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: 9 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. Ruvbl2 Ruvbl1 Polr2e Skp1a Pfdn2 Stap1 Num ofGenesinQueryGeneset:9.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Skp2 Cul1 Uri1

Ruvbl1 Ruvbl2 Pfdn2 Skp2 Skp1a Cul1 Uri1 Stap1 Polr2e Singletons CEM 1(212datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page1 Ebna1bp2 Zmynd19 Snrnp40 Ranbp1 Rbmxl1 Nup107 Snrpd3 Snrpa1 Dctpp1 Rbm8a Stoml2 Ruvbl2 Ruvbl1 Rsl1d1 Psmg1 Magoh Polr2h C1qbp Nsun2 Nop16 Nup85 Nop56 Actl6a Ddx39 Ddx18 Apex1 Skp1a Prmt5 Gmps Gspt1 Rrp15 Prmt1 Pfdn2 Phf5a Pold2 Emg1 Cct6a Sf3a3 Cse1l Lsm2 Nhp2 Dkc1 Skp2 Cct7 Adsl Cct5 Cul1 Dis3 Lyar Gart 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE20954 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE12465 [14] GSE6998 [32] GSE13692 [8] GSE48204 [6] GSE6837 [8] GSE48790 [8] GSE18135 [18] GSE13874 [14] GSE13873 [27] GSE51483 [45] GSE27605 [8] GSE19885 [9] GSE47414 [18] GSE38831 [7] GSE7275 [8] GSE51628 [15] GSE26568 [6] GSE21299 [12] GSE7875 [16] GSE34215 [6] GSE28389 [20] GSE42548 [29] GSE19528 [8] GSE37029 [15] GSE11220 [44] GSE15872 [18] GSE11201 [18] GSE7705 [10] GSE6689 [12] GSE5671 [18] GSE12464 [23] GSE46091 [8] GSE15541 [12] GSE16874 [12] GSE5333 [16] GSE17316 [12] GSE32598 [11] GSE45619 [6] GSE46090 [12] GSE6065 [100] GSE8555 [8] GSE16925 [15] GSE7897 [60] GSE46797 [6] GSE31598 [12] GSE46606 [30] GSE11222 [42] GSE45941 [8] GSE22005 [23] GSE39449 [6] GSE7784 [12] GSE35366 [78] GSE54207 [9] GSE24789 [9] GSE6933 [15] GSE12498 [12] GSE23972 [6] GSE39233 [40] GSE24813 [10] GSE35998 [20] GSE27786 [20] GSE17617 [18] GSE5841 [6] GSE7050 [18] GSE46970 [15] GSE11356 [9] GSE48203 [9] GSE46724 [6] GSE22824 [24] GSE15161 [26] GSE21063 [24] GSE7683 [12] GSE33308 [10] GSE20987 [12] GSE27114 [6] GSE15624 [12] GSE27379 [6] GSE21491 [9] GSE16676 [11] GSE14012 [24] GSE21272 [44] GSE38463 [41] GSE21902 [31] GSE12454 [13] GSE40282 [6] GSE34723 [101] GSE16679 [8] GSE39458 [6] GSE20398 [30] GSE48397 [10] GSE21944 [6] GSE19732 [20] GSE8836 [56] GSE32386 [13] GSE11990 [20] GSE15808 [29] GSE41005 [8] GSE7012 [13] GSE10525 [18] GSE34839 [6] GSE20100 [15] GSE20391 [11] GSE10176 [6] GSE5976 [12] GSE56345 [9] GSE15772 [8] GSE9763 [20] GSE8025 [21] GSE19176 [10] GSE37907 [24] GSE18042 [18] GSE14406 [54] GSE35593 [6] GSE7759 [112] GSE21278 [48] GSE27092 [6] GSE6957 [12] GSE9297 [27] GSE16902 [21] GSE12982 [53] GSE2527 [6] GSE50813 [24] GSE23833 [12] GSE32986 [18] GSE6526 [16] GSE4288 [36] GSE46088 [8] GSE7460 [52] GSE26096 [10] GSE10273 [9] GSE8431 [12] GSE39469 [6] GSE46600 [44] GSE23845 [15] GSE17263 [6] GSE38304 [8] GSE10913 [6] GSE18224 [32] GSE28830 [9] GSE15871 [18] GSE33199 [64] GSE7342 [12] GSE17553 [16] GSE44261 [12] GSE10912 [6] GSE11973 [6] GSE25252 [10] GSE15155 [12] GSE21033 [12] GSE5861 [6] GSE22086 [6] CEM+ CEM GSE1479 [36] GSE13408 [14] GSE4535 [6] GSE9146 [27] GSE15267 [8] GSE29975 [6] 0.0 GSE21018 [6] GSE44162 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 132.56 132.59 133.14 133.57 133.76 134.18 134.23 134.55 134.65 134.90 134.90 135.43 136.96 137.67 137.92 138.26 138.28 138.73 138.92 139.65 139.79 140.12 140.85 141.06 141.66 141.90 142.04 142.53 143.03 143.78 144.31 144.95 145.32 145.60 146.60 147.77 148.80 149.41 150.08 151.09 151.18 151.70 155.74 158.41 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page2 Hnrnpab Tamm41 Cacybp Nup155 Nup133 Exosc3 Exosc2 Mrps22 Skiv2l2 Psmc4 Prpf31 Polr2d Nup43 Nop58 Aimp2 Nup54 Rpp30 Nup93 Pdap1 Dpy30 Cdca7 Pa2g4 Snrpb Mcm7 Mcm5 Hirip3 Alyref Gins1 Uchl5 Nol11 U2af1 Lsm3 Eif3g Uba2 Ddx1 Rpa2 Hells Ppil1 Exo1 Tipin Pes1 Fen1 Tcp1 Ftsj3 Drg1 Utp6 Nip7 Rfc5 Nifk Ncl 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 118.58 118.75 119.09 119.12 119.15 119.18 119.24 119.59 119.69 119.97 120.18 120.26 120.29 120.52 120.78 120.79 121.57 121.57 121.99 123.05 123.24 124.20 124.40 124.75 125.11 125.23 125.50 125.53 125.54 126.89 126.90 127.02 127.05 127.58 127.66 128.31 128.81 128.89 128.96 129.03 129.06 129.33 129.51 129.72 129.90 130.32 130.81 131.39 132.06 132.10 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page3 Mybbp1a Psmd12 Ccdc58 Exosc7 Metap2 Cmss1 Mthfd1 Eef1e1 Grwd1 Cirh1a G3bp1 Gtf2e2 Polr2c Ncbp1 Nup35 Wdr74 Pbdc1 Rad51 Haus1 Eif2b3 Ddx27 Rpl7l1 Mcm2 Mcm6 Prim1 Ssrp1 Banf1 Yars2 Nme1 Ptcd3 Pwp1 Snrpf Msh2 Strap Nop9 Nudc Eif3d Pno1 Stip1 Rcc1 Orc6 Hn1l Ppat Cct2 Rfc4 Pfas Eif3l Ipo5 Aatf Atic 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 109.57 109.91 110.10 110.19 110.35 110.37 110.68 110.69 110.75 110.95 111.17 111.29 111.29 111.42 111.88 112.05 112.21 112.50 112.57 112.59 113.11 113.49 113.66 114.17 114.31 114.34 114.45 114.81 114.94 114.95 115.04 115.06 115.16 115.28 115.30 115.48 115.74 115.80 115.81 115.82 116.05 116.22 116.61 117.17 117.42 117.49 117.57 117.95 118.12 118.15 1.0 Notes 3110082I17Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page4 BC055324 Hsp90aa1 Suv39h1 Prpf38a Nudcd2 Nudcd1 Topbp1 Hnrnpu Ppp1r8 Nudt21 Mrpl18 Gtf2h2 Polr2b Kpnb1 Wdr18 Kpna2 Dtymk Trip13 Cks1b Ahsa1 Ddx56 Znhit3 Naa10 Naa15 Naa50 Tex30 Polr2f Mcm4 Pfdn4 Xrcc6 Noc4l Smu1 Tfdp1 Prpf3 Cdc6 Eif3b Phb2 Rrs1 Gnl3 Dctd Hat1 Rfc3 Tbl3 Isy1 Srm Ung Ttf2 Itpa Ilf2 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 100.22 100.38 100.59 101.03 101.11 101.17 101.26 101.39 101.48 101.53 101.75 101.80 101.83 102.28 102.34 102.46 103.16 103.50 103.55 103.75 104.07 104.09 104.23 104.38 104.64 104.69 104.76 104.87 105.00 105.03 105.16 105.27 105.68 105.71 106.01 106.30 106.56 106.86 107.30 107.33 107.51 107.67 107.80 107.81 107.84 108.03 108.04 108.52 108.60 108.67 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page5 Rps19bp1 Rnaseh2a Wbscr22 Suv39h2 Sssca1 H2-Ke2 Dnttip2 Psmg3 Tcerg1 Trim37 Hnrnpf Psmc1 Psma1 Mrpl11 Polr1b Apitd1 Polr1e Cops5 Rqcd1 Rpp40 Nup62 Ercc6l Ube2k Cdc45 Usp10 Dhx15 Usp14 Eif2b5 Fignl1 Gmnn Cfdp1 Gins2 Polr2j Dimt1 Bccip Noc2l Mrpl3 Ttc27 Rrm1 Plrg1 Bub1 Rpa3 Rad1 Rae1 Tdp1 Ezh2 Imp4 Ctps Cct4 Tsr2 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 93.65 93.68 93.69 93.72 93.75 93.87 93.94 94.06 94.55 94.72 94.73 94.90 94.92 94.94 95.16 95.33 95.41 95.54 95.59 95.63 95.69 95.78 96.10 96.38 96.50 96.51 96.56 96.63 96.64 96.67 96.96 97.26 97.37 97.94 97.99 98.06 98.11 98.20 98.55 98.61 98.61 98.79 99.17 99.22 99.45 99.67 99.84 99.95 100.14 100.19 1.0 Notes 2700094K13Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page6 Thumpd1 Rsl24d1 Hnrnpm Chchd1 Sephs1 Tsen15 Ppp1r7 Chaf1b Dnaaf2 Ppm1g Wdhd1 Spata5 Trim28 Dcaf13 Psma7 Psma6 Srfbp1 Heatr1 Mak16 Cops3 Usp39 Abce1 Cdca5 Kif20a Znhit6 Eif4a1 Fkbp3 Tsen2 Gtf2f2 Tex10 Snrpc Mcm8 Larp7 Sf3b3 Bms1 Pola1 Pole2 Paics Uhrf1 Msh6 Nop2 Wdr3 Dhx9 Pus7 Rars Nxt1 Pole Taf9 Set 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 88.01 88.02 88.02 88.21 88.45 88.52 88.63 88.68 88.97 89.09 89.24 89.28 89.48 89.55 89.57 89.69 89.89 89.95 89.96 90.15 90.39 90.48 90.48 90.49 90.51 90.67 90.71 90.74 90.80 91.06 91.11 91.37 91.77 91.90 91.93 92.00 92.01 92.11 92.27 92.32 92.41 92.46 92.46 92.48 92.85 92.92 93.04 93.15 93.24 93.62 1.0 Notes 1110004F10Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page7 Rad51ap1 Mrps18b Enoph1 Anp32b Pdcd11 Rbmx2 Psmd6 Psmd2 Psmc5 Psma4 Zwilch Cenph Polr1c Rpap3 Bend3 Cand1 Wdr55 Cdc20 Hspe1 Ddx20 Hspa4 Tubg1 Thoc3 Thoc6 Nudt1 Utp15 Utp20 Nif3l1 Dus1l Smn1 Tcof1 Lsm4 Gpn1 Srsf9 Wdr4 Xpo1 Shq1 Hus1 Cdk1 Pcna Eif4e Rrp8 Hdgf Cdt1 Tsr1 Ppie Rcl1 Lig1 Nkrf 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 83.24 83.26 83.27 83.32 83.33 83.36 83.66 83.81 83.90 84.19 84.30 84.32 84.38 84.52 84.56 84.66 84.70 84.76 84.79 84.83 84.92 85.13 85.27 85.42 85.54 85.58 85.67 85.86 85.93 85.98 86.07 86.15 86.27 86.30 86.36 86.40 86.44 86.53 86.62 86.68 86.73 86.95 87.01 87.04 87.08 87.14 87.23 87.38 87.68 87.80 1.0 Notes 2700029M09Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page8 Tomm70a Tomm40 Psmd14 Timm23 Fastkd5 Fam98b Ndufaf6 Gemin5 Nup160 Cdc123 Mthfd1l Mrps10 Gtpbp4 Aarsd1 Rbm19 Trmt11 Psmd1 Cenpw Psmc2 Bub1b Lrrc40 Wdr43 Cpsf3l Ddx21 Ddx46 Eif2b1 Syce2 Aurkb Aurka Cetn3 Trmt6 Abcf2 Pcgf6 Rpl14 Spdl1 Bzw1 Cnbp Pycrl Rpa1 Xpo5 Tfam Orc1 Melk Hars Dbf4 Naf1 Bysl Plk4 Ltv1 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 79.04 79.11 79.12 79.18 79.24 79.25 79.49 79.67 79.72 79.82 79.96 79.97 80.00 80.12 80.32 80.36 80.38 80.41 80.49 80.74 80.92 80.97 80.98 80.99 81.07 81.37 81.65 81.81 81.83 81.84 81.99 82.04 82.11 82.25 82.26 82.27 82.32 82.35 82.40 82.43 82.44 82.46 82.52 82.69 82.85 82.90 83.04 83.09 83.09 83.12 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page9 Rnaseh2b Timeless Smarcc1 Magohb Ndufaf2 Gemin2 Chchd4 Exosc4 Mrps27 Psmb6 Smyd5 Psmc3 Mrpl37 Mrpl12 Mrpl22 Gtf2e1 Dnmt1 Ythdf2 Chtf18 Cops4 Nop10 Wdr36 Spc24 Fbxo5 Rrp12 Prps1 Parp1 l7Rn6 Asf1a Eme1 Mbd3 Myg1 Med4 Srsf1 Bop1 Nob1 Kti12 Kif22 Ppa1 Qtrt1 Leo1 Mars Dbr1 Clpp Krr1 Dhfr Blm Pbk Ssb Mif 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 73.58 73.58 73.63 73.72 73.85 73.90 73.90 73.94 74.23 74.41 74.52 74.53 74.56 74.62 74.80 74.82 75.03 75.04 75.26 75.40 75.45 75.72 75.74 75.76 75.76 76.13 76.17 76.34 76.39 76.59 76.60 76.80 76.93 76.98 77.12 77.22 77.36 77.38 77.43 77.59 77.75 78.16 78.20 78.25 78.28 78.31 78.43 78.58 78.93 78.95 1.0 Notes 1810009A15Rik 1110004E09Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page10 Mphosph6 Hsp90ab1 Cdk2ap1 Psmc3ip Dnajc11 Ctnnbl1 Ncapd2 Zc3hc1 Atad3a Nap1l1 Psmb2 Psmb5 Pgam5 Dnph1 Nufip1 Srsf10 Aimp1 Ncbp2 Ncaph Ssbp1 Rfwd3 Snrpg Prmt3 Gins4 Brca1 Pprc1 Amd1 Atad2 Nat10 Riok2 Pold1 Siva1 Lsm6 Txnl1 Gtf3a Gsg2 Wdr5 Pop1 Ppan Cdc7 Dcps Aaas Cks2 Lsg1 Drg2 Rrp9 Dars Parl 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 68.62 68.64 68.65 68.75 68.88 68.88 69.02 69.21 69.25 69.26 69.30 69.49 69.68 69.83 69.84 70.03 70.53 70.59 70.87 71.29 71.31 71.33 71.35 71.49 71.49 71.56 71.64 71.70 71.73 71.75 71.94 72.21 72.23 72.51 72.54 72.54 72.58 72.62 72.65 72.67 72.74 72.83 72.85 72.95 72.96 73.01 73.22 73.28 73.30 73.40 1.0 Notes Mphosph10 Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page11 Fam60a Prps1l3 Shcbp1 Nucks1 Mrps30 Zc3h15 Tada2a Rbm34 Psmb3 Dnajc9 Psmd5 Lmnb2 Psma2 Mrpl42 Incenp Mrpl47 Lrpprc Pitrm1 Polr3h Rbbp7 Polr1a Ncapg Cdca4 Cdca8 Tnpo3 Snrpe Cenpi Ube2t Eif3m Sf3b5 Pus7l Ipo11 Vwa9 Bzw2 Prpf4 Gps1 Blmh Pus1 Rcc2 Mtbp Lap3 Orc2 Urb2 Api5 Tars Esf1 Plk1 Fxn Tk1 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 63.33 63.72 63.78 63.99 64.02 64.37 64.40 64.55 64.96 64.96 65.26 65.33 65.37 65.37 65.68 65.81 65.89 65.94 66.05 66.06 66.10 66.20 66.30 66.38 66.42 66.45 66.56 66.58 66.64 66.74 66.75 66.97 66.97 67.10 67.17 67.18 67.37 67.39 67.45 67.60 67.69 67.77 67.77 68.16 68.21 68.32 68.41 68.44 68.51 68.57 1.0 Notes 9130401M01Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page12 Timm17a Smarca5 Wbscr16 Tomm20 Tmem11 Timm13 Caprin1 Mms22l Anp32e Nup188 Rad54b Mrps17 Hmgb3 Psmb7 Psmb4 Mrpl50 Whsc1 Rangrf Wdr77 Cenpk Nup88 Nop14 Ddx49 Pcbp1 Nsfl1c Gstcd Sarnp Mybl2 Myef2 Prim2 Atad5 Psip1 Espl1 Smc3 Mnd1 Rrm2 Ccnh Hax1 Eif3c Ints7 Tpx2 Rrn3 Oip5 Abt1 Sfpq Rtcb Rfc2 Ipo9 Iars 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 58.37 58.39 58.40 58.44 58.44 58.51 58.60 58.76 58.79 58.86 58.95 58.97 59.02 59.16 59.17 59.40 59.44 59.46 59.64 59.86 60.09 60.10 60.13 60.33 60.43 60.92 60.99 61.03 61.04 61.07 61.19 61.21 61.27 61.37 61.37 61.54 61.58 61.66 61.75 61.99 62.07 62.08 62.17 62.36 62.44 62.80 62.97 63.07 63.20 63.26 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page13 Arhgap11a Mis18bp1 Nsmce4a Anapc15 Tmem97 Rabggtb Ankrd32 Fam72a Prpf40a Syncrip Anapc1 Exosc1 Zmym1 Otud6b Serbp1 Nt5dc2 Mrpl44 Cenpn Hsph1 Wdr73 Ppp5c Ddx51 Pspc1 Ewsr1 Eif2s2 Fancb Lrwd1 Asf1b Trub1 Galk1 Nol10 Sgol1 H2afx Noc3l Pms2 Etaa1 Mogs Glrx3 Brix1 Birc5 Srsf7 Cstf2 Nelfe Ybx1 Ppil3 Ints2 Rfc1 Ifrd2 Eed Aqr 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 52.47 52.60 52.62 52.62 52.72 52.76 53.11 53.12 53.25 53.32 53.41 53.42 53.45 53.51 53.85 53.97 54.25 54.33 54.46 54.53 54.56 54.57 54.65 54.67 54.82 54.84 55.28 55.41 55.44 55.55 55.56 55.60 55.64 56.02 56.07 56.13 56.17 56.27 56.32 56.41 56.47 56.71 56.83 56.93 57.02 57.11 57.25 57.66 57.78 58.34 1.0 Notes 0610009D07Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page14 Tmem209 Aasdhppt Rnaseh1 Snrnp25 Champ1 Trmt10c Timm10 Tubb4b Cdc25a Exosc9 Exosc5 Mrps35 Prkrip1 Mettl13 Recql4 Mrpl46 Mrpl13 Heatr3 Cenpp Knop1 Shmt2 Wdr46 Haus3 Haus5 Enkd1 Ube2c Naa25 Mrps7 Thoc5 Gtf2f1 Mettl1 Parp2 Kntc1 Cpsf3 Park7 Eef1d Pole3 Pcid2 Ndc1 Diexf Noa1 Ece2 Ska3 Mtx1 Gnl2 Slirp Ccnf Elp3 Taf5 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 47.51 47.54 47.67 47.73 47.80 47.81 47.86 47.91 48.03 48.07 48.65 48.73 48.87 48.96 49.05 49.06 49.06 49.19 49.37 49.41 49.42 49.44 49.65 49.69 49.71 49.81 49.82 49.91 49.92 49.96 49.98 50.05 50.12 50.20 50.23 50.29 50.33 50.40 50.51 50.55 50.71 50.81 50.99 51.12 51.20 51.32 51.58 51.88 51.91 51.99 1.0 Notes D030056L22Rik A430005L14Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page15 D2Wsu81e BC003965 Xrcc6bp1 Mmachc Ppp2r1b Trmt10a Mrps28 Dazap1 Isg20l2 Cnot11 Rnf219 Rbm12 Rps27l Nap1l4 Rad54l Mrpl28 Mrpl45 Mrpl40 Mrpl39 Cenpu Cops2 Ckap2 Ccna2 Ccne2 Cdca2 Eif1ad Spag5 Qtrtd1 Esco2 Pus10 Msto1 Dars2 Cpsf1 Trmt5 Pycr2 Clhc1 Mrpl2 Sart3 Srsf3 Coa7 Kif11 Adss Usp1 Ftsj1 Ect2 Gtl3 Coil Nvl 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 43.08 43.43 43.71 43.74 43.74 43.84 43.90 43.95 44.17 44.18 44.22 44.24 44.38 44.49 44.57 44.65 44.67 44.78 44.79 44.94 45.09 45.10 45.31 45.34 45.36 45.41 45.43 45.55 45.58 45.61 45.89 45.89 46.03 46.09 46.19 46.23 46.35 46.36 46.56 46.59 46.60 46.68 46.80 46.80 46.93 47.09 47.20 47.26 47.36 47.47 1.0 Notes 4930579G24Rik 2610318N02Rik 2410127L17Rik Gadd45gip1 Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page16 Fam133b Racgap1 Tomm22 Timm44 Slc19a1 Mcmbp Arl6ip4 Mis18a Rnf126 Wbp11 Mrpl49 Mrpl16 Prpf4b Gtf3c4 Nubp2 Cenpq Nup50 Nelfcd Cenpe Wdr89 Kpna3 Cdc37 Kif18a Ppp4c Rad18 Hspa9 Dhx29 Vprbp Rrp1b Xrcc5 Bola2 Puf60 Pold3 Pms1 Tars2 Elac2 Pwp2 Tyw3 Coq7 Pop4 Toe1 Gars Mlh1 Utp3 E2f7 Eri1 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 37.35 37.54 37.56 37.57 37.68 38.29 38.43 38.53 38.72 38.92 38.95 38.95 39.08 39.20 39.23 39.25 39.53 39.59 39.59 39.66 39.78 39.88 40.40 40.47 40.54 40.59 40.65 40.78 40.87 41.20 41.21 41.27 41.42 41.42 41.43 41.59 41.61 41.68 41.74 42.01 42.02 42.06 42.18 42.27 42.30 42.47 42.51 42.67 42.69 42.85 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page17 Casp8ap2 Thumpd3 Ndufaf4 Mrps33 Mrps25 Kansl2 Cbwd1 Lmnb1 Smc1a Dhodh Polr2g Polr1d Nubp1 Lrrc47 Ubap2 Nedd8 Cops6 Hddc2 Eif2b4 Sdad1 Ndc80 Haus6 Ddx47 Cep57 Dtwd1 Gtse1 Cpsf2 Hmbs Chd1l Nme7 Nme6 Sfxn1 Palb2 Gpn3 Surf6 Mns1 Dohh Trnt1 Xpo7 Eif5b Nek2 Tdp2 Anln Xpot Nuf2 Rtca Eif3i Lars Nbn Mtrr 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 31.78 31.82 32.07 32.31 32.34 32.41 32.49 32.51 32.59 32.75 32.75 32.83 32.90 33.19 33.21 33.46 33.55 33.61 33.64 33.95 33.96 33.98 33.99 33.99 34.01 34.04 34.33 34.50 34.61 34.79 34.81 34.83 34.97 35.12 35.43 35.44 35.52 35.96 36.26 36.30 36.38 36.39 36.46 36.62 36.69 36.74 36.96 37.00 37.24 37.32 1.0 Notes 2310057M21Rik D19Bwg1357e Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page18 Smarce1 Samm50 Hnrnpa0 Gpatch4 Hmgxb4 Fam98a Ncapg2 Ccp110 Pphln1 Eefsec Psme3 Mcph1 Gtf2h5 Lrrc59 Pacrgl Ccnb2 Rpp14 Cops8 Cep55 Cdc26 Mrps9 Mettl2 Mettl5 Brca2 Cpsf4 Abcf1 Phf10 Larp1 Emc6 Taf11 Bub3 Cdk8 Dap3 Eif4b Nelfa Eif3a Phax Taf5l Orc3 Prep Prc1 Vars Nol8 Nle1 Gfer Srrt Stil Atr 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 26.16 26.21 26.22 26.34 26.47 27.19 27.69 27.73 27.78 27.96 28.15 28.17 28.20 28.40 28.41 28.51 28.54 28.61 28.69 28.69 28.75 28.94 29.22 29.27 29.29 29.52 29.87 30.13 30.16 30.32 30.39 30.51 30.68 30.75 30.84 30.91 30.93 30.93 30.95 31.00 31.06 31.16 31.16 31.28 31.44 31.57 31.62 31.66 31.67 31.77 1.0 Notes 2410016O06Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page19 Ube2cbp Ccdc101 Trmt61a L3mbtl2 N6amt2 Ccdc34 Cdc25c Mrps12 Hnrnpc Parpbp U2surp Cenpm Trmt2a Supt16 Smyd2 Psmd3 Pmpca Ino80e Grpel1 Pitpnb Ccne1 Rad50 Cd320 Haus4 Ddx11 Dhx33 Spag7 Poc1a Cenpf Pfdn1 Trap1 Sgol2 Pinx1 Lsm1 Brip1 Prpf8 Dph2 Nanp Hint1 Nmt2 Xpo4 Elof1 Nde1 Mtfr2 Eif5a Nars Iws1 Elp5 Me2 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 20.34 20.38 20.49 20.49 20.55 20.56 20.70 20.90 20.90 20.91 21.13 21.23 21.26 21.61 21.70 21.87 22.04 22.09 22.16 22.23 22.27 22.30 22.38 22.45 22.57 22.62 23.29 23.37 23.64 23.75 24.37 24.39 24.42 24.76 24.79 25.09 25.14 25.23 25.42 25.42 25.57 25.63 25.71 25.74 25.75 25.82 25.89 25.95 25.96 26.12 1.0 Notes 9430016H08Rik 1110008L16Rik 4632434I11Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page20 BC027231 Smarcad1 Tmem201 Fra10ac1 Slc39a10 Hspbp1 Cep192 Arpp19 Polr2m Ubqln4 Rnf168 Rbm14 Kdm1a Txnrd1 Kdelc1 Mthfd2 Cwc27 Cwc22 Gtf2h3 Med17 Armc6 Ythdf1 Dhx36 Pds5b Cep78 Apex2 Slmo2 Sap30 Sec13 Jagn1 Tcea1 Mis12 Pomp Adat2 Nol12 Recql H2afz Ttll12 Wee1 Glmn Crls1 Dsn1 Cyc1 Imp3 Mtx2 Fus Dut 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 16.90 17.05 17.12 17.16 17.18 17.18 17.20 17.41 17.45 17.52 17.53 17.58 17.70 17.77 17.82 17.86 17.95 18.02 18.10 18.12 18.13 18.29 18.40 18.46 18.58 18.63 18.66 18.82 18.88 18.89 19.05 19.07 19.15 19.26 19.28 19.46 19.50 19.50 19.51 19.52 19.53 19.71 19.87 19.90 20.08 20.10 20.12 20.16 20.21 20.25 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page21 Cdkn2aipnl BC030867 Eif4enif1 Tubgcp2 Hnrnph1 Mrps18a Khdrbs1 Dnajc24 Gabpb1 Ncaph2 Pabpc4 Ddx19a Mrps26 Arl6ip6 Agpat5 Hmgn5 Dmap1 Sumo1 Cdca7l Dnaja1 Isyna1 Carm1 Polr3g Gtf3c5 Cactin Usp37 Cdc73 Mcrs1 Foxk2 Prmt6 Gnb1l Rars2 Aspm Aifm1 Nupl1 Xrcc1 Sf3b4 Luc7l Psph Nae1 Pask Mtap Orc5 Zzz3 Lias Eri2 Kif4 Pnn Rif1 Ak2 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 12.06 12.09 12.14 12.15 12.26 12.30 12.31 12.42 12.47 12.49 12.90 12.92 13.05 13.13 13.13 13.19 13.20 13.21 13.29 13.34 13.40 13.49 13.50 13.70 13.88 14.08 14.25 14.40 14.44 14.48 14.53 14.61 14.86 14.95 15.14 15.17 15.40 15.52 15.60 15.91 15.99 16.13 16.15 16.28 16.31 16.54 16.57 16.62 16.76 16.77 1.0 Notes 2810417H13Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page22 Rnaseh2c Depdc1a Snrnp35 Pak1ip1 Timm22 Fgfr1op Armc10 Ranbp3 Cenpc1 Morf4l2 Sac3d1 Mrps23 Rprd1b Kbtbd8 Atp5g1 Rnmtl1 Psmg4 Psmd4 Efcab7 Psmd9 Mrpl34 Mrpl36 Ppwd1 Med21 G3bp2 Rbbp8 Acbd6 Ddx10 Cep44 Vdac1 Zc3h8 Mnat1 Chtop Jade3 Polr2i Cenpl Setd6 Mastl Gen1 Ddb1 Aven Nek4 Bora Ctu2 Ttc4 Lin9 Ttll4 Rdx Vcp 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 7.80 7.88 7.88 8.12 8.13 8.18 8.18 8.24 8.24 8.37 8.73 8.74 8.76 8.86 9.31 9.53 9.63 9.64 9.78 9.84 9.85 9.95 9.99 10.00 10.15 10.20 10.27 10.40 10.44 10.46 10.49 10.53 10.63 10.83 10.95 11.06 11.09 11.14 11.25 11.27 11.28 11.39 11.49 11.50 11.63 11.64 11.66 11.85 11.91 12.00 1.0 Notes 2700097O09Rik Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page23 Fam203a Commd1 Mrps18c Hnrnpa3 Chordc1 Ankrd26 Ankrd49 Nsmce2 Timm21 Nusap1 Wrap53 Ccdc43 Sapcd2 Mapre1 Mrps31 Ckap2l Trim59 Mrpl20 Mrpl55 Adrm1 Srsf11 Stmn1 Ddx52 Ddx31 Pdcd2 Pebp1 Hdac1 Ddx41 Srp68 U2af2 Metrn Fancf Fanci Ngdn Snx5 Tefm Ska2 Yrdc Npat Rnf4 Ssr2 Alg3 Alg6 Ydjc Taf2 Rtf1 Pigf Hn1 Pdf 0.0 1.0

