-BET-762 on T-cell mediated inflammation were not due to inhibition of expression of the pro-inflammatory cytokines, IFN-. or IL-17, but correlated with the ability to suppress GM-CSF production from CNS-infiltrating T cells, resulting in decreased recruitment of macrophages and granulocytes. The effects of I-BET-762 were distinct from those of the fumarate ester, dimethyl fumarate (DMF), a candidate drug for treatment of multiple sclerosis (MS). Our data suggest that I-BET and DMF could have complementary roles in the treatment of MS, and provide a strong rationale for inhibitors of BET-family proteins in the treatment of autoimmune diseases, based on their dual ability to suppress granulocyte and macrophage recruitment by T cells as well as production of pro-inflammatory proteins by macrophages.

Overall design: RNA from resting or activated CD4+ T cells grown in the presence of a control substance (DMSO or Control-768) or two different concentrations of I-BET-762, was hybridized to the chip. There are 3 biological replicates for a total of 2 (cell states) x 4 (conditions) x 3 (replicates) = 24 samples.

Background corr dist: KL-Divergence = 0.1425, L1-Distance = 0.0653, L2-Distance = 0.0080, Normal std = 0.4122

1.069 Kernel fit Pairwise Correlations Normal fit

Density 0.535

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

CD4Tcells_resting_DMSO_rep1CD4Tcells_resting_68A_rep1CD4Tcells_resting_62A_0.5_rep1CD4Tcells_resting_62A_0.25_rep1CD4Tcells_activated_DMSO_rep1 (0.0265336) (0.0198031)CD4Tcells_activated_68A_rep1CD4Tcells_activated_62A_0.5_rep1 (0.0283746)CD4Tcells_activated_62A_0.25_rep1 (0.0187913)CD4Tcells_resting_DMSO_rep2 (0.0199255)CD4Tcells_resting_68A_rep2 (0.0240523)CD4Tcells_resting_62A_0.5_rep2 (0.0437037)CD4Tcells_resting_62A_0.25_rep2 (0.017732)CD4Tcells_activated_DMSO_rep2 (0.0328798) (0.0355493)CD4Tcells_activated_68A_rep2CD4Tcells_activated_62A_0.5_rep2 (0.0177442)CD4Tcells_activated_62A_0.25_rep2 (0.0201484)CD4Tcells_resting_DMSO_rep3 (0.0219372)CD4Tcells_resting_68A_rep3 (0.0292191)CD4Tcells_resting_62A_0.5_rep3 (0.0101604)CD4Tcells_resting_62A_0.25_rep3 (0.010651)CD4Tcells_activated_DMSO_rep3 (0.0477083) (0.0640664)CD4Tcells_activated_68A_rep3CD4Tcells_activated_62A_0.5_rep3 (0.124241)CD4Tcells_activated_62A_0.25_rep3 (0.0243705) (0.0448703) (0.0396379) (0.239245)[ min (0.0386546) ] [ medium ] [ max ] CEM 1 Utp20 467.1 2589.4 4046.2 P ( S | Z, I ) = 1.00 Nop14 451.4 1619.6 2407.6 Mean Corr = 0.86645 Wdr36 536.9 1264.7 1776.3 Tbl3 156.2 574.1 1186.5 Utp14a 66.8 161.9 290.5 Nop2 829.4 4324.6 5766.4 Rrp12 226.2 1167.9 2011.7 Heatr1 1044.2 3685.7 6435.2 Mybbp1a 436.1 2910.5 4440.7 Grwd1 249.1 1664.3 3015.0 CEM 1 + Ftsj3 312.3 1967.1 3181.3 Top 10 Genes Nat10 305.5 907.2 1779.9 Ddx18 968.8 2797.2 4626.3 Cirh1a 1390.5 5060.1 6980.4 Pwp2 166.2 1035.3 1977.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE26096" 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=GSE26096 Status: Public on Jan 03 2011 Title: Widespread targeted chromatin remodeling during the initial phase of somatic cell reprogramming [expression] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21211784 Summary & Design: Summary: Despite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency or developmentally related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.

Overall design: Gene expression was measured by Affymetric microarrays during the initial phase of the reprogramming of mouse embryonic fibroblasts.

Background corr dist: KL-Divergence = 0.0618, L1-Distance = 0.0293, L2-Distance = 0.0012, Normal std = 0.5376

0.765 Kernel fit Pairwise Correlations Normal fit

Density 0.383

0.000 CEM 1

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

Pre-normalization Quantiles

Serum-starvedSerum-starved 96control, hr doxycycline 96control, biological hr doxycyclineMEFdox0Div_rep1 biological induction, rep1MEFdox0Div_rep2 (0.136375) induction, rep2 biologicalMEFdox1Div_rep1 (0.136364) (0.0374748) biologicalMEFdox1Div_rep2 rep1 (0.0417797) (0.157825)MEFdox2Div_rep1 rep2 (0.0587213) (0.327615)MEFdox2Div_rep2 (0.0135545) (0.0481285) (0.042163) [ min ] [ medium ] [ max ] CEM 1 Utp20 1089.3 1837.4 3016.9 P ( S | Z, I ) = 1.00 Nop14 587.4 1071.6 2029.4 Mean Corr = 0.86518 Wdr36 694.8 1117.9 1841.8 Tbl3 323.0 504.0 1238.6 Utp14a 83.6 107.9 130.5 Nop2 453.2 1115.4 2464.5 Rrp12 167.3 291.1 630.0 Heatr1 476.0 829.0 1790.8 Mybbp1a 504.4 936.3 1916.3 Grwd1 527.1 1063.3 2063.8 CEM 1 + Ftsj3 380.4 699.4 1253.3 Top 10 Genes Nat10 336.4 519.9 1222.0 Ddx18 1527.3 2266.5 4418.8 Cirh1a 1372.3 2335.6 4988.1 Pwp2 276.2 415.4 730.1

Null module Rps7 Utp14b Utp11l GEO Series "GSE32386" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32386 Status: Public on Apr 01 2012 Title: Expression profiling of murine neuroblastoma in transgenic mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22764207 Summary & Design: Summary: Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK.

