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: 14 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. Polr2b Polr2a Cpsf3l Ints10 Ints12 Num ofGenesinQueryGeneset:14.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Ints8 Ints6 Ints5 Ints2 Ints9 Ints4 Ints1 Ints7 Ints3

Cpsf3l Polr2b Ints3 Ints7 Ints1 Ints4 Ints9 Ints2 Polr2a Ints5 Ints6 Ints12 Ints8 Ints10 Singletons CEM 1(130datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page1 Smarcc1 Smarca4 Tamm41 Nup214 Nup188 Nup107 Nup155 Nup133 Ruvbl1 Trim28 Polr2b Chtf18 Polr2a Ncbp1 Nup85 Cpsf3l Rfwd3 Lrwd1 Prmt5 Mcm6 Mcm5 Mcm7 Parp1 Cpsf1 Cpsf3 Xrcc6 Pold2 Noc2l Sf3b2 Sf3a3 Cse1l Msh6 Prpf8 Msh2 Sart3 Xpo5 Ints2 Ints9 Ints4 Ints1 Ints7 Ints3 Mlh1 Rfc1 Pole Eif3l Lig1 Gart Atic Ttf2 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE26568 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE44175 [18] GSE16925 [15] GSE32598 [11] GSE17886 [16] GSE27546 [51] GSE31849 [18] GSE6998 [32] GSE54207 [9] GSE26096 [10] GSE6689 [12] GSE27605 [8] GSE28593 [9] GSE13149 [25] GSE51483 [45] GSE28389 [20] GSE15155 [12] GSE17794 [44] GSE12454 [13] GSE15580 [14] GSE48790 [8] GSE8024 [8] GSE54490 [12] GSE5976 [12] GSE17796 [39] GSE13408 [14] GSE26355 [6] GSE30745 [12] GSE38531 [35] GSE47959 [8] GSE27159 [8] GSE54653 [6] GSE28261 [72] GSE43419 [20] GSE30868 [8] GSE11220 [44] GSE14308 [12] GSE21299 [12] GSE13874 [14] GSE30873 [6] GSE40513 [6] GSE31106 [18] GSE17266 [59] GSE20954 [14] GSE31028 [6] GSE29081 [6] GSE5671 [18] GSE47414 [18] GSE21278 [48] GSE6933 [15] GSE15610 [12] GSE15541 [12] GSE30160 [6] GSE31598 [12] GSE20391 [11] GSE17462 [8] GSE27378 [8] GSE12001 [6] GSE11222 [42] GSE39621 [51] GSE9013 [12] GSE28417 [12] GSE46209 [21] GSE11274 [20] GSE12465 [14] GSE15741 [6] GSE39458 [6] GSE11898 [9] GSE38031 [8] GSE26616 [6] GSE16707 [6] GSE1479 [36] GSE44923 [16] GSE15161 [26] GSE14012 [24] GSE48338 [8] GSE34324 [12] GSE56755 [13] GSE46970 [15] GSE15325 [23] GSE17728 [12] GSE16454 [24] GSE7404 [144] GSE32624 [6] GSE54581 [21] GSE54349 [6] GSE21063 [24] GSE1986 [17] GSE39391 [21] GSE24350 [8] GSE13707 [20] GSE21755 [25] GSE29241 [6] GSE23398 [7] GSE6065 [100] GSE19657 [21] GSE7275 [8] GSE42688 [8] GSE26668 [6] GSE46724 [6] GSE34629 [6] GSE32386 [13] GSE20398 [30] GSE46094 [10] GSE13692 [8] GSE46443 [12] GSE21033 [12] GSE51628 [15] GSE8091 [16] GSE28277 [10] GSE46797 [6] GSE2197 [6] GSE38001 [12] GSE56542 [8] GSE20390 [6] GSE12881 [6] GSE28025 [18] GSE11201 [18] GSE35998 [20] GSE40856 [8] GSE15872 [18] GSE14585 [9] GSE18326 [8] GSE47421 [24] GSE17513 [12] GSE29572 [21] GSE36384 [12] GSE15326 [10] GSE42061 [12] GSE18135 [18] GSE12518 [6] GSE42238 [9] GSE35091 [11] GSE7897 [60] GSE50813 [24] GSE4193 [8] GSE18993 [13] GSE42049 [8] GSE36814 [20] GSE9061 [6] GSE16874 [12] GSE31570 [6] GSE13224 [6] GSE58296 [9] GSE43197 [27] GSE11165 [6] GSE26076 [12] GSE42473 [15] GSE8025 [21] GSE41342 [26] GSE27261 [8] GSE45222 [27] CEM+ CEM GSE15268 [16] GSE8621 [12] GSE28093 [6] GSE3203 [16] GSE45619 [6] GSE32653 [6] 0.0 GSE51608 [6] GSE55607 [18]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 57.66 57.74 57.86 58.14 58.21 58.31 58.59 58.70 59.33 59.38 59.98 60.25 60.56 61.06 61.20 61.68 62.45 62.59 62.76 62.87 63.15 63.26 63.87 63.89 63.94 63.94 64.10 64.29 64.68 65.67 65.67 65.73 66.34 66.56 66.75 68.35 70.93 71.52 72.80 74.88 82.46 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page2 BC055324 Timeless Snrnp40 Ncapd2 Pdcd11 Skiv2l2 Ppp1r8 Ruvbl2 Rbm19 Ppm1g Wdhd1 Lmnb2 Heatr1 Prpf31 G3bp1 Dnmt1 Apitd1 Polr1a Dtymk Nup93 Nelfcd Eif2b5 Ddx20 Cdca5 Haus1 Actl6a Thoc5 Mcm4 Mcm2 Parp2 Pprc1 Cpsf4 Utp20 Xrcc1 Nat10 Bms1 Pold1 Espl1 Prpf3 Scrib Uba2 Rpa2 Rcc1 Ezh2 Fen1 Rfc5 Adsl Pfas Srrt Aqr 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 50.48 50.60 50.77 50.79 51.37 51.42 51.56 51.56 51.71 52.06 52.12 52.26 52.29 52.43 52.71 52.84 52.87 53.05 53.21 53.70 53.81 53.84 54.16 54.18 54.35 54.42 54.48 54.58 54.60 54.66 54.78 55.04 55.25 55.25 55.39 55.64 55.86 55.88 56.10 56.11 56.22 56.23 56.61 56.67 56.70 56.73 56.76 57.01 57.03 57.03 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page3 Mybbp1a Wbscr22 Tubgcp6 Mcm3ap Ctnnbl1 Mms22l Gemin5 Ranbp3 Zmym1 Cnot10 Incenp Bub1b Kpnb1 Wdr33 Ubap2 Rpap1 Ddx39 Dhx16 Ddx18 Rad51 Kif20a Dhx29 Cdca7 Prmt1 Rrp12 Prim2 Dars2 Gins1 Ssrp1 Chd1l Trmt6 Sf3b3 Pms2 Tcof1 Uhrf1 Gpn1 Wdr3 Eif3b Kif22 Rpa1 Cdc7 Aaas Hells Tdp1 Pes1 Melk Cdt1 Rfc2 Lyar Tbl3 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 44.98 44.99 45.10 45.26 45.40 45.43 45.45 45.56 45.58 45.60 45.64 45.70 45.81 45.95 45.95 45.97 46.07 46.15 46.23 46.42 46.44 46.54 46.55 46.81 46.99 47.12 47.13 47.39 47.83 48.06 48.22 48.23 48.32 48.41 48.42 48.60 48.65 48.91 48.99 49.26 49.30 49.34 49.38 49.93 50.06 50.11 50.19 50.22 50.41 50.42 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page4 Wrap53 Topbp1 Tada2a Supt16 Zbtb45 Zwilch Polr2h Med17 Lrrc40 Cactin Rqcd1 Nup43 Trip13 Cdc20 Cdca8 Cep78 Apex1 Cdc45 Haus5 Snrpb Tex10 Prmt3 Brca2 Brca1 Ercc3 Nol11 Phf5a H2afx Pole2 Eme1 Smc3 Taf1c Lsm4 Phrf1 Bop1 Nop2 Diexf Eif3d Cdc6 Ppil1 Exo1 Tcp1 Imp4 Ccnf Cct5 Ppie Plk1 Coil Tti1 Ncl 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 40.20 40.37 40.41 40.57 40.64 40.80 40.91 40.91 41.08 41.12 41.29 41.29 41.30 41.31 41.36 41.55 41.76 41.84 41.94 42.50 42.72 42.79 42.85 43.09 43.19 43.20 43.23 43.25 43.40 43.64 43.67 43.75 43.78 43.84 43.85 43.92 44.04 44.17 44.24 44.31 44.39 44.40 44.40 44.43 44.47 44.50 44.57 44.93 44.98 44.98 1.0 Notes 2700094K13Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page5 Rad51ap1 Nsmce4a Rbmxl1 Anapc1 Cep192 Chaf1b Rbm12 Cenph Polr1e Ncaph Bend3 Ercc6l Eif2b4 Ddx11 Rad50 Spc24 Fignl1 Fbxo5 Aurkb Gmnn Mum1 Hirip3 Mcm8 Prim1 Atad5 Spdl1 Noc4l Pold3 Ttc27 Patz1 Prpf4 Nop9 Xpo1 Ppan Ddx1 Noa1 Nelfa Rcc2 Tipin Rtcb Vars Rfc4 Cct7 Cct2 Fiz1 Ctcf Ung Blm Set 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 36.19 36.39 36.43 36.49 36.52 36.54 36.60 36.64 36.84 36.88 36.89 36.90 36.97 36.99 37.00 37.02 37.12 37.13 37.14 37.20 37.25 37.33 37.43 37.63 37.81 37.83 37.87 37.92 38.22 38.23 38.40 38.48 38.54 38.72 38.84 38.93 39.22 39.32 39.36 39.39 39.44 39.56 39.58 39.61 39.80 39.81 39.89 39.93 40.14 40.17 1.0 Notes 2410016O06Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page6 Ebna1bp2 Rnaseh2a Eif4enif1 Ranbp1 Anp32b Nup160 Rprd1b Snrpa1 Ubqln4 Kdm2b Dnaaf2 Rad54l Wbp11 Lmnb1 Polr1b Rbbp5 Lrrc47 Nop56 Ncapg Nup62 Ddx54 Hdac1 Ddx27 Usp10 Ddx46 Vps16 Zc3h4 Tsen2 Gmps Gon4l Atad2 Larp7 Pola1 Tonsl Gsg2 Bub1 Eif3g Hus1 Shq1 Pus7 Xab2 Ska3 Tpx2 Dbr1 Urb2 Lars Dis3 Elp3 Aatf 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 33.50 33.58 33.62 33.69 33.71 33.78 33.79 33.79 33.84 33.87 33.88 33.92 33.94 33.94 33.97 34.00 34.01 34.02 34.02 34.04 34.07 34.10 34.23 34.38 34.52 34.53 34.74 34.76 34.84 34.97 34.97 34.98 35.00 35.00 35.03 35.17 35.38 35.41 35.42 35.42 35.45 35.46 35.52 35.63 35.92 35.93 35.94 35.97 36.06 36.11 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page7 Rnaseh2b Mis18bp1 Rnaseh1 Exosc7 Dazap1 Cnot11 Nudt21 Trmt2a Stoml2 Recql4 Spata5 Cmss1 Mthfd1 Smc1a Huwe1 Med23 Gtf3c5 Polr3a Cops3 Wdr74 Wdr73 Wdr77 Spag5 Ddx41 Dpy30 Naa10 Pa2g4 Aurka Cenpt Kntc1 Supt5 U2af2 Emg1 Ttll12 Lsm2 Rrm1 Myg1 Srsf4 Nudc Rpa3 Nelfe Skp2 Edc4 Taf5l Rnf8 Cct4 Tsr1 Taf5 Taf2 Taf6 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 30.85 30.92 30.96 30.98 31.06 31.20 31.22 31.31 31.42 31.49 31.64 31.66 31.69 31.70 31.79 31.82 31.88 31.93 31.95 32.05 32.08 32.20 32.34 32.39 32.39 32.40 32.41 32.41 32.42 32.43 32.45 32.48 32.78 32.81 32.87 32.92 32.94 33.03 33.10 33.13 33.15 33.22 33.26 33.28 33.28 33.29 33.32 33.36 33.38 33.47 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page8 Hsp90ab1 Tmem39b Tubgcp2 Hnrnpab Hnrnpm Shcbp1 Mthfd1l Exosc2 Zc3h18 Kdm1a Rbm8a Psmg1 Psmg3 Grwd1 Knop1 Ythdf2 C1qbp Nsun2 Bud13 Rpp30 Aimp2 Ddx56 Cdca2 Pbdc1 Cdca4 Tnpo3 Tubg1 Ep400 Thoc6 Msto1 Cnot3 Nudt1 Banf1 Sgol1 Dus1l Ipo11 Snrpf Med4 Plrg1 Nhp2 Wdr4 Cdk1 Rad1 Cks2 Mars Toe1 Orc1 Orc6 Tcf3 Ipo5 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 28.12 28.22 28.36 28.39 28.45 28.54 28.61 28.64 28.74 28.75 28.78 28.81 28.85 28.98 28.99 29.01 29.06 29.06 29.19 29.27 29.42 29.44 29.49 29.63 29.66 29.72 29.80 29.84 29.84 30.03 30.03 30.08 30.10 30.13 30.17 30.19 30.30 30.32 30.37 30.37 30.38 30.44 30.52 30.52 30.64 30.64 30.68 30.81 30.81 30.84 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page9 Tmem209 Tmem201 Thumpd3 Racgap1 Ccdc101 Armc10 Prps1l3 Zc3hc1 Dmap1 Rbmx2 Gtf2h2 Carm1 Cenpp Polr1c Kif18b Kpna2 Nup88 Ddx51 Ube2c Usp39 Ddx21 Cks1b Znhit6 Naa15 Vac14 Fanca Mettl3 Cfdp1 Prkdc Utp15 Pycr2 Ptcd3 Paics Fanci Lsm3 Pwp1 Gtf3a Srsf1 Kif11 Nek2 Eif3c Qtrt1 Mtbp Pask Grk6 Api5 Hat1 Rfc3 Ttll4 Ubtf 