GSE13693 [9] GSE30160 [6]

GSE1435 [27] Scale ofaveragePearsoncorrelations GSE4260 [6] GSE11766 [48] GSE6085 [43] GSE11572 [12] GSE14698 [12] GSE23040 [6] 0.2 GSE53946 [6] GSE50865 [12] GSE15121 [6] GSE24628 [16] GSE7324 [10] GSE12430 [21] GSE57543 [6] GSE36814 [20] GSE3126 [6] 0.4 GSE5236 [8] GSE28417 [12] GSE13225 [6] GSE10813 [12] GSE46185 [6] GSE27159 [8] GSE6030 [6] GSE33942 [12] GSE23600 [10] 0.6 GSE40230 [15] GSE34324 [12] GSE10871 [32] GSE23923 [8] GSE5309 [7] GSE43197 [27] GSE27378 [8] GSE9725 [16] GSE43381 [26] 0.8 GSE14753 [6] GSE12518 [6] GSE13149 [25] GSE49194 [14] Score 2.27 2.35 2.59 2.61 2.66 2.81 3.16 3.19 3.21 3.21 3.58 3.71 3.75 3.78 3.79 3.90 4.29 4.37 4.39 4.41 4.50 4.55 4.66 4.66 5.10 5.17 5.17 5.25 5.29 5.29 5.76 5.85 5.89 5.96 6.07 6.09 6.33 6.39 6.43 6.44 6.65 6.69 6.80 6.85 6.90 6.95 7.00 7.45 7.72 7.77 1.0 Notes Symbol Num ofCEMGenes:6.Predicted1177.SelectedDatasets:212.Strength:1.4 CEM 1,Geneset"[C]URIcomplex",Page24 Ccdc124 Ccdc115 Smchd1 Cops7a Zdhhc6 Dhrs13 Rbm27 Alkbh1 Smek1 Zfp566 Hnrnpl Med14 Atpaf2 Kif18b Wdr90 Cep76 Cebpz Naa20 Fancl Srsf4 Bag2 Pop7 Vbp1 Pdhx Tufm Lipt2 Ints3 Gle1 Rbl1 Hprt Sfr1 Lzic Aen 0.0 1.0

GSE13693 [9] GSE30160 [6]

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 (0.181983)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.182794)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.196861)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.102334) (0.172109)[ min(0.120994) (0.0184904)] (0.00981973)[ (0.0146147) medium ] [ max ] CEM 1 Ruvbl1 99.1 1798.6 3430.5 P ( S | Z, I ) = 1.00 Ruvbl2 801.3 3537.4 4675.6 Mean Corr = 0.95666 Pfdn2 210.7 1344.0 2607.6 Skp2 11.2 1026.7 1573.8 Skp1a 1207.2 3742.5 4159.2 Cul1 2272.2 3190.8 3843.1 Prmt1 117.6 2183.1 4329.4 Lyar 164.8 2735.4 3850.5 Cse1l 102.6 4073.4 5438.9 Ebna1bp2 569.0 2759.1 3094.8 Gart 768.0 4374.1 6668.8 CEM 1 + Cct5 2225.7 9662.1 12413.9 Top 10 Genes Apex1 39.4 2873.5 6647.1 Sf3a3 239.7 2372.2 2903.6 Ddx18 68.3 1544.0 2204.4 C1qbp 71.3 4783.5 8819.7

Null module Uri1 Stap1 Polr2e 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 (0.40568)knockin replicate 2 (0.0641174)knockin replicate 3 (0.0423092)knock replicate 1 (0.180141) in replicate 2 (0.14426) 3 (0.163493)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 595.6 930.0 1338.9 P ( S | Z, I ) = 1.00 Ruvbl2 935.2 1661.8 1957.2 Mean Corr = 0.91914 Pfdn2 2068.5 3235.0 4225.7 Skp2 622.7 736.9 976.0 Skp1a 6408.4 6728.5 7358.7 Cul1 1471.4 1802.5 2027.9 Prmt1 1965.6 5279.2 6893.9 Lyar 592.3 1314.6 2067.9 Cse1l 1462.2 2577.8 3593.6 Ebna1bp2 968.7 2048.0 2786.5 Gart 594.8 1240.3 2122.0 CEM 1 + Cct5 8475.3 10634.0 12343.5 Top 10 Genes Apex1 1901.6 4572.6 6302.3 Sf3a3 1456.4 1829.1 2353.5 Ddx18 879.8 1390.0 1806.5 C1qbp 3445.2 7003.9 8124.8

Null module Uri1 Stap1 Polr2e 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 (0.119056) day lung-embryoMouse 14-rep1 (0.123895) day lung-embryoMouse 14-rep2 (0.0908429) day lung-embryoMouse 16-rep1 (0.0786238) day lung-embryoMouse 16-rep2 (0.0324516) day lung-postnatalMouse 18-rep1 (0.0413877) day lung-postnatalMouse 18-rep2 (0.0420464) lung-postnatalMouseday (0.0244404) 2-rep1 lung-postnatalMouseday (0.0235738)2-rep2 lung-postnatalMouseday (0.0416957)10-rep1 lung-postnatalday 10-rep2 (0.0504915) day 30-rep1 (0.046797) day 30-rep2 (0.146221)[ min (0.138477) ] [ medium ] [ max ] CEM 1 Ruvbl1 575.6 909.4 2606.2 P ( S | Z, I ) = 1.00 Ruvbl2 1614.3 2471.8 5246.8 Mean Corr = 0.90918 Pfdn2 765.1 1182.3 2222.8 Skp2 211.2 724.0 5533.3 Skp1a 4268.7 5066.0 7703.7 Cul1 1473.2 2174.3 2683.0 Prmt1 1436.3 2954.3 11153.7 Lyar 594.6 725.0 2749.1 Cse1l 1314.9 1992.3 5345.2 Ebna1bp2 737.5 975.6 2171.0 Gart 594.8 763.9 2397.9 CEM 1 + Cct5 4203.3 7271.5 11387.3 Top 10 Genes Apex1 504.0 1010.6 5123.2 Sf3a3 903.2 1178.3 3102.8 Ddx18 835.1 1094.4 2984.6 C1qbp 1112.9 1403.9 4761.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE12465" 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=GSE12465 Status: Public on May 20 2009 Title: Transcriptional signatures of Itk-deficiency using CD3+, CD4+ and CD8+ T-cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19450280 Summary & Design: Summary: The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3+ T-cells, including CD4+ and CD8+ subsets, using Affymetrix microarrays. The largest difference between Itk-/- and Wt CD3+ T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4+ and CD8+ T-cell subsets identified a greater differential expression than in total CD3+ cells. Cyclosporin (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the Bub1, IL7R, Ctla2a, Ctla2b, and Schlafen1 genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found. Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.

Overall design: CD3+ CD4+ and CD8+ T-cells from pooled suspensions of spleen and lymph nodes of Wt and Itk knockout mice on C57BL/6 background were isolated after negative depletion. Unstimulated as well as stimulated T-cells were studied. Stimulations were done with anti-CD3 (1 mg/ml) for 24 hrs. For the CD4+ T-cells we collected triplicates from the Itk knockout mice and duplicates from the Wt group. For the CD8+ T-cells, we got duplicates from Itk knockout , while we obtained a single sample from Wt owing to the low cell yield for resting Wt CD8+ T-cells. After CD3-stimulation we got a single sample from the CD8+ subset of both Wt and Itk knockout, while for the CD4+ subsets we collected duplicates.

Background corr dist: KL-Divergence = 0.0403, L1-Distance = 0.0459, L2-Distance = 0.0032, Normal std = 0.6284

0.635 Kernel fit Pairwise Correlations Normal fit

Density 0.317

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 CD4+ typeItk unstimulated CD4+knockoutItk unstimulated knockout CD4+ 1Itk (0.050686) knockout unstimulated CD4+ 2Wild (0.0288194) unstimulated typeCD4+Itk CD8+1knockout unstimulated(0.0686715)Itk unstimulated 2knockout (0.0747526) CD8+Wild 3 unstimulated (0.0542132) typeCD8+ (0.0422677)Wild CD4+ unstimulated typeItk CD3-stimulated CD4+1knockout (0.0643316)Itk CD3-stimulated 2knockout (0.0498897) CD4+Wild 1 (0.164842)CD3-stimulated typeCD4+Itk 2 CD8+knockout (0.119797)CD3-stimulated CD3-stimulated 1CD8+ (0.0566112) CD3-stimulated 2 (0.0449856) (0.168869)[ min (0.0112633) ] [ medium ] [ max ] CEM 1 Ruvbl1 479.1 981.4 2571.6 P ( S | Z, I ) = 1.00 Ruvbl2 919.5 1780.4 3410.2 Mean Corr = 0.90427 Pfdn2 1504.0 1915.1 3529.3 Skp2 134.4 341.9 939.7 Skp1a 3376.9 4593.7 6065.6 Cul1 1460.6 2009.6 3116.4 Prmt1 1011.5 1473.2 3651.0 Lyar 954.0 1616.3 6607.6 Cse1l 2346.3 3134.0 6019.1 Ebna1bp2 1369.2 2029.6 4931.7 Gart 2380.7 3945.4 7213.3 CEM 1 + Cct5 5897.3 8398.7 12594.9 Top 10 Genes Apex1 1189.5 2458.8 4680.8 Sf3a3 1556.6 2057.2 3292.8 Ddx18 812.7 1596.4 2940.3 C1qbp 1752.7 3362.1 8543.8

Null module Uri1 Stap1 Polr2e GEO Series "GSE6998" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 32 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6998 Status: Public on Feb 09 2007 Title: Expression profiling of developmental and regenerating liver in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17227769 Summary & Design: Summary: Normal adult liver is uniquely capable of renewal

and repair after injury. Whether this response

represents simple hyperplasia of various liver elements

or requires recapitulation of the genetic program of

the developing liver is not known. To study these possibilities,

we examined transcriptional programs of

adult liver after partial hepatectomy and contrasted

these with developing embryonic liver. Principal component

analysis demonstrated that the time series of

gene expression during liver regeneration does not segregate

according to developmental transcription patterns.

Gene ontology analysis revealed that liver restoration

after hepatectomy and liver development differ

dramatically with regard to transcription factors

and chromatin structure modification. In contrast, the

tissues are similar with regard to proliferationassociated

genes. Consistent with these findings, realtime

polymerase chain reaction showed transcription

factors known to be important in liver development

are not induced during liver regeneration. These three

lines of evidence suggest that at a transcriptional level,

restoration of liver mass after injury is best described

as hepatocyte hyperplasia and not true regeneration.

We speculate this novel pattern of gene expression may

underlie the unique capacity of the liver to repair itself

after injury.

Keywords: time course

Overall design: Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.