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

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

0.775 Kernel fit Pairwise Correlations Normal fit

Density 0.387

0.000 CEM 1

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

Pre-normalization Quantiles

66389_lo66977_ro (0.0380661)66977_ru (0.0661294)70660_lu (0.064195)74128_wlr (0.0560865)74128_wr (0.142644)74129_wl (0.147331)C57Bl6_1 (0.118246)C57Bl6_2 (0.0833613)C57Bl6_3 (0.129449)86823-2x (0.0577556)82743-lo (0.00846932)77204-10 (0.0577271) (0.0305406) [ min ] [ medium ] [ max ] CEM 1 Utp20 519.6 880.6 1869.7 P ( S | Z, I ) = 1.00 Nop14 474.8 798.2 1267.4 Mean Corr = 0.86327 Wdr36 430.2 618.5 1041.3 Tbl3 260.9 376.7 658.2 Utp14a 46.3 77.1 110.8 Nop2 369.6 646.2 1204.5 Rrp12 189.3 314.9 686.0 Heatr1 648.0 944.4 1734.9 Mybbp1a 222.8 491.2 1320.0 Grwd1 687.6 918.2 2021.8 CEM 1 + Ftsj3 142.3 335.2 736.9 Top 10 Genes Nat10 254.6 412.7 756.9 Ddx18 734.3 1344.9 2681.1 Cirh1a 752.7 1175.8 1885.4 Pwp2 468.7 640.5 1028.5

Null module Rps7 Utp14b Utp11l GEO Series "GSE46185" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.604 Kernel fit Pairwise Correlations Normal fit

Density 0.302

0.000 CEM 1

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

Pre-normalization Quantiles

Th2 (controlTh2 (control siRNA)Th2 (Gata3 siRNA)(0.294115)Th2-4th siRNA) a-TCRTh2-4th (control a-TCR stimTh2-4th (control siRNA)(0.108243) stim (Gata3(0.132788) siRNA)(0.298426) siRNA) a-TCR a-TCR stim (0.112153) stim[ min (0.0542756) ] [ medium ] [ max ] CEM 1 Utp20 427.0 2411.7 2633.1 P ( S | Z, I ) = 1.00 Nop14 440.7 1182.1 1326.6 Mean Corr = 0.86315 Wdr36 468.0 724.0 889.4 Tbl3 100.4 282.2 438.2 Utp14a 91.9 249.5 312.7 Nop2 289.0 1304.5 1571.3 Rrp12 109.5 928.0 1069.4 Heatr1 865.5 3051.9 3826.0 Mybbp1a 170.7 1301.4 1412.2 Grwd1 134.5 2324.5 2725.2 CEM 1 + Ftsj3 447.7 2391.2 3770.4 Top 10 Genes Nat10 496.2 1439.4 1597.9 Ddx18 1224.2 4565.6 4955.9 Cirh1a 639.2 2327.6 3065.4 Pwp2 199.8 1364.9 1763.4

Null module Rps7 Utp14b Utp11l GEO Series "GSE16691" 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=GSE16691 Status: Public on Oct 01 2009 Title: Transcriptional regulation by Norrin-Frizzled4 signaling in the embryonic yolk sac Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19837032 Summary & Design: Summary: Transcriptional profiles of the embryonic yolk sac from embryos with ectopic Norrin expression were compared to their wild type littermate controls. The goal is to identify the transcriptional response to Norrin-Frizzled 4 signaling during embryonic angiogenesis.

Overall design: Ectopic Norrin expression was achieved using a conditional over-expression strategy. Yolk sacs from 3-5 embryos were pooled for each sample and 3 replicates of both control and experimental groups were analyzed.

Background corr dist: KL-Divergence = 0.0423, L1-Distance = 0.0287, L2-Distance = 0.0014, Normal std = 0.5865

0.680 Kernel fit Pairwise Correlations Normal fit

Density 0.340

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild mouse typewild yolkmouse type sacZ/Norrin yolkmouse E8.5 sacZ/Norrin replicatemouse yolk E8.5 sacZ/Norrin replicateyolkmouse 1 E8.5 (0.0343772) sacwild replicateyolkmouse E8.52 (0.0791921)type sac wildreplicate yolk mouseE8.53 (0.0888043)type sac wildreplicate 1yolk mouseE8.5 (0.144827) type sac Z/Norrinreplicate 2yolkmouse E10.5(0.156548) sacZ/Norrin mouse 3yolkreplicate E10.5(0.0603133) sacZ/Norrin yolkmouse replicate E10.51 (0.0507761)sac yolkmouse replicateE10.5 2 (0.1339)sac yolkreplicate E10.5 3 (0.0429351)sac replicate E10.51 (0.042686)[ replicate min2 (0.0648497) 3 ](0.100791) [ medium ] [ max ] CEM 1 Utp20 962.7 2121.3 3030.4 P ( S | Z, I ) = 1.00 Nop14 443.3 636.4 846.2 Mean Corr = 0.86246 Wdr36 888.5 1165.6 1605.4 Tbl3 288.7 662.1 716.5 Utp14a 119.6 195.0 316.3 Nop2 1007.7 1564.8 1978.7 Rrp12 249.5 501.9 896.9 Heatr1 635.8 1242.4 2607.4 Mybbp1a 1363.2 2737.5 3959.9 Grwd1 846.7 1798.4 2316.6 CEM 1 + Ftsj3 464.7 774.7 1824.5 Top 10 Genes Nat10 565.5 1133.5 1520.9 Ddx18 1185.3 2113.8 3519.5 Cirh1a 1214.5 2548.2 3957.9 Pwp2 784.6 1077.7 1548.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE33156" 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=GSE33156 Status: Public on Jan 01 2013 Title: Hedgehog signaling in T cell differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23408837 Summary & Design: Summary: Despite Hedgehogs influence on T-cell activation and proliferation, the transcriptional targets of Gli2 in lymphocytes are not known. We therefore examined the Hedgehog-dependent transcriptional response of resting and early-stage activated T-cells in order to define their transcriptional response to Hedgehog pathway activation.

We have established transgenic models where transcription of target genes by Gli2 is either constitutively activated or repressed in cells of the T-lineage. Gli2 has an N-terminal repressor domain and a C-terminal activator domain. Lck-Gli2˛N2 (Gli2A) mice carry a transgene encoding a truncated form of Gli2 that acts as a permanent transcriptional activator of Hh target genes. Conversely, Lck-Gli2˛C2 (Gli2R) mice express a repressor of Gli2-dependent transcription, which by binding to Gli binding sites inhibits physiological Hh-dependent transcription, and hence Hh signal transduction, in the cell. These transgenes are driven by the Lck promoter and are only expressed in T-lineage cells

Overall design: Purified fresh, resting CD4 cells (unstimulated) and from CD4 cells stimulated with anti-CD3/CD28 for 6h (stimulated) were analysed in order to obtain transcriptional profiles before and during the early stages of T-cell activation.

Background corr dist: KL-Divergence = 0.0709, L1-Distance = 0.0778, L2-Distance = 0.0097, Normal std = 0.5606