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 25.32 25.34 25.34 25.37 25.41 25.44 25.44 25.47 25.57 25.58 25.64 25.64 25.68 25.77 25.80 25.97 26.08 26.11 26.13 26.21 26.23 26.28 26.33 26.48 26.51 26.55 26.58 26.61 26.67 26.82 26.82 27.04 27.11 27.18 27.22 27.29 27.31 27.33 27.43 27.54 27.60 27.69 27.74 27.76 27.79 27.80 27.82 27.83 27.89 28.04 1.0 Notes 1200014J11Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page10 Anapc15 Snrnp25 Hdgfrp2 Rpusd4 Nucks1 Sephs1 Hnrnpu Exosc5 Morc2a Snrpd3 Tarbp2 Cdca7l Mrpl37 Cirh1a Gtf3c2 Cenpu Nop58 Nup50 Cand1 Ccna2 Haus4 Hspa4 Ylpm1 Ndc80 Cep44 Fkbp3 Snrpe Cenpf Srpk1 Aspm Smu1 Uspl1 Smn1 Puf60 Tars2 Pcid2 Elac2 Vwa9 Surf6 Srsf7 Nob1 Wdr5 Drg1 Rrp8 Drg2 Utp6 Nxt1 E2f7 Ipo9 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 23.25 23.32 23.35 23.36 23.36 23.38 23.42 23.47 23.47 23.48 23.48 23.51 23.79 23.81 23.83 23.89 23.93 23.96 23.98 24.03 24.03 24.10 24.11 24.25 24.39 24.40 24.41 24.45 24.55 24.60 24.60 24.61 24.61 24.76 24.76 24.77 24.83 24.89 24.92 24.96 24.99 24.99 25.04 25.07 25.09 25.10 25.14 25.16 25.23 25.29 1.0 Notes 2700029M09Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page11 Suv39h1 Dnajc11 Gemin2 Enoph1 Anapc7 Cc2d1b Ccdc61 Mcmbp Mettl13 Dnttip2 Psmd2 Samd1 Psmd3 Isyna1 Gtf2e1 Nubp1 Mak16 Nup35 Cenpe Wdr90 Ewsr1 Mcrs1 Ctdp1 Gtse1 Hmbs Clhc1 Nol10 Uchl5 Smg5 Rpl14 Mbd3 Prpf6 Tyw1 Stip1 Dap3 Pop1 Phb2 Rae1 Dkc1 Ftsj3 Orc5 Ctc1 Nfyc Elp2 Zfp7 Isy1 Iars Tk1 Tpr 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 21.07 21.13 21.20 21.23 21.33 21.38 21.39 21.42 21.43 21.44 21.55 21.56 21.58 21.62 21.68 21.70 21.73 21.75 21.81 21.86 21.88 21.95 22.03 22.06 22.14 22.20 22.24 22.24 22.25 22.29 22.33 22.40 22.40 22.42 22.45 22.46 22.47 22.50 22.72 22.72 22.74 22.77 22.83 22.87 23.10 23.11 23.14 23.21 23.23 23.25 1.0 Notes 1810009A15Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page12 Arhgap11a Zmynd19 Fam203a Tomm40 Champ1 Nup210 Rad54b Pkmyt1 Mettl14 Isg20l2 Dnajc9 Sympk Nap1l1 Smyd5 Cenpn Ccnb2 Cdan1 Ccne1 Ddx47 Ppp4c Pdap1 Dhx35 Dhx15 Pcbp1 Poc1a Mettl2 Vprbp Ube2t Trmt5 Xrcc5 Cct6a Pms1 Pus7l Asxl1 Brpf1 Msh3 Chtf8 Eif3a Tfam Bora Hdgf Rars Dctd Nkrf Eri2 Nifk Eed Ilf2 Atr 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 19.01 19.04 19.17 19.18 19.22 19.23 19.35 19.41 19.42 19.45 19.51 19.52 19.52 19.55 19.69 19.75 19.80 19.84 19.87 19.87 19.92 19.95 19.95 19.96 19.98 19.98 19.99 20.01 20.18 20.18 20.24 20.36 20.43 20.49 20.52 20.58 20.59 20.67 20.69 20.70 20.72 20.76 20.81 20.89 20.97 21.00 21.01 21.03 21.04 21.06 1.0 Notes 2610318N02Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page13 Cdkn2aipnl D2Wsu81e Thumpd1 Cdk2ap1 Ppp2r1b Ccp110 Cdc25c Exosc3 Mrps27 Zcchc8 Trim37 Dcaf15 Tcerg1 Pgam5 Eefsec Mrpl28 Magoh Ino80e Prpf4b Pitrm1 Nufip1 Hddc2 Aimp1 Wdr55 Wdr46 Ssbp1 Thoc3 Mettl8 Rrp15 Mybl2 Gnb1l Gins4 Gins2 Cenpi Pcgf6 Snip1 Sf3b4 Etaa1 Zfp64 Birc5 Dph2 Dhx9 Dcps Xpo6 Lsg1 Oip5 Mtf2 Atm Itpa 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 16.40 16.44 16.52 16.56 16.60 16.74 16.76 16.77 16.84 17.09 17.22 17.24 17.25 17.28 17.29 17.31 17.37 17.39 17.43 17.49 17.60 17.66 17.77 17.81 17.85 17.87 17.97 17.99 18.09 18.09 18.10 18.19 18.24 18.28 18.28 18.34 18.39 18.44 18.63 18.65 18.68 18.70 18.75 18.75 18.82 18.83 18.87 18.87 18.89 19.00 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page14 Psmc3ip Atp13a1 Tubb4b Cep152 Ccdc77 Ppp1r7 Dctpp1 Rnf126 Atad3a Rbm14 Psmd5 Dcaf13 Cenpw Zfp566 Prdm4 Polr2d Arid1a Cep57 Haus3 Ddx42 Ddx49 Alyref Polr2j Rars2 Abcf1 U2af1 Sin3a Palb2 Psip1 H2afz Telo2 Fbxl6 Rrm2 Mdc1 Brip1 Gen1 Dna2 Eif5b Eif4b Pcna Edc3 Taf6l Orc2 Ctu2 Ctps Dbf4 Bysl Srm Kif4 Pbk 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 14.11 14.23 14.24 14.36 14.40 14.47 14.49 14.60 14.60 14.69 14.73 14.80 14.81 14.81 14.82 14.88 14.95 15.01 15.02 15.11 15.13 15.15 15.18 15.30 15.31 15.34 15.36 15.41 15.46 15.46 15.60 15.64 15.64 15.67 15.73 15.74 15.81 15.84 15.84 15.86 15.92 15.95 16.01 16.13 16.17 16.26 16.28 16.28 16.29 16.34 1.0 Notes Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page15 BC030867 Smarcad1 Casp8ap2 Smarcal1 Suv39h2 Rsl24d1 L3mbtl2 Rpgrip1 Anp32e Mrps35 Mis18a Kansl2 Mrpl49 Cwc27 Mcph1 Map1s Wdr89 Rpap3 Rpp40 Pdcd7 Eif2b3 Rexo4 Senp3 Ckap2 Enkd1 Haus6 Pus10 Pspc1 Snrpg Rrp1b Snrpc Sgol2 Sf3b5 Tfdp1 Tfap4 Srsf3 Kti12 Bag6 Orc3 Rrp9 Rrn3 Mta2 Naf1 Ppat Dvl2 Eif3i Plk4 Me2 Nvl Mtr 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 12.17 12.18 12.22 12.28 12.31 12.36 12.37 12.40 12.42 12.42 12.43 12.46 12.48 12.52 12.69 12.74 12.75 12.76 12.80 12.85 12.86 12.87 12.87 12.88 12.90 12.94 13.07 13.08 13.10 13.17 13.30 13.33 13.35 13.41 13.42 13.43 13.44 13.45 13.51 13.53 13.60 13.62 13.62 13.66 13.70 13.72 13.83 13.89 14.06 14.08 1.0 Notes 4930579G24Rik 9430015G10Rik 2700049A03Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page16 Fam207a Fgfr1op Stk11ip Sapcd2 Ddx19a Exosc9 Tsen54 H2-Ke2 Aarsd1 Cenpm Raver1 Mrpl18 Cwc22 Gtf3c4 Dnph1 Dicer1 Nop16 Cenpk Nop14 Ppp5c Cdc37 Ahsa1 Usp37 Kif18a Chek2 Cep55 Eif2b1 Dcakd Ddx52 Fancb Khsrp Gtf2f1 Mki67 Trmt1 Pinx1 Lsm6 Mogs Ddb1 Peo1 Pogz Tdp2 Sfpq Det1 Nip7 Ect2 Szt2 Dut 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 10.24 10.25 10.26 10.29 10.35 10.37 10.40 10.41 10.42 10.45 10.48 10.48 10.52 10.55 10.58 10.60 10.66 10.67 10.75 10.76 10.92 10.93 10.99 11.00 11.01 11.07 11.22 11.28 11.28 11.35 11.37 11.37 11.47 11.51 11.52 11.54 11.70 11.81 11.85 11.85 11.86 11.89 11.96 11.99 12.04 12.08 12.09 12.10 12.13 12.14 1.0 Notes D19Bwg1357e Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page17 Mphosph9 Depdc1b Wbscr16 Hmgxb4 Smchd1 Pom121 Fastkd5 Fam83d Zswim1 Cd2bp2 Cdc25a Cdc123 Parpbp Arl6ip4 Rpp25l Trmt11 Rbm27 Dnajc8 Yeats4 Psmc4 Mrpl40 Hnrnpl Dhodh Nup54 Akap8 Apex2 Tex30 Aggf1 Abcf2 Asf1b Nosip Axin1 Mrpl2 Siva1 Fancl Pwp2 Mns1 Bzw2 Nde1 Xpo7 Ccz1 Leo1 Utp3 Prc1 Hn1l Ttc4 Kri1 Mtrr Fus 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 7.64 7.72 7.73 7.88 7.90 7.97 8.12 8.14 8.36 8.36 8.45 8.47 8.57 8.58 8.67 8.73 8.75 8.78 8.79 8.79 8.86 8.87 8.88 8.89 8.89 8.94 8.95 8.96 8.99 9.17 9.21 9.23 9.25 9.28 9.31 9.31 9.34 9.45 9.45 9.52 9.71 9.79 9.81 9.89 9.91 9.91 9.93 9.99 10.04 10.18 1.0 Notes A430005L14Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page18 BC027231 BC052040 Fam192a Mrps18b Adprhl2 Prpf38a Cacybp Wrap73 Ncaph2 Sssca1 Tsen15 Mettl25 Akr1b3 Rbm34 Trim59 Ckap2l Hnrnpf Mrpl22 Rangrf Fbxl14 Heatr2 Polr3h Rbbp7 Wdr36 Wdr18 Ncbp2 Sdad1 Bckdk C2cd3 Alms1 Ddx55 Senp1 Esco2 Polr2f Sarnp Gstcd Upf3b Asf1a Mrpl3 Dhx8 Bap1 Ndc1 Pan2 Fasn Mta1 Nle1 Nrm Hira Stil 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 5.42 5.43 5.52 5.52 5.54 5.56 5.67 5.70 5.71 5.77 5.81 5.83 5.84 5.85 5.90 5.96 6.02 6.07 6.08 6.09 6.15 6.26 6.29 6.34 6.37 6.38 6.42 6.47 6.52 6.63 6.63 6.74 6.77 6.78 6.83 6.87 6.96 6.98 7.00 7.00 7.03 7.07 7.17 7.22 7.22 7.34 7.36 7.42 7.48 7.51 1.0 Notes D030056L22Rik 1110038F14Rik D11Wsu47e Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page19 Smarca5 Nsmce2 Fam72a Pabpc4 Mrps22 Thap11 Dlgap5 Nt5dc2 Rbm22 Rnf168 Ppwd1 Lrpprc Ahctf1 Reep4 Qtrtd1 Znhit3 Mrps9 Mettl1 Srbd1 Ccar1 Gins3 Znrd1 Cpsf2 Kdm8 Sars2 Nme4 Recql Scaf4 Txlna Gps1 Nelfb G2e3 Usp1 Traf7 Phax Pus1 Tgs1 Ofd1 Brd4 Gnl3 Gle1 Sltm Esf1 Tsr2 E2f8 Tti2 Cit 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 3.17 3.19 3.20 3.24 3.37 3.38 3.38 3.39 3.39 3.39 3.40 3.56 3.57 3.60 3.61 3.65 3.66 3.71 3.76 3.77 4.05 4.05 4.05 4.11 4.17 4.26 4.30 4.40 4.45 4.45 4.48 4.49 4.53 4.56 4.56 4.82 4.94 4.94 4.96 5.13 5.17 5.17 5.21 5.21 5.24 5.24 5.34 5.35 5.37 5.42 1.0 Notes E430025E21Rik 1110008L16Rik 3110082I17Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page20 Rps19bp1 Xrcc6bp1 Arhgef39 Prpsap1 Caprin1 Hspbp1 Depdc5 Ppp1cc Ccdc14 Tango6 Sac3d1 Mrps30 Mrps25 Prkrip1 Mms19 Ppp2r4 Gnb2l1 Pagr1a Nap1l4 Whsc1 Zfp740 Gtf2h3 Srfbp1 Armc6 Strada Cenpq Polr3c Acbd6 Ddx31 Cep72 Mutyh Syce2 Gnpat Supt6 Safb2 Mnd1 Prr12 Gga3 Pmf1 Usp5 Rev1 Tbcd Parg Rrs1 Faf1 Lig3 Ltv1 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 1.61 1.70 1.73 1.76 1.77 1.81 1.82 1.83 1.84 1.90 1.92 1.94 2.02 2.07 2.11 2.12 2.13 2.19 2.20 2.27 2.27 2.28 2.35 2.41 2.47 2.49 2.52 2.53 2.59 2.65 2.73 2.79 2.80 2.81 2.81 2.83 2.84 2.85 2.87 2.87 2.88 2.92 2.94 2.94 3.01 3.07 3.09 3.09 3.10 3.15 1.0 Notes 9130401M01Rik 2810004N23Rik Symbol Num ofCEMGenes:9.Predicted1041.SelectedDatasets:130.Strength:1.5 CEM 1,Geneset"[C]Integrator-RNAPIIcomplex",Page21 Suv420h2 Zkscan17 Secisbp2 Ube2cbp Fam58b Fam60a Nudcd2 Nusap1 N6amt2 Ccdc94 Sap130 Exosc1 Katnb1 Mrpl45 Zfp472 Med30 Polr3g Polr2c Klhl12 Pdcd2 Rpl7l1 Rad9a Caap1 Casc5 Cxxc1 Sass6 Trub1 Dimt1 Park7 Pars2 Nme7 Rpl12 Eef1d Nme1 Cdc5l Mastl Nanp Pycrl Dsn1 Terf1 Coa6 Mtfr2 Snx5 Iws1 Lin9 Rtf1 Pnn Lbr 0.0 1.0