Background corr dist: KL-Divergence = 0.0534, L1-Distance = 0.0220, L2-Distance = 0.0006, Normal std = 0.5487

0.727 Kernel fit Pairwise Correlations Normal fit

Density 0.364

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

baselinebaseline sampleregeneration sampleat T0,regeneration rep1 at T0, (0.0107465)sampleregeneration rep2 (0.0158557) sampleatregeneration T1, rep1 sampleatregeneration T1, (0.0347793) rep2 sampleatregeneration T2, (0.0333565) rep1 sampleatregeneration T2, (0.0225209) rep2 sampleatregeneration T6, (0.0286595) rep1 sampleatregeneration T6, (0.020922) rep2 sampleatregeneration T12, (0.0578479) samplerep1atregeneration T12, (0.0180222) samplerep2atregeneration T18, (0.028763) samplerep1atregeneration T18, (0.0235944) samplerep2atregeneration T24, (0.022483) samplerep1atregeneration T24, (0.0153861) samplerep2atregeneration T30, (0.0161903) samplerep1atregeneration T30, (0.0120116) samplerep2atregeneration T48, (0.0113763) samplerep1atdevelopmental T48, (0.0153045) samplerep2atdevelopmental T72, (0.033849) rep1at developmentalsample T72, (0.00954771) rep2 developmental sampleat T105,(0.0199789) developmental sampleat rep1 T105, (0.0764031) developmental sampleat rep2 T115, (0.121127) developmental sampleat rep1 T115, (0.0689259) developmental sampleat rep2 T125, (0.0936337) developmental sampleat rep1 T125, (0.0303131) developmental sampleat rep2 T135, (0.0406151) developmental sampleat rep1 T135, (0.0284261) developmental sampleat rep2 T145, (0.031185) sampleat rep1 T145, (0.0153751) sampleat rep2 T165, (0.0184522) at rep1 T165, (0.0138054)[ rep2min (0.0105433) ] [ medium ] [ max ] CEM 1 Ruvbl1 337.7 571.5 2260.6 P ( S | Z, I ) = 1.00 Ruvbl2 130.9 519.4 4070.4 Mean Corr = 0.89389 Pfdn2 209.3 1181.8 2560.5 Skp2 3.5 28.0 2059.3 Skp1a 1349.0 2539.0 5226.3 Cul1 1105.6 1384.9 2429.0 Prmt1 272.8 493.6 5441.7 Lyar 323.2 534.8 3406.1 Cse1l 670.5 993.2 4288.8 Ebna1bp2 329.9 647.0 1821.7 Gart 296.1 566.5 3078.0 CEM 1 + Cct5 1217.9 2622.9 8179.1 Top 10 Genes Apex1 1205.5 2496.8 5230.3 Sf3a3 699.3 1134.9 2540.7 Ddx18 327.8 515.9 1703.8 C1qbp 1203.6 2220.1 6083.2

Null module Uri1 Stap1 Polr2e GEO Series "GSE13692" 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=GSE13692 Status: Public on Feb 06 2009 Title: Expression profiling of MLL-AF10 myeloid leukemia cellular subsets Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.

Overall design: Leukemic splenocytes from four mice with MLL-AF10 AML were sub-fractionated in to c-kit high and c-kit negative sub-populations by FACS.

Background corr dist: KL-Divergence = 0.0464, L1-Distance = 0.0346, L2-Distance = 0.0017, Normal std = 0.6099

0.681 Kernel fit Pairwise Correlations Normal fit

Density 0.341

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

MLL-AF10MLL-AF10 LEUKEMICMLL-AF10 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_948 LEUKEMIC MLL-AF10SPLENOCYTES_CD117POS_948 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_951 LEUKEMIC MLL-AF10SPLENOCYTES_CD117POS_951 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_952 LEUKEMIC(0.159074) SPLENOCYTES_CD117POS_952 LEUKEMIC(0.12458) SPLENOCYTES_CD117NEG_953 (0.11982) SPLENOCYTES_CD117POS_953 (0.119037)[ min(0.0903306) (0.160658) ] (0.0979608) [(0.128539) medium ] [ max ] CEM 1 Ruvbl1 816.3 1598.6 2774.2 P ( S | Z, I ) = 1.00 Ruvbl2 1487.6 3044.8 3674.0 Mean Corr = 0.89256 Pfdn2 928.4 2089.2 2444.0 Skp2 724.1 2201.0 2998.2 Skp1a 2244.2 4384.4 5087.2 Cul1 3738.9 4553.5 4990.0 Prmt1 838.4 2100.4 4536.5 Lyar 1002.6 1872.6 2496.2 Cse1l 2803.1 3744.9 5952.0 Ebna1bp2 1262.4 2291.4 2731.3 Gart 1257.7 4182.9 5234.6 CEM 1 + Cct5 6486.9 8703.5 11094.5 Top 10 Genes Apex1 1610.6 3397.9 4563.7 Sf3a3 1048.0 1329.1 2265.5 Ddx18 557.2 730.0 1532.4 C1qbp 1424.5 3168.0 5039.1

Null module Uri1 Stap1 Polr2e GEO Series "GSE48204" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl NMuMGNMuMG NMuMG cells, NMuMGreplicate cells cells, treated NMuMGreplicate cells 1 (0.172453) treatedbyNMuMG cells 211 (0.207969) days treatedby cells 11 with days treatedby 4ng/ml 11 with days by TGF-Î²,4ng/ml 11 with days [ TGF-Î²,4ng/mlfollowed minwith TGF-Î²,4ng/mlfollowed by ] TGF-Î² TGF-Î²,replicate by withdrawlTGF-Î² replicate 1[ (0.0968111) withdrawlmedium for 2 another(0.13143) for another 13 days,] 13 replicate days, replicate[ 1 max(0.216611) 2 (0.174726) ] CEM 1 Ruvbl1 967.1 1540.7 2351.3 P ( S | Z, I ) = 1.00 Ruvbl2 1468.5 3163.1 3898.4 Mean Corr = 0.85417 Pfdn2 2759.2 3745.9 3815.2 Skp2 284.7 1074.2 1373.9 Skp1a 8458.6 9268.6 12111.6 Cul1 1056.6 1162.4 1587.6 Prmt1 4867.8 9136.1 9771.6 Lyar 1105.2 3272.1 3519.4 Cse1l 1940.9 3299.5 4171.2 Ebna1bp2 1758.8 3247.6 3573.8 Gart 1112.6 1822.9 1926.1 CEM 1 + Cct5 11205.6 14540.7 15499.6 Top 10 Genes Apex1 2984.6 3234.2 4009.2 Sf3a3 1086.9 1809.7 1856.2 Ddx18 1731.7 2794.6 2994.4 C1qbp 6558.3 8011.7 8880.4

Null module Uri1 Stap1 Polr2e 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,(0.0840079) rep1 fibroblasts biological embryonicrep1WT,(0.0928484) fibroblasts biological(0.14308) rep2KO, fibroblasts biological (0.0404194) rep3KO,[ biological (0.0347104) min rep1KO, biological(0.270969) rep2] (0.0647898) rep3 (0.269175)[ medium ] [ max ] CEM 1 Ruvbl1 601.9 2828.9 3700.3 P ( S | Z, I ) = 1.00 Ruvbl2 906.7 3785.9 5512.5 Mean Corr = 0.84227 Pfdn2 1481.0 2857.3 3186.3 Skp2 5.3 1721.8 2100.1 Skp1a 5985.8 8626.6 9153.2 Cul1 1599.1 2507.4 2739.4 Prmt1 2017.2 13177.9 16741.7 Lyar 763.8 4210.6 8007.9 Cse1l 1208.2 5246.4 8290.8 Ebna1bp2 892.8 4043.1 5345.1 Gart 645.4 2355.6 3580.1 CEM 1 + Cct5 4900.7 19432.1 21766.2 Top 10 Genes Apex1 740.0 4770.1 6224.9 Sf3a3 881.9 2318.6 4022.3 Ddx18 508.4 3064.4 3210.6 C1qbp 1358.6 9243.0 11592.2

Null module Uri1 Stap1 Polr2e GEO Series "GSE48790" 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=GSE48790 Status: Public on Jul 12 2013 Title: Expression data from GTF2i mutated ES cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23831514 Summary & Design: Summary: Data present the expression analysis of different mouse ES cell line with altered expression of GTF2I.

Overall design: We used microarrays to detail the global programme of gene expression underlying altered expression of GTF2I and identified distinct classes of deregulated genes

Background corr dist: KL-Divergence = 0.0303, L1-Distance = 0.0391, L2-Distance = 0.0018, Normal std = 0.6989

0.613 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

HPRTKO,HPRTKO, biologicalGTF2iTrap biological rep1GTF2iTrap (0.210808)line, rep2Wild-type, biological (0.258489)line,Wild-type, biological biological rep Gtf2i1 (0.0650828) biological rep Mutant rep1 Gtf2i2 (0.0438744) (0.152143) Mutantline, rep2 biological (0.126541) line, biological rep 1 (0.0468171) rep[ 2min (0.0962449) ] [ medium ] [ max ] CEM 1 Ruvbl1 2462.4 2840.7 3407.2 P ( S | Z, I ) = 1.00 Ruvbl2 2199.8 2815.7 4402.3 Mean Corr = 0.83882 Pfdn2 4052.3 5339.4 6446.0 Skp2 1009.3 1153.8 1395.9 Skp1a 10930.1 11473.8 13021.1 Cul1 1522.1 1622.2 1874.9 Prmt1 9395.5 10206.7 12155.4 Lyar 2732.0 3708.9 4751.9 Cse1l 3452.0 4382.8 5063.2 Ebna1bp2 3254.5 3586.9 5554.1 Gart 2157.1 2792.6 5740.2 CEM 1 + Cct5 13935.3 15053.3 15703.3 Top 10 Genes Apex1 7046.5 7800.7 8439.8 Sf3a3 2765.2 3391.0 3785.8 Ddx18 2664.5 2980.8 3478.3 C1qbp 7958.9 8744.7 11695.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE18135" 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=GSE18135 Status: Public on Jan 15 2010 Title: Gene Expression Profile of Androgen Modulated Genes in the Murine Fetal Developing Lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20064212 Summary & Design: Summary: Accumulating evidences suggest that sex affects lung development. During the fetal period, male lung maturation is delayed compared with female and surfactant production appears earlier in female than in male fetal lungs.

We analyzed by microarrays the expression of genes showing a sexual difference and those modulated by endogenous androgens (flutamide).

Overall design: Following flutamide or vehicle administration to pregnant mothers, fetal mouse lungs were studied at gestational day 17 (GD17) and GD18. RNA was extracted and hybridized on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0822, L1-Distance = 0.0567, L2-Distance = 0.0049, Normal std = 0.5081

0.862 Kernel fit Pairwise Correlations Normal fit

Density 0.431

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

FlutamideFlutamide treatedFlutamide treatedmaleVehicule at treatedmaleGD 17,Vehicule at (control) malebiologicalGD 17,Vehicule at (control) biologicalfemaleGD rep1 17,Vehicule (control) at biologicalfemale(0.0341248) GD rep2Vehicule (control)17, at female(0.0297889) biologicalGD rep3Vehicule (control)17, at male(0.0413694) biologicalGDFlutamide rep1 at(control)17, maleGD biological(0.0635288) Flutamide17, rep2at treated malebiologicalGD (0.0416577) Flutamide17, rep3at treated malebiologicalGD (0.0596303)rep1 Vehicule17, at treatedmaleGD biological(0.0805787) rep2 18,Vehicule at (control) malebiologicalGD (0.0506563) rep3 18,Vehicule at (control) biologicalfemaleGD (0.0636731) rep1 18,Vehicule (control) at biologicalfemale(0.0834881) GD rep2Vehicule (control)18, at female(0.0519056) biologicalGD rep3Vehicule (control)18, at male(0.0545283) biologicalGD rep1 at(control)18, maleGD biological(0.0604328) 18, rep2at malebiologicalGD (0.0375378) 18, rep3at biologicalGD (0.0624698)rep1 [18, min biological(0.0979905) rep2 (0.0275428)] rep3 (0.0590962)[ medium ] [ max ] CEM 1 Ruvbl1 726.6 1124.3 1306.7 P ( S | Z, I ) = 1.00 Ruvbl2 2050.8 2788.7 2880.7 Mean Corr = 0.83878 Pfdn2 1535.3 2029.1 2485.3 Skp2 1586.6 3794.1 4600.3 Skp1a 4596.0 6202.6 7358.3 Cul1 1483.8 1668.5 1829.3 Prmt1 2306.3 4535.0 5714.0 Lyar 586.2 1122.2 1544.2 Cse1l 1783.4 3157.1 3753.4 Ebna1bp2 719.4 1044.2 1360.5 Gart 593.5 1022.5 1249.4 CEM 1 + Cct5 6350.2 7913.8 8969.3 Top 10 Genes Apex1 1465.3 3341.2 3974.6 Sf3a3 1371.9 2116.3 2704.0 Ddx18 762.9 1325.0 1472.0 C1qbp 1282.5 2379.7 3173.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE13874" 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=GSE13874 Status: Public on Mar 05 2009 Title: microRNA-1 negatively regulates expression of the hypertrophy-associated genes calmodulin and Mef2a Organism: Mus musculus Experiment type: Non-coding RNA profiling by array Platform: GPL1261 Pubmed ID: 19188439 Summary & Design: Summary: Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, precise regulation of calmodulin expression may be an important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3-untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through the calcineurin to NFAT. miR-1 also negatively regulated expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, Mef2a, and Gata4.

Overall design: We show that miR-1 is downregulated in a murine heart failure model. miRNAs expression changes were measured in calcineurin transgenic model of heart failure and control mice using a Luminex platform. Reduced miR-1 expression was associated with broad alteration in expression of predicted target genes. To test this, we measured miRs including miR-1 and genome wide transcriptome changes in vivo and in vitro system. Calcineurin transgenic heart was compared to nontransgenic heart (NTg vs. CNTg). We also investigated the gene expression changes during the course of cardiomyocytes differentiation using DMSO treated P19CL6 cell lines. Two time points (day 6 and day 10) were compared to identified the gene expression changes of predicted miR-1 targets (Day 6 vs. Day 10).

Background corr dist: KL-Divergence = 0.0212, L1-Distance = 0.0629, L2-Distance = 0.0054, Normal std = 0.8282

0.482 Kernel fit Pairwise Correlations Normal fit

Density 0.241

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

NTg, biologicalNTg, biologicalNTg, replicate biologicalNTg, replicate 1 (Affymetrix) biologicalCalcineurin replicate 2 (Affymetrix)Calcineurin replicate (0.0479724) 3 (Affymetrix)Tg,Calcineurin biological (0.0645268) 4 (Affymetrix)Tg,Calcineurin biological (0.0755842) replicate Tg,Differentiating biological (0.0455596) replicate Tg, 1 (Affymetrix)Differentiating biological replicate 2 P19CL6(Affymetrix)Differentiating replicate (0.0349019) 3 P19CL6(Affymetrix)Differentiating cells (0.0344448) 4at P19CL6(Affymetrix)Differentiating cellsday (0.0250569)6 at afterP19CL6Differentiating cellsday DMSO(0.0379034)6 at afterP19CL6 cellsday treatment, DMSO6 at afterP19CL6 cellsday treatment, DMSO10 at replicate aftercellsday treatment, 10 DMSOat replicate[ afterday 1min (Affymetrix) 10 treatment,DMSO replicate after 2 (Affymetrix)] treatment,DMSO (0.0519049)replicate 3 (Affymetrix) treatment, (0.173897)replicate [1 (Affymetrix)medium (0.139606)replicate 2 (Affymetrix) (0.140325) 3 (Affymetrix) ] (0.0632599) (0.0650564)[ max ] CEM 1 Ruvbl1 414.8 527.3 1963.8 P ( S | Z, I ) = 1.00 Ruvbl2 482.5 730.4 3776.1 Mean Corr = 0.83479 Pfdn2 1413.6 1718.1 5762.8 Skp2 5.2 39.7 1402.0 Skp1a 4192.4 4949.2 11017.3 Cul1 1288.2 1514.0 4218.9 Prmt1 688.2 1608.6 9474.3 Lyar 653.8 856.9 2457.3 Cse1l 1511.4 1758.7 5019.7 Ebna1bp2 469.2 581.3 3128.2 Gart 754.0 1116.6 3612.0 CEM 1 + Cct5 3192.1 3719.6 16262.0 Top 10 Genes Apex1 882.1 1393.6 7127.6 Sf3a3 633.7 850.5 3021.5 Ddx18 647.6 727.1 2675.5 C1qbp 2944.3 4445.1 8171.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE13873" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 27 -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=GSE13873 Status: Public on Mar 05 2009 Title: Expression data from murine gastric epithelium Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19454706 Summary & Design: Summary: Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in a majority of individuals. We report here that the C57Bl6 mouse model of experimental infection with the closely related H. felis recapitulates this wide range in host susceptibility. A majority of infected mice develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia and intestinal metaplasia, whereas a minority is completely protected from preneoplasia. Protection is associated with the failure to mount an IFN-gamma response to the infection and an associated high Helicobacter burden. We demonstrate that IFN-gamma is essential for clearance of Helicobacter, but also mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a specific transcriptional program in murine gastric epithelial cells in vitro and in vivo, and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could provide an explanation for the differential susceptibility to H. pylori-induced gastric pathology in the human population.

Keywords: response to in vitro stimulus / comparison of histopathological states

Overall design: We chose mice for gene expression profiling that following Helicobacter infection had (a) symptoms of gastritis, but no epithelial changes, (b) atrophic gastritis accompanied by corpus gland hyperplasia or (c) atrophic gastritis accompanied by intestinal metaplasia. An uninfected control group was also included in the analysis, as were two groups of mice that lacked mature T- and B-cells due to a deletion mutation in the rag1 gene (Rag-1-/-) and that were either experimentally infected or served as Rag-1-/- uninfected controls. To see the effects of IFNg on murine gastric epithelial cells we analysed an immortalized murine primary gastric epithelial cell line treated with three different concentrations of IFNg in comparison to an untreated control.

Background corr dist: KL-Divergence = 0.0517, L1-Distance = 0.0400, L2-Distance = 0.0031, Normal std = 0.5764

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

IMPGE untreatedIMPGE IFNGIMPGE (0.1337) 1 (0.126848)IFNGIMPGE 2 (0.142994)IFNGstomach 3 (0.109556)stomach uninfectedstomach uninfected 1 (0.0175433)stomach infected 2 (0.0175684)stomach infected gastritisstomach infected gastritis 1 (0.00539448)stomach infected gastritis 2 (0.00710818)stomach infected gastritis 3 (0.0185515)stomach infected metaplasia 4 (0.0119726)stomach infected hyperplasia 1stomach (0.0108796)infected hyperplasia stomach1 infected(0.0176725) hyperplasia stomach2 infected(0.00728038) hyperplasia stomach3 infected(0.0233635) hyperplasia stomach4 infected(0.0262911) metaplasia stomach5 infected(0.0126363) metaplasia 2stomach (0.0457475)infected metaplasia 3stomach (0.0594548)uninfected metaplasia 4stomach (0.00867396)uninfected Rg 5stomach (0.0397673) infected1 (0.0546924) Rgstomach infected2 Rg (0.00918635) 1stomach (0.0132342)infected Rg 2stomach (0.0136187)infected Rg 3 (0.0201806)infected Rg 4 (0.0075115) Rg 5 (0.0385726)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 238.2 397.4 1870.7 P ( S | Z, I ) = 1.00 Ruvbl2 1151.2 1708.7 3495.9 Mean Corr = 0.83057 Pfdn2 532.1 817.9 2270.5 Skp2 114.4 274.4 1310.3 Skp1a 3309.9 5043.0 6480.5 Cul1 780.2 1079.1 2129.6 Prmt1 95.5 680.3 9846.4 Lyar 446.4 805.8 2400.9 Cse1l 929.8 1265.2 4938.3 Ebna1bp2 642.7 951.6 2528.1 Gart 570.2 1125.3 2325.2 CEM 1 + Cct5 4523.9 6904.0 13945.6 Top 10 Genes Apex1 595.5 1121.8 2287.0 Sf3a3 614.4 907.1 2482.0 Ddx18 558.2 763.7 2021.9 C1qbp 2443.4 4189.0 8214.6

Null module Uri1 Stap1 Polr2e 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 (0.0725804) R1.2E7.5Mouse Cells (0.0685976)whole R1.3E7.5Mouse embryo (0.0678779)whole E7.5Mouse embryo tissuewhole E8.5Mouse E7.1embryo tissuewhole E8.5Mouse (0.0498723) E7.2heart tissuewhole E8.5Mouse (0.0504436) tissue E7.3heart whole E9.5Mouse (0.0687887)(heart tissue heart left E9.5Mousetube) ventricle(heart tissue left E8.1 E9.5Mousetube) ventricle(heart tissue (0.0205326) left E8.2 E9.5Mousetube) ventricle E9L.1 tissue (0.026283) right E8.3 E9.5Mouse (0.0147595) E9L.2ventricletissue (0.0251693) right E9.5Mouse (0.0113594) E9L.3ventricle tissueright E12.5Mouse (0.0125223) ventricle E9R.1 tissue left E12.5Mouse ventricle(0.0157855) E9R.2 tissue left E12.5Mouse ventricle(0.0181777) E9R.3tissue left E12.5Mouse ventricle(0.0126628) E12L.1 tissue right E12.5Mouse (0.0017664)E12L.2ventricletissue right E12.5Mouse (0.00246361)E12L.3ventricle tissueright E14.5Mouse (0.00204437)ventricle E12R.1 tissueleft E14.5Mouse ventricle E12R.2(0.00266942) tissueleft E14.5Mouse ventricle tissue E12R.3(0.00301747) left E14.5Mouse ventricle E14L.1 tissue (0.00068388) right E14.5Mouse (0.0036494)E14L.2ventricletissue right E14.5Mouse (0.0105779)E14L.3ventricle tissueright E18.5Mouse (0.00541446)ventricle E14R.1 tissueleft E18.5Mouse ventricle E14R.2(0.00399445) tissueleft E18.5Mouse ventricle tissue E14R.3(0.00243504) left E18.5Mouse ventricle E18L.1 tissue (0.00327598) right E18.5Mouse (0.0238388)E18L.2ventricletissue right E18.5Mouse (0.0102241)E18L.3ventricle tissueright leftMouse (0.00887597)ventricle E18R.1 tissue leftMouse ventricle E18R.2 (0.0072192)tissue leftMouse ventricle atE18R.3 (0.00829485)tissue 3rightMouse days at (0.0069212)ventricletissue after3rightMouse days birth atventricle aftertissue3rightAdult days D3L.1 birth ventricle mouseat aftertissueAdult 3(0.0264854) D3L.2 days birth leftmouseat tissueAdult after3(0.0146034) ventricleD3L.3 days leftbirthmouseatAdult after3(0.0444885) ventricle days D3R.1tissue leftbirthmouseAdult after ventricle (0.0125935) AdltL.1D3R.2tissue rightbirthmouseAdult (0.0143373) AdltL.2(0.0499829)ventricleD3R.3tissue rightmouse (0.0170574) AdltL.3(0.0282934)ventricle tissueright (0.0340378)ventricle AdltR.1 tissue AdltR.2(0.036216)tissue[ min AdltR.3(0.0468087) ] (0.0323166) [ medium ] [ max ] CEM 1 Ruvbl1 486.1 1303.4 4027.2 P ( S | Z, I ) = 1.00 Ruvbl2 433.1 1138.7 3894.8 Mean Corr = 0.82519 Pfdn2 2667.3 3756.3 5996.4 Skp2 37.3 1356.7 4599.1 Skp1a 10660.8 12844.2 20435.1 Cul1 1162.9 1639.6 2764.0 Prmt1 1831.8 9954.9 14747.2 Lyar 1034.6 1580.0 8054.5 Cse1l 1685.6 3459.1 7713.4 Ebna1bp2 667.8 1480.6 4945.6 Gart 585.3 1046.5 6322.8 CEM 1 + Cct5 6219.2 12740.3 22754.6 Top 10 Genes Apex1 884.1 3425.5 9124.8 Sf3a3 741.4 1917.2 4833.6 Ddx18 661.7 1240.8 4987.0 C1qbp 6763.3 8892.0 13261.4

Null module Uri1 Stap1 Polr2e 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(0.141328) (0.0704789)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.0950608)intestine-EphB2Medium-R2 (0.0656116)intestine-EphB2Low-R2 (0.219148) (0.120078) (0.0669704) (0.221324)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 625.5 1795.9 2402.4 P ( S | Z, I ) = 1.00 Ruvbl2 1150.5 3269.6 4237.6 Mean Corr = 0.82466 Pfdn2 408.3 690.4 943.3 Skp2 94.3 232.7 259.4 Skp1a 4951.5 5186.8 5371.0 Cul1 2771.3 3138.8 3252.7 Prmt1 747.7 3029.2 4091.6 Lyar 408.5 1948.3 2603.5 Cse1l 1192.3 2886.3 3530.8 Ebna1bp2 2111.3 3722.0 4601.5 Gart 715.3 2389.8 3064.5 CEM 1 + Cct5 3399.4 5328.1 6016.0 Top 10 Genes Apex1 998.1 3460.4 4513.5 Sf3a3 733.9 1364.5 2025.8 Ddx18 723.5 1921.5 2174.6 C1qbp 4278.2 7839.2 8566.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE19885" 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=GSE19885 Status: Public on Feb 08 2013 Title: Gene expression data from rapamycin resistant and sensitive cell lines Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23300087 Summary & Design: Summary: The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. Antagonists of oncogenic miRNA families and mimics of tumor suppressor miRNAs (let-7) restored rapamycin sensitivity in resistant tumor cells. This study identified miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors.