0.823 Kernel fit Pairwise Correlations Normal fit

Density 0.412

0.000 CEM 1

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

Pre-normalization Quantiles

UnstimulatedUnstimulated WTUnstimulated CD4 WT UnstimulatedT cells, CD4 WT UnstimulatedTrep1 cells, CD4 (0.0378174) Gli2A UnstimulatedTrep2 cells, Tg(0.0536624) Gli2A Unstimulated rep3CD4 Tg(0.0685833)T Gli2A Unstimulatedcells, CD4 TgT rep1Gli2R Unstimulatedcells, CD4 (0.0609552) TgT rep2Gli2R Stimulatedcells, CD4 (0.0368541) TgT rep3Gli2R Stimulatedcells, CD4 (0.0452064)WT TgTrep1 Stimulatedcells, CD4CD4 (0.0432141)WT TTrep2 cells,Stimulatedcells,CD4 (0.0475866)WT T rep1rep3 cells, StimulatedCD4 (0.0987426) (0.0438243)Gli2A Trep2 cells,Stimulated Tg(0.0376308) Gli2A rep3CD4Stimulated Tg(0.0510881)T Gli2A cells, CD4Stimulated TgT rep1Gli2R cells, CD4Stimulated (0.0775373) TgT rep2Gli2R cells, CD4 (0.0288277) TgT rep3Gli2R cells, CD4 (0.0776694) TgTrep1 cells, CD4 (0.0545248) Trep2 cells,[ (0.0629837) minrep3 (0.0732918) ] [ medium ] [ max ] CEM 1 Utp20 514.6 3058.6 4002.4 P ( S | Z, I ) = 1.00 Nop14 362.7 716.1 1765.3 Mean Corr = 0.86161 Wdr36 480.9 2405.3 3192.6 Tbl3 598.8 3563.5 4698.5 Utp14a 34.5 123.0 202.7 Nop2 876.0 3601.4 4548.8 Rrp12 226.1 1682.6 2176.0 Heatr1 1781.7 7912.5 9265.6 Mybbp1a 651.3 1238.3 3560.6 Grwd1 1224.5 5405.2 7785.7 CEM 1 + Ftsj3 482.5 1801.9 2966.0 Top 10 Genes Nat10 459.6 1905.6 2503.0 Ddx18 2006.5 3585.7 5973.1 Cirh1a 2373.5 9660.9 13013.4 Pwp2 690.0 3295.6 4710.7

Null module Rps7 Utp14b Utp11l GEO Series "GSE46091" 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=GSE46091 Status: Public on Apr 17 2013 Title: Genes regulated by the gamma secretase inhibitor in WT and Ikaros deficient DN3 cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24643801 Summary & Design: Summary: Lineage-negative thymocytes were cultured on OP9-DL1 stromal cells for 16h in the presence of DMSO or the gamma secretase inhibitor MRK-003. DN3 cells cells were then sorted and their transcriptome analyzed.

Overall design: 8 samples

Background corr dist: KL-Divergence = 0.0511, L1-Distance = 0.0209, L2-Distance = 0.0005, Normal std = 0.5665

0.717 Kernel fit Pairwise Correlations Normal fit

Density 0.358

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 DN3WT cells, DN3 DMSOWT cells, DN3 treated,DMSOWT cells, DN3 treated,GSIrep1IkL/L cells, treated, (0.139568) DN3 GSIrep2IkL/L cells, treated, rep1(0.0265638) DN3IkL/L DMSO (0.145215) cells, rep2 DN3IkL/L treated,DMSO (0.100473) cells, DN3 treated, GSIrep1 cells, treated, (0.225274) GSIrep2 treated, rep1(0.0906204) (0.10844) rep2[ min (0.163847) ] [ medium ] [ max ] CEM 1 Utp20 651.4 1745.9 2553.6 P ( S | Z, I ) = 1.00 Nop14 490.6 802.3 1263.1 Mean Corr = 0.85682 Wdr36 397.5 611.8 1228.0 Tbl3 369.9 718.4 1231.8 Utp14a 60.9 88.6 113.9 Nop2 441.6 924.5 1482.2 Rrp12 193.3 593.5 908.5 Heatr1 998.3 2225.7 3199.4 Mybbp1a 220.1 896.1 1228.8 Grwd1 283.1 916.9 1935.2 CEM 1 + Ftsj3 153.6 721.7 991.1 Top 10 Genes Nat10 426.7 1111.5 1916.2 Ddx18 761.2 2019.3 2803.7 Cirh1a 1188.9 2504.1 3331.6 Pwp2 442.8 749.2 1447.2

Null module Rps7 Utp14b Utp11l GEO Series "GSE7069" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7069 Status: Public on Apr 20 2007 Title: Zfx controls the self-renewal of embryonic and hematopoietic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17448993 Summary & Design: Summary: Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult bone marrow HSC, but did not affect erythromyeloid progenitors or fetal HSC. In both ESC and HSC, Zfx activated a common set of direct target genes. In addition, the loss of Zfx resulted in the induction of immediate-early and/or stress-inducible genes in both SC types but not in their differentiated progeny. These studies identify the first shared transcriptional regulator of ESC and HSC, suggesting a common molecular basis of self-renewal in embryonic and adult SC.

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

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

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

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

ESC_Zfx-flox_Replicate1ESC_Zfx-flox_Replicate2ESC_Zfx-null_Replicate1ESC_Zfx-null_Replicate2 (0.158478)HSC_Zfx-cko_Replicate1 (0.0904092)HSC_Zfx-cko_Replicate2 (0.115469)HSC_Zfx-flox_Replicate1 (0.140033)HSC_Zfx-flox_Replicate2 (0.160068) (0.168962) (0.068969) (0.0976121)[ min ] [ medium ] [ max ] CEM 1 Utp20 1250.4 2275.9 2626.3 P ( S | Z, I ) = 1.00 Nop14 176.7 927.5 1204.2 Mean Corr = 0.87343 Wdr36 591.3 1336.0 1700.9 Tbl3 224.5 671.7 852.2 Utp14a 190.7 329.2 476.3 Nop2 435.0 1445.5 1770.7 Rrp12 266.0 812.0 1002.2 Heatr1 1940.2 2993.6 3563.2 Mybbp1a 49.5 2667.4 4109.8 Grwd1 480.9 2352.6 2672.5 CEM 1 + Ftsj3 90.9 1708.5 2497.4 Top 10 Genes Nat10 954.3 1298.8 1586.7 Ddx18 1009.1 3449.8 4079.5 Cirh1a 1580.5 4091.5 4562.4 Pwp2 663.9 952.7 1041.8

Null module Rps7 Utp14b Utp11l GEO Series "GSE7342" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

Keywords: time course

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

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

0.703 Kernel fit Pairwise Correlations Normal fit

Density 0.352

0.000 CEM 1

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

Pre-normalization Quantiles

p38alphap38alpha knockp38alpha out knock fetalp38alpha out knockliver fetal p38alphaE13.5, out wildliver fetal typebiological p38alphaE13.5, wildliver fetal typebiological p38alphaE13.5, liverwildrep1 fetal E13.5, typebiologicalp38alpha(0.0346387) liverknockrep2 fetal biological E13.5, p38alpha(0.111935) out liverknockrep3 fetal biological E13.5, p38alpha(0.0647533) outrep1 knockliver fetal biological(0.101075) p38alphaE15.5, outrep2 wildliver fetal (0.086578)typebiological p38alphaE15.5, rep3 wildliver fetal (0.175944)typebiological E15.5, liverwildrep1 fetal E15.5, typebiological(0.0497114) liver rep2 fetal biological E15.5, (0.0762423) liver rep3 biological E15.5, (0.0616143)[ rep1 min biological(0.102357) rep2 ] (0.0862808) rep3 (0.0488707)[ medium ] [ max ] CEM 1 Utp20 738.3 908.2 1210.3 P ( S | Z, I ) = 1.00 Nop14 731.5 867.5 1119.7 Mean Corr = 0.85088 Wdr36 860.4 1008.6 1272.2 Tbl3 687.4 793.5 1030.9 Utp14a 69.3 92.6 139.9 Nop2 954.9 1138.9 1429.9 Rrp12 284.0 394.4 526.5 Heatr1 1583.4 1821.2 2485.4 Mybbp1a 1270.2 1631.0 2335.7 Grwd1 1091.3 1284.9 1725.2 CEM 1 + Ftsj3 885.1 1098.1 1772.6 Top 10 Genes Nat10 455.0 556.7 876.8 Ddx18 1636.6 2131.0 2782.4 Cirh1a 1832.9 2246.3 2879.5 Pwp2 615.0 710.7 855.0