GSE33308 [10] GSE16679 [8]

GSE12769 [20] Scale ofaveragePearsoncorrelations GSE20696 [8] GSE21711 [6] GSE6846 [6] GSE28621 [21] GSE22841 [12] GSE8683 [11] 0.2 GSE11356 [9] GSE25645 [17] GSE6957 [12] GSE17316 [12] GSE32330 [12] GSE47694 [10] GSE29766 [40] GSE10182 [7] GSE20918 [6] 0.4 GSE35357 [12] GSE44084 [8] GSE9316 [12] GSE13693 [9] GSE31099 [24] GSE9297 [27] GSE41925 [8] GSE11759 [6] GSE8034 [17] 0.6 GSE35785 [10] GSE31752 [6] GSE46090 [12] GSE47205 [10] GSE11333 [6] GSE50603 [12] GSE10871 [32] GSE23505 [10] GSE27563 [93] 0.8 GSE19885 [9] GSE45430 [9] GSE53299 [6] GSE9146 [27] Score 0.03 0.04 0.08 0.15 0.17 0.18 0.21 0.21 0.25 0.25 0.27 0.27 0.30 0.39 0.47 0.47 0.54 0.54 0.58 0.58 0.66 0.68 0.74 0.79 0.88 0.89 0.90 0.98 0.99 0.99 1.01 1.02 1.03 1.08 1.10 1.14 1.19 1.28 1.30 1.30 1.33 1.35 1.38 1.40 1.50 1.54 1.56 1.56 1.57 1.59 1.0 Notes GEO Series "GSE33308" 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=GSE33308 Status: Public on Jan 01 2013 Title: Keratinocyte Growth Factor and Dexamethasone Plus Elevated cAMP Levels Synergistically Support Pluripotent Stem Cell Differentiation into Alveolar Epithelial Type II Cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23176317 Summary & Design: Summary: Alveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.

Overall design: mESCs at d24 of differentiation with KGF and DCI treatment

Background corr dist: KL-Divergence = 0.0344, L1-Distance = 0.0193, L2-Distance = 0.0005, Normal std = 0.6401

0.623 Kernel fit Pairwise Correlations Normal fit

Density 0.312

0.000 CEM 1

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

Pre-normalization Quantiles

mESCs mESCsat d8 of mESCsat differentiation d8 of mESCsat differentiation d17 of mESCs at(Control) differentiation d17 of mESCs atwith differentiation (0.311296)d17 KGF of mESCsat (Control)differentiation d17treatment of mESCsat withdifferentiation d24 (0.0242724) (0.23951) KGFof mESCsat withdifferentiation d24 treatment DCIof mESCsat withdifferentiation d24 treatment KGF(0.0252348)of at (Control)differentiation d24 and (0.0223908) of DCI withdifferentiation (0.0734196) treatment KGF with treatment DCI[ (0.0155358) withmin treatment KGF(0.073829) and] (0.127175) DCI treatment[ medium (0.0873366) ] [ max ] CEM 1 Cpsf3l 696.4 843.1 1025.9 P ( S | Z, I ) = 1.00 Polr2b 2009.1 2954.1 4210.8 Mean Corr = 0.90933 Ints3 123.1 203.8 384.3 Ints7 513.6 1081.9 1743.4 Ints1 239.0 318.6 618.0 Ints4 436.3 542.7 659.5 Ints9 318.3 466.8 712.8 Ints2 728.0 1105.8 1693.8 Polr2a 1047.5 1260.3 2324.4 Trim28 2415.4 3248.8 5401.4 Nup133 548.4 899.0 1755.8 Gart 592.8 938.7 1645.4 Xpo5 397.1 623.9 1031.3 Ttf2 235.6 442.4 820.7 CEM 1 + Eif3l 3773.3 4008.6 5627.9 Top 10 Genes Cpsf3 1382.3 1665.0 1899.3 Ruvbl1 793.4 1225.3 1999.2 Cpsf1 961.9 1304.1 2353.3 Msh2 610.0 1116.9 1806.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE16679" 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=GSE16679 Status: Public on Aug 01 2010 Title: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20679399 Summary & Design: Summary: The goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis.

To study this, we transduced an immortalized (but not transformed) cell line (derived from Gata1s mutant fetal liver progenitor through insertional mutagenesis) by Plag1-expressing retrovirus. This turned a non-transformed cell line to a leukemogenic cell line. To study whether Plag1 overexpression led to deregulation of signaling pathways that may contribute to leukemic transformation, we generated microarray gene expression profiles of this cell line transduced with either Plag1 or the empty vector.

Overall design: We generated gene expression profiles by microarray from stable cell lines transduced with either the empty vector or the Plag1-expressing vector.