Overall design: Total RNA extraction and hybridization on Affymetrix microarrays of rapamycin sensitive (RS) cells (BC3H1, mouse brain tumor cell line with myogenic properties, ATCC) cultured in Dulbeccos modified essential medium (DMEM) media supplemented with 20% fetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (100 mg/ml). Rapamycin resistant cells (RR1) were developed by culturing BC3H1 cells in the presence of 1 uM rapamycin for 6 months. Three samples in triplicates: 1) Rapamycin sensitive cells treated with DMSO for 24 h(BC3H1, reference), 2) Rapamycin sensitive cells treated for 24 h with 100 nM rapamycin (BC3H1+R), 3) Rapamycin resistant cells constantly treated with 1uM Rapamycion (RR1+R).

Background corr dist: KL-Divergence = 0.0520, L1-Distance = 0.0558, L2-Distance = 0.0044, Normal std = 0.6110

0.719 Kernel fit Pairwise Correlations Normal fit

Density 0.359

0.000 CEM 1

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

Pre-normalization Quantiles

RS_DMSO_rep1RS_DMSO_rep2RS_DMSO_rep3 (0.0383036)RS_Rap_rep1 (0.0407545)RS_Rap_rep2 (0.0945211) (0.0811348)RS_Rap_rep3 (0.0948566)RR_Rap_rep-1 (0.0627434)RR_Rap_rep-2 RR_Rap_rep-3(0.168341) (0.195016) (0.224329) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 885.5 1411.2 3138.5 P ( S | Z, I ) = 1.00 Ruvbl2 1363.6 3125.2 10304.8 Mean Corr = 0.81636 Pfdn2 2340.4 3038.8 6131.7 Skp2 483.0 1415.9 5195.9 Skp1a 8940.7 10999.0 12367.1 Cul1 1971.1 2120.5 2918.2 Prmt1 5566.7 8035.9 16967.7 Lyar 722.2 2057.3 7540.4 Cse1l 2942.0 5418.5 10245.3 Ebna1bp2 2015.2 4218.6 7176.2 Gart 970.3 1412.8 3736.7 CEM 1 + Cct5 10315.2 14436.6 27263.0 Top 10 Genes Apex1 3173.2 4784.8 7358.8 Sf3a3 1475.1 2109.3 3181.0 Ddx18 1362.1 1955.1 4347.7 C1qbp 4791.4 7126.6 14414.7

Null module Uri1 Stap1 Polr2e GEO Series "GSE47414" 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=GSE47414 Status: Public on Jun 12 2013 Title: Expression data from bone marrow macrophage derived from lean and obese mice after 1,4, and 24h exposition to P.gingivalis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Obesity is a chronic inflammatory disease that weakens macrophage innate immune response to infections. Since M1 polarization is crucial during acute infectious diseases, we hypothesized that diet-induced obesity inhibits M1 polarization of macrophages in the response to bacterial infection.

Using a computational approach in conjunction with microarray data, we identified switching genes that may differentially control the behavior of response pathways in macrophages from lean and obese mice.

Overall design: Bone marrow macrophages (BMMÎ¦) from lean and obese mice were exposed to live Porphyromonas gingivalis (P. gingivalis) for three incubation times (1 h, 4 h and 24 h). cDNA from BMMÎ¦ of lean and obese mice were hybridized on Affymetrix Mouse Genome 430 2.0 Arrays. Hybridization was performed on three replicates at each time point (18 arrays total).

Background corr dist: KL-Divergence = 0.0932, L1-Distance = 0.0325, L2-Distance = 0.0014, Normal std = 0.4688

0.877 Kernel fit Pairwise Correlations Normal fit

Density 0.439

0.000 CEM 1

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

Pre-normalization Quantiles

lean macrophagelean macrophagelean at macrophage T1,lean replicate at macrophage T1,lean replicate at1 macrophage (0.0449678)T1,lean replicate at2 macrophage (0.0499424)T4,lean replicate at3 macrophage (0.0316659)T4,lean replicate at1 macrophage (0.0508389)T4,lean replicate at2 macrophage (0.0390455)T24,obese replicate at3 (0.0555945)T24, macrophageobese replicateat 1 T24, (0.0382733)macrophageobese replicate 2at (0.053973)macrophage T1,obese replicate 3at (0.0940055)macrophage T1,obese replicate at1 macrophage (0.028319)T1,obese replicate at2 macrophage (0.0331479)T4,obese replicate at3 macrophage (0.0312849)T4,obese replicate at1 macrophage (0.0418382)T4,obese replicate at2 macrophage (0.0276544)T24, replicate at3 (0.0352572)T24, replicateat 1 T24, (0.134061) replicate 2[ (0.11245) min 3 (0.0976801) ] [ medium ] [ max ] CEM 1 Ruvbl1 297.8 371.5 524.3 P ( S | Z, I ) = 1.00 Ruvbl2 606.5 728.2 1240.3 Mean Corr = 0.81454 Pfdn2 891.3 1075.7 1389.6 Skp2 105.6 235.4 540.0 Skp1a 2501.0 2751.3 3498.2 Cul1 1230.8 1512.7 1703.7 Prmt1 1220.1 1581.9 1887.1 Lyar 456.9 636.2 789.0 Cse1l 1024.5 1313.5 1741.4 Ebna1bp2 876.1 1114.1 1359.5 Gart 619.7 870.4 981.6 CEM 1 + Cct5 5754.0 6683.3 7951.4 Top 10 Genes Apex1 1044.8 1351.0 1585.8 Sf3a3 944.8 1341.6 1415.8 Ddx18 476.7 653.3 866.6 C1qbp 1578.9 2052.5 2837.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE38831" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.606 Kernel fit Pairwise Correlations Normal fit

Density 0.303

0.000 CEM 1

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

Pre-normalization Quantiles

C57BL/6JE13.5C57BL/6JE14.5C57BL/6JE15.5 (0.27206)C57BL/6JE16.5 (0.18962)C57BL/6JE17.5 (0.113865)C57BL/6JE18.5 (0.00980954)C57BL/6JADULT (0.070936) (0.0946438) COLON (0.249066)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 309.9 649.6 902.4 P ( S | Z, I ) = 1.00 Ruvbl2 445.0 515.8 737.8 Mean Corr = 0.81207 Pfdn2 463.7 742.8 1242.6 Skp2 59.0 151.4 245.0 Skp1a 2397.7 2685.0 4223.1 Cul1 1063.2 1236.8 1543.5 Prmt1 392.6 1328.6 2415.8 Lyar 707.6 1175.9 1876.6 Cse1l 593.5 1242.4 2226.1 Ebna1bp2 756.5 1211.2 1469.3 Gart 567.4 784.4 993.3 CEM 1 + Cct5 2452.1 2812.6 4226.7 Top 10 Genes Apex1 442.9 1246.1 1908.0 Sf3a3 528.9 740.7 1018.0 Ddx18 312.7 433.0 856.9 C1qbp 1470.9 2380.3 2667.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE7275" 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=GSE7275 Status: Public on Sep 05 2007 Title: Evaluation of murine mast cells derived exosomal RNA versus their parental cells MC/9. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17486113 Summary & Design: Summary: Exosomes are vesicles of endocytic origin released by many types of cells into the extracellular environment. In an attempt to further examine the exosome-mediated cellular communication, we show that exosomes from a mouse mast cell line (MC/9), exosomes from primary bone marrow derived mast cells, and exosomes from a human mast cell line (HMC-1) contain RNA but not DNA.

Microarray assessments of exosome-derived RNA revealed that these vesicles contain mRNA from approximately 1200 genes, many of which are unique and not present in the cytoplasmic RNA pool in the donor cell.

Keywords: Exosomal RNA versus their parental cells, MC/9

Overall design: Exosomes were prepared from the supernatant of MC/9 cells by differential centrifugations and filtration. RNA was isolated from the exosomes and their parental cells using Trizo. The microarray experiments were performed by SweGene (www.swegene.org/) according to Affymetrix microarray DNA chip analysis. The experiment was performed in quadruple samples. ExoRNA1, ExoRNA2, ExoRNA3, and ExoRNA4 for the exosomes samples and Mast_cells1, Mast_cells2, Mast_cells3, and Mast_cells4 for the MC/9 cells.

Background corr dist: KL-Divergence = 0.0228, L1-Distance = 0.0688, L2-Distance = 0.0086, Normal std = 0.8711

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

ExosomalExosomal RNA,Exosomal biological RNA,Exosomal biological RNA, rep1Mast biological(0.148753) RNA, rep2 cellsMast biological(0.187099) RNA, rep3 cellsMast biological(0.0930279) RNA, rep4 cellsMast biological(0.113019) RNA, rep1 cells biological(0.0982548) RNA, rep2 biological(0.119671) rep3 (0.13004) rep4[ (0.110136)min ] [ medium ] [ max ] CEM 1 Ruvbl1 303.3 1730.0 2258.5 P ( S | Z, I ) = 1.00 Ruvbl2 23.4 3052.9 3782.8 Mean Corr = 0.81350 Pfdn2 56.6 893.4 1251.4 Skp2 51.9 583.8 762.9 Skp1a 798.6 3448.3 4307.3 Cul1 170.4 2137.7 2595.5 Prmt1 213.3 4101.1 5682.0 Lyar 675.6 1786.8 3393.2 Cse1l 154.8 2298.1 2753.7 Ebna1bp2 314.9 2712.9 5164.3 Gart 32.9 1966.5 2749.4 CEM 1 + Cct5 65.7 9421.0 16298.6 Top 10 Genes Apex1 371.3 2432.5 3260.6 Sf3a3 171.6 2174.4 3750.1 Ddx18 64.5 1529.3 1759.0 C1qbp 60.1 3195.7 6459.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE51628" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.843 Kernel fit Pairwise Correlations Normal fit

Density 0.422

0.000 CEM 1

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

Pre-normalization Quantiles

TICNX_48h_rep1TICNX_48h_rep2TICNX_48h_rep3 (0.0743624)TICNX_48h_rep4 (0.0745243)TICNX_96h_rep1 (0.102333)TICNX_96h_rep2 (0.0264179)TICNX_96h_rep3 (0.0643103)MTB/TICNX_48h_rep1 (0.0368787)MTB/TICNX_48h_rep2 (0.0331453)MTB/TICNX_48h_rep3 MTB/TICNX_48h_rep4(0.020338) MTB/TICNX_96h_rep1(0.0661407) MTB/TICNX_96h_rep2(0.0581989) MTB/TICNX_96h_rep3(0.0297219) MTB/TICNX_96h_rep4(0.0588372) (0.126948) (0.0916748) (0.136169)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 499.8 682.3 948.3 P ( S | Z, I ) = 1.00 Ruvbl2 548.7 687.3 1099.3 Mean Corr = 0.80303 Pfdn2 1601.1 1776.8 1960.5 Skp2 124.5 490.7 963.8 Skp1a 11458.8 12410.6 13532.1 Cul1 1089.1 1191.7 1478.2 Prmt1 1769.0 2681.9 4857.0 Lyar 838.6 1207.7 1612.2 Cse1l 1411.0 1695.5 2390.7 Ebna1bp2 695.0 1030.1 1376.4 Gart 673.9 861.4 1283.9 CEM 1 + Cct5 5563.5 7569.1 9635.9 Top 10 Genes Apex1 921.8 1333.0 2282.5 Sf3a3 765.8 1006.6 1611.7 Ddx18 852.0 1053.9 1226.1 C1qbp 2622.9 3222.4 4172.9

Null module Uri1 Stap1 Polr2e 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(0.160998) rep. CTL, 2 transduced(0.214347) rep. biological CTL, 3 (0.152624) biological CTL, rep. 1biological (0.142659)[ rep. min 2 (0.242657) rep. ] 3 (0.0867154)[ medium ] [ max ] CEM 1 Ruvbl1 1282.7 2180.1 2398.8 P ( S | Z, I ) = 1.00 Ruvbl2 1891.9 2979.3 3345.5 Mean Corr = 0.79999 Pfdn2 2286.4 3095.1 3204.3 Skp2 495.7 541.6 586.2 Skp1a 7392.8 8035.9 8628.8 Cul1 1381.1 1794.3 1887.1 Prmt1 5120.9 7898.2 8933.1 Lyar 2546.2 3337.1 4078.1 Cse1l 2466.3 3735.0 3882.7 Ebna1bp2 3043.8 3460.9 4390.0 Gart 2200.7 3036.6 3800.6 CEM 1 + Cct5 12610.2 14599.3 15355.4 Top 10 Genes Apex1 1570.9 2410.9 3238.7 Sf3a3 2429.8 3172.6 3566.4 Ddx18 2045.4 2935.1 3376.5 C1qbp 5859.1 8112.0 9089.3

Null module Uri1 Stap1 Polr2e GEO Series "GSE21299" 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=GSE21299 Status: Public on Feb 01 2011 Title: Expression data from murine cell line transduced with epitope tagged forms of Hoxa9 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20541477 Summary & Design: Summary: Importantly increasing evidence shows that Hox genes such as Hoxa9 are key regulators of stem cell self-renewal and hematopoiesis. Hoxa9 is expressed in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast Hoxa9 down regulation is associated with hematopoietic differentiation. In addition to its role in development, HOXA9 has been intensively studied because of its central role in human acute leukemias. Despite their obvious biomedical importance, the mechanisms through which Hoxa9 and its partner proteins exert their downstream functions are poorly understood.

Using whole-genome gene expression profiling, we identified direct targets of Hoxa9 in murine MHPs after 4-OHT withdraw, resulting in cell differentiation.

Overall design: Bone marrow cells were harvested from 5-Fluorouracil treated female 6-8 week old C57BL/6 mice and transduced with an MSCV-based retrovirus expressing Hoxa9 fused to a modified estrogen receptor ligand binding domain (Hoxa9-ER). Hoxa9-ER cells were washed 3x and resuspended in IL-3+ media with/without 100 nM 4-OHT (Sigma). At selected intervals, cells were removed for flow cytometric analysis using anti-Gr1 and anti-Mac1 antibodies (BD biosciences), morphologic assessment by cytocentrifugation and staining with Diff-Quick reagents (Intl. Med. Equip.), and RNA collection. For RNA, Pellets were lysed in Trizol reagent (Invitrogen) and RNA was extracted following manufacturer's instructions until phase separation, after which RNeasy columns (Qiagen) were employed for further purification. cRNA probes were synthesized at the University of Michigan microarray core. Probes were hybridized to Affymetrix Mouse 430 2.0 array.

Background corr dist: KL-Divergence = 0.0290, L1-Distance = 0.0372, L2-Distance = 0.0028, Normal std = 0.6739

0.592 Kernel fit Pairwise Correlations Normal fit

Density 0.296

0.000 CEM 1

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

Pre-normalization Quantiles

Hoxa9-ERHoxa9-ER on dayHoxa9-ER 3,on rep dayHoxa9-ER 1 3,on(0.046148) rep dayHoxa9-ER 2 3,on(0.0563429) rep dayHoxa9-ER 3 4,on(0.030873) rep dayHoxa9-ER 1 4,on(0.116102) rep dayHoxa9-ER 2 4,on(0.0362531) rep dayHoxa9-ER 3 5,on(0.047154) rep dayHoxa9-ER 1 5,on(0.139038) rep dayHoxa9-ER 2 5,on(0.177155) rep dayHoxa9-ER 3 0,on(0.179079) rep day 1 0,on(0.0568556) rep day 2 0,(0.0699241) rep 3 (0.0450746)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 625.7 1576.1 1900.1 P ( S | Z, I ) = 1.00 Ruvbl2 1599.6 4564.8 5072.8 Mean Corr = 0.78671 Pfdn2 1540.5 2024.1 2721.3 Skp2 293.5 960.4 1215.4 Skp1a 3127.2 5769.0 6905.2 Cul1 1259.4 1341.6 1433.2 Prmt1 1955.2 3575.5 4536.0 Lyar 651.5 1708.0 1870.2 Cse1l 1270.3 2592.7 2721.1 Ebna1bp2 1210.5 2791.8 2969.6 Gart 1080.0 2735.8 3352.7 CEM 1 + Cct5 7369.9 10256.1 10850.8 Top 10 Genes Apex1 1545.0 2817.4 3498.9 Sf3a3 1090.6 1856.6 1959.7 Ddx18 1287.1 2259.1 2424.7 C1qbp 3557.2 6820.2 7360.0

Null module Uri1 Stap1 Polr2e GEO Series "GSE7875" 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=GSE7875 Status: Public on Oct 03 2007 Title: Deletion of PKBalpha/Akt1 affects thymic development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17912369 Summary & Design: Summary: The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development.

Keywords: Genetic modification

Overall design: Early thymocyte subsets (DN3 and ISP8) were sorted by FACS from 4 PKBalpha-/- / PKBalpha+/+ mouse littermate pairs. The same number of DN3 or ISP8 cells was sorted (7 000 to 25 000 cells) within a PKBalpha-/- / PKBalpha+/+ pair. Four replicates per condition were then analysed (4xPKBalpha-/- DN3, 4xPKBalpha+/+ DN3, 4xPKBalpha-/- ISP8, 4xPKBalpha+/+ ISP8). Total RNA was extracted using PicoPureTM RNA isolation kit (Arcturus, Sunnyvale, CA, USA) and RNA quality was controlled using the 2100 Bioanalyser (Agilent Technologies, Santa Clara, CA, USA). Total RNA was amplified and labeled using the Affymetrix 2-cycle 3 labelling kit according to manufacturers instructions. After fragmentation, 10 ug cRNA was hybridised to mouse genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA). The supplementary file represents the expression values estimated using the GC-RMA function provided by Refiner 3.1 (Genedata, Basel, Switzerland) for each of the samples.