Null module Rps7 Utp14b Utp11l GEO Series "GSE6526" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6526 Status: Public on Mar 01 2007 Title: Expression time course data HEY2 KO and WT MASMC treated with PDGF Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17327490 Summary & Design: Summary: The cardiovascular restricted transcription factor CHF1/Hey2 has been previously shown to regulate the smooth muscle response to growth factors. To determine how CHF1/Hey2 affects the smooth muscle response to growth factors, we performed a genomic screen for transcripts that are differentially expressed in wild type and knockout smooth muscle cells after stimulation with platelet derived growth factor.

We screened 45101 probes representing more than 39,000 transcripts derived from at least 34,000 genes, at eight different time points. We analyzed the expression data utilizing an algorithm based on Bayesian statistics to derive the best polynomial clustering model to fit the expression data. We found that in a total of 9827 transcripts the normalized ratio of knockout to wild type expression diverged more than 3 fold from baseline in at least one time point, and these transcripts separated into 17 distinct clusters. Further analysis of each cluster revealed distinct alterations in gene expression patterns for immediate early genes, transcription factors, matrix metalloproteinases, signaling molecules and other molecules important in vascular biology.

Keywords: time course

Overall design: WT and Hey2 knockout mouse aortic smooth muscle cells were treated in parallel with PDGF and harvested at successive time points for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify differentially expressed transcripts through Bayesian statistical methods that would explain the differential response to PDGF observed in vitro.

Background corr dist: KL-Divergence = 0.1370, L1-Distance = 0.0306, L2-Distance = 0.0015, Normal std = 0.3962

1.009 Kernel fit Pairwise Correlations Normal fit

Density 0.505

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

MASMC_Hey2_KO_PDGF_T0MASMC_Hey2_KO_PDGF_T120MASMC_Hey2_KO_PDGF_T15MASMC_Hey2_KO_PDGF_T180 (0.0520162)MASMC_Hey2_KO_PDGF_T240MASMC_Hey2_KO_PDGF_T30 (0.0157789)MASMC_Hey2_KO_PDGF_T480 (0.0501268)MASMC_Hey2_KO_PDGF_T60 (0.00792639)MASMC_WT_PDGF_T0 (0.020019)MASMC_WT_PDGF_T120 (0.0306692)MASMC_WT_PDGF_T15 (0.0789823)MASMC_WT_PDGF_T180 (0.0431973)(0.0277947)MASMC_WT_PDGF_T240 (0.0763593)MASMC_WT_PDGF_T30 (0.0160141)MASMC_WT_PDGF_T480 (0.0427271)MASMC_WT_PDGF_T60 (0.107058) (0.0995494) (0.0193387) (0.312443)[ min ] [ medium ] [ max ] CEM 1 Utp20 1525.6 2000.0 4006.1 P ( S | Z, I ) = 1.00 Nop14 750.9 1235.5 2320.6 Mean Corr = 0.84736 Wdr36 512.6 718.8 1443.9 Tbl3 411.9 592.9 1375.2 Utp14a 48.9 94.4 199.9 Nop2 746.4 1685.1 4571.0 Rrp12 173.1 436.1 1390.2 Heatr1 865.1 1531.8 3986.0 Mybbp1a 479.6 810.7 2537.3 Grwd1 548.3 1218.3 2891.3 CEM 1 + Ftsj3 286.6 609.0 1874.4 Top 10 Genes Nat10 465.7 676.5 1301.7 Ddx18 851.4 1602.2 3914.6 Cirh1a 1381.4 3283.6 5512.5 Pwp2 452.0 1005.5 2064.1

Null module Rps7 Utp14b Utp11l GEO Series "GSE15267" 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=GSE15267 Status: Public on Mar 18 2009 Title: Expression data of induced pluripotent stem cell Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20595395 Summary & Design: Summary: We present a robust serum-free system for the rapid and efficient reprogramming of mouse somatic cells by Oct4, Sox2 and Klf4. The elimination of fetal bovine serum and oncogene c-Myc allowed reprogramming cells to be detected as early as Day 2 and reached greater than 10% of the population at Day 7 post retroviral transduction. The resulting iPS colonies were isolated with high efficiency to establish pluripotent cell lines. Based on this method, we further developed iPS-SF1 as a dedicated reprogramming medium for chemical screening and mechanistic investigations.

Comparasion of iPS cell lines derived from serum-free culture condition, MEF cells cultured in serum and serum-free condition and ES cell lines was shown.

Overall design: Selected induced pluripotent stem cell lines and its original mouse embroynic fibroblast were comparaed to defined mouse embroynic stem cell lines: R1 and CGR8.

Background corr dist: KL-Divergence = 0.0267, L1-Distance = 0.0218, L2-Distance = 0.0006, Normal std = 0.7121

0.569 Kernel fit Pairwise Correlations Normal fit

Density 0.284

0.000 CEM 1

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

Pre-normalization Quantiles

embryonicMEF stem culturedMEF cell cultured lineinembryonic serum-free CGR8 in4F-serumfree serum(0.0473355) stem medium4F-serumfree medium cell lineiPS(0.304481)3F-serumfree (0.180445) R1cell (0.109289)iPS line3F-serumfree cell S2C12 iPS line cell (0.0744137)S2C16 iPS line cell (0.144032)S53C1 line (0.0517142)S53C5[ min(0.0882899) ] [ medium ] [ max ] CEM 1 Utp20 1086.1 2316.9 2874.7 P ( S | Z, I ) = 1.00 Nop14 520.1 1825.7 2467.9 Mean Corr = 0.84678 Wdr36 490.7 1712.2 2005.0 Tbl3 592.3 1561.8 1893.9 Utp14a 83.1 190.9 247.1 Nop2 619.7 1885.4 2529.9 Rrp12 137.2 793.0 994.8 Heatr1 557.3 3282.0 3762.0 Mybbp1a 1122.1 4943.1 5692.5 Grwd1 614.9 1993.0 2672.3 CEM 1 + Ftsj3 370.8 1279.6 1572.2 Top 10 Genes Nat10 362.4 1174.1 1412.2 Ddx18 1385.7 4790.3 5599.0 Cirh1a 1262.2 4141.6 5072.7 Pwp2 402.4 1014.2 1220.2

Null module Rps7 Utp14b Utp11l GEO Series "GSE27605" 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=GSE27605 Status: Public on Mar 14 2011 Title: The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21419747 Summary & Design: Summary: Using EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.

A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. The intestinal stem cell signature predicts disease relapse in CRC and identifies a stem cell-like population that displays robust tumor- initiating capacity in immunodeficient mice as well as long-term self-renewal potential.