Background corr dist: KL-Divergence = 0.0435, L1-Distance = 0.0264, L2-Distance = 0.0008, Normal std = 0.6089

0.677 Kernel fit Pairwise Correlations Normal fit

Density 0.338

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

cell line2_Plag1_KT_subline1_Acell line2_Plag1_KT_subline2_Acell line2_Vector_KT_subline1_Acell line2_Vector_KT_subline2_Acell (0.159763) line2_Plag1_KT_subline1_Bcell (0.173776) line2_Plag1_KT_subline2_Bcell (0.110962)line2_Vector_KT_subline1_Bcell (0.0921692)line2_Vector_KT_subline2_B (0.159274) (0.131556) (0.0661222)[ min (0.106377) ] [ medium ] [ max ] CEM 1 Cpsf3l 774.1 1196.8 1418.0 P ( S | Z, I ) = 1.00 Polr2b 1485.7 2448.9 2813.6 Mean Corr = 0.86667 Ints3 177.8 224.5 251.3 Ints7 344.4 1273.9 1623.6 Ints1 393.5 652.1 733.8 Ints4 424.9 581.0 762.0 Ints9 847.5 1239.3 1538.4 Ints2 696.3 1426.1 1657.9 Polr2a 1494.9 2573.7 2806.6 Trim28 3315.4 5640.6 6389.9 Nup133 524.4 1036.8 1325.3 Gart 715.8 2425.9 2979.6 Xpo5 65.2 643.0 765.8 Ttf2 420.2 675.2 726.9 CEM 1 + Eif3l 3467.9 4750.5 5042.5 Top 10 Genes Cpsf3 715.7 1860.8 2040.5 Ruvbl1 853.6 2313.3 2646.7 Cpsf1 2054.4 2368.6 2553.8 Msh2 1133.4 1624.2 1823.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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(0.226417) rep. CTL, 2 transduced(0.157581) rep. biological CTL, 3 (0.0883143) biological CTL, rep. 1biological (0.132738)[ rep. min 2 (0.233459) rep. ] 3 (0.161491)[ medium ] [ max ] CEM 1 Cpsf3l 1881.4 1989.3 2038.3 P ( S | Z, I ) = 1.00 Polr2b 3876.3 4949.0 5082.3 Mean Corr = 0.86519 Ints3 436.7 528.6 613.7 Ints7 1437.0 1976.9 2292.6 Ints1 739.1 988.9 1028.6 Ints4 552.2 654.3 756.9 Ints9 1172.8 1469.6 1631.3 Ints2 860.9 1049.0 1175.6 Polr2a 1542.7 1941.0 2306.3 Trim28 3375.9 4662.6 5122.8 Nup133 1081.1 1605.6 1730.1 Gart 2200.7 3036.6 3800.6 Xpo5 768.1 974.2 1198.7 Ttf2 864.3 963.8 1024.4 CEM 1 + Eif3l 9934.3 10541.9 11147.1 Top 10 Genes Cpsf3 1248.9 1624.5 1743.7 Ruvbl1 1282.7 2180.1 2398.8 Cpsf1 1919.1 2500.0 2557.7 Msh2 1186.4 1958.2 2256.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE44175" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

EmbyonicEmbyonic stemEmbyonic cell, stem Hmgn1+/+,Neural cell, stem Hmgn1+/+, progenitor,Neural cell, biological Hmgn1+/+, progenitor,Neural biological Hmgn1+/+, rep1 progenitor,Neuron, biological (0.0956741) Hmgn1+/+, rep2Neuron, biological Hmgn1+/+, (0.0718881) Hmgn1+/+, rep3Neuron, biological Hmgn1+/+, (0.0594036)rep1 biologicalEmbyonic biological(0.0187265)Hmgn1+/+, rep2 biologicalEmbyonic rep1(0.0175743) stem rep3 biological(0.0662659)Embyonic rep2cell,(0.0220819) stem (0.0684127)Hmgn1-/-,Neural rep3cell, stem (0.0726463)Hmgn1-/-, progenitor,Neural cell, biological Hmgn1-/-, progenitor,Neural biological Hmgn1-/-,rep1 progenitor,Neuron, biological(0.0762479) Hmgn1-/-,rep2 biologicalNeuron, Hmgn1-/-, (0.0801568) Hmgn1-/-,rep3 biologicalNeuron, Hmgn1-/-, (0.0572124)rep1 biological biological(0.0206687) Hmgn1-/-, rep2 biological rep1(0.02916) rep3 biological(0.0732578) rep2(0.0219766) (0.0764129) rep3[ min (0.0722335) ] [ medium ] [ max ] CEM 1 Cpsf3l 450.5 1068.1 1815.5 P ( S | Z, I ) = 1.00 Polr2b 4899.5 6364.8 7032.3 Mean Corr = 0.86298 Ints3 120.6 213.7 471.6 Ints7 839.3 2381.3 2743.0 Ints1 338.0 591.0 673.9 Ints4 546.0 640.4 1400.6 Ints9 361.1 838.1 1649.5 Ints2 819.5 1314.5 2121.1 Polr2a 539.0 1466.8 1870.2 Trim28 1842.6 4406.5 11224.1 Nup133 626.7 1628.5 3839.7 Gart 386.3 1997.1 6598.6 Xpo5 485.4 1034.8 1368.5 Ttf2 145.9 783.0 1613.7 CEM 1 + Eif3l 4324.3 7733.3 10506.3 Top 10 Genes Cpsf3 1797.0 2018.9 3297.7 Ruvbl1 963.3 2296.4 4505.3 Cpsf1 1009.3 1824.9 2429.7 Msh2 1038.6 2461.2 5719.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0243311)CL11-rep3 (0.0385521)MEF-rep1 (0.0591184)MEF-rep2 (0.173812)MEF-rep3 (0.172581)IP14D-1-rep1 (0.180385)IP14D-1-rep2 (0.0402715)IP14D-1-rep3 (0.0317285)IP14D-101-rep1 (0.0277504)IP14D-101-rep2IP14D-101-rep3 (0.0350616)IP20D-3-rep1 (0.0417833)IP20D-3-rep2 (0.121241) (0.0168307)IP20D-3-rep3 (0.0178785) (0.0186755) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1050.2 2305.8 3454.9 P ( S | Z, I ) = 1.00 Polr2b 1968.5 4793.3 6163.9 Mean Corr = 0.84506 Ints3 302.1 750.2 1004.7 Ints7 603.1 2165.7 2634.3 Ints1 498.3 825.7 950.6 Ints4 378.3 1752.5 2055.3 Ints9 427.9 1013.5 1278.4 Ints2 1370.7 2681.0 2985.6 Polr2a 2329.2 6070.7 8283.5 Trim28 4189.1 19637.2 24030.3 Nup133 985.9 4536.8 6638.5 Gart 832.3 7373.6 12365.5 Xpo5 820.6 1613.4 1992.6 Ttf2 480.9 1825.9 2683.6 CEM 1 + Eif3l 5476.1 11980.3 13608.8 Top 10 Genes Cpsf3 1056.7 2633.4 3445.1 Ruvbl1 1233.3 4594.7 6054.9 Cpsf1 983.8 3255.3 4363.9 Msh2 401.5 7165.4 8946.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0550461)ViPSCs, rep2 (0.0545756)TiPSCs, rep3 (0.0517048)TiPSCs, rep1 (0.0467276)TiPSCs, rep2 (0.0282186)mESCs, rep3 (0.0115276)mESCs, rep1 (0.0683978)mESCs, rep2 (0.063303)Tail rep3 tip (0.0517809) fibroblastsVentricular (0.179612)cardiomyocytes (0.389106)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 576.4 1794.4 2066.7 P ( S | Z, I ) = 1.00 Polr2b 2332.6 8315.1 8719.5 Mean Corr = 0.82063 Ints3 86.4 481.6 632.1 Ints7 712.4 2033.6 2463.0 Ints1 505.9 867.5 1046.0 Ints4 692.7 1493.7 1654.5 Ints9 462.8 1151.6 1390.0 Ints2 392.1 1561.8 2394.5 Polr2a 911.8 2652.6 3429.2 Trim28 3540.2 18027.6 19553.5 Nup133 473.4 3114.3 4387.6 Gart 1053.0 5721.0 6128.7 Xpo5 652.8 1415.4 1750.5 Ttf2 313.7 1711.3 1949.3 CEM 1 + Eif3l 5243.5 10960.7 12779.2 Top 10 Genes Cpsf3 947.9 2829.0 3018.9 Ruvbl1 863.7 3870.3 4801.9 Cpsf1 1633.1 3644.5 4053.1 Msh2 282.0 6028.2 6720.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE17886" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.588 Kernel fit Pairwise Correlations Normal fit

Density 0.294

0.000 CEM 1

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

Pre-normalization Quantiles

BBB two-cellBBB two-cell embryos,BBB two-cell embryos,BBB Sample1 two-cell embryos,BCB Sample2 (0.0682569) two-cell embryos,BCB Sample3 (0.0690388) two-cell embryos,BCB Sample4 (0.0321383) two-cell embryos,BCB Sample1 (0.0532398) two-cell embryos,Î±-amantin-treated Sample2 (0.0799796) embryos,Î±-amantin-treated Sample3 (0.0624776)Î±-amantin-treated Sample4 (0.0828088) BBBÎ±-amantin-treated two-cell (0.0467401) BBBÎ±-amantin-treated two-cell embryos, BBBÎ±-amantin-treated two-cell embryos, BBB Sample1Î±-amantin-treated two-cell embryos, BCB Sample2 (0.0448923)Î±-amantin-treated two-cell embryos, BCB Sample3 (0.0784097) two-cell embryos, BCB Sample4 (0.0520933) two-cell embryos, BCB Sample1 (0.061574) two-cell embryos, Sample2 (0.0899507)[ embryos,min Sample3 (0.057906) ] Sample4 (0.0569604) (0.0635338)[ medium ] [ max ] CEM 1 Cpsf3l 222.3 632.9 897.3 P ( S | Z, I ) = 1.00 Polr2b 799.8 9885.1 11010.1 Mean Corr = 0.81280 Ints3 186.3 300.9 419.7 Ints7 5.4 296.4 552.1 Ints1 82.0 1069.7 1612.7 Ints4 347.5 1095.0 1345.2 Ints9 215.9 342.4 516.3 Ints2 259.9 801.5 1603.4 Polr2a 360.9 1359.9 1673.7 Trim28 489.4 6736.0 8700.3 Nup133 196.7 1260.6 1945.4 Gart 14.5 559.2 773.4 Xpo5 100.2 169.4 220.4 Ttf2 99.5 294.5 407.5 CEM 1 + Eif3l 306.4 1663.5 2354.3 Top 10 Genes Cpsf3 219.0 460.9 644.1 Ruvbl1 337.9 2588.8 3467.8 Cpsf1 220.3 1917.1 2580.7 Msh2 223.0 546.3 737.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE27546" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27546 Status: Public on Feb 28 2011 Title: Effects of HMGN variants on cellular transcription profile Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21278158 Summary & Design: Summary: HMGN (high mobility group N) is a family of intrinsically disordered nuclear proteins that binds to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family.

Here we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. The results reveal an HMGN-variant specific effect on the fidelity of the cellular transcription profile, indicating that functionally, the various HMGN subtypes are not fully redundant.

Overall design: RNA was collected from either primary knock-out MEFs or SV40-transformed MEFs and MIN6 cells over expressing various HMGN proteins and mutants and hybridized to Affymetrix arrays. We obtained a double ammount of HMGN proteins in MEFs and MIN6 cells by retroviral infection and subsequent selection procedure. We collected all infected cells (pools, not clones) in order to eliminate the effect of viral integration in the genome.