Background corr dist: KL-Divergence = 0.1420, L1-Distance = 0.0394, L2-Distance = 0.0024, Normal std = 0.3992

1.035 Kernel fit Pairwise Correlations Normal fit

Density 0.518

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

bh20061128m430v2_A_16_pTN3-PKBa-2435bh20061128m430v2_A_15_pTN3-PKBa-2432bh20061128m430v2_A_14_pTN3-PKBa-2425bh20061128m430v2_A_13_pTN3-PKBa-2424bh20061128m430v2_A_12_pTN3-PKBa-2420bh20061128m430v2_A_11_pTN3-PKBa-2416 (0.077218)bh20061128m430v2_A_10_pTN3-PKBa-2402 (0.0649949)bh20061128m430v2_A_09_pTN3-PKBa-2401 (0.0326607)bh20061128m430v2_A_08_preDP-PKBa-2435 (0.0423299)bh20061128m430v2_A_07_preDP-PKBa-2432 (0.0565605)bh20061128m430v2_A_06_preDP-PKBa-2425 (0.0265705)bh20061128m430v2_A_05_preDP-PKBa-2424 (0.123144)bh20061128m430v2_A_04_preDP-PKBa-2420 (0.0636324)bh20061128m430v2_A_03_preDP-PKBa-2416bh20061128m430v2_A_02_preDP-PKBa-2402 (0.0550851)bh20061128m430v2_A_01_preDP-PKBa-2401 (0.0536719) (0.0535849) (0.16162) (0.0501333)[ (0.0403209) min (0.03514) ] (0.0633328)[ medium ] [ max ] CEM 1 Ruvbl1 2059.3 2896.7 3141.6 P ( S | Z, I ) = 1.00 Ruvbl2 1870.5 2607.7 2883.4 Mean Corr = 0.78654 Pfdn2 397.3 706.3 1218.8 Skp2 988.5 2273.0 3385.4 Skp1a 6141.9 8050.5 11499.0 Cul1 3215.2 4998.2 5883.5 Prmt1 2283.4 4142.4 5935.2 Lyar 3550.4 5591.1 7716.8 Cse1l 5670.7 8350.7 10204.4 Ebna1bp2 3488.5 4066.0 4836.4 Gart 3426.0 5276.3 6477.3 CEM 1 + Cct5 15266.6 17472.8 19609.9 Top 10 Genes Apex1 3556.4 5126.9 6216.9 Sf3a3 3157.4 5299.5 5998.3 Ddx18 1628.4 2186.4 2553.0 C1qbp 4437.8 7509.1 8565.3

Null module Uri1 Stap1 Polr2e GEO Series "GSE34215" 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=GSE34215 Status: Public on Dec 06 2012 Title: Knockout of GPx4 gene in mouse keratinocyte Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23364477 Summary & Design: Summary: Comparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice.

Selenoproteins are essential for skin function, as targeted abolition of selenoproteins in epidermal tissue results in newborn mice manifesting gross abnormalities of skin and hair, accompanied by retarded growth and premature death. To investigate whether lack of a single selenoprotein could induce similar phenotypic effect in mice, we generated keratinocyte-specific knockout mice lacking glutathione peroxidase 4 (GPx4), an essential selenoprotein in skin, to examine phenotypic changes resulting from the lack of GPx4 in skin. Ablation of GPx4 results in focal alopecia and disturbed hair follicle morphogenesis, with GPx4 being essential during early stages of hair follicle morphogenesis as well as for keratinocyte adhesion and proliferation in culture.

Overall design: We have generated mice with selective removal of the GPx4 gene in keratinocytes under the control of Keratin-14-cre (K14-cre) promoter. Comparative microarray analysis was performed on RNA samples taken from pooled primary keratinocytes from knockout and control mice from the same litter. Array replicates were performed using RNA samples from three different litters.

Background corr dist: KL-Divergence = 0.0401, L1-Distance = 0.0263, L2-Distance = 0.0009, Normal std = 0.6210

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

Control-culturedControl-culturedControl-cultured keratinocytesKnockout-cultured keratinocytesKnockout-cultured from keratinocytes litterKnockout-cultured from keratinocytesA (0.281943)litter from keratinocytesB (0.122822)litter from keratinocytesC (0.339568) litter from A[ (0.0819815)litter min from B (0.105295)litter ] C (0.0683898)[ medium ] [ max ] CEM 1 Ruvbl1 911.1 1207.7 1309.6 P ( S | Z, I ) = 1.00 Ruvbl2 1901.2 2785.6 2819.7 Mean Corr = 0.78090 Pfdn2 963.3 1430.8 2032.1 Skp2 544.5 720.3 858.0 Skp1a 4979.9 5604.5 6238.1 Cul1 2251.4 2629.0 2980.2 Prmt1 4169.0 4986.2 5543.1 Lyar 1239.3 1901.4 2271.7 Cse1l 3159.7 3596.0 3989.9 Ebna1bp2 2491.7 3719.0 4211.4 Gart 1387.6 1529.0 1705.9 CEM 1 + Cct5 12025.1 14284.5 16152.1 Top 10 Genes Apex1 3974.1 4606.1 4688.3 Sf3a3 2125.0 2482.0 2511.6 Ddx18 1322.4 2165.6 2329.1 C1qbp 3998.8 4953.2 5955.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE28389" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28389 Status: Public on Apr 05 2011 Title: [E-MTAB-368] Transcription profiling by array of mouse embryos at 8 different stages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21427719 Summary & Design: Summary: Transcription profiling of mouse development

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

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

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

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.353

0.000 CEM 1

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

Pre-normalization Quantiles

[E-MTAB-368][E-MTAB-368] Mouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMousestage[E-MTAB-368] E7.5 developmentalMousestage[E-MTAB-368] 1 (0.0543277) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0343053) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.038142) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0482121) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0396939) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0474293) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0510286) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.028253) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0194193) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0304424) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0133767) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0186947) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0359978) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0299417) developmentalMousestage 1 E14.5 (0.0373286) developmentalMousestage 2 E16.5 (0.0355025) developmentalstage 1 E16.5(0.0561106) stage[ min 2 E18.5(0.112828) stage 1] E18.5(0.142571) 2 (0.126394)[ medium ] [ max ] CEM 1 Ruvbl1 855.1 3080.1 4771.4 P ( S | Z, I ) = 1.00 Ruvbl2 1378.7 7538.1 10765.0 Mean Corr = 0.77152 Pfdn2 1280.1 2823.0 3617.7 Skp2 1419.9 4192.0 4995.0 Skp1a 6711.5 11184.5 12735.2 Cul1 1766.1 3148.7 3933.8 Prmt1 4266.9 16277.5 19752.6 Lyar 860.9 3870.4 8219.8 Cse1l 2521.7 7344.9 11198.6 Ebna1bp2 1228.3 2836.2 4947.0 Gart 806.9 3321.8 6494.6 CEM 1 + Cct5 7448.6 18928.1 24054.1 Top 10 Genes Apex1 2446.6 9467.6 11811.0 Sf3a3 1345.0 4774.3 5554.7 Ddx18 1066.4 2720.3 5253.4 C1qbp 2964.9 7912.0 13305.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE42548" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 29 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.633 Kernel fit Pairwise Correlations Normal fit

Density 0.316

0.000 CEM 1

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

Pre-normalization Quantiles

primaryprimary abdominalprimary abdominal NBprimary tumorabdominal NB ttt010primary tumorabdominal NB (0.00550672) ttt012primary tumorabdominal NB (0.00682083) ttt013primary tumorabdominal NB (0.0142931) ttt015primary tumorabdominal NB (0.0173804) ttt016primary tumorabdominal NB (0.0133974) ttt017primary tumorabdominal NB (0.0157057) ttt018primary tumorabdominal NB (0.013868) ttt019primary tumorabdominal NB (0.0258174) ttt020primary tumorabdominal NB (0.0149066) ttt021primary tumorabdominal NB (0.0130195) ttt100primary tumorabdominal NB (0.0140808) ttt101primary tumorabdominal NB (0.00659563) ttt102primary tumorabdominal NB (0.00994758) ttt104primary tumorabdominal NB (0.0121396) ttt105primary tumorabdominal NB (0.00873351) ttt106primary tumorabdominal NB (0.0103036) ttt107primary tumorabdominal NB (0.0179096) ttt108Total tumorabdominal NB bone(0.0304583) ttt109aTotal tumor marrow NB bone (0.0134403)ttt110primary tumor marrow ttt112 (0.0153763) ttt111primary abdominal (0.109711) ttt114a (0.0178605)primary abdominal (0.106272)NBTotal tumorabdominal NB bone ttt115Total tumor marrow NB bone(0.00604521) ttt116Total tumor marrow ttt118 bone(0.0141094) ttt117 (0.132465)marrow ttt119 (0.0424549) (0.13362) ttt120a (0.157761)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 808.4 2499.5 2987.8 P ( S | Z, I ) = 1.00 Ruvbl2 1196.2 2383.1 3412.1 Mean Corr = 0.77474 Pfdn2 1126.4 3474.2 4132.7 Skp2 985.8 2571.6 3414.7 Skp1a 8016.3 12133.2 13245.8 Cul1 1648.3 2680.8 3681.1 Prmt1 1271.6 5094.4 7738.2 Lyar 1671.0 2816.5 3539.3 Cse1l 2207.8 4527.8 6081.3 Ebna1bp2 1390.2 3221.0 4104.4 Gart 1404.3 1967.1 2481.5 CEM 1 + Cct5 9203.8 15434.2 17815.4 Top 10 Genes Apex1 1777.4 7414.3 9196.9 Sf3a3 1438.6 2606.4 2921.9 Ddx18 1233.4 1825.3 2336.5 C1qbp 4629.1 8988.1 10897.1

Null module Uri1 Stap1 Polr2e GEO Series "GSE19528" 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=GSE19528 Status: Public on Jan 22 2010 Title: Effect of c-Myb deficiency on pre-selection DP thymocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20142358 Summary & Design: Summary: Comparing the mRNA expression profiles of c-Myb deficient and c-Myb sufficient Tcra-/- DP thymocytes.

Results provide insight into the role of c-Myb in the regulation of survival and differentiation during the pre-selection DP stage where c-Myb expression is abundant during T cell development.

Overall design: DP thymocytes were purified from four c-Myb deficient and four c-Myb sufficient mice over magnetic columns. RNA from each biological replicate was individually hybridized onto a total of eight MOE430 2.0 Chips.

Background corr dist: KL-Divergence = 0.0791, L1-Distance = 0.0206, L2-Distance = 0.0007, Normal std = 0.4804

0.830 Kernel fit Pairwise Correlations Normal fit

Density 0.415

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl biologicalControl biological rep1Control biological(0.0654071) rep2Mutant biological(0.218669) rep3 Mutantbiological (0.104084) rep4 Mutantbiological (0.205699) rep1 Mutant biological(0.0342836) rep2 biological(0.107989) rep3 (0.173424) rep4 (0.0904438)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 1033.8 1382.6 1610.3 P ( S | Z, I ) = 1.00 Ruvbl2 1961.0 2523.3 2879.3 Mean Corr = 0.75478 Pfdn2 1145.2 1387.7 1525.6 Skp2 1556.2 2180.2 2730.6 Skp1a 9669.7 11537.3 12259.6 Cul1 1437.8 1520.4 1797.6 Prmt1 3654.9 4614.1 5266.8 Lyar 1454.9 2002.0 2474.5 Cse1l 2582.4 3476.7 4175.3 Ebna1bp2 1501.5 1906.8 2212.3 Gart 1469.2 1857.1 2154.5 CEM 1 + Cct5 7950.0 9846.0 11382.8 Top 10 Genes Apex1 1163.6 1820.1 2262.9 Sf3a3 2386.3 2693.7 3225.8 Ddx18 1342.4 1589.2 1860.3 C1qbp 2044.7 3354.0 3664.8

Null module Uri1 Stap1 Polr2e GEO Series "GSE37029" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37029 Status: Public on May 21 2012 Title: Microarray analysis of WT bone marrow myeloid progenitors, BM cultured with GM-CSF and M-CSF, and monocytes treated with GM-CSF Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Analysis of genes induced in DC precursors and in BM cells and monocytes treated with GM-CSF

Overall design: For progenitor arrays, bone marrow progenitors (CMP, GMP, CDP, and pre-cDC) were harvested from WT C57Bl/6 mice. For culture arrays, BM was cultured in the presence of GM-CSF or M-CSF and adherent and non-adherent cells sorted. For monocyte cultures, sorted BM monocytes were treated with GM-CSF for 0, 24 or 48 hours.

Background corr dist: KL-Divergence = 0.0614, L1-Distance = 0.0519, L2-Distance = 0.0049, Normal std = 0.5449

0.732 Kernel fit Pairwise Correlations Normal fit

Density 0.366

0.000 CEM 1

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

Pre-normalization Quantiles

GM-CSFGM-CSF Adh (0.0940905)MCSF CD11c AdhMono (0.0639562) (0.132392) GMCSFMono GMCSF 0hrMono (0.0432476) GMCSF 24hrWT1 (0.0263916)CMP 48hrWT1 (0.0817357) (0.0348009)GMPWT1 (0.0978743) CDPWT1 (0.0399984) PrecDCWT1 PrecDC BMWT2 (0.0258513) CMP SplWT2 (0.0785385) (0.0818212) GMPWT2 (0.105077) CDPWT2 (0.0376991) PrecDC BM (0.0565258) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 451.9 1133.2 3385.5 P ( S | Z, I ) = 1.00 Ruvbl2 546.3 1654.8 5023.6 Mean Corr = 0.75265 Pfdn2 1057.0 1909.5 3883.4 Skp2 200.0 938.1 1944.3 Skp1a 2433.9 4224.7 7815.2 Cul1 1828.4 2950.1 3279.5 Prmt1 1219.2 2434.0 7705.2 Lyar 726.7 1237.0 5485.4 Cse1l 2019.6 5004.3 7200.1 Ebna1bp2 732.1 1390.0 4071.6 Gart 316.5 2471.3 6531.4 CEM 1 + Cct5 6030.6 7910.1 12415.0 Top 10 Genes Apex1 1210.2 3807.1 7630.8 Sf3a3 733.3 1669.2 2793.7 Ddx18 610.1 1340.8 2827.2 C1qbp 1775.6 3548.5 11239.3

Null module Uri1 Stap1 Polr2e GEO Series "GSE11220" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 44 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11220 Status: Public on Apr 23 2008 Title: Timecourse of developing mouse placenta, with placental and decidual tissues profiled separately Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18340042 Summary & Design: Summary: We used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0).

At each stage, the fetal placenta and maternal decidual tissues were dissected and profiled separately

Keywords: time course

Overall design: Mouse placentas were obtained from timed pregnant female mice at each timepoint, and fetal tissues were used to confirm embryo staging. Fetal placenta and maternal decidual tissues were dissected and pooled separately for each litter prior to RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1391, L1-Distance = 0.0310, L2-Distance = 0.0019, Normal std = 0.3911

1.020 Kernel fit Pairwise Correlations Normal fit

Density 0.510

0.000 CEM 1

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

Pre-normalization Quantiles

PlacentaPlacenta e8.5, biologicalPlacenta e8.5, biologicalPlacenta e8.5, rep1, biologicalPlacenta technical e8.5, rep2, biologicalPlacenta technical e8.5, rep1,rep1 biologicalPlacenta (0.0609913)technical e9.0, rep2,rep1 biologicalPlacenta (0.0851513)technical e9.0, rep3rep2 biologicalPlacenta (0.0464557)(0.0507689) e9.0, rep1rep2 biologicalPlacenta (0.0238448)(0.0743517) e10.5, rep2 Placenta(0.0272491) biological e10.5, rep3 Placenta(0.0152188) biological e10.5, rep1Placenta biological (0.0365576)e12.0, rep2Placenta biological (0.0210077)e12.0, rep3Placenta biological (0.031911)e12.0, rep1Placenta biological (0.0281223)e13.5, rep2Placenta biological (0.0131416)e13.5, rep3Placenta biological (0.0232325)e15.0, rep1Placenta biological (0.00869631)e15.0, rep2Placenta biological (0.0115624)e15.0, rep1Placenta biological (0.00914931)e17.0, rep2Placenta biological (0.0118076)e17.0, rep3Placenta biological (0.0130554)e17.0, rep1Placenta biological (0.00987083)e19.0, rep2Placenta biological (0.0184478)e19.0, rep3Placenta biological (0.021966)P0, rep1 biologicalDecidua (0.0129447)P0, rep2 biologicalDecidua rep1e8.5,(0.0116998) (0.0113844)biologicalDecidua rep2e8.5, (0.0248661)biologicalDecidua e8.5, rep1, biological Deciduatechnical e8.5, rep2, biological Deciduatechnical e9.0, rep1,rep1 biological Decidua(0.0089509)technical e9.0, rep2,rep1 biological Decidua(0.00884942)technical e10.5, rep1rep2 (0.0264124)Decidua(0.0243553)biological e10.5, rep2rep2 (0.0155779)Decidua(0.0130057)biological e12.0, rep1 Decidua biological (0.0118669)e12.0, rep2 Decidua biological (0.0150709)e15.0, rep1 Decidua biological (0.0223826)e15.0, rep2 Decidua biological (0.0230693)e17.0, rep1 Decidua biological (0.0195175)e17.0, rep2 Decidua biological (0.0122305)e19.0, rep1 Decidua biological (0.0202251)e19.0, rep2 Decidua biological (0.0149208)P0, rep1 biological (0.0205924)P0, rep2 biological rep1(0.00896212) (0.0198375) rep2 (0.0107177)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 216.1 454.9 2430.8 P ( S | Z, I ) = 1.00 Ruvbl2 490.3 962.4 4875.8 Mean Corr = 0.75247 Pfdn2 472.1 1151.1 2750.0 Skp2 169.1 288.4 2451.8 Skp1a 2010.1 3729.1 6084.8 Cul1 632.6 1848.6 2792.2 Prmt1 520.8 1139.3 5392.1 Lyar 192.9 456.2 3160.0 Cse1l 920.0 2199.8 4980.5 Ebna1bp2 430.8 672.8 1990.3 Gart 358.4 640.4 3237.7 CEM 1 + Cct5 2070.9 3935.4 8963.1 Top 10 Genes Apex1 315.4 660.6 2509.8 Sf3a3 345.0 528.7 1682.9 Ddx18 494.6 630.9 2839.3 C1qbp 717.7 1720.8 6983.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE15872" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.638 Kernel fit Pairwise Correlations Normal fit

Density 0.319

0.000 CEM 1

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

Pre-normalization Quantiles

stomachstomach at E14.5,stomach at biological E14.5,pylorus at biological E14.5, rep1pylorus at E14.5, biological(0.0351234) rep2pylorus at biological E14.5, (0.0410144) rep3duodenum at biological E14.5, (0.0516629) rep1duodenum biological(0.0259897) at rep2 E14.5,duodenum (0.050708) at rep3biological E14.5,stomach (0.0663051) at biological E14.5,stomach rep1 at E16.5, biological(0.0444435)stomach rep2 at biological E16.5, (0.0441207)pylorus rep3 at biological E16.5, (0.0811362)rep1pylorus at E16.5, biological(0.0557853) rep2pylorus at biological E16.5, (0.054074) rep3duodenum at biological E16.5, (0.0563594) rep1duodenum biological(0.0171832) at rep2 E16.5,duodenum (0.0309166) at rep3biological E16.5, (0.0438205) at biological E16.5, rep1 biological(0.0649621) rep2 (0.0859231)[ rep3 min (0.150472) ] [ medium ] [ max ] CEM 1 Ruvbl1 528.5 1219.5 1650.0 P ( S | Z, I ) = 1.00 Ruvbl2 1101.9 2774.3 3488.2 Mean Corr = 0.75187 Pfdn2 1174.0 2130.0 2946.6 Skp2 1006.9 2869.6 3485.7 Skp1a 3917.5 6479.4 7903.4 Cul1 1552.3 2119.9 2498.1 Prmt1 2027.8 6140.1 8470.6 Lyar 554.8 1222.3 1946.4 Cse1l 1815.0 3915.1 4418.1 Ebna1bp2 873.2 1291.5 1882.3 Gart 668.9 1768.0 2382.5 CEM 1 + Cct5 5277.8 10224.8 11254.8 Top 10 Genes Apex1 1827.6 3225.8 4062.8 Sf3a3 1057.0 2264.3 2755.8 Ddx18 795.5 1623.4 2047.7 C1qbp 3944.8 5342.5 6935.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE11201" 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=GSE11201 Status: Public on Apr 18 2008 Title: Coordinated Regulation of Signaling Pathways and Biological Processes during Liver Development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Understanding congenital liver disease requires elucidation of the signaling pathways and transcriptional events in the developing liver. Comprehensive assessment of gene expression between 10.5 and 16.5 dpc in the developing mouse liver and comparison with adult liver and non-hepatic embryonic tissue was validated with real-time PCR and in situ hybridization. The broad nature of the analysis provides insights into patterns of genetic control of hepatogenesis. Pathways implicated in human disease are highly regulated at the transcriptional level. Rather than activating or inhibiting a pathway or biological process by altering the expression of a single signaling molecule, transcriptional changes in large numbers of genes in a pathway or process are regulated in a coordinated manner. For example, both TGF-beta and Notch signaling is inhibited during hepatogenesis not just by decreasing transcription of multiple pathway members, but also with a complementary increase in the transcription of a pathway inhibitor. Similarly, genes related to specific biological processes exhibit strong temporal synchronization in which multiple members of the pathway have similar transcriptional regulation over time. Global coordination of signaling or functional families at the transcriptional level may be a mechanism to produce robustness of the desired outcomes. In addition, this comprehensive analysis provides a database for the further study of transcriptional events during liver development by identifying liver-specific, highly regulated genes.

Keywords: time course

Overall design: In order to provide transcriptional profile of the developing liver compared both to normal adult liver and non-hepatic embryonic tissueswe performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for embryonic liver samples at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc), embryo-minus liver tissues at 10.5, 11.5, 12.5, and 14.5 dpc, and normal 10-week-old adult mouse liver. Each sample consisted of at least five embryos.