Overall design: We FACS purified mouse intestinal crypt cells according to their EphB2 or Lgr5 contents. We used Affymetrix chips to hybridize 2 samples from EphB2 high, 2 samples from EphB2 medium and 2 samples from EphB2 low cells (one sample from each group in a first hybridization on February 2009 plus an additional sample from each group on March 2009). Additionally, we hybridized one sample from Lgr5-EGFP high and one sample from Lgr5-EGFP low cells, obtained from Lgr5-EGFP knock-in mice (Barker et al., 2007).

Background corr dist: KL-Divergence = 0.0298, L1-Distance = 0.0338, L2-Distance = 0.0014, Normal std = 0.6870

0.614 Kernel fit Pairwise Correlations Normal fit

Density 0.307

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

intestine-Lgr5High-R1intestine-Lgr5Low-R1intestine-EphB2High-R1 intestine-EphB2Medium-R1(0.0985219) (0.0143278)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.176488)intestine-EphB2Medium-R2 (0.0330433)intestine-EphB2Low-R2 (0.251191) (0.0861667) (0.043199) (0.297062)[ min ] [ medium ] [ max ] CEM 1 Utp20 369.5 1191.6 1549.1 P ( S | Z, I ) = 1.00 Nop14 565.7 1616.3 2208.6 Mean Corr = 0.84392 Wdr36 634.6 1136.0 1618.3 Tbl3 882.3 1404.0 1750.7 Utp14a 5.7 15.7 20.1 Nop2 773.4 1787.4 2213.7 Rrp12 194.0 429.7 580.5 Heatr1 578.5 1515.0 1852.9 Mybbp1a 386.9 1408.6 1880.0 Grwd1 292.8 1102.2 1527.7 CEM 1 + Ftsj3 263.6 865.8 1116.7 Top 10 Genes Nat10 335.6 882.4 1205.0 Ddx18 723.5 1921.5 2174.6 Cirh1a 539.8 1491.0 1635.7 Pwp2 326.1 969.7 1359.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE8621" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: pre and restimulation with LPS, tolerance induction

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

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

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.325

0.000 CEM 1

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

Pre-normalization Quantiles

no_pre_no_restimulation_rep_Ano_pre_no_restimulation_rep_Bno_pre_no_restimulation_rep_Cno_pre_LPS_restimulation_rep_Ano_pre_LPS_restimulation_rep_B (0.03606)no_pre_LPS_restimulation_rep_C (0.0687556)LPS_pre_no_restimulation_rep_A (0.0383186)LPS_pre_no_restimulation_rep_B (0.100919)LPS_pre_no_restimulation_rep_C (0.024235)LPS_pre_LPS_restimulation_rep_A (0.369979)LPS_pre_LPS_restimulation_rep_B (0.113502)LPS_pre_LPS_restimulation_rep_C (0.02721) (0.0300191) (0.0704549) (0.0173001)[ min (0.103247) ] [ medium ] [ max ] CEM 1 Utp20 470.5 733.2 1479.6 P ( S | Z, I ) = 1.00 Nop14 426.4 607.7 1222.5 Mean Corr = 0.84121 Wdr36 825.8 1076.1 1639.7 Tbl3 419.6 569.5 750.5 Utp14a 44.0 57.7 83.4 Nop2 550.4 788.3 1739.7 Rrp12 85.8 167.1 332.2 Heatr1 1077.1 1474.7 2154.1 Mybbp1a 489.3 821.0 1659.2 Grwd1 442.6 754.8 1834.2 CEM 1 + Ftsj3 375.3 590.0 979.4 Top 10 Genes Nat10 171.7 354.7 462.9 Ddx18 702.9 932.4 1826.8 Cirh1a 689.9 1240.8 2252.8 Pwp2 262.7 371.8 779.5

Null module Rps7 Utp14b Utp11l GEO Series "GSE32598" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.704 Kernel fit Pairwise Correlations Normal fit

Density 0.352

0.000 CEM 1

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

Pre-normalization Quantiles

ViPSCs,ViPSCs, rep1 (0.0309236)ViPSCs, rep2 (0.0323923)TiPSCs, rep3 (0.0311728)TiPSCs, rep1 (0.0193292)TiPSCs, rep2 (0.021993)mESCs, rep3 (0.037192)mESCs, rep1 (0.0479252)mESCs, rep2 (0.0353491)Tail rep3 tip (0.057443) fibroblastsVentricular (0.323485)cardiomyocytes (0.362795)[ min ] [ medium ] [ max ] CEM 1 Utp20 1072.9 4081.2 4895.7 P ( S | Z, I ) = 1.00 Nop14 727.9 1950.9 2291.3 Mean Corr = 0.83439 Wdr36 489.9 1766.4 2054.1 Tbl3 395.7 1284.5 1491.6 Utp14a 54.0 147.8 272.3 Nop2 824.4 3091.4 3715.4 Rrp12 277.9 1399.2 1823.9 Heatr1 658.6 3624.1 3920.2 Mybbp1a 728.5 4001.0 5668.0 Grwd1 729.7 3438.7 4164.4 CEM 1 + Ftsj3 356.1 1408.4 2114.3 Top 10 Genes Nat10 369.6 1142.5 1359.0 Ddx18 848.8 3740.9 4244.9 Cirh1a 1839.9 4992.1 7142.6 Pwp2 345.3 1380.6 1424.5

Null module Rps7 Utp14b Utp11l 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(0.141811)3 hrep2 post-estradiol,biological (0.0632782)3 hrep3 post-estradiol,biological (0.103404)7 h post-estradiol,biological rep17 h post-estradiol,biological(0.0241738) rep27 h post-estradiol,biological(0.021724) rep314 h (0.0485195) post-estradiol,biological rep114 h (0.0185023) post-estradiol,biological rep214 h (0.0189376) post-estradiol,biological rep321 h (0.0134147) post-estradiol,biological rep121 h post-estradiol,biological(0.0244831) rep221 h post-estradiol,biological(0.00949335) rep330 h post-estradiol,biological(0.015544) rep130 h post-estradiol,biological(0.0327962) rep230 h post-estradiol,biological(0.0592789) rep3 (0.0523406) rep1 (0.122693) rep2 (0.127393) rep3[ min (0.102212) ] [ medium ] [ max ] CEM 1 Utp20 315.8 1496.6 2253.4 P ( S | Z, I ) = 1.00 Nop14 597.2 1435.8 2119.7 Mean Corr = 0.83418 Wdr36 430.3 1223.5 1752.9 Tbl3 620.6 1026.6 1204.1 Utp14a 27.4 46.5 86.2 Nop2 479.0 2051.7 3204.3 Rrp12 269.1 741.0 839.7 Heatr1 663.2 1773.6 2883.7 Mybbp1a 187.4 1361.4 2107.7 Grwd1 106.3 718.1 1251.6 CEM 1 + Ftsj3 417.2 933.9 1082.0 Top 10 Genes Nat10 322.4 1100.3 1822.8 Ddx18 944.3 2972.9 3698.3 Cirh1a 593.1 1684.4 2669.1 Pwp2 145.7 583.6 894.2