Background corr dist: KL-Divergence = 0.0270, L1-Distance = 0.0406, L2-Distance = 0.0025, Normal std = 0.6975

0.572 Kernel fit Pairwise Correlations Normal fit

Density 0.286

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

MEFs HMGN1MEFs HMGN1 knockMEFs outHMGN1 knockMEFs rep outHMGN1 1knockMEFs (0.0186471) rep outHMGN1 2WTMEFs (0.0212521) rep rep HMGN1 3WT MEFs 1(0.0199538) (0.0192833) rep HMGN3 WT MEFs2 (0.019136) rep HMGN3 knock MEFs3 (0.0178935) outHMGN3 knockMEFs rep outHMGN3 1knockMEFs (0.0246841) rep outHMGN3 2WTMEFs (0.0258997) rep rep HMGN3 3WT MEFs 1(0.023074) (0.0236486) rep HMGN5 WT MEFs2 (0.0244183) rep HMGN5 knock MEFs3 (0.0279135) outHMGN5 knockMEFs rep outHMGN5 1knockMEFs (0.0220453) rep outHMGN5 2WTMEFs (0.0184566) rep rep HMGN5 3WT MEFs 1(0.0224988) (0.0228827) rep empty WT MEFs2 (0.0222177) rep vector empty MEFs3 (0.0214148) OEvector emptyMEFs rep OE1vector HMGN1 (0.0130986)MEFs rep OE2 HMGN1 (0.011654)OEMEFs rep rep 3 HMGN1 (0.0122046)OE1MEFs (0.0328255) rep HMGN2 OE2MEFs (0.0349206) rep HMGN2 OE3MEFs (0.0354716) rep HMGN2 OE1MEFs (0.0130755) rep HMGN3a OE2MEFs (0.0172667) rep HMGN3a 3MEFs OE (0.0227047) rep HMGN3aMEFs OE1 (0.0143622) rep HMGN5MEFs OE2 (0.0131908) rep HMGN5 OEMEFs 3 (0.0118454) rep HMGN5 OE1MEFs (0.0216446) rep HMGN5SE OE2MEFs (0.0192119) rep HMGN5SE 3MEFs (0.018375) OE repHMGN5SEMEFs OE1 (0.0113045) repHMGN1_N2swapMEFs OE2 (0.0131734) repHMGN1_N2swapMEFs 3 (0.0154228) HMGN1_N2swapMEFs rep 1 HMGN1_N3swap (0.0298911)MEFs rep 2 HMGN1_N3swap (0.0208195)MEFs rep 3 HMGN1_N3swap (0.0159714)MIN6 rep 1empty (0.0292364)MIN6 rep vector 2empty (0.0233277)MIN6 rep OEvector 3empty (0.0184434)MIN6 rep OE1vector HMGN1 (0.012488)MIN6 rep OE2 HMGN1 (0.0151426)OEMIN6 rep rep 3 HMGN1 (0.0204831)OE1MIN6 (0.0208631) rep HMGN3a OE2MIN6 (0.0131313) rep HMGN3a 3 MIN6OE (0.0199198) rep HMGN3a OE1 (0.0104694) rep OE2 (0.011201) rep 3 (0.0115398)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 843.2 1318.4 2805.5 P ( S | Z, I ) = 1.00 Polr2b 2360.9 4919.0 6065.9 Mean Corr = 0.81062 Ints3 97.8 530.3 965.3 Ints7 541.9 1645.1 2620.5 Ints1 425.8 898.3 1525.3 Ints4 289.4 648.5 1025.7 Ints9 392.6 576.9 1410.6 Ints2 780.2 1363.5 2011.0 Polr2a 1092.1 1829.2 6509.8 Trim28 2973.3 4481.8 9481.3 Nup133 547.4 2462.3 3946.3 Gart 949.4 1500.5 2913.1 Xpo5 784.8 962.2 2237.7 Ttf2 261.4 421.6 1385.5 CEM 1 + Eif3l 4935.1 7457.2 13048.7 Top 10 Genes Cpsf3 1010.6 1478.5 1882.1 Ruvbl1 663.8 1541.9 4039.7 Cpsf1 1076.9 2606.8 3630.8 Msh2 392.7 1607.6 2405.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE31849" 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=GSE31849 Status: Public on Sep 08 2011 Title: Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function [cultured cortical neurons] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To examine potential differences in activity-dependent gene expression, we analyzed mRNA expression in cultured neurons isolated from Wild-type vs MeCP2 S421A mice at 0 (unstimulated), 1 or 6 hours after membrane depolarization by exposure to high extracellular KCl (55mM)

All mice were male littermates from one of three litters.

Overall design: We isolated RNA from dissociated cortical cultures (E16+7DIV) isolated from Wild-Type or MeCP2 S421A knock-in mice littermates. Cells were either left unstimulated or depolarized for 1 or 6 hours by addition of 55mM KCl to the media. mRNA expression was analyzed using the Affymetrix GeneChip Mouse Expression Set 430 2.0 microarray platform.

Background corr dist: KL-Divergence = 0.1022, L1-Distance = 0.0832, L2-Distance = 0.0119, Normal std = 0.4971

0.932 Kernel fit Pairwise Correlations Normal fit

Density 0.466

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

unstim_WT_RepA_sc1unstim_S421A_RepA_sc21hrKCl_WT_RepA_sc31hrKCl_S421A_RepA_sc4 (0.0508349)6hrKCl_WT_RepA_sc5 (0.0368704)6hrKCl_S421A_RepA_sc6 (0.0262363)unstim_WT_RepB_sc7 (0.0309334)unstim_S421A_RepB_sc8 (0.0817723)1hrKCl_WT_RepB_sc9 (0.107843)1hrKCl_S421A_RepB_sc10 (0.0458262)6hrKCl_WT_RepB_sc11 (0.0447286)6hrKCl_S421A_RepA_sc12 (0.0482022)unstim_WT_RepC_sc13 (0.0386889)unstim_S421A_RepC_sc14 (0.0858919)1hrKCl_WT_RepC_sc15 (0.0745188)1hrKCl_S421A_RepC_sc16 (0.0232577)6hrKCl_WT_RepC_sc17 (0.0616444)6hrKCl_S421A_RepC_sc18 (0.0342394) (0.0383148) (0.0923906) (0.0778062)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 411.4 606.4 684.5 P ( S | Z, I ) = 1.00 Polr2b 3720.3 4703.6 4974.2 Mean Corr = 0.81028 Ints3 116.5 238.1 285.0 Ints7 674.0 965.8 1230.5 Ints1 633.3 730.9 782.4 Ints4 270.0 490.2 584.1 Ints9 201.5 367.8 416.0 Ints2 267.6 578.3 680.9 Polr2a 407.8 894.5 1025.9 Trim28 3230.0 3650.4 3894.2 Nup133 471.5 610.3 673.7 Gart 269.8 578.4 678.2 Xpo5 266.7 660.4 708.4 Ttf2 47.7 109.2 131.8 CEM 1 + Eif3l 3280.8 4186.9 4449.8 Top 10 Genes Cpsf3 621.5 1319.2 1455.2 Ruvbl1 1078.5 1317.6 1386.2 Cpsf1 1223.0 1360.6 1461.0 Msh2 229.4 785.7 853.9

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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, (0.0196589)sampleregeneration rep2 (0.0219966) sampleatregeneration T1, rep1 sampleatregeneration T1, (0.016647) rep2 sampleatregeneration T2, (0.0229128) rep1 sampleatregeneration T2, (0.036681) rep2 sampleatregeneration T6, (0.0138208) rep1 sampleatregeneration T6, (0.0245822) rep2 sampleatregeneration T12, (0.0206522) samplerep1atregeneration T12, (0.0152811) samplerep2atregeneration T18, (0.0477281) samplerep1atregeneration T18, (0.0164022) samplerep2atregeneration T24, (0.019365) samplerep1atregeneration T24, (0.0155125) samplerep2atregeneration T30, (0.024742) samplerep1atregeneration T30, (0.0189541) samplerep2atregeneration T48, (0.019378) samplerep1atdevelopmental T48, (0.0198712) samplerep2atdevelopmental T72, (0.0282162) rep1at developmentalsample T72, (0.0165412) rep2 developmental sampleat T105,(0.0161009) developmental sampleat rep1 T105, (0.0808608) developmental sampleat rep2 T115, (0.109632) developmental sampleat rep1 T115, (0.0690656) developmental sampleat rep2 T125, (0.0779624) developmental sampleat rep1 T125, (0.0259961) developmental sampleat rep2 T135, (0.0249378) developmental sampleat rep1 T135, (0.0337953) developmental sampleat rep2 T145, (0.0463264) sampleat rep1 T145, (0.0284343) sampleat rep2 T165, (0.0294981) at rep1 T165, (0.0263169)[ rep2min (0.0121304) ] [ medium ] [ max ] CEM 1 Cpsf3l 310.6 504.6 1261.5 P ( S | Z, I ) = 1.00 Polr2b 568.7 906.3 2690.7 Mean Corr = 0.80991 Ints3 24.3 210.6 509.8 Ints7 188.9 448.9 1079.6 Ints1 44.3 161.9 289.1 Ints4 349.5 656.3 873.5 Ints9 319.0 524.0 706.0 Ints2 91.2 377.5 1580.8 Polr2a 313.4 552.7 2033.1 Trim28 366.1 736.0 5136.3 Nup133 48.6 222.3 1559.0 Gart 296.1 566.5 3078.0 Xpo5 51.5 155.3 578.9 Ttf2 115.2 229.9 1194.8 CEM 1 + Eif3l 1496.0 2277.2 5654.4 Top 10 Genes Cpsf3 814.6 943.9 1762.7 Ruvbl1 337.7 571.5 2260.6 Cpsf1 779.0 1211.1 2001.2 Msh2 269.6 500.7 1477.5

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE54207" 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=GSE54207 Status: Public on Jan 18 2014 Title: Expression data from mouse limb tendon cells during development. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We have undertaken a screen of mouse limb tendon cells in order to identify molecular pathways involved in tendon development. Mouse limb tendon cells were isolated based on Scleraxis (Scx) expression at different stages of development: E11.5, E12.5 and E14.5

Microarray comparisons were carried out between tendon progenitor and differentiated stages.

Overall design: Forelimbs from E11.5, E12.5 and E14.5 Scx-GFP embryos were collected and dissociated with trypsin to obtain cell suspensions. Scx-positive tendon cells were isolated by FACS. RNA was extracted and Fragmented biotin-labelled cRNA samples were hybridized on Affymetrix Gene Chip Mouse Genome 430 2.0 arrays.