Background corr dist: KL-Divergence = 0.0374, L1-Distance = 0.0354, L2-Distance = 0.0018, Normal std = 0.6265

0.637 Kernel fit Pairwise Correlations Normal fit

Density 0.318

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

baselinebaseline liver sampledevelopmental liver sampleatdevelopmental T0, biological at developmentalliver T0, samplebiological developmentalliver rep1 sample at(0.189468) developmental liver T105,rep2 sample at(0.226478) biological developmental liverT105, sampleat biological developmental liverT115, rep1 sampleat biological(0.0315738) developmental liverT115, rep2 sampleat biological(0.0680332) developmental liverT125, rep1 sampleat biological(0.0216028) developmental liverT125, rep2 sampleat biological(0.0474159) developmental liverT135, rep1 sampleat biological(0.00720224) developmental liverT135, rep2 sampleat biological(0.00502986) embryonic liverT145, rep1 sampleat biological(0.0079463) embryonic liverT145, rep2 liver sampleat biological(0.00910921)embryonic T165,sample rep1 liver at biological(0.0109147)embryonic T165, sampleat rep2 liver105, biological(0.0094532) samplebiologicalat rep1 liver115, (0.024025) samplebiologicalat rep2 125,rep1 (0.0223022) biologicalat(0.104803) 145,rep1[ biological (0.0894301)min rep1 (0.0836913) rep1] (0.0415212)[ medium ] [ max ] CEM 1 Ruvbl1 443.6 1887.1 2857.1 P ( S | Z, I ) = 1.00 Ruvbl2 411.5 2925.0 4070.4 Mean Corr = 0.74838 Pfdn2 982.0 1929.8 4594.2 Skp2 3.6 1156.9 2059.3 Skp1a 2069.9 4000.4 7374.8 Cul1 1239.3 1835.7 2429.0 Prmt1 314.1 3467.8 8414.7 Lyar 324.1 2381.1 3406.1 Cse1l 874.8 3643.4 5489.3 Ebna1bp2 443.0 1441.0 1997.2 Gart 478.0 2097.6 3078.0 CEM 1 + Cct5 2107.2 7380.9 10596.7 Top 10 Genes Apex1 1487.8 3765.0 6765.5 Sf3a3 867.1 2271.4 2803.2 Ddx18 327.8 1325.1 1772.2 C1qbp 1376.1 4265.8 6083.2

Null module Uri1 Stap1 Polr2e GEO Series "GSE7705" 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=GSE7705 Status: Public on May 01 2008 Title: Microarray analysis of CD4+T cells in murine arthritis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Although activated CD4+ T cell-driven overproduction of cytokines, especially TNF and IL1, is generally regarded as the major factor in the development of rheumatoid arthritis (RA), little is known about the precise role of CD4+ T cells in the initiation and progression of this disease. In this study, this issue was addressed using a time-course microarray analysis in a mouse model of RA, Il1rn deficient mice.No obvious cytokine gene expression changes reflecting T cell activation was observed in CD4+ T cells in the Il1rn deficient mice during the course of spontaneous arthritis. On the contrast, majority of dysregulated genes were those predominantly expressed in myeloid lineage cells, suggesting T cell reprogramming involvement in arthritis development. Distinct gene expression patterns were identified for different stages of disease, including downregulated expression of immunoglobulin heavy chain constant region genes and increased expression of inflammatory genes in the early phase, and downregulation of MHC class II genes in the late phase. The common changes occurred in both early and late phases included upregulation of Arl2bp and Mfap1, which are involved in the regulation of cytoskeletal dynamics.

Keywords: Time course

Overall design: Two KO mice and three WT mice for each time point (1 month and 4 month) were used for this study.

Background corr dist: KL-Divergence = 0.0808, L1-Distance = 0.0282, L2-Distance = 0.0010, Normal std = 0.4856

0.836 Kernel fit Pairwise Correlations Normal fit

Density 0.418

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

CD4+ cellsCD4+ IL1RN cellsCD4+ knockout IL1RN cellsCD4+ knockout IL1RN 1cells monthCD4+ knockout IL1RN 1cells rep1monthCD4+ knockout IL1RN (0.215865) 4cells rep2monthCD4+ wild IL1RN (0.162711) 4cells rep1 monthCD4+type wild IL1RN (0.0805124) 1 cells rep2month CD4+type wild IL1RN (0.0603499) 1 cells rep1month CD4+type wild IL1RN(0.0726282) 1 cells rep2month type wild IL1RN(0.0622048) 4 rep3month type wild (0.124213) 4 rep1month type (0.0757737) 4 rep2month[ min (0.0421024) rep3 (0.103639)] [ medium ] [ max ] CEM 1 Ruvbl1 1413.2 2076.5 2642.3 P ( S | Z, I ) = 1.00 Ruvbl2 2740.2 3027.2 5206.1 Mean Corr = 0.74392 Pfdn2 2389.8 2651.1 3388.8 Skp2 404.2 811.8 1561.9 Skp1a 8145.1 12143.8 16272.9 Cul1 1374.1 1882.5 2600.1 Prmt1 3524.8 4873.3 6142.3 Lyar 2164.6 3820.6 5084.1 Cse1l 2857.6 4189.2 6014.8 Ebna1bp2 2282.4 2875.1 4179.1 Gart 2246.7 2789.3 3594.6 CEM 1 + Cct5 10542.5 12393.6 15981.3 Top 10 Genes Apex1 2261.9 3023.8 4502.9 Sf3a3 2203.4 2684.9 3485.3 Ddx18 2153.1 3195.2 3772.4 C1qbp 5343.9 7931.8 10554.3

Null module Uri1 Stap1 Polr2e GEO Series "GSE6689" 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=GSE6689 Status: Public on Jan 07 2008 Title: Expression data during stem cell differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18184438 Summary & Design: Summary: Stem cell development requires selection of specific genetic programs to direct cellular fate. Using microarray technology, we profile expression trends at selected timepoints during stem cell differentiation to characterize these changes.

Keyword(s): timecourse

Overall design: Total RNA was isolated using the Micro-to-Midi isolation kit (Invitrogen), and subjected to comparative gene expression profiling by labelled cRNA hybridization to the mouse genome 430 2.0 microarray (Affymetrix). Data acquired using the GeneChip Scanner 3000 was analyzed with the Genespring GX 7.3 microarray data software bioinformatics suite (Agilent Technologies) restricting the derived gene list to identify differentially expressed genes defined by a >1.5-fold difference and P<0.05. Data population sets were normalized to the undifferentiated phenotype, and quality filtered to eliminate background noise prior to hierarchical clustering.

Background corr dist: KL-Divergence = 0.0505, L1-Distance = 0.0486, L2-Distance = 0.0033, Normal std = 0.5968

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Control_ES-LIF(+)_rep1Timepoint1_ES-LIF(-)_rep1Timepoint2_CM_rep1Control_ES-LIF(+)_rep2 (0.133585)Timepoint1_ES-LIF(-)_rep2 (0.0838754) (0.199905)Timepoint2_CM_rep2Timepoint1b_CP_rep1 (0.0581448)Control_ES-LIF(+)_rep3 (0.112096) (0.0939146)Timepoint1_ES-LIF(-)_rep3 Timepoint2_CM_rep3(0.0260011)Timepoint1b_CP_rep2 (0.0723342)Timepoint1b_CP_rep3 (0.048109) (0.118996) (0.0302651) (0.0227734)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 1499.6 3098.0 3833.1 P ( S | Z, I ) = 1.00 Ruvbl2 2302.3 7382.0 8332.4 Mean Corr = 0.74266 Pfdn2 1969.1 2823.1 3808.2 Skp2 697.4 1705.3 1998.2 Skp1a 9217.9 10713.0 12432.5 Cul1 1680.6 2075.4 3017.3 Prmt1 6996.8 12493.3 14593.5 Lyar 1594.4 4930.3 6572.2 Cse1l 3614.8 6826.3 7709.3 Ebna1bp2 2301.8 5589.5 7086.8 Gart 2588.2 7001.2 7694.2 CEM 1 + Cct5 8153.8 15098.6 15703.5 Top 10 Genes Apex1 3595.0 5942.6 7040.4 Sf3a3 1596.8 3506.3 3933.9 Ddx18 1714.6 4662.8 5262.6 C1qbp 7197.3 12242.7 15392.6

Null module Uri1 Stap1 Polr2e GEO Series "GSE5671" 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=GSE5671 Status: Public on Aug 30 2007 Title: Cardiac differentiation of embryonic stem cells recapitulates embryonic cardiac development. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18246200 Summary & Design: Summary: Mouse embryonic stem cells can differentiate in vitro into spontaneously contracting cardiomyocytes. The main objective of this study was to investigate cardiogenesis in cultures of differentiating embryonic stem cells (ESCs) and to determine how closely it mimics in vivo cardiac development. We identified and isolated a population of cardiac progenitor cells (CPCs) through the use of a reporter DNA construct that allowed the expression of a selectable marker under the control of the Nkx2.5 enhancer. We proceeded to characterize these CPCs by examining their capacity to differentiate into cardiomyocytes and to proliferate. We then performed a large-scale temporal microarray expression analysis in order to identify genes that are uniquely upregulated or downregulated in the CPC population. We determined that the transcriptional profile of the mESC derived CPCs was consistent with pathways known to be active during embryonic cardiac development. We conclude that in vitro differentiation of mESCs recapitulates the early steps of mouse cardiac development.

Keywords: embryonic stem cell, differentiation, cardiac progenitor, cardiogenesis

Overall design: The Spotfire DecisionSite software package was used for the identification of uniquely upregulated or downregulated (at least 1.5 times increase or decrease in the expression value) probe sets in the CPC population when compared to the rest of the cells in the differentiating EBs. Probe sets that were considered unique for the CPC population were found to be commonly upregulated or downregulated during all four days of analysis. Probe sets that exhibited an increasing or decreasing pattern of expression with at least 1.5 times increase or decrease in the expression values of day 5 CPCs and day 8 CPCs were also reported. Probe sets of the CPC population that exhibited upregulation or downregulation by at least 1.5 times when compared to the mESC derived cardiomyocytes were also reported. The final analysis included probe sets that exhibited a different temporal pattern of expression in the CPC population when compared to the rest of the cells along the four days of differentiation. Specifically in order to identify these probe sets gene expression curve over time was modeled flexibly

Background corr dist: KL-Divergence = 0.1448, L1-Distance = 0.0419, L2-Distance = 0.0032, Normal std = 0.3990

1.040 Kernel fit Pairwise Correlations Normal fit

Density 0.520

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

Day 5 GFPDay Negative 5 GFPDay Positive 6 Batch GFPDay Negative 61Batch GFP(0.0330638)Day Positive 17 Batch (0.0536005)GFPDay Positive 71Batch GFP(0.0232491)Day Negative 1 8Batch (0.0150098)GFPDay Positive 18 Batch (0.0235201)GFPDay Negative 51Batch GFP(0.0259177)Day Negative 15 Batch (0.0596162)GFPDay Positive 61 Batch GFP(0.0580371)Day Negative 62Batch GFP(0.0488127)Day Positive 27 Batch (0.0657429)GFPDay Negative 72Batch GFP(0.0526542)Day Positive 28 Batch (0.102292)GFPDay Negative 82Batch GFP(0.0497788)Mouse Positive2 Batch(0.0086589) embryonicMouse 2Batch (0.0603011) embryonic stem2 (0.0800907) cell stem derived cell derived cardiomyocytes[ min cardiomyocytes ] 1 (0.117865) 2 (0.12179)[ medium ] [ max ] CEM 1 Ruvbl1 1304.7 4274.1 6255.1 P ( S | Z, I ) = 1.00 Ruvbl2 1881.9 7202.5 10253.6 Mean Corr = 0.73326 Pfdn2 2066.3 4283.7 5438.1 Skp2 885.6 2208.9 3405.6 Skp1a 5271.1 7791.6 10500.1 Cul1 2412.3 4460.4 5881.8 Prmt1 4998.9 8520.4 13761.7 Lyar 731.0 5090.7 7635.5 Cse1l 5221.1 9311.5 12561.3 Ebna1bp2 1344.6 4088.1 5672.0 Gart 2311.8 5569.0 7749.7 CEM 1 + Cct5 14719.1 20960.6 24816.2 Top 10 Genes Apex1 5077.2 8256.3 13205.2 Sf3a3 2610.9 6435.0 9195.1 Ddx18 1100.5 2936.3 4251.5 C1qbp 5020.7 9369.1 11524.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE12464" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 23 -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=GSE12464 Status: Public on May 20 2009 Title: Transcriptional signatures of Itk-deficiency using CD3+ T-cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19450280 Summary & Design: Summary: The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3+ T-cells, including CD4+ and CD8+ subsets, using Affymetrix microarrays. The largest difference between Itk-/- and Wt CD3+ T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4+ and CD8+ T-cell subsets identified a greater differential expression than in total CD3+ cells. Cyclosporin (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the Bub1, IL7R, Ctla2a, Ctla2b, and Schlafen1 genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found. Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.

Overall design: CD3+ T-cells from pooled suspensions of spleen and lymph nodes of Wt and Itk knockout mice on C57BL/6 background were isolated after negative depletion. Unstimulated as well as stimulated T-cells were studied. Stimulations were done with anti-CD3 (1 mg/ml) with or without anti-CD28 (3 mg/ml) in the presence or absence of CsA (1 mg/ml) for 24 hrs. For each stimulus, at least duplicate samples were used.

Background corr dist: KL-Divergence = 0.1100, L1-Distance = 0.0376, L2-Distance = 0.0025, Normal std = 0.4333

0.938 Kernel fit Pairwise Correlations Normal fit

Density 0.469

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 unstimulated typeWild unstimulated typeItk 1 unstimulatedknockout(0.102699)Itk 2 knockout(0.0483158) unstimulatedWild 3 (0.0450678) typeunstimulatedWild CD3-stimulated 1 type (0.0365019)Wild CD3-stimulated 2 type (0.0584269)Wild CD3-stimulated 1 typedayWild 1CD3-stimulated 2(0.0524003) typedayItk 1 CD3-stimulatedknockout 3(0.0290111) dayItk 1 knockout 1(0.0503385) dayCD3-stimulatedWild 2 2(0.028432) typedayCD3-stimulatedWild 2CD3CD28-stimulated (0.0205147) type 1Wild (0.0161139) CD3CD28-stimulated type 2Wild (0.0115307) CD3CD28-stimulated typeWild 1 CD3CD28-stimulated day type Itk1 2(0.0844882) CD3CD28-stimulatedknockoutday Itk1 3(0.0343088) knockoutday CD3CD28-stimulated Wild1 1(0.0336905) day typeCD3CD28-stimulated Wild2 2(0.0180448) CD3-stimulated day type Wild2 (0.0108704) CD3-stimulated 1type (0.0421028)Wild CD3CD28-stimulated and 2type (0.0298785) CsA-treated CD3CD28-stimulated and CsA-treated 1 (0.0587316) and 2CsA-treated (0.0634635)[ and min CsA-treated 1] (0.0714523) 2 (0.0536162)[ medium ] [ max ] CEM 1 Ruvbl1 743.4 2297.5 4452.6 P ( S | Z, I ) = 1.00 Ruvbl2 986.7 2821.6 6771.6 Mean Corr = 0.73285 Pfdn2 1429.5 2785.8 5107.4 Skp2 131.4 472.0 1008.1 Skp1a 3295.1 4452.9 5539.3 Cul1 1700.8 2630.5 3811.3 Prmt1 1097.6 3041.0 5546.0 Lyar 1348.6 5271.8 8333.7 Cse1l 2202.9 4040.9 5661.4 Ebna1bp2 1548.4 4405.2 6878.6 Gart 2076.4 6448.6 10368.4 CEM 1 + Cct5 6937.0 12005.2 16835.0 Top 10 Genes Apex1 1269.3 3699.2 7545.4 Sf3a3 1588.8 2786.0 4438.5 Ddx18 1126.8 2337.3 4131.9 C1qbp 1873.3 6855.5 11537.0

Null module Uri1 Stap1 Polr2e 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, (0.118826) DN3 GSIrep2IkL/L cells, treated, rep1(0.0927808) DN3IkL/L DMSO (0.116255) cells, rep2 DN3IkL/L treated,DMSO (0.202165) cells, DN3 treated, GSIrep1 cells, treated, (0.209471) GSIrep2 treated, rep1(0.0739325) (0.117052) rep2[ min (0.069518) ] [ medium ] [ max ] CEM 1 Ruvbl1 1046.6 1959.6 3473.9 P ( S | Z, I ) = 1.00 Ruvbl2 1376.8 3218.4 4944.9 Mean Corr = 0.73080 Pfdn2 1131.4 2562.0 3720.5 Skp2 586.8 1887.8 4179.8 Skp1a 9649.1 11335.3 12810.1 Cul1 2278.5 3024.2 4153.4 Prmt1 572.2 2181.9 3643.6 Lyar 877.6 3720.6 5200.2 Cse1l 2819.7 5533.6 7220.2 Ebna1bp2 1545.5 3292.0 5102.3 Gart 1106.9 3495.8 5833.8 CEM 1 + Cct5 10235.7 15535.5 18603.0 Top 10 Genes Apex1 1161.2 3420.4 5506.8 Sf3a3 1934.5 4120.1 5924.4 Ddx18 761.2 2019.3 2803.7 C1qbp 1433.1 5749.1 7500.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE15541" 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=GSE15541 Status: Public on Apr 09 2009 Title: Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18375036 Summary & Design: Summary: OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX and NUP98-HOX fusion proteins to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. MATERIALS AND METHODS: To further resolve these mechanisms, we conducted a structure-function analysis of MEIS1 and gene-expression profiling, in the context of NUP98-HOXD13 (ND13) leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the PBX-interaction domain, the homeodomain, and the C-terminal domain of MEIS1, are all required for leukemogenic collaboration with ND13. In contrast, the N-terminal domain of MEIS1 is dispensable for collaboration with ND13, but is required for Flt3 upregulation, indicating additional roles for MEIS1 in induction of leukemia independent of alterations in Flt3 expression. Gene-expression profiling of a cloned ND13 preleukemic cell line transduced with wild-type or Meis1 mutant forms revealed deregulation of multiple genes, including a set not previously implicated as MEIS1 targets. Chromatin immunoprecipitation revealed the in vivo occupancy of MEIS1 on regulatory sequences of Trib2, Flt3, Dlk1, Ccl3, Ccl4, Pf4, and Rgs1. Furthermore, engineered overexpression of Trib2 complements ND13 to induce AML while Ccl3 potentiates the repopulating ability of ND13. CONCLUSION: This study shows that Meis1-induced leukemogenesis with ND13 can occur in the absence of Flt3 upregulation and reveals the existence of other pathways activated by MEIS1 to promote leukemia.

Overall design: Establishment of pre-leukemic bone marrow cell lines following transduction with ND13 have been previously described (Pineault, Abramovich et al. 2005). In brief, lines were established from BM cells previously treated with 5-fluorouracil (5-FU) from (C57Bl/6Ly-Pep3b x C3H/HeJ) F1 (PepC3) (Ly5.1+/Ly5.2+) mice freshly transduced with the ND13-GFP or ND13pac virus and maintained in liquid culture. To generate ND13+Meis1 or ND13+Meis1 mutant BM cell lines, the ND13 BM cells were transduced by co-cultivation on irradiated (4,000 cGy) E86 producers for Meis1-YFP (or Meis1 mutant forms), respectively, for a period of 2 days in the presence of 5 ´g/ml of protamine sulfate. Three independent experiments were performed for each of the four different conditions included in the study.

Background corr dist: KL-Divergence = 0.0967, L1-Distance = 0.0283, L2-Distance = 0.0010, Normal std = 0.4561

0.888 Kernel fit Pairwise Correlations Normal fit

Density 0.444

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

NUP98-HOXD13+MIY-ctrl_rep1NUP98-HOXD13_MIY-ctrl_rep2NUP98-HOXD13+MIY-ctrl_rep3NUP98-HOXD13+MEIS1-WT_rep1NUP98-HOXD13+MEIS1-WT_rep2 (0.209842)NUP98-HOXD13+MEIS1-WT_rep3 (0.266079)NUP98-HOXD13+MEIS1-deltaHD_rep1 (0.132293)NUP98-HOXD13+MEIS1-deltaHD_rep2 (0.0186828)NUP98-HOXD13+MEIS1-deltaHD_rep3 (0.0862127)NUP98-HOXD13+M33-MEIS1_rep1 (0.0586677)NUP98-HOXD13+M33-MEIS1_rep2NUP98-HOXD13+M33-MEIS1_rep3 (0.069755) (0.0422805) (0.0223346) (0.0153605) (0.0256602)[ min (0.0528321) ] [ medium ] [ max ] CEM 1 Ruvbl1 2158.3 3424.2 3771.6 P ( S | Z, I ) = 1.00 Ruvbl2 5028.2 7225.0 8310.3 Mean Corr = 0.72401 Pfdn2 1249.5 2398.9 2927.4 Skp2 649.7 1429.0 1550.8 Skp1a 4702.1 6944.7 8001.9 Cul1 2367.4 2832.2 3166.4 Prmt1 6078.6 11122.6 12211.1 Lyar 2624.3 5769.5 6675.9 Cse1l 2514.2 5952.2 6411.0 Ebna1bp2 2541.9 4716.1 5525.5 Gart 2592.4 4303.0 4881.5 CEM 1 + Cct5 14620.2 18288.6 19356.9 Top 10 Genes Apex1 6125.3 9729.6 10698.8 Sf3a3 2989.9 3781.9 4240.4 Ddx18 1517.1 2773.7 3101.5 C1qbp 7076.2 9980.8 11460.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE16874" 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=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(0.065302) BCells_Transgenic_day0_REP3(0.0568687) BCells_WildType_day2_REP1(0.0771583)BCells_WildType_day2_REP2 (0.114952)BCells_WildType_day2_REP3 (0.0875644)BCells_Transgenic_day2_REP1 (0.118561) BCells_Transgenic_day2_REP2(0.0727152) BCells_Transgenic_day2_REP3(0.0628277) (0.127785) (0.0480222) (0.0546466)[ (0.113597)min ] [ medium ] [ max ] CEM 1 Ruvbl1 887.3 3334.2 4288.9 P ( S | Z, I ) = 1.00 Ruvbl2 1450.9 5102.8 6065.4 Mean Corr = 0.72182 Pfdn2 1047.5 1621.7 2280.8 Skp2 101.5 455.4 611.6 Skp1a 1918.1 3684.1 4375.9 Cul1 1996.6 2481.6 2959.2 Prmt1 1214.3 3075.0 8641.2 Lyar 1154.7 5538.8 6856.0 Cse1l 2344.8 5685.8 6476.4 Ebna1bp2 1214.3 4345.6 5333.9 Gart 805.2 3856.7 4858.8 CEM 1 + Cct5 6188.7 17024.8 19096.0 Top 10 Genes Apex1 1272.4 6406.6 7918.4 Sf3a3 1326.4 4116.1 4547.9 Ddx18 1181.1 3380.8 4200.6 C1qbp 2098.9 11772.6 14129.1

Null module Uri1 Stap1 Polr2e GEO Series "GSE5333" 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=GSE5333 Status: Public on Jul 22 2006 Title: Gene expression profiling of whole epididymis in embryonic (gestational day 12, 14, 16 & 18) and postnatal day 2 mice. (GUDMAP Series ID: 4) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events.