Null module Rps7 Utp14b Utp11l GEO Series "GSE10912" 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=GSE10912 Status: Public on Mar 22 2008 Title: Gene expression profiling in BCR/ABL expressing HSCs Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22431519 Summary & Design: Summary: The BCR-ABL oncogene, generated by Philadelphia chromosome, is present in about 95% human Chronic myeloid leukemia (CML) and 20~30% acute lymphoblastic leukemia (ALL). One of BCR-ABL isoforms, P210, is more often detected in CML and ALL patients. Although BCR-ABL kinase inhibitors are effective in controlling the diseases, they do not provide cure due to the development of drug resistance and the insensitivity of leukemia stem cells to these drugs. Identification of new therapeutic targets is critical. To identify potential target against leukemia stem cells, we studied gene expression in leukemia stem cells, which were identified in mice in our lab (Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY, Li S. 2006. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia. Proc Natl Acad Sci USA 103(45):16870-16875.). The sorted leukemia stem cells that expressed BCR-ABL were used for isolation of RNA, followed by the analysis of gene expression using the DNA microarray. The same lineage of non-BCR-ABL-expressing normal hematopoietic stem cells was used as control. We have identified some interesting genes that are up- or down-regulated by BCR-ABL in these leukemia stem cells. We are currently studying the functions of these identified genes.

Keywords: Genetic modification

Overall design: Bone marrow cells are isolated from the long bones of CML mice that are untreated or treated with imatinib. BCR-ABL-expressing or non-BCR-ABL-expressing (transduced with the empty GFP vector) hematopoietic stem cells (GFP+Lin-c-Kit+Sca-1+) are stored by FACS directly into RNAlater (Ambion, Austin, TX) and are homogenized in RLT Buffer (RNeasy Micro Kit (Qiagen, Valencia, CA)). Total RNA is isolated by following the protocol for the RNeasy Micro Kit, and quality is assessed using a 2100 Bioanalyzer instrument and RNA 6000 Pico LabChip assay (Agilent Technologies, Palo Alto, CA). Utilizing the GeneChip Whole Transcript Sense Target Labeling Assay kit (Affymetrix, Santa Clara, CA.) between 100-300ng of total RNA undergoes reverse transcription with random hexamers tagged with T7 sequence. The double stranded cDNA that is generated is then amplified by T7 RNA polymerase to produce cRNA. Second cycle first strand cDNA synthesis then takes place incorporating dUTP which is later used as sites where fragmentation occurs by utilizing an uracil DNA glycosylase and apurinic/apyrimidinic endonuclease 1 enzyme mix. The fragmented cDNA is then labeled by terminal transferase attaching a biotin molecule using Affymetrix proprietary DNA labeling Reagent. Approximately 2.0´g of fragmented and biotin-labeled cDNA is then hybridized onto a Mouse Gene ST 1.0 Array (Affymetrix, Santa Clara, CA.) for 16 hours at 45´C. Post-hybridization staining and washing are performed according to manufacturer's protocols using the Fluidics Station 450 instrument (Affymetrix). Finally, the arrays are scanned with a GeneChip? Scanner 3000. Images are acquired and cel files generated which are then used for analysis.

Background corr dist: KL-Divergence = 0.0432, L1-Distance = 0.0407, L2-Distance = 0.0025, Normal std = 0.6321

0.684 Kernel fit Pairwise Correlations Normal fit

Density 0.342

0.000 CEM 1

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

Pre-normalization Quantiles

Vector_1BCR/ABL_1 (0.0977881)BCR/ABL_treated_1 (0.224486)Vector_2BCR/ABL_2 (0.0647577) (0.206185)BCR/ABL_treated_2 (0.191353) (0.215431)[ min ] [ medium ] [ max ] CEM 1 Utp20 811.6 1345.3 1730.6 P ( S | Z, I ) = 1.00 Nop14 1015.9 1246.8 1692.1 Mean Corr = 0.83195 Wdr36 773.9 1067.4 1338.7 Tbl3 677.6 1340.5 1838.3 Utp14a 31.2 45.0 47.8 Nop2 1033.4 1725.4 2066.7 Rrp12 200.5 496.2 671.5 Heatr1 1209.8 1863.7 2445.8 Mybbp1a 890.9 1611.3 1809.3 Grwd1 516.4 947.9 1222.6 CEM 1 + Ftsj3 382.9 678.7 772.6 Top 10 Genes Nat10 442.5 722.2 901.0 Ddx18 1313.8 2181.7 2425.7 Cirh1a 1049.3 1475.7 2050.6 Pwp2 870.8 1170.1 1382.9

Null module Rps7 Utp14b Utp11l GEO Series "GSE32986" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.966 Kernel fit Pairwise Correlations Normal fit

Density 0.483

0.000 CEM 1

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

Pre-normalization Quantiles

BMDC-Unstimulated-1BMDC-Unstimulated-2BMDC-Unstimulated-3 BMDC-GMCSF-1(0.0685818) BMDC-GMCSF-2(0.0580457) BMDC-GMCSF-3(0.0799998) (0.0496683)BMDC-Curdlan1-1 (0.0484291)BMDC-Curdlan1-2 (0.060998)BMDC-Curdlan1-3 (0.110935)BMDC-Curdlan100-1 (0.0624841)BMDC-Curdlan100-2 (0.0335368)BMDC-Curdlan100-3 (0.0201728)BMDC-Curdlan1/GMCSF-1 (0.0141191)BMDC-Curdlan1/GMCSF-2 (0.0266711)BMDC-Curdlan1/GMCSF-3BMDC-Curdlan100/GMCSF-1 (0.0614426)BMDC-Curdlan100/GMCSF-2 (0.067414)BMDC-Curdlan100/GMCSF-3 (0.0610512) (0.0726174) (0.0577451) (0.0460886)[ min ] [ medium ] [ max ] CEM 1 Utp20 597.5 935.0 1044.9 P ( S | Z, I ) = 1.00 Nop14 579.7 752.2 865.2 Mean Corr = 0.82762 Wdr36 440.4 510.3 602.7 Tbl3 422.7 519.4 601.8 Utp14a 113.5 145.7 189.9 Nop2 749.8 1341.0 1628.9 Rrp12 194.1 350.4 404.5 Heatr1 906.1 1614.4 2224.4 Mybbp1a 671.0 1040.3 1198.1 Grwd1 631.2 1133.4 1325.5 CEM 1 + Ftsj3 225.3 349.0 441.3 Top 10 Genes Nat10 341.3 520.4 639.2 Ddx18 1026.5 1413.2 1670.4 Cirh1a 870.2 1436.3 1673.1 Pwp2 420.9 663.9 703.6

Null module Rps7 Utp14b Utp11l GEO Series "GSE9878" 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=GSE9878 Status: Public on Dec 15 2007 Title: Gene expression analysis of Pax5-/- proB cells transduced with control or EBF retrovirus. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18176567 Summary & Design: Summary: We have determined that sustained expression of EBF suppresses alternate lineage genes independently of Pax5.