Background corr dist: KL-Divergence = 0.0661, L1-Distance = 0.0279, L2-Distance = 0.0010, Normal std = 0.5212

0.781 Kernel fit Pairwise Correlations Normal fit

Density 0.391

0.000 CEM 1

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

Pre-normalization Quantiles

E11.5 AE12.5 (0.126047) AE14.5 (0.0272724) AE11.5 (0.165054) BE12.5 (0.29572) BE14.5 (0.0241224) BE11.5 (0.0897129) CE12.5 (0.0386313) CE14.5 (0.0706098) C (0.16283) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 819.9 1121.1 1360.2 P ( S | Z, I ) = 1.00 Polr2b 3087.4 4863.0 6615.9 Mean Corr = 0.80585 Ints3 311.5 506.0 813.3 Ints7 1396.0 2115.7 2898.8 Ints1 664.1 943.0 1482.7 Ints4 681.9 960.1 1333.0 Ints9 549.9 778.0 1055.4 Ints2 1353.2 2137.8 3168.3 Polr2a 1931.3 2573.4 3891.0 Trim28 4668.3 7469.5 11247.1 Nup133 1027.7 1820.3 2869.0 Gart 1007.7 1214.1 1656.2 Xpo5 770.9 1065.7 1448.2 Ttf2 567.6 1036.1 1501.0 CEM 1 + Eif3l 5531.6 6436.7 7440.7 Top 10 Genes Cpsf3 1575.0 2260.9 2535.5 Ruvbl1 1528.2 1940.9 2823.3 Cpsf1 2051.4 2929.6 3806.0 Msh2 1176.5 2267.4 3022.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE26096" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.765 Kernel fit Pairwise Correlations Normal fit

Density 0.383

0.000 CEM 1

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

Pre-normalization Quantiles

Serum-starvedSerum-starved 96control, hr doxycycline 96control, biological hr doxycyclineMEFdox0Div_rep1 biological induction, rep1MEFdox0Div_rep2 (0.113103) induction, rep2 biologicalMEFdox1Div_rep1 (0.115812) (0.054584) biologicalMEFdox1Div_rep2 rep1 (0.0566067) (0.148961)MEFdox2Div_rep1 rep2 (0.0548251) (0.315616)MEFdox2Div_rep2 (0.0232067) (0.0573044) (0.0599818)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 469.2 704.6 1088.3 P ( S | Z, I ) = 1.00 Polr2b 2867.7 3537.5 4602.5 Mean Corr = 0.78790 Ints3 161.4 240.3 345.2 Ints7 464.1 1052.4 1434.0 Ints1 368.2 451.3 853.7 Ints4 710.3 1009.1 1477.1 Ints9 530.0 659.7 882.0 Ints2 606.3 953.8 1694.8 Polr2a 692.6 944.6 1074.1 Trim28 2601.6 3482.1 4833.8 Nup133 485.4 780.6 1350.2 Gart 916.7 1853.8 4139.7 Xpo5 607.4 834.6 1272.8 Ttf2 222.9 455.2 774.1 CEM 1 + Eif3l 5575.4 7999.6 10464.2 Top 10 Genes Cpsf3 1366.3 1935.2 2574.9 Ruvbl1 1086.8 1727.1 3298.0 Cpsf1 1226.2 1663.2 2531.7 Msh2 247.4 381.5 687.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0870495)Timepoint1_ES-LIF(-)_rep2 (0.0755375) (0.151565)Timepoint2_CM_rep2Timepoint1b_CP_rep1 (0.0856331)Control_ES-LIF(+)_rep3 (0.0988248) (0.12913)Timepoint1_ES-LIF(-)_rep3 Timepoint2_CM_rep3(0.0508451)Timepoint1b_CP_rep2 (0.0790475)Timepoint1b_CP_rep3 (0.0848153) (0.110786) (0.0358902) (0.0108762)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1197.8 2142.3 2515.5 P ( S | Z, I ) = 1.00 Polr2b 2322.0 4956.5 5677.1 Mean Corr = 0.78198 Ints3 265.3 547.4 617.2 Ints7 481.3 1408.4 1591.1 Ints1 755.6 955.8 1199.3 Ints4 729.2 1065.9 1618.3 Ints9 922.5 1388.3 1862.9 Ints2 1098.8 2788.6 3208.4 Polr2a 2342.0 5753.0 6655.7 Trim28 6414.5 15266.3 19136.7 Nup133 1877.0 5350.0 6359.9 Gart 2588.2 7001.2 7694.2 Xpo5 677.4 1411.8 1868.6 Ttf2 693.2 2063.4 2355.9 CEM 1 + Eif3l 6877.0 10476.3 11704.7 Top 10 Genes Cpsf3 1030.9 1944.3 2329.1 Ruvbl1 1499.6 3098.0 3833.1 Cpsf1 1597.9 3117.1 3698.5 Msh2 1454.5 6068.3 7136.6

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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(0.158342) (0.0703367)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.197866)intestine-EphB2Medium-R2 (0.0459995)intestine-EphB2Low-R2 (0.157146) (0.115759) (0.0237988) (0.230751)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 645.5 1064.2 1168.1 P ( S | Z, I ) = 1.00 Polr2b 1425.9 2368.9 2822.7 Mean Corr = 0.76973 Ints3 467.1 507.4 595.5 Ints7 2222.3 4425.3 5017.4 Ints1 994.0 1322.8 1695.9 Ints4 1986.8 2533.9 3035.4 Ints9 705.5 1103.2 1474.2 Ints2 201.9 316.0 462.4 Polr2a 1601.5 2096.8 2284.7 Trim28 2350.2 5135.6 6369.3 Nup133 705.7 2941.1 3956.9 Gart 715.3 2389.8 3064.5 Xpo5 167.1 505.7 625.9 Ttf2 126.0 481.0 555.0 CEM 1 + Eif3l 4400.9 5745.6 6566.9 Top 10 Genes Cpsf3 2272.1 3569.9 4251.0 Ruvbl1 625.5 1795.9 2402.4 Cpsf1 1090.5 1782.5 2129.4 Msh2 692.6 2286.1 2965.5

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE28593" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28593 Status: Public on Apr 15 2011 Title: KMT1E Mediated H3K9 Methylation Is Required for the Maintenance of Embryonic Stem Cells by Repressing Trophectoderm Differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20014010 Summary & Design: Summary: Dynamic regulation of histone methylation by methyltransferases and demethylases plays a central role in regulating the fate of embryonic stem (ES) cells. The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene results in peri-implantation lethality and prevents the propagation of ES cells. However, Setdb1- null blastocysts do not display global changes in H3K9 methylation or DNA methylation, arguing against a genome- wide defect. Here we show that conditional deletion of the Setdb1 gene in ES cells results in the upregulation of lineage differentiation markers, especially trophectoderm-specific factors, similar to effects observed upon loss of Oct3/4 expression in ES cells. We demonstrate that KMT1E deficiency in ES cells leads to a decrease in histone H3K9 methylation at and derepression of trophoblast-associated genes such as Cdx2. Furthermore, we find genes that are derepressed upon Setdb1 deletion to overlap with known targets of polycomb mediated repression, suggesting that KMT1E mediated H3K9 methylation acts in concert with polycomb controlled H3K27 methylation. Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells.

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

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

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.291

0.000 CEM 1

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

Pre-normalization Quantiles

Setdb1 Setdb12lox/1lox Setdb12lox/1lox plus tamoxifenSetdb12lox/1lox plus tamoxifenSetdb12lox/1lox/Cre plus1 (0.0802276) tamoxifenSetdb12lox/1lox/Cre 2 (0.0415272) minus Setdb12lox/1lox/Cre 3 (0.0614795) tamoxifen minus Setdb12lox/1lox/Cre tamoxifen minus Setdb12lox/1lox/Cre 1 (0.126271) tamoxifen plus 2lox/1lox/Cre 2 (0.180958) tamoxifen plus 3 (0.151711) tamoxifen plus1 (0.0852271) tamoxifen 2[ (0.113427) min 3 (0.159172) ] [ medium ] [ max ] CEM 1 Cpsf3l 1558.3 2002.1 2459.2 P ( S | Z, I ) = 1.00 Polr2b 6674.8 7277.7 9101.5 Mean Corr = 0.76947 Ints3 391.0 615.1 703.1 Ints7 1160.3 1379.6 2275.0 Ints1 812.6 881.1 1020.0 Ints4 869.1 1241.3 1549.7 Ints9 770.3 1155.7 1608.5 Ints2 1384.2 1772.7 1994.5 Polr2a 1832.4 2142.1 2288.8 Trim28 5082.8 10786.7 16416.9 Nup133 2141.6 3328.7 3475.0 Gart 3445.2 6081.3 6983.5 Xpo5 806.1 1053.2 1494.9 Ttf2 734.9 1563.9 2013.3 CEM 1 + Eif3l 8097.8 9418.4 13764.0 Top 10 Genes Cpsf3 1832.2 2640.0 3211.3 Ruvbl1 1857.4 2881.5 3223.5 Cpsf1 2362.7 3185.7 3859.9 Msh2 3939.9 5636.0 6154.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE13149" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 25 -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=GSE13149 Status: Public on Oct 30 2008 Title: Multi-stage analysis of gene expression in C57/B6 mouse liver development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19015022 Summary & Design: Summary: The liver performs a number of essential functions for life. The development of such a complex organ relies on finely regulated gene expression profiles which change over time in the development and determine the phenotype and function of the liver.

We used high-density oligonucleotide microarrays to study the gene expression and transcription regulation at 14 time points across the C57/B6 mouse liver development, which include E11.5 (embryonic day 11.5), E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5, Day0 (the day of birth), Day3, Day7, Day14, Day21, and normal adult liver. With these data, we made a comprehensive analysis on gene expression patterns, functional preferences and transcriptional regulations during the liver development.

Keywords: time course

Overall design: Totally 25 microarrays have been used in this experiment, and 11 of the 14 time points have two technique repeat experiments.

Background corr dist: KL-Divergence = 0.0590, L1-Distance = 0.0653, L2-Distance = 0.0079, Normal std = 0.5560

0.718 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

Liver_development_E11.5_rep1Liver_development_E11.5_rep2Liver_development_E12.5_rep1Liver_development_E12.5_rep2Liver_development_E13.5_rep1 (0.129043)Liver_development_E13.5_rep2 (0.169993)Liver_development_E14.5_rep1 (0.0766395)Liver_development_E14.5_rep2 (0.0460138)Liver_development_E15.5_rep1 (0.024338)Liver_development_E15.5_rep2 (0.030015)Liver_development_E16.5_rep1 (0.0374805)Liver_development_E16.5_rep2 (0.0235)Liver_development_E17.5_rep1 (0.0450203)Liver_development_E17.5_rep2 (0.025332)Liver_development_E18.5_rep1 (0.0140641)Liver_development_Day0_rep1 (0.0303424)Liver_development_Day0_rep2 (0.013054)Liver_development_Day3_rep1 (0.00817862)Liver_development_Day3_rep2 (0.0263649)Liver_development_Day7_rep1 (0.0214903)Liver_development_Day14_rep1 (0.0175088)Liver_development_Day21_rep1 (0.0349193)Liver_development_Day21_rep2 (0.0148641)Liver_development_NL_rep1 (0.06043)Liver_development_NL_rep2 (0.0374399) (0.034749) (0.0278695) (0.028859) (0.0224906)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 362.6 520.0 1092.9 P ( S | Z, I ) = 1.00 Polr2b 869.3 2007.5 4110.0 Mean Corr = 0.76248 Ints3 112.3 143.1 412.6 Ints7 536.4 1045.9 2628.4 Ints1 251.9 328.3 484.9 Ints4 285.8 472.1 655.7 Ints9 415.5 603.1 1217.1 Ints2 205.1 544.3 2602.7 Polr2a 558.3 1410.3 3599.4 Trim28 871.4 2144.2 9248.4 Nup133 257.5 853.1 1628.3 Gart 510.3 961.7 4498.6 Xpo5 206.8 459.8 1409.8 Ttf2 173.8 455.3 888.8 CEM 1 + Eif3l 2188.5 4228.8 9361.9 Top 10 Genes Cpsf3 1120.3 1382.8 2723.4 Ruvbl1 354.3 611.0 2750.0 Cpsf1 954.3 1597.1 3013.4 Msh2 278.6 601.6 1806.6