Keywords: developmental time course

Overall design: Day to day comparison in whole epididymus throughout development with triplicates at each time point. Each sample is a pair of epididymus from a single animal and each animal is taken from a different dam.

Background corr dist: KL-Divergence = 0.1487, L1-Distance = 0.0469, L2-Distance = 0.0047, Normal std = 0.4166

1.009 Kernel fit Pairwise Correlations Normal fit

Density 0.504

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

Gaido_Epididymus_pnd2_1_25May2006Gaido_Epididymus_pnd2_2_25May2006Gaido_Epididymus_pnd2_3_25May2006Gaido_Epididymus_gd18_4_25May2006Gaido_Epididymus_gd18_5_25May2006Gaido_Epididymus_gd18_6_25May2006 (0.0496699)Gaido_Epididymus_gd16_7_25May2006 (0.0518588)Gaido_Epididymus_gd16_8_25May2006 (0.147212)Gaido_Epididymus_gd16_9_25May2006 (0.042707)Gaido_Epididymus_gd14_10_25May2006 (0.020128)Gaido_Epididymus_gd14_11_25May2006 (0.0151873)Gaido_Epididymus_gd14_12_25May2006 (0.0419673)Gaido_Epididymus_gd12_13_25May2006 (0.0173267)Gaido_Epididymus_gd12_14_25May2006 (0.0222074)Gaido_Epididymus_gd12_15_25May2006 (0.0169363)Gaido_WholeLitterReference_pnd0.5_16_25May2006 (0.00694204) (0.0537605) (0.119218) (0.171877)[ min (0.0678299) ] (0.155171)[ medium ] [ max ] CEM 1 Ruvbl1 1083.1 2459.4 3808.3 P ( S | Z, I ) = 1.00 Ruvbl2 362.6 1410.7 2245.1 Mean Corr = 0.71534 Pfdn2 500.7 1824.8 3469.7 Skp2 712.2 4035.1 6141.4 Skp1a 5848.1 7204.4 9614.3 Cul1 2468.1 4028.4 5927.9 Prmt1 1570.5 3651.5 5501.5 Lyar 570.0 904.8 4310.0 Cse1l 2943.5 4417.9 8451.6 Ebna1bp2 874.6 1437.9 2619.5 Gart 759.3 2104.9 3682.9 CEM 1 + Cct5 9529.3 11815.6 17199.2 Top 10 Genes Apex1 1900.4 3622.0 6542.1 Sf3a3 1512.2 2153.0 3781.2 Ddx18 612.4 811.2 1256.9 C1qbp 2477.0 2959.9 5673.7

Null module Uri1 Stap1 Polr2e GEO Series "GSE17316" 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=GSE17316 Status: Public on Nov 23 2009 Title: Reprogramming of a B cell line into macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19896445 Summary & Design: Summary: Transcription factor induced reprogramming of one specialized cell type into another is a promising approach for regenerative medicine. However, the process still remains poorly understood, in large part because of the lack of adequate experimental models. Here we describe a robust cell reprogramming system consisting of a B cell line with an inducible form of C/EBPa that can be converted into macrophages with essentially 100% efficiency in only 2 to 3 days. The conversion involves reciprocal changes in cell surface antigen expression, increase in cell granularity and size, alterations in cellular structures, formation of membrane extensions, acquisition of phagocytic capacity and an increased inflammatory responsiveness as well as migratory activity. Analysis of the transcriptome shows complex reciprocal regulation of B cell and macrophage genes, including transcription factors required for the formation of the two lineages. The fact that the cells become irreversibly committed to a macrophage fate within 1 to 2 days after activation of C/EBPa show that they are truly reprogrammed. The system should be useful to study epigenetic and cell biological mechanisms of transcription factor induced cell reprogramming.

Overall design: time points: vehicle control, 3h, 12h, 24h, 48h.

Background corr dist: KL-Divergence = 0.0922, L1-Distance = 0.0474, L2-Distance = 0.0035, Normal std = 0.4812

0.883 Kernel fit Pairwise Correlations Normal fit

Density 0.441

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

HAFTL HAFTLcell line C10cell treated linecellC10 treatedwithline cell withbetaC10 withline an estradiol cell withinduciblebetaC10 line an estradiol cell samplewithinducibleC10 formline an cell samplewith1inducibleof (0.0562348)C10 formC/EBPa,line an cell with2inducibleof (0.0635241)C10 formC/EBPa,line treatedan cell withinducibleofC10 formC/EBPa,line treatedwithan cell withinducibleof ethanolC10 formC/EBPa,line treatedwithan cell withinducibleof ethanol C10 sampleformC/EBPa,line treatedwithan cell withinducibleof beta sampleform1C/EBPa,line treatedwith(0.0741509)an estradiol withinducibleof beta form2C/EBPa, treatedwith(0.0572314)an estradiol inducibleof for beta formC/EBPa, treatedwith3 hoursestradiol of for beta [ formC/EBPa, treatedwith3 minsample hoursestradiol of for beta C/EBPa, treatedwith12 sample1 ]estradiol (0.127057)hours for beta treatedwith12 2 sampleestradiol (0.123038)hours for beta with24[ sampleestradiol1 hoursmedium for(0.0429324) beta 24 sampleestradiol2 hours for(0.0501696) 48 sample1 hours for(0.0867876) ] 48 sample2 hours (0.107514) sample1 (0.107501)[ max 2 (0.10386) ] CEM 1 Ruvbl1 542.6 1916.7 2423.1 P ( S | Z, I ) = 1.00 Ruvbl2 869.9 3993.1 5565.3 Mean Corr = 0.71494 Pfdn2 802.6 1466.2 1975.0 Skp2 331.9 1202.3 3969.3 Skp1a 3757.8 5592.5 6639.5 Cul1 1533.9 2050.7 2420.4 Prmt1 325.9 1314.9 2163.8 Lyar 748.6 2930.3 6139.2 Cse1l 1622.3 4359.9 6363.6 Ebna1bp2 1292.4 3516.3 5129.5 Gart 378.4 1757.8 2190.1 CEM 1 + Cct5 5943.0 13868.9 17587.7 Top 10 Genes Apex1 435.7 5066.3 10654.8 Sf3a3 1283.8 2001.2 3686.9 Ddx18 830.1 2940.1 3141.1 C1qbp 1516.4 8111.5 11120.4

Null module Uri1 Stap1 Polr2e 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 (0.061428)ViPSCs, rep2 (0.032061)TiPSCs, rep3 (0.0356224)TiPSCs, rep1 (0.0515016)TiPSCs, rep2 (0.0355707)mESCs, rep3 (0.0285764)mESCs, rep1 (0.0217568)mESCs, rep2 (0.0288884)Tail rep3 tip (0.0464617) fibroblastsVentricular (0.27829)cardiomyocytes (0.379843)[ min ] [ medium ] [ max ] CEM 1 Ruvbl1 863.7 3870.3 4801.9 P ( S | Z, I ) = 1.00 Ruvbl2 978.3 8137.9 9220.2 Mean Corr = 0.70955 Pfdn2 2610.3 6362.9 7014.9 Skp2 83.8 1543.6 1828.8 Skp1a 12245.9 22552.0 27897.9 Cul1 1851.5 2982.0 3812.6 Prmt1 4814.9 11421.6 13261.1 Lyar 1135.4 6586.1 7110.9 Cse1l 2835.7 7684.0 8113.1 Ebna1bp2 1066.0 5236.1 5676.2 Gart 1053.0 5721.0 6128.7 CEM 1 + Cct5 9188.8 18196.9 19741.6 Top 10 Genes Apex1 1752.0 5742.1 7743.0 Sf3a3 882.1 3280.8 3719.2 Ddx18 848.8 3740.9 4244.9 C1qbp 5549.3 14217.1 19569.9

Null module Uri1 Stap1 Polr2e GEO Series "GSE45619" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45619 Status: Public on Mar 29 2013 Title: Expression analysis of GATA1s murine megakaryocyte progenitors from bone marrow and fetal Liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.

kewywords: Mouse megakaryocyte progenitors

Overall design: Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from GATA1s fetal liver and bone marrow

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

0.596 Kernel fit Pairwise Correlations Normal fit

Density 0.298

0.000 CEM 1

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

Pre-normalization Quantiles

Gs_MKP_BM_1Gs_MKP_BM_2Gs_MKP_BM_3 (0.130134)Gs_MKP_FL_1 (0.10719)Gs_MKP_FL_2 (0.188711) Gs_MKP_FL_3(0.11599) (0.294344) (0.163632) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 2430.0 3155.4 3990.0 P ( S | Z, I ) = 1.00 Ruvbl2 2398.9 2715.0 3313.9 Mean Corr = 0.70030 Pfdn2 1467.5 1941.4 2426.9 Skp2 183.6 485.3 668.6 Skp1a 4503.3 5465.5 5517.2 Cul1 3106.6 3575.6 4007.7 Prmt1 3078.2 4479.6 4745.8 Lyar 1821.8 2303.9 2657.9 Cse1l 3143.3 3909.1 4041.6 Ebna1bp2 2525.8 3020.3 4174.7 Gart 1586.7 1973.3 2583.5 CEM 1 + Cct5 5254.6 5819.8 6385.4 Top 10 Genes Apex1 3027.9 3421.0 3956.0 Sf3a3 911.6 1107.7 1408.4 Ddx18 2026.5 2658.4 2736.0 C1qbp 6141.1 6856.6 7572.4

Null module Uri1 Stap1 Polr2e 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 (0.0300196) repWT cells 2 DN4 (0.0623986) repWT cells 1 DP (0.128147) rep cellsWT 2 DP (0.0600795)rep cellsDN3 1 (0.119724) cellsrepDN3 2 rep (0.117784) cells 1DN4 (0.0224815) rep cells 2DN4 (0.0367264) rep cells 1DP (0.125845) rep cells 2DP (0.0817488)rep cells 1 (0.12449) rep 2 (0.0905554) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 940.9 3160.0 3751.6 P ( S | Z, I ) = 1.00 Ruvbl2 1463.0 4221.1 5110.8 Mean Corr = 0.69834 Pfdn2 963.4 1783.5 2085.1 Skp2 512.0 979.3 2075.6 Skp1a 11225.2 12555.3 13254.4 Cul1 1460.5 2656.6 3062.1 Prmt1 1018.4 5272.4 5914.2 Lyar 927.0 4879.0 5784.7 Cse1l 2055.8 5151.1 6069.2 Ebna1bp2 820.2 3533.0 3910.7 Gart 745.5 3571.4 4449.2 CEM 1 + Cct5 9593.2 17717.5 20492.6 Top 10 Genes Apex1 479.1 4586.4 5222.3 Sf3a3 2724.3 5497.4 5665.7 Ddx18 723.2 2595.6 3129.0 C1qbp 1396.5 10295.5 11383.1

Null module Uri1 Stap1 Polr2e GEO Series "GSE6065" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 100 -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=GSE6065 Status: Public on Oct 21 2006 Title: Murine host cell response to Aeromonas infection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17897183 Summary & Design: Summary: Aims: To assess the virulence of multiple Aeromonas spp. using two models, a neonatal mouse assay and a mouse intestinal cell culture.

Methods and Results: Transcriptional responses to both infection models were evaluated using microarrays. After artificial infection with a variety of Aeromonas spp., mRNA extracts from the two models were processed and hydridized to murine microarrays to determine host gene response. Definition of virulence was determined based on host mRNA production in murine neonatal intestinal tissue and mortality of infected animals. Infections of mouse intestinal cell cultures were then performed to determine whether this simpler model system's mRNA responses correlated to neonatal results and therefore be predictive of virulence of Aeromonas spp. Virulent aeromonads up-regulated transcripts in both models including multiple host defense gene products (chemokines, regulation of transcription and apoptosis, cell signaling). Avirulent species exhibited little or no host response in neonates. Mortality results correlated well with both bacterial dose and average fold change of up-regulated transcripts in the neonatal mice.

Conclusions: Cell culture results were less discriminating but showed promise as potentially being able to be predictive of virulence. Jun oncogene up-regulation in murine cell culture is potentially predictive of Aeromonas virulence.

Significance and Impact of the Study: Having the ability to determine virulence of waterborne pathogens quickly would potentially assist public health officials to rapidly assess exposure risks.

Keywords: Aeromonas; Virulence; Gene expression; Host response

Overall design: Two infection models were assessed, live, whole animals (neonatal Swiss Webster mice) and a murine small intestinal cell culture. Biological replicates (n=5) were infected with different Aeromonas species/strains and compared to uninfected controls.

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0755, L2-Distance = 0.0103, Normal std = 0.5327

0.881 Kernel fit Pairwise Correlations Normal fit

Density 0.441

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

NRMRLNRMRL controlNRMRL replicatereplicate01,NRMRL control control02, batch032405NRMRL controlreplicate03, batch032405NRMRL controlreplicate04, (0.0203778) batch032405NRMRL testreplicate05, (0.013634) replicate01, batch032405NRMRL test (0.0125826) replicate02, batch032405NRMRL test EPA1, (0.0154431) replicate03,NRMRL test batch032405 EPA1 (0.0216603) replicate04,NRMRL testbatch032405 EPA1 replicate05, (0.0167092)NRMRL testbatch032405 EPA1 replicate01, (0.0162286)NRMRL testbatch032405 EPA1 replicate02, (0.0136321)NRMRL testbatch032405 EPA5 replicate03, (0.0193764)NRMRL testbatch032405 EPA5 replicate04, (0.0218429)NRMRL testbatch032405 EPA5 replicate05, (0.0172906)NRMRL testbatch032405 EPA5 replicate01, (0.0166641)NRMRL testbatch032405 EPA5 replicate02, (0.0290438)NRMRL testbatch032405 EPA9 replicate03, (0.012849)NRMRL testbatch032405 EPA9, replicate04, (0.0145438)NRMRL test batch032405 EPA9 replicate05, (0.00548289)NRMRL testbatch032405 EPA9 replicate01, (0.00459317)NRMRL testbatch032405 EPA9 replicate02, (0.0149286)NRMRL testbatch032405 EPA61 replicate03, (0.0126292)NRMRL test batch032405EPA61 replcate04, (0.00462168)NRMRL test batch032405EPA61 replicate05, NRMRL(0.0151191)test EPA61batch replicate01, NRMRL (0.00775342)test032405 batch032405 EPA61 replicate02,NRMRL test(0.0108799) batch032405EPA63 replicate03, (0.00821234)NRMRL test batch032405EPA63 replicate04, NRMRL(0.0101697)test batch032405EPA63 replicate05, NRMRL(0.0164516)test batch032405EPA63 replicate01, NRMRL(0.0118037)test batch032405EPA63 replicate02, NRMRL(0.0120429)test batch032405EPA71 replicate03, NRMRL(0.00782904)test batch032405EPA71 replicate04, NRMRL(0.0127177)test batch032405EPA71 replicate05, NRMRL(0.0158654)control batch032405EPA71 NRMRL (0.0122063)controlreplicate01, batch032405EPA71 NRMRL (0.0153185)controlreplicate02, batch032405 uninfected, NRMRL (0.0135177)controlreplicate03, uninfected NRMRL (0.0101514)controlreplicate04, batch051905 uninfectedNRMRL testreplicate05, batch051905 replicate01, uninfectedNRMRL test(0.00350346) batch051905 replicate02, uninfected NRMRL (0.00398965)test batch051905EPA2 replicate03, NRMRL (0.0105342)testbatch051905 batch051905EPA2 replicate04, NRMRL (0.00983445)testbatch051905 EPA2 replicate05, (0.00592241) NRMRL (0.00282341)testbatch051905 EPA2 replicate01, (0.00707789)NRMRL testbatch051905 EPA2 replicate02, (0.00623655)NRMRL testbatch051905 EPA5 replicate03, (0.00608361)NRMRL testbatch051905 EPA5 replicate04, (0.00942254)NRMRL testbatch051905 EPA5 replicate05, (0.00809188)NRMRL testbatch051905 EPA5 replicate01, (0.00889275)NRMRL testbatch051905 EPA5 replicate02, (0.00622496)NRMRL testbatch051905 EPA9 replicate03, (0.00800006)NRMRL testbatch051905 EPA9 replicate04, (0.00972071)NRMRL testbatch051905 EPA9 replicate05, (0.00440407)NRMRL testbatch051905 EPA9 replicate01, (0.0065883)NRMRL testbatch051905 EPA9 replicate02, (0.00780222)NRMRL testbatch051905 EPA10 replicate03, (0.00862435)NRMRL test batch051905EPA10 replicate04, (0.00818217)NRMRL test batch051905EPA10 replicate05, NRMRL(0.00761438)test batch051905EPA10 replicate01, NRMRL(0.00669487)test batch051905EPA10 replicate02, NRMRL(0.00577705)test batch051905EPA61 replicate03, NRMRL(0.00708819)test batch051905EPA61 replicate04, NRMRL(0.00792287)test batch051905EPA61 replicate05, NRMRL(0.00653045)test batch051905EPA61 replicate01, NRMRL(0.0048454)test batch051905EPA61 replicate02, NRMRL(0.00526464)test batch051905EPA72 replicate03, NRMRL(0.00464395)test batch051905EPA72 replicate04, NRMRL(0.00606662)test batch051905EPA replicate05, 72 NRMRL(0.0262408)test EPA72batch replicate01, NRMRL(0.00783416)test 051905 batch051905EPA replicate02, 72NRMRL test (0.00565152) EPA51batch051905 replicate03, NRMRL(0.0122595)test batch093005EPA51 replicate04,NRMRL test(0.00618934) batch093005EPA51 replicate05, NRMRL(0.00469465)test batch093005EPA51 replicate01, NRMRL(0.00715158)test batch093005EPA51 replicate02, NRMRL(0.0147357)test batch093005EPA52 replicate04, NRMRL(0.00557649)test batch093005EPA52 replicate03, NRMRL(0.00379013)test batch093005EPA52 replicate05, NRMRL(0.00470287)test batch093005EPA52 replicate01, NRMRL(0.0114817)test batch093005EPA52 replicate02, NRMRL(0.016477)test batch093005EPA73 replicate03, NRMRL(0.0104343)test batch093005EPA73 replicate04, NRMRL(0.0131486)test batch093005EPA73 replicate05, NRMRL(0.00834906)test batch093005EPA73 replicate01, NRMRL(0.00401824)test batch093005EPA73 replicate02, NRMRL(0.00740173)test batch093005EPA80 replicate03, NRMRL(0.00825166)test batch093005EPA80 replicate04, NRMRL(0.00648582)test batch093005EPA80 replicate05, NRMRL(0.0117331)test batch093005EPA80 replicate01, NRMRL(0.00764835)test batch093005EPA80 replicate02, NRMRL(0.00720929)test batch093005EPA82 replicate03, NRMRL(0.0100799)test batch093005EPA82 replicate04, NRMRL(0.00555654)test batch093005EPA82 replicate05, NRMRL(0.00942194)control batch0930 CEM 1 Ruvbl1 264.3 445.4 1427.0 P ( S | Z, I ) = 1.00 Ruvbl2 648.8 1215.3 4603.7 Mean Corr = 0.69747 Pfdn2 633.1 1032.1 2802.8 Skp2 98.1 412.1 1156.6 Skp1a 1779.0 3834.5 5994.5 Cul1 1082.6 1376.4 1938.6 Prmt1 620.9 2379.4 7114.5 Lyar 419.4 615.0 1896.3 Cse1l 892.9 1401.7 7532.5 Ebna1bp2 411.5 741.1 2941.0 Gart 318.9 574.2 1430.2 CEM 1 + Cct5 2981.9 4229.8 13369.1 Top 10 Genes Apex1 1135.6 1683.6 4170.5 Sf3a3 528.0 796.2 1742.9 Ddx18 725.4 1024.0 2732.2 C1qbp 1944.0 2444.6 7507.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE8555" 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=GSE8555 Status: Public on Jul 25 2007 Title: Genome-wide analysis of Phgdh inactivation in murine embryonic head Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18228065 Summary & Design: Summary: D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion.