Keywords: Transcription factor EBF restricts alternate lineage options and promotes B cell fate commitment independently of Pax5.

Overall design: Pax5-/- pro-B cells transduced with control or EBF retrovirus. Transduced cells were FACS sorted based on GFP expression and total RNA was isolated. RNA isolated from control or EBF transduced cells was analyzed using the Affymetrix Rat 230A microarrays.

Background corr dist: KL-Divergence = 0.0260, L1-Distance = 0.0124, L2-Distance = 0.0002, Normal std = 0.6863

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.291

0.000 CEM 1

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

Pre-normalization Quantiles

Pax5-/- Pax5-/-pro-B cells Pax5-/-pro-B transduced cells Pax5-/-pro-B transduced cells Pax5-/-pro-B with transduced EBFcells Pax5-/-pro-B with (Mig-EBF) transduced EBFcells pro-B with (Mig-EBF) transduced EBFcellsretrovirus with (Mig-EBF) transduced controlretrovirus with repl1 control(MigR1)retrovirus (0.349567)[ with repl2min control(MigR1) retrovirus(0.156813) repl3 ] (MigR1) retrovirus(0.0475004) repl1 retrovirus (0.0900026) repl2[ medium (0.179066) repl3 (0.177051) ] [ max ] CEM 1 Utp20 785.8 1047.5 1312.6 P ( S | Z, I ) = 1.00 Nop14 525.5 592.3 732.2 Mean Corr = 0.82649 Wdr36 1115.1 1226.7 1298.5 Tbl3 644.4 721.8 786.2 Utp14a 121.2 131.9 142.3 Nop2 1017.2 1123.6 1508.8 Rrp12 265.3 300.2 368.3 Heatr1 1459.6 1793.0 1959.6 Mybbp1a 1569.1 1806.8 2171.9 Grwd1 1190.4 1303.6 1519.8 CEM 1 + Ftsj3 868.9 982.1 1090.0 Top 10 Genes Nat10 1098.8 1230.3 1310.1 Ddx18 1736.4 1800.4 1833.6 Cirh1a 1696.9 1776.1 1781.9 Pwp2 521.4 629.2 682.1

Null module Rps7 Utp14b Utp11l GEO Series "GSE5976" 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=GSE5976 Status: Public on Jul 01 2008 Title: Mesp1-induced gene expression changes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18593559 Summary & Design: Summary: During gastrulation, cells of the prospective mesoderm ingress through the primitive streak and acquire fates based on complex spatial and temporal cues. Progenitors of the cardiogenic mesoderm are first found at E6.5 in the posterior lateral epiblast and subsequently migrate laterally and anteriorly to form the cardiac crescent at E7.5, when regionalized cell fates are first delineated . Lineage tracing and heterotopic transplantation studies suggest that precursors in the earliest heart field possess potential to generate myocardium, endocardium, and pericardium. The mechanisms by which inductive signals in the primitive streak effect the development of this pancardiac progenitor field, however, remain poorly understood

In mice, the earliest restricted progenitors of the cardiovascular system are marked by expression of the basic helix-loop-helix transcription factor, Mesp1. We therefore use microarray analysis to determine the early and intermediate effects of transiently forced Mesp1 expression during ES cell differentiation.

Keywords: time course

Overall design: ES cells bearing a targeted, doxycycline inducible Mesp1 transgene were differentiated in the absence or presence of DKK1 from day 0-4, either with or without transient doxycycline treatment from day 2-4.

Background corr dist: KL-Divergence = 0.0893, L1-Distance = 0.0268, L2-Distance = 0.0010, Normal std = 0.4657

0.866 Kernel fit Pairwise Correlations Normal fit

Density 0.433

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

A2lox.mesp1A2lox.mesp1 (dayA2lox.mesp1 3) (0.144572)(dayA2lox.mesp1 3 + (day dox)A2lox.mesp1 3 (0.0552446) + (day3 DKK1)A2lox.mesp1 + (dayDKK1(0.0982793)A2lox.mesp1 4) + (0.0351211)(day dox)A2lox.mesp1 4 (0.0439171)+ (day dox)A2lox.mesp1 4 (0.034384) + (day DKK1)A2lox.mesp1 4 + (day (0.141421)DKK1A2lox.mesp1 6) +(0.0381915)(day A2lox.mesp1dox) 6 +(0.0456445) (day dox) 6 (0.168304) + (day DKK1) 6 + (0.021064)DKK1 + [dox) min (0.173856) ] [ medium ] [ max ] CEM 1 Utp20 705.2 1621.2 2186.1 P ( S | Z, I ) = 1.00 Nop14 1032.9 1498.6 1634.0 Mean Corr = 0.82521 Wdr36 657.6 1441.0 1840.4 Tbl3 512.1 1197.8 1302.6 Utp14a 44.2 123.6 333.9 Nop2 1495.0 3098.2 4113.7 Rrp12 203.4 669.9 1065.2 Heatr1 652.7 2229.1 3032.6 Mybbp1a 1322.4 3443.2 4138.7 Grwd1 735.3 1896.7 2629.1 CEM 1 + Ftsj3 839.4 2030.5 2697.1 Top 10 Genes Nat10 476.2 1193.5 1465.2 Ddx18 1161.0 3072.3 3831.2 Cirh1a 2776.6 5144.8 6089.0 Pwp2 340.6 878.1 1073.8

Null module Rps7 Utp14b Utp11l GEO Series "GSE7012" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7012 Status: Public on May 01 2007 Title: Identif. of oscillatory genes in somitogenesis from functional genomic analysis of C2C12 myoblast line Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17362910 Summary & Design: Summary: During somitogenesis, oscillatory expression of genes in the notch and wnt signaling pathways plays a key role in regulating segmentation. These oscillations in expression levels are elements of a species-specific developmental mechanism. To date, the periodicity and components of the human clock remain unstudied. Here we show that a human mesenchymal stem/stromal cell (MSC) model can be induced to display oscillatory gene expression. We observed that the known cycling gene HES1 oscillated with a 5 hour period, consistent with available data on the rate of somitogenesis in humans. We also observed cycling of Hes1 expression in mouse C2C12 myoblasts with a period of 2 hours, consistent with previous in vitro and embryonic studies. Furthermore, we used microarray and quantitative PCR (Q-PCR) analysis to identify additional genes that display oscillatory expression both in vitro and in mouse embryos. We confirmed oscillatory expression of the notch pathway gene Maml3 and the wnt pathway gene Nkd2 by whole mount in situ hybridization analysis and Q-PCR. Expression patterns of these genes were disrupted in Wnt3atm1Amc mutants but not in Dll3pu mutants. Our results demonstrate that human and mouse in vitro models can recapitulate oscillatory expression observed in embryo and that a number of genes in multiple developmental pathways display dynamic expression in vitro.

Keywords: time series

Overall design: Synchronization of C2C12 myoblasts was carried out as follows: T-25 cm flasks were set up in parallel. These cells were grown to 90% confluence in DMEM supplemented with 5% FBS then incubated in DMEM with only 0.2% FBS for 24 hours, and returned to DMEM supplemented with FBS. Samples were collected every 30 min. for 8 hours.