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0559208) R1.2E7.5Mouse Cells (0.0613637)whole R1.3E7.5Mouse embryo (0.0660106)whole E7.5Mouse embryo tissuewhole E8.5Mouse E7.1embryo tissuewhole E8.5Mouse (0.0797301) E7.2heart tissuewhole E8.5Mouse (0.0653816) tissue E7.3heart whole E9.5Mouse (0.091545)(heart tissue heart left E9.5Mousetube) ventricle(heart tissue left E8.1 E9.5Mousetube) ventricle(heart tissue (0.0649927) left E8.2 E9.5Mousetube) ventricle E9L.1 tissue (0.0329974) right E8.3 E9.5Mouse (0.0163146) E9L.2ventricletissue (0.0358359) right E9.5Mouse (0.00794916) E9L.3ventricle tissueright E12.5Mouse (0.007444) ventricle E9R.1 tissue left E12.5Mouse ventricle(0.0112911) E9R.2 tissue left E12.5Mouse ventricle(0.00760762) E9R.3tissue left E12.5Mouse ventricle(0.0127873) E12L.1 tissue right E12.5Mouse (0.0105065)E12L.2ventricletissue right E12.5Mouse (0.00806197)E12L.3ventricle tissueright E14.5Mouse (0.0100255)ventricle E12R.1 tissueleft E14.5Mouse ventricle E12R.2(0.00539115) tissueleft E14.5Mouse ventricle tissue E12R.3(0.00494014) left E14.5Mouse ventricle E14L.1 tissue (0.0108088) right E14.5Mouse (0.00510324)E14L.2ventricletissue right E14.5Mouse (0.00307168)E14L.3ventricle tissueright E18.5Mouse (0.00207489)ventricle E14R.1 tissueleft E18.5Mouse ventricle E14R.2(0.0101526) tissueleft E18.5Mouse ventricle tissue E14R.3(0.0102199) left E18.5Mouse ventricle E18L.1 tissue (0.00702927) right E18.5Mouse (0.0194013)E18L.2ventricletissue right E18.5Mouse (0.0169375)E18L.3ventricle tissueright leftMouse (0.0102639)ventricle E18R.1 tissue leftMouse ventricle E18R.2 (0.00819926)tissue leftMouse ventricle atE18R.3 (0.00758792)tissue 3rightMouse days at (0.0121558)ventricletissue after3rightMouse days birth atventricle aftertissue3rightAdult days D3L.1 birth ventricle mouseat aftertissueAdult 3(0.0165289) D3L.2 days birth leftmouseat tissueAdult after3(0.010745) ventricleD3L.3 days leftbirthmouseatAdult after3(0.0156445) ventricle days D3R.1tissue leftbirthmouseAdult after ventricle (0.0155613) AdltL.1D3R.2tissue rightbirthmouseAdult (0.0149325) AdltL.2(0.0238758)ventricleD3R.3tissue rightmouse (0.0120524) AdltL.3(0.026484)ventricle tissueright (0.0275522)ventricle AdltR.1 tissue AdltR.2(0.0206922)tissue[ min AdltR.3(0.0156021) ] (0.0212264) [ medium ] [ max ] CEM 1 Cpsf3l 379.3 604.0 1910.8 P ( S | Z, I ) = 1.00 Polr2b 1700.2 2912.8 6769.7 Mean Corr = 0.75767 Ints3 93.3 248.0 574.7 Ints7 336.6 1456.1 2738.5 Ints1 211.9 320.4 808.4 Ints4 328.9 442.9 888.7 Ints9 298.1 405.1 1409.4 Ints2 219.4 613.6 2070.2 Polr2a 441.8 795.3 1832.8 Trim28 849.5 3368.4 16593.6 Nup133 327.2 908.4 3017.9 Gart 585.3 1046.5 6322.8 Xpo5 223.9 385.9 1255.3 Ttf2 87.9 388.7 1200.1 CEM 1 + Eif3l 2870.7 4484.6 10491.6 Top 10 Genes Cpsf3 983.3 1453.6 2596.9 Ruvbl1 486.1 1303.4 4027.2 Cpsf1 571.0 1038.5 2383.5 Msh2 369.1 977.4 5203.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0700502) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0502249) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.054437) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0527508) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0377927) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0339053) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0292586) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.0153416) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0186305) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0442678) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0232639) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0225506) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0330518) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.047615) developmentalMousestage 1 E14.5 (0.0576992) developmentalMousestage 2 E16.5 (0.0555562) developmentalstage 1 E16.5(0.0557143) stage[ min 2 E18.5(0.0828434) stage 1] E18.5(0.100487) 2 (0.11456)[ medium ] [ max ] CEM 1 Cpsf3l 719.2 1772.1 2424.2 P ( S | Z, I ) = 1.00 Polr2b 1750.4 6051.9 7399.8 Mean Corr = 0.75217 Ints3 198.0 539.9 684.6 Ints7 1228.9 2600.3 3083.6 Ints1 289.8 561.7 770.6 Ints4 750.2 1468.0 1903.7 Ints9 620.8 1297.4 2115.4 Ints2 1210.6 2189.3 2434.8 Polr2a 348.7 704.7 1085.5 Trim28 2391.8 9887.2 11885.9 Nup133 694.9 2390.7 3212.9 Gart 806.9 3321.8 6494.6 Xpo5 466.4 1354.8 1695.7 Ttf2 320.0 1153.1 1647.6 CEM 1 + Eif3l 5773.5 11384.8 14903.5 Top 10 Genes Cpsf3 1332.7 3159.4 3473.2 Ruvbl1 855.1 3080.1 4771.4 Cpsf1 890.9 2690.8 3887.3 Msh2 928.0 3639.9 4516.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE15155" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.672 Kernel fit Pairwise Correlations Normal fit

Density 0.336

0.000 CEM 1

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

Pre-normalization Quantiles

quiescentquiescent satellitequiescent satellite cell_adultactivated satellite cell_adult muscle_rep1activated satellite cell_adult muscle_rep2activated satellite cell_adult (0.141043) muscle_rep3activated satellite cell_adult (0.111845) regeneratingactivated satellite cell_adult (0.0888467) regeneratingactivated satellite cell_1wk mdx regeneratingactivated muscle_rep1satellite cell_1wk mdxoldactivated growing muscle_rep2satellite cell_1wk mdxoldactivated (0.0241894) growing muscle_rep3 satellite muscle_rep1cell_cultured old (0.0229097) growing satellite muscle_rep2cell_cultured (0.0217199) (0.0542812) 3days_rep1 muscle_rep3cell_cultured (0.0390195) 3days_rep2 (0.152827)[ (0.0330406) 3days_rep3min (0.206535) ] (0.103743) [ medium ] [ max ] CEM 1 Cpsf3l 486.5 1142.1 1815.0 P ( S | Z, I ) = 1.00 Polr2b 4037.2 7989.8 11289.9 Mean Corr = 0.73898 Ints3 54.0 238.9 399.7 Ints7 809.0 1570.8 2011.9 Ints1 447.9 856.2 1196.0 Ints4 389.4 769.5 967.8 Ints9 274.9 549.0 744.7 Ints2 368.1 810.5 1414.1 Polr2a 433.7 1103.1 1451.3 Trim28 3011.7 7600.6 9313.0 Nup133 632.1 1757.0 2073.5 Gart 978.2 1809.0 5168.3 Xpo5 290.3 624.8 1349.5 Ttf2 283.6 852.9 1063.0 CEM 1 + Eif3l 6164.3 7716.7 9600.1 Top 10 Genes Cpsf3 2120.2 2700.1 4255.3 Ruvbl1 1024.6 1816.1 4637.6 Cpsf1 3107.5 5440.0 6300.6 Msh2 248.9 512.9 1123.4

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE17794" 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=GSE17794 Status: Public on Jan 11 2010 Title: Expression data from B6C3F1 mice treated with 2-butoxyethanol Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.

Overall design: Mice were euthanased by cervical dislocation under ketamine / acepromazine (100 mg/kg / 5 mg/kg, I.P) anesthesia. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 44 arrays.

Background corr dist: KL-Divergence = 0.0249, L1-Distance = 0.0283, L2-Distance = 0.0013, Normal std = 0.6953

0.574 Kernel fit Pairwise Correlations Normal fit

Density 0.287

0.000 CEM 1

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

Pre-normalization Quantiles

liver-vehicle-4hours-repliver-vehicle-4hours-repliver-vehicle-4hours-repliver-2BE-4hours-rep 1 (0.0303809)liver-2BE-4hours-rep 2 (0.0305976)liver-2BE-4hours-rep 3 (0.0346089) 1liver-2BE-4hours-rep (0.0237519) 2spleen-vehicle-4hours-rep (0.030903) 3spleen-vehicle-4hours-rep (0.0333853) 4spleen-vehicle-4hours-rep (0.033044)spleen-vehicle-4hours-rep 1 (0.0162848)spleen-2BE-4hours-rep 2 (0.00696197)spleen-2BE-4hours-rep 3 (0.0126427)spleen-2BE-4hours-rep 4 (0.0100782)spleen-2BE-4hours-rep 1 (0.017181)liver-vehicle-7days-rep 2 (0.0107156)liver-vehicle-7days-rep 3 (0.0136285)liver-vehicle-7days-rep 4 (0.0179068)liver-vehicle-7days-rep 1 (0.0274491)liver-2BE-7days-rep 2 (0.0334182)liver-2BE-7days-rep 3 (0.028457)liver-2BE-7days-rep 4 (0.0298566) 1 (0.025961)liver-2BE-7days-rep 2 (0.0267915)liver-2BE-7days-rep 3 (0.0259722)bone 4marrow-vehicle-7days-rep (0.0259203)bone 5marrow-vehicle-7days-rep (0.0299972)bone marrow-vehicle-7days-repbone marrow-vehicle-7days-repbone 1 (0.0205496) marrow-vehicle-7days-repbone 2 (0.020123) marrow-2BE-7days-repbone 3 (0.0204444) marrow-2BE-7days-repbone 4 (0.0198208) marrow-2BE-7days-repbone 5 (0.0211653) marrow-2BE-7days-rep 1bone (0.0340735) marrow-2BE-7days-rep 2spleen-vehicle-7days-rep (0.0198058) 3spleen-vehicle-7days-rep (0.0220304) 4spleen-vehicle-7days-rep (0.0205888) 5spleen-vehicle-7days-rep (0.0192904) 1 (0.0201054)spleen-vehicle-7days-rep 2 (0.0197727)spleen-2BE-7days-rep 3 (0.0228066)spleen-2BE-7days-rep 4 (0.0114392)spleen-2BE-7days-rep 5 (0.0146539) spleen-2BE-7days-rep1 (0.0329882) spleen-2BE-7days-rep2 (0.0214594) 3 (0.0196714) 4 (0.0246143) 5 (0.0187027)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 530.2 923.2 1254.7 P ( S | Z, I ) = 1.00 Polr2b 2377.2 2906.6 3733.1 Mean Corr = 0.72277 Ints3 82.9 244.6 325.8 Ints7 674.5 1930.7 2429.4 Ints1 260.1 547.8 697.2 Ints4 473.0 555.6 856.8 Ints9 404.3 679.0 978.4 Ints2 159.0 1027.9 1263.3 Polr2a 384.9 1249.8 2266.5 Trim28 1203.6 3213.7 4169.0 Nup133 271.4 838.8 1785.9 Gart 752.6 974.5 1384.5 Xpo5 196.9 674.4 790.4 Ttf2 153.0 349.2 644.4 CEM 1 + Eif3l 3493.1 4085.2 5116.6 Top 10 Genes Cpsf3 1028.1 1442.8 2268.0 Ruvbl1 606.3 805.9 1081.0 Cpsf1 1227.9 1646.8 2030.5 Msh2 194.7 664.5 1006.5

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE12454" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12454 Status: Public on Aug 01 2009 Title: The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18842153 Summary & Design: Summary: Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.