Keywords: genetic modification

Overall design: RNA of 4 biological replicates was hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0165, L2-Distance = 0.0003, Normal std = 0.6997

0.570 Kernel fit Pairwise Correlations Normal fit

Density 0.285

0.000 CEM 1

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

Pre-normalization Quantiles

Gene expressionGene expressionGene profiling expressionGene profiling of expression PhgdhGene profiling of expression knockoutPhgdhGene profiling of expression knockoutPhgdhGene embryo profiling of expression knockoutPhgdhGene embryo wild1profiling of expression knockoutPhgdh (0.149045) embryo KO1profiling of knockout Phgdh(0.0536335) embryo wild2profiling of knockoutPhgdh (0.139912) embryo KO2 of knockout Phgdh(0.190625)[ embryo wild3min knockout (0.063073) embryo KO3 ] (0.132924) embryo wild4 (0.100194) KO4[ medium (0.170593) ] [ max ] CEM 1 Ruvbl1 928.4 1654.7 1947.2 P ( S | Z, I ) = 1.00 Ruvbl2 1917.9 2484.3 2730.5 Mean Corr = 0.70082 Pfdn2 1512.9 2533.1 2960.9 Skp2 2339.0 3248.7 3916.3 Skp1a 6457.7 9920.8 13995.9 Cul1 1443.1 3374.1 4012.1 Prmt1 5147.5 6914.9 7336.1 Lyar 813.0 1343.8 1654.6 Cse1l 2746.1 3565.7 3971.0 Ebna1bp2 792.9 1264.0 1802.0 Gart 919.8 1278.4 1437.4 CEM 1 + Cct5 5222.2 11692.5 12877.4 Top 10 Genes Apex1 2979.5 4058.9 4680.7 Sf3a3 1253.0 1982.6 2704.4 Ddx18 1155.4 1336.6 1425.4 C1qbp 1885.3 2536.4 3002.2

Null module Uri1 Stap1 Polr2e GEO Series "GSE16925" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16925 Status: Public on Aug 03 2009 Title: Expression data from mouse ES and iPS cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19672241 Summary & Design: Summary: Induced pluripotent stem (iPS) cells were produced from reprogramming of somatic cells, and they are shown to possess pluripotent properties similar to embryonic stem (ES) cells. Here we used microarrays to detail the global expression pattern among the ES cells and iPS cells, as well as the original mouse embryo fibroblast (MEF), to identify important players involved in the reprogramming process.

Overall design: Mouse ES cell cultures, as well as selected iPS cell lines and the original MEF cells they were derived from, were used for RNA extraction and hybridization on Affymetrix microarrays. Three biological replicates for each sample were processed. GeneChips were processed and data were analyzed as previously described (Zeng et al., Dev Biol 20004).

Background corr dist: KL-Divergence = 0.0695, L1-Distance = 0.0886, L2-Distance = 0.0130, Normal std = 0.6146

0.785 Kernel fit Pairwise Correlations Normal fit

Density 0.393

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

CL11-rep1CL11-rep2 (0.0275231)CL11-rep3 (0.0451909)MEF-rep1 (0.0545219)MEF-rep2 (0.177828)MEF-rep3 (0.157901)IP14D-1-rep1 (0.201481)IP14D-1-rep2 (0.0210325)IP14D-1-rep3 (0.0302876)IP14D-101-rep1 (0.0202342)IP14D-101-rep2IP14D-101-rep3 (0.0422817)IP20D-3-rep1 (0.0360288)IP20D-3-rep2 (0.0658008) (0.0183068)IP20D-3-rep3 (0.0489846) (0.0525982) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 1233.3 4594.7 6054.9 P ( S | Z, I ) = 1.00 Ruvbl2 1716.0 9043.3 12865.7 Mean Corr = 0.68866 Pfdn2 1079.0 2008.7 3245.8 Skp2 1210.3 2896.0 4019.3 Skp1a 3808.4 9546.0 11351.2 Cul1 2077.4 2564.5 3093.2 Prmt1 6483.2 12506.8 15431.7 Lyar 1046.1 5048.4 6033.0 Cse1l 1966.7 6658.0 7791.3 Ebna1bp2 2054.1 4792.1 5589.3 Gart 832.3 7373.6 12365.5 CEM 1 + Cct5 10060.4 16473.2 20243.7 Top 10 Genes Apex1 2206.7 9023.6 10638.8 Sf3a3 1499.9 3356.7 4204.4 Ddx18 1650.4 5187.4 5771.5 C1qbp 5294.0 14824.7 18751.5

Null module Uri1 Stap1 Polr2e GEO Series "GSE7897" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 60 -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=GSE7897 Status: Public on Aug 09 2008 Title: Expression data from Mouse Lymphoma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18922927 Summary & Design: Summary: We have made use of the EÎ¼-myc transgenic mouse, a model for the study of B-cell lymphoma development that is initiated through a defined genetic alteration, to explore the contributions of additional somatic alterations that contribute to the heterogeneity of the resulting tumors. As one example of such heterogeneity, we have focused on the observation that lymphomas develop in EÎ¼-myc mice with a variable time of onset. Twenty-five early-onset, 25 late-onset lymphomas and 10 normal samples were each assayed on an Affymetrix Mouse Genome 430 2.0 array.

Keywords: Myc induced lymphomas with various time-of-onset

Overall design: To focus on events that might distinguish early and late onset tumors, we performed genome-wide expression analyses of early- and late-onset lymphomas from E´-myc transgenic mice using expression microarray techniques. Total RNA was prepared from 25 early-onset (32-76 days, 62.6+/-11.0 days, median 65 days), 25 late-onset tumors (253-649 days, 391.5+/-101.8 days, median 398 days) and 10 normal tissues (lymph nodes or spleen, 38-438 days, 181.0+/-175.2 days, median 62.5 days) and subjected to Affymetrix GeneChip analyses.

Background corr dist: KL-Divergence = 0.3081, L1-Distance = 0.0449, L2-Distance = 0.0038, Normal std = 0.2815

1.417 Kernel fit Pairwise Correlations Normal fit

Density 0.709

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 Myc-inducedMouse Myc-inducedMouse lymphoma Myc-inducedMouse lymphoma Myc-inducedMouse 1 (0.0178826) lymphoma Myc-inducedMouse 2 (0.019318) lymphoma Myc-inducedMouse 3 (0.0102891) lymphoma Myc-inducedMouse 4 (0.00360277) lymphoma Myc-inducedMouse 5 (0.0166239) lymphoma Myc-inducedMouse 6 (0.025067) lymphoma Myc-inducedMouse 8 (0.00764886) lymphoma Myc-inducedMouse 9 (0.0175853) lymphoma Myc-inducedMouse 10 (0.00707686) lymphoma Myc-inducedMouse 11 (0.00464509) lymphoma Myc-inducedMouse 12 (0.00773959) lymphoma Myc-inducedMouse 13 (0.0127291) lymphoma Myc-inducedMouse 14 (0.0075355) lymphoma Myc-inducedMouse 15 (0.0256158) lymphoma Myc-inducedMouse 16 (0.00610051) lymphoma Myc-inducedMouse 17 (0.0139727) lymphoma Myc-inducedMouse 19 (0.0162788) lymphoma Myc-inducedMouse 20 (0.0195586) lymphoma Myc-inducedMouse 21 (0.0148851) lymphoma Myc-inducedMouse 22 (0.0114323) lymphoma Myc-inducedMouse 23 (0.0091279) lymphoma Myc-inducedMouse 24 (0.00524664) lymphoma Myc-inducedMouse 26 (0.0100163) lymphoma Myc-inducedMouse 28 (0.0139756) lymphoma Myc-inducedMouse 29 (0.0124869) lymphoma Myc-inducedMouse 111 lymphoma(0.0129106) Myc-inducedMouse 112 lymphoma(0.00778502) Myc-inducedMouse 113 lymphoma(0.017694) Myc-inducedMouse 114 lymphoma(0.0129471) Myc-inducedMouse 116 lymphoma(0.00834686) Myc-inducedMouse 117 lymphoma(0.0115416) Myc-inducedMouse 118 lymphoma(0.0119135) Myc-inducedMouse 119 lymphoma(0.00330077) Myc-inducedMouse 120 lymphoma(0.0336834) Myc-inducedMouse 121 lymphoma(0.00933835) Myc-inducedMouse 123 lymphoma(0.00880003) Myc-inducedMouse 124 lymphoma(0.00519545) Myc-inducedMouse 125 lymphoma(0.0130989) Myc-inducedMouse 126 lymphoma(0.0125548) Myc-inducedMouse 127 lymphoma(0.0108007) Myc-inducedMouse 128 lymphoma(0.00619779) Myc-inducedMouse 129 lymphoma(0.0171299) Myc-inducedMouse 130 lymphoma(0.0505993) Myc-inducedMouse 131 lymphoma(0.0183828) Myc-inducedMouse 133 lymphoma(0.0130671) Myc-inducedMouse 135 lymphoma(0.00859787) Myc-inducedMouse 136 lymphoma(0.0171929) WildtypeMouse 137 lymphoma(0.0274921) WildtypeMouse Normal138 (0.031319) WildtypeMouse Normal141Lymph (0.00837426) WildtypeMouse NormalLymphNode Wildtype Mouse1 NormalLymphNode(0.0298924) Wildtype Mouse2 NormalLymphNode(0.031518) Wildtype Mouse3 NormalLymphNode(0.0301397) Wildtype Mouse4 NormalLymphNode(0.0322291) Wildtype Mouse5 NormalSpleenNode(0.034188) Wildtype 6 NormalLymph7(0.0272658) (0.0315787) NormalLymphNode 8 LymphNode(0.0265217) [9 Node(0.0363192)min 10 (0.0256427)] [ medium ] [ max ] CEM 1 Ruvbl1 520.2 2200.1 3366.1 P ( S | Z, I ) = 1.00 Ruvbl2 963.6 4493.2 6329.5 Mean Corr = 0.68039 Pfdn2 902.9 2365.3 3643.3 Skp2 131.6 1094.9 2384.4 Skp1a 3253.4 5513.8 9182.3 Cul1 627.5 1387.9 2280.1 Prmt1 1776.8 7223.0 9825.4 Lyar 606.0 3620.1 7191.3 Cse1l 1461.7 4869.1 6812.5 Ebna1bp2 790.8 2966.3 4951.6 Gart 973.1 4421.2 7435.2 CEM 1 + Cct5 4192.3 9939.9 15510.8 Top 10 Genes Apex1 803.6 4616.0 7741.1 Sf3a3 895.2 2200.3 3669.7 Ddx18 1139.4 3310.6 4659.5 C1qbp 1658.8 8970.1 12719.2

Null module Uri1 Stap1 Polr2e GEO Series "GSE46797" 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=GSE46797 Status: Public on May 10 2013 Title: Expression data from c-Myc+ Notch1 T-ALL initiating cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23791182 Summary & Design: Summary: Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity.

Overall design: Three independent Notch1 T-ALL were derived on c-Myc-GFP background and sorted from the spleen of leukemic mice on the basis of GFP expression for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0376, L1-Distance = 0.0289, L2-Distance = 0.0011, Normal std = 0.6371

0.637 Kernel fit Pairwise Correlations Normal fit

Density 0.318

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

Notch1 Notch1T-ALL MycGFP Notch1T-ALL MycGFP Notch1T-ALL negative MycGFP Notch1T-ALL negative replicate MycGFP Notch1T-ALL negative replicate 1 (0.0779985) MycGFP T-ALL positive replicate 2 (0.125142) MycGFP positive replicate 3 (0.202487) positive replicate 1 (0.354783)[ replicatemin 2 (0.144234) 3] (0.0953558) [ medium ] [ max ] CEM 1 Ruvbl1 1573.1 2507.7 3227.6 P ( S | Z, I ) = 1.00 Ruvbl2 934.9 1865.2 2410.5 Mean Corr = 0.69056 Pfdn2 2934.1 4239.4 5607.2 Skp2 103.3 358.0 450.4 Skp1a 6371.3 7252.9 8056.8 Cul1 952.1 1706.2 2286.7 Prmt1 1318.0 2968.3 3314.7 Lyar 545.9 2279.2 3251.5 Cse1l 1664.3 3642.5 5802.1 Ebna1bp2 967.1 2234.2 2704.2 Gart 483.1 1655.4 2216.2 CEM 1 + Cct5 1884.7 3261.1 4013.0 Top 10 Genes Apex1 288.2 1369.5 1932.0 Sf3a3 878.5 1827.6 2384.5 Ddx18 663.9 1669.5 2214.6 C1qbp 1830.7 6170.7 6829.7

Null module Uri1 Stap1 Polr2e GEO Series "GSE31598" 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=GSE31598 Status: Public on Apr 01 2012 Title: Expression data from directly induced neural stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22467474 Summary & Design: Summary: Induced pluripotent stem (iPS) cells give rise to neural stem cells, which are applicable for therapeutic transplantation in treatment of neural diseases. However, generation of neural stem cells from iPS cells requires a careful selection of safe iPS clones. We sought to determine whether direct induction of neural stem cells from partially reprogrammed somatic cells is able to generate safer cells rapidly. We have successfully established direct induction system from fibroblast to neural stem cells. To characterize these directly induced neural stem cells, Gene expression profiles were compared with iPS cell or ES cell-derived neurosphere. We used affymetrix microarrays to compare the global gene expression of neurospheres prepared several method.

Overall design: The mouse strain used in this study except ES/iPS cells was C57BL/6.

Background corr dist: KL-Divergence = 0.1105, L1-Distance = 0.0565, L2-Distance = 0.0068, Normal std = 0.4455

0.907 Kernel fit Pairwise Correlations Normal fit

Density 0.454

0.000 CEM 1

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

Pre-normalization Quantiles

E14_NeurosphereMouse_adult_fibroblast38C2_iPSC (0.088256)iPSC_PNS (0.155393)iPSC_SNS (0.110653) (0.115458)iNSC_1 (0.0448662) iNSC_2(0.0286541) EB3_ESC(0.0115357)ESC_PNS (0.262745)ESC_SNS (0.0569666)iNSC_3_embryo (0.0459861)iNSC_4_embryo (0.0463336) (0.033153) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 600.3 2150.5 5419.2 P ( S | Z, I ) = 1.00 Ruvbl2 858.8 2283.3 6692.6 Mean Corr = 0.67557 Pfdn2 2239.3 3584.3 9098.9 Skp2 557.3 1802.9 3766.9 Skp1a 9833.4 12838.5 17804.8 Cul1 1580.3 1727.7 2832.3 Prmt1 3985.4 10774.4 15189.3 Lyar 545.0 2212.5 8003.1 Cse1l 2213.6 4747.4 10029.6 Ebna1bp2 1150.8 2373.4 6753.1 Gart 635.4 1728.2 7164.1 CEM 1 + Cct5 8608.2 13801.4 22862.1 Top 10 Genes Apex1 2250.9 4622.4 11704.0 Sf3a3 964.4 2264.5 4902.6 Ddx18 1268.3 3185.9 7493.5 C1qbp 3620.7 6994.6 13501.7

Null module Uri1 Stap1 Polr2e 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(0.0515114) rep1 4KO-loD3(0.0125066) rep1 4KO-zeroD0(0.0281131) rep1 4KO-zeroD1(0.0131742) rep14KO-zeroD3 (0.0433139) rep14KO-hiD1 (0.016262) rep14KO-hiD3 rep2(0.0210423) 4KO-loD1(0.0294748) rep2 4KO-loD3(0.018041) rep2 4KO-zeroD0(0.0149711) rep2 4KO-zeroD1(0.00981959) rep24KO-zeroD3 (0.0438029) rep24KO-hiD1 (0.0190288) rep24KO-hiD3 rep3(0.0321557) 4KO-loD1(0.0222492) rep3 4KO-loD3(0.0103294) rep3 4KO-zeroD0(0.0191121) rep3 4KO-zeroD1(0.0066717) rep34KO-zeroD3 (0.0435144) rep3WT-D0 (0.0179451) rep3 rep1WT-D1 (0.0329468) (0.0594937) rep1WT-D3 (0.0487076) rep1WT-D0 (0.0467134) rep2WT-D1 (0.0818721) rep2WT-D3 (0.0504762) rep2WT-D0 (0.0536151) rep3WT-D1 (0.0759269) rep3WT-D3 (0.0355503) rep3 (0.0416585) [ min ] [ medium ] [ max ] CEM 1 Ruvbl1 799.0 1878.9 3136.8 P ( S | Z, I ) = 1.00 Ruvbl2 730.3 1877.2 2837.3 Mean Corr = 0.67428 Pfdn2 1910.6 2656.5 4271.6 Skp2 127.4 594.6 862.2 Skp1a 4145.0 5303.1 6057.4 Cul1 1679.0 2025.0 2354.1 Prmt1 1655.6 3676.6 6982.8 Lyar 1161.6 2462.0 4789.2 Cse1l 2993.4 4188.0 5348.8 Ebna1bp2 870.5 1994.5 4377.4 Gart 1036.9 2381.9 4339.4 CEM 1 + Cct5 5652.9 8916.4 11628.0 Top 10 Genes Apex1 1536.6 3791.9 6394.5 Sf3a3 980.9 1937.1 2893.5 Ddx18 1432.4 2017.9 3855.5 C1qbp 2818.4 5940.6 9561.4

Null module Uri1 Stap1 Polr2e GEO Series "GSE11222" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 42 -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=GSE11222 Status: Public on Apr 23 2008 Title: Placental and decidual timecourse samples normalized and modeled with an undissected e17 sample Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18340042 Summary & Design: Summary: We used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0). For these samples, at each stage the fetal placenta and maternal decidual tissues were dissected and profiled separately (See series 1).

For this experiment (Series 2), placental and decidual timecourse samples were normalized and modeled with two undissected (including placental and decidual tissue) e17 placentas to allow for scaling of values for comparison to the undissected placenta samples used in the publicly available mouse GeneAtlas dataset

Keywords: time course

Overall design: Mouse placentas were obtained from timed pregnant female mice at each timepoint, and fetal tissues were used to confirm embryo staging. For all dissected samples, fetal placenta and maternal decidual tissues were dissected and pooled separately for each litter prior to RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1507, L1-Distance = 0.0356, L2-Distance = 0.0027, Normal std = 0.3773

1.057 Kernel fit Pairwise Correlations Normal fit

Density 0.529

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

PlacentaPlacenta e8.5, biologicalPlacenta e9.0, biologicalPlacenta e9.0, rep3 biologicalPlacenta(Series e9.0, rep1 biologicalPlacenta(Series2) e10.5, rep2(0.0924963) Placenta(Series 2)biological e10.5, rep3(0.0516156) Placenta(Series 2)biological e10.5, (0.0594464) rep1 Placenta 2) biological (Seriese12.0, (0.0339961) rep2Placenta biological (Series2)e12.0, rep3(0.05928)Placenta biological (Series2)e12.0, rep1(0.0377503)Placenta biological (Series2)e13.5, rep2(0.0543217)Placenta biological (Series2)e13.5, rep3(0.045756)Placenta biological (Series2)e15.0, rep1(0.0233875)Placenta biological (Series2)e15.0, rep2(0.0425087)Placenta biological (Series2)e15.0, rep1(0.0105709)Placenta biological (Series2)e17.0, rep2(0.0113038)Placenta biological (Series2)e17.0, rep3(0.0102721)Placenta biological (Series2)e17.0, rep1(0.0134398)Placenta biological (Series2)e19.0, rep2(0.011694)Placenta biological (Series2)e19.0, rep3(0.00765981)Placenta biological (Series2)P0, rep1(0.0180583) biologicalDecidua (Series2)P0, rep2(0.0247752) biologicalDecidua rep1e8.5,(Series2) (0.0108442) (SeriesbiologicalDecidua rep2e8.5,2) (0.0121812) (Series2)biologicalDecidua (0.0135116)e8.5, rep1, 2)biological Deciduatechnical (0.020871)e8.5, rep2, biological Deciduatechnical e9.0, rep1,rep1 biological Decidua(Seriestechnical e9.0, rep2,rep1 biological Decidua(Seriestechnical2) e10.5, rep1rep2(0.00869205) (SeriesDecidua(Series2)biological e10.5, rep2rep2(0.00805215) (Series2)Decidua(Series2)biological e12.0, (0.0269304) (0.0300213)rep1 2)Decidua 2)biological (Seriese12.0, (0.0138344) (0.0105289)rep2 Decidua biological (Series2)e15.0, rep1(0.0113486) Decidua biological (Series2)e15.0, rep2(0.0125803) Decidua biological (Series2)e17.0, rep1(0.0223103) Decidua biological (Series2)e17.0, rep2(0.0188631) Decidua biological (Series2)e19.0, rep1(0.0169728) Decidua biological (Series2)e19.0, rep2(0.0117307) Decidua biological (Series2)P0, rep1(0.0172479) biologicalPlacenta (Series2)P0, rep2(0.0110894) biologicalPlacenta rep1(Series2) and (0.0171213) (SeriesDecidua rep22) and (0.00816557) (Series2)Decidua e17.0, (0.0171868) 2) biological e17.0, (0.0100507) biological[ repmin 1 (Series rep ] 2 (Series2) (0.0131466) 2) (0.0483862)[ medium ] [ max ] CEM 1 Ruvbl1 217.0 421.5 2358.4 P ( S | Z, I ) = 1.00 Ruvbl2 492.3 851.1 4888.1 Mean Corr = 0.67359 Pfdn2 473.1 1127.6 2204.4 Skp2 150.4 266.2 2269.5 Skp1a 2016.5 3644.8 5750.3 Cul1 634.6 1657.0 2799.2 Prmt1 522.3 1115.0 5404.4 Lyar 193.6 444.1 2781.2 Cse1l 922.8 1820.6 4773.7 Ebna1bp2 431.9 643.3 1972.4 Gart 359.7 548.2 2919.5 CEM 1 + Cct5 2079.1 3796.6 8983.3 Top 10 Genes Apex1 317.3 559.3 2441.0 Sf3a3 346.3 490.9 1686.9 Ddx18 496.3 617.6 2442.6 C1qbp 720.2 1366.1 6891.2

Null module Uri1 Stap1 Polr2e