Background corr dist: KL-Divergence = 0.1130, L1-Distance = 0.0298, L2-Distance = 0.0017, Normal std = 0.4214

0.947 Kernel fit Pairwise Correlations Normal fit

Density 0.473

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

C2C12_0_hrC2C12_0.5_hr (0.14272)C2C12_1.0_hr (0.18751)C2C12_1.5_hr (0.0581662)C2C12_2.0_hr (0.0745277)C2C12_2.5_hr (0.015989)C2C12_3.0_hr (0.0272237)C2C12_4.0_hr (0.0260201)C2C12_4.5_hr (0.0118672)C2C12_5.0_hr (0.104654)C2C12_5.5_hr (0.0979528)C2C12_6.0_hr (0.161185)C2C12_3.5_hr (0.0693803) (0.0228048) [ min ] [ medium ] [ max ] CEM 1 Utp20 405.1 461.5 643.0 P ( S | Z, I ) = 1.00 Nop14 420.1 508.6 546.7 Mean Corr = 0.82478 Wdr36 452.3 508.6 646.2 Tbl3 405.2 503.4 621.1 Utp14a 376.4 498.6 549.0 Nop2 358.2 502.0 583.6 Rrp12 336.9 508.5 682.1 Heatr1 341.6 483.0 629.8 Mybbp1a 403.2 508.8 754.2 Grwd1 370.1 505.4 605.0 CEM 1 + Ftsj3 396.3 501.6 803.3 Top 10 Genes Nat10 403.8 500.1 680.6 Ddx18 373.0 522.8 592.9 Cirh1a 364.1 497.0 546.0 Pwp2 341.7 468.6 544.1

Null module Rps7 Utp14b Utp11l GEO Series "GSE46090" 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=GSE46090 Status: Public on Apr 17 2013 Title: Gene expression in WT and Ikaros-deficient DN3, DN4 and DP thymocyte populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24643801 Summary & Design: Summary: DN3, DN4 and DP cells were sorted from 3-4 week old WT and mice and subjected to transcriptome analysis

Overall design: Cells from 3 mice were pooled for sorting.

Background corr dist: KL-Divergence = 0.0692, L1-Distance = 0.0334, L2-Distance = 0.0015, Normal std = 0.5233

0.791 Kernel fit Pairwise Correlations Normal fit

Density 0.396

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 DN3WT cells DN3 repWT cells 1 DN4 (0.0488193) repWT cells 2 DN4 (0.0638978) repWT cells 1 DP (0.0653568) rep cellsWT 2 DP (0.191995)rep cellsDN3 1 (0.152072) cellsrepDN3 2 rep (0.159912) cells 1DN4 (0.0293944) rep cells 2DN4 (0.0364911) rep cells 1DP (0.0198466) rep cells 2DP (0.0283162)rep cells 1 (0.118522) rep 2 (0.0853762) [ min ] [ medium ] [ max ] CEM 1 Utp20 554.8 2652.9 3038.5 P ( S | Z, I ) = 1.00 Nop14 377.6 823.6 1199.3 Mean Corr = 0.82454 Wdr36 355.0 710.7 974.9 Tbl3 282.8 998.2 1354.9 Utp14a 117.3 156.5 243.4 Nop2 465.3 1393.4 2233.2 Rrp12 51.5 345.1 540.4 Heatr1 1005.0 2828.1 3334.0 Mybbp1a 106.1 1058.1 1706.0 Grwd1 308.5 1554.9 2208.6 CEM 1 + Ftsj3 177.1 745.6 929.7 Top 10 Genes Nat10 278.6 1359.8 1667.4 Ddx18 723.2 2595.6 3129.0 Cirh1a 886.5 2536.7 3336.4 Pwp2 457.2 1209.9 1507.9

Null module Rps7 Utp14b Utp11l GEO Series "GSE8091" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8091 Status: Public on May 29 2008 Title: Transcriptome and proteome analysis of early embryonic mouse brain development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18283662 Summary & Design: Summary: Embryonic mouse brain development involves a sequential differentiation of multipotent progenitor cells into neurons and glia. Using microarrays and large 2-D electrophoresis, we investigated the transcriptome and proteome of mouse brains at embryonic days 9.5, 11.5 and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between the time points investigated but interestingly, the rate of alteration was about 10% to 13% of all proteins and mRNAs during every two days of development. Furthermore, up- and downregulation was balanced. This was confirmed for two additional stages of development, embryonic day 16 and 18. We hypothesize that during embryonic development, the rate of protein expression alteration is rather constant due to a limitation of cellular resources such as energy, space and free water. The similar complexity found at the transcriptome and proteome level at all stages suggests, that changes in relative concentration of gene products rather than an increased number of gene products dominate throughout cellular differentiation. We found that metabolism and cell cycle related gene products were downregulated in expression when precursor cells switched from proliferation to neuronal differentiation (day 9.5 to 11.5), whereas neuron specific gene products were upregulated. A detailed analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch and Wnt signaling pathways.

Keywords: time course, development, transcriptome, proteome

Overall design: E13.5: 6 biological replicates

Background corr dist: KL-Divergence = 0.0442, L1-Distance = 0.0296, L2-Distance = 0.0011, Normal std = 0.5980

0.691 Kernel fit Pairwise Correlations Normal fit

Density 0.346

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

E9.5 embryoE9.5 embryo headE9.5 sample13 embryo headE9.5 sample embryo head (0.206589)E9.5 sample15 embryo head (0.123901)E11.5 sample16 headembryo (0.0670097)E11.5 sample19 embryo head(0.0402466)E11.5 22 sample embryo head(0.0319734)E11.5 sample33 embryo headE13.5 (0.0496832) sample36 embryo headE13.5 (0.0305732) sample51 embryo headE13.5 (0.0365023) sample52 embryo headE13.5 (0.0933723) sampleB62E6K embryo headE13.5 sampleB62E7K embryo (0.034767)headE13.5 sampleB62E8K embryo (0.0433848)headE9.5 sampleembryoB63E5K (0.0470143)head sample B63E6Khead (0.046099) sample B63E7K (0.0335483) 24 (0.0400381) (0.0752975)[ min ] [ medium ] [ max ] CEM 1 Utp20 686.2 892.4 2274.8 P ( S | Z, I ) = 1.00 Nop14 482.3 774.6 1495.6 Mean Corr = 0.82288 Wdr36 394.6 892.4 1235.5 Tbl3 314.3 550.3 1495.4 Utp14a 77.4 113.2 184.4 Nop2 667.7 1098.9 2386.8 Rrp12 114.4 204.5 827.2 Heatr1 682.4 1040.2 2718.1 Mybbp1a 452.9 800.2 2795.6 Grwd1 836.8 1623.0 2647.7 CEM 1 + Ftsj3 254.8 361.8 1462.3 Top 10 Genes Nat10 522.5 649.0 1506.7 Ddx18 1083.7 1559.9 2710.5 Cirh1a 974.1 1313.6 3632.7 Pwp2 402.5 464.1 967.5

Null module Rps7 Utp14b Utp11l