Overall design: At P0.5, n = 4 biological replicates of littermate-matched wt/ko pairs (for pair #2 there is one wt and 2 Atrx-null samples (2A & 2B) and we count this as 2 pairs).

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0308, L2-Distance = 0.0011, Normal std = 0.6463

0.648 Kernel fit Pairwise Correlations Normal fit

Density 0.324

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

E13.5 wildE13.5 type wildE13.5 #1 type(0.136938) wildE13.5 #2 type(0.0681298) Atrx-nullE13.5 #3 (0.083407) Atrx-null E13.5#1 (0.116402) Atrx-null P0.5#2 (0.103927) wild P0.5#3 type (0.056397) wild #1P0.5 type(0.043599) wild #2P0.5 type(0.0619542) Atrx-null #3P0.5 (0.0550957) Atrx-null #1P0.5 (0.0692056) Atrx-null #2AP0.5 (0.0650838) Atrx-null #2B (0.074635) #3 (0.0652261) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 692.2 958.6 1765.3 P ( S | Z, I ) = 1.00 Polr2b 1931.2 2576.0 3934.2 Mean Corr = 0.72173 Ints3 224.2 361.3 578.6 Ints7 814.6 1779.7 2997.4 Ints1 643.1 842.8 1016.3 Ints4 342.8 518.7 1103.4 Ints9 358.6 777.0 1491.4 Ints2 938.0 1234.8 1678.8 Polr2a 1024.2 1729.2 3958.7 Trim28 4243.5 6324.3 9267.9 Nup133 886.7 1133.0 2139.7 Gart 506.7 676.5 1679.8 Xpo5 597.7 1025.3 1757.0 Ttf2 125.7 281.2 1276.7 CEM 1 + Eif3l 3233.7 4229.3 5218.8 Top 10 Genes Cpsf3 751.4 1153.7 1755.3 Ruvbl1 693.5 983.4 1672.7 Cpsf1 1320.7 1944.5 2381.2 Msh2 657.6 990.6 2115.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE15580" 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=GSE15580 Status: Public on Apr 29 2009 Title: Molecular Signatures of Fetal and Adult Prostate Stem Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19478945 Summary & Design: Summary: The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer. A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-Î² has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg. Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors.

Overall design: In order to identify molecules and pathways that are active in primitive prostate populations we determined the transcriptional profiles of four populations of cells: (i) fetal urogenital sinus epithelial cells, enriched in fetal prostate stem cells, (ii) Sca-1Hi, cells that express high levels of Sca-1, enriched in adult prostate stem cells, (iii) Sca-1Lo, cells that express medium to low levels of Sca-1 and are enriched in transit-amplifying cells, and (iv) Sca-1Neg, cells with no Sca expression, that represent the most mature population and have almost no in vivo regenerative potential.

Background corr dist: KL-Divergence = 0.0772, L1-Distance = 0.0539, L2-Distance = 0.0056, Normal std = 0.5032

0.793 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

Adult_Prostate_Sca-1Hi_rep1Adult_Prostate_Sca-1Hi_rep2Adult_Prostate_Sca-1Hi_rep3Adult_Prostate_Sca-1Lo_rep2 Adult_Prostate_Sca-1Lo_rep3(0.0596242) Adult_Prostate_Sca-1Lo_rep1(0.0780299) Adult_Prostate_Sca-1Lo_rep4(0.0223849)Adult_Prostate_Sca-1Neg_rep1 (0.0259731)Adult_Prostate_Sca-1Neg_rep2 (0.0369909)Adult_Prostate_Sca-1Neg_rep3 (0.0320711)Adult_Prostate_Sca-1Neg_rep4 (0.0276189)urogenital_sinus_epithelium_rep1 (0.0518054)urogenital_sinus_epithelium_rep2 (0.110401)urogenital_sinus_epithelium_rep3 (0.0462871) (0.0417229) (0.0851993) (0.250984)[ min (0.130907) ] [ medium ] [ max ] CEM 1 Cpsf3l 493.9 631.7 1087.2 P ( S | Z, I ) = 1.00 Polr2b 2579.7 3904.5 7554.1 Mean Corr = 0.71274 Ints3 127.9 230.9 434.3 Ints7 467.0 614.5 2060.0 Ints1 301.8 468.4 783.9 Ints4 578.1 929.9 1290.7 Ints9 476.2 635.0 981.1 Ints2 446.9 879.4 1634.3 Polr2a 1049.9 1526.2 2289.2 Trim28 2297.8 3208.9 9372.4 Nup133 421.4 667.0 1494.7 Gart 1022.1 1246.5 2310.1 Xpo5 260.5 473.9 1018.5 Ttf2 299.1 440.8 1634.5 CEM 1 + Eif3l 3375.9 4283.7 8937.6 Top 10 Genes Cpsf3 1376.7 2043.4 3173.0 Ruvbl1 556.2 764.2 1668.1 Cpsf1 1650.8 2983.1 6030.8 Msh2 502.2 892.2 3534.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.26318)line, rep2Wild-type, biological (0.188508)line,Wild-type, biological biological rep Gtf2i1 (0.0514739) biological rep Mutant rep1 Gtf2i2 (0.117019) (0.143028) Mutantline, rep2 biological (0.106657) line, biological rep 1 (0.0613314) rep[ 2min (0.0688024) ] [ medium ] [ max ] CEM 1 Cpsf3l 1356.2 1832.3 2474.2 P ( S | Z, I ) = 1.00 Polr2b 4270.4 6050.0 7337.6 Mean Corr = 0.71199 Ints3 157.2 344.2 493.7 Ints7 1163.4 1344.0 1652.0 Ints1 420.0 540.9 778.1 Ints4 651.7 957.4 1200.2 Ints9 667.3 889.3 1391.5 Ints2 1310.5 1453.3 1726.5 Polr2a 1974.8 2603.1 3065.3 Trim28 8728.8 10135.7 10650.3 Nup133 1638.9 1800.6 2721.0 Gart 2157.1 2792.6 5740.2 Xpo5 710.5 1004.0 1068.7 Ttf2 828.4 1268.8 1751.8 CEM 1 + Eif3l 8112.2 10108.2 12221.4 Top 10 Genes Cpsf3 1523.3 2082.4 2309.1 Ruvbl1 2462.4 2840.7 3407.2 Cpsf1 1599.1 2142.8 2741.4 Msh2 2291.6 3968.5 4275.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE8024" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8024 Status: Public on Jun 25 2007 Title: Murine ES cells, neural precursor cells and embryonic fibroblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17603471 Summary & Design: Summary: Expression profiles for isogenic (129SvJae x C57BL/6) murine embryonic stem (ES) cells, neural precursors (NPC) obtained through in vitro differentiation of the ES cells, and embryonic fibroblasts (MEF) obtained at day 13.5.

Keywords: cell type comparison

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

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

0.621 Kernel fit Pairwise Correlations Normal fit

Density 0.311

0.000 CEM 1

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

Pre-normalization Quantiles

ES_wt_rep1ES_wt_rep2 (0.100001)ES_wt_rep3 (0.0875208)NPC_wt_rep1 (0.181287)NPC_wt_rep2 (0.10916)NPC_wt_rep3 (0.124576)MEF_wt_rep1 (0.0715527)MEF_wt_rep2 (0.16727) (0.158633) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1262.6 1674.9 2024.6 P ( S | Z, I ) = 1.00 Polr2b 3049.3 3983.0 6310.5 Mean Corr = 0.69862 Ints3 305.4 379.9 657.9 Ints7 923.4 2303.5 2575.1 Ints1 540.8 659.0 784.5 Ints4 593.6 1903.1 2183.0 Ints9 460.5 631.0 1034.6 Ints2 1272.8 1979.3 2848.2 Polr2a 560.8 1061.1 1711.3 Trim28 4251.4 6042.9 14130.7 Nup133 1180.4 1453.6 3995.2 Gart 1224.6 2244.0 7538.7 Xpo5 894.7 1070.7 1369.0 Ttf2 708.6 825.9 2106.4 CEM 1 + Eif3l 8179.2 9413.8 10609.4 Top 10 Genes Cpsf3 1174.9 2275.1 3840.8 Ruvbl1 1376.0 1843.3 4418.0 Cpsf1 1454.3 2355.2 3950.8 Msh2 951.0 1398.7 8638.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE54490" 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=GSE54490 Status: Public on Feb 16 2014 Title: FoxA1 directs the lineage and immunosuppressive properties of FoxA1+ regulatory T cells in EAE and MS Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24531377 Summary & Design: Summary: Affymetrix gene expression analysis was carried out to investigate the differences in gene profile of MBP89-101-reactive encephalitogenic T cells before and after co-culture with cerebellar granular neurons (CGNs). Co-culture of MBP89-101-reactive encephalitogenic T cells with CGNs leads to generation of T cells with regulatory T cells phenotype (CD4+CD25+membrane bound TGF-b+ T cells) or a new regulatory phenotype (CD4highPD-L1high T cells). CGN-induced CD4+CD25+membrane bound TGF-b+ T regulatory cells, CD4highPD-L1high T cells were purified by FACSAria. IFN-beta induced T lymphocytes (CD4highPD-L1high T cells) were also FACSAria purified. All these populations were compared to MBP89-101-reactive encephalitogenic T cells. Samples were prepared from biological triplicates for each FACSAria sorted population.

Overall design: There are four different cell types, as determined by cell surface markers, in triplicate in the experiment.

Background corr dist: KL-Divergence = 0.0239, L1-Distance = 0.0546, L2-Distance = 0.0040, Normal std = 0.7910

0.572 Kernel fit Pairwise Correlations Normal fit

Density 0.286

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

EncephalitogenicEncephalitogenicEncephalitogenic Tcellsneuron rep1 Tcells (0.0703689)neuroninduced rep2 Tcells (0.0302675)neuroninduced FoxA1Treg rep3 (0.0188084)Treginduced FoxA1Treg rep1rep1Treg FoxA1Treg (0.0303412)(0.0345323) rep2rep2Treg (0.0421906)(0.0457623) rep3rep3IFN-beta (0.0691909)(0.0813676)IFN-beta inducedIFN-beta induced FoxA1Treg induced FoxA1Treg rep1 FoxA1Treg (0.223875) rep2 (0.155917) rep3[ min (0.197378) ] [ medium ] [ max ] CEM 1 Cpsf3l 792.5 1455.5 1544.5 P ( S | Z, I ) = 1.00 Polr2b 3093.5 3707.4 3876.4 Mean Corr = 0.68722 Ints3 227.9 387.0 494.3 Ints7 1546.5 2177.3 2372.2 Ints1 300.0 731.7 819.6 Ints4 955.5 1210.6 1416.3 Ints9 784.1 1181.3 1292.8 Ints2 737.8 1085.7 1142.4 Polr2a 2352.8 2867.2 2986.9 Trim28 1496.3 4264.1 4811.3 Nup133 747.8 1188.7 1326.8 Gart 1241.6 2125.8 2387.4 Xpo5 277.1 636.3 691.9 Ttf2 787.4 2496.0 2812.4 CEM 1 + Eif3l 4601.9 7752.1 8144.0 Top 10 Genes Cpsf3 1567.9 2019.3 2223.5 Ruvbl1 1075.9 1172.1 1374.5 Cpsf1 1878.0 2485.3 2806.1 Msh2 835.4 1827.3 1952.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE5976" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

Keywords: time course

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

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

0.866 Kernel fit Pairwise Correlations Normal fit

Density 0.433

0.000 CEM 1

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

Pre-normalization Quantiles

A2lox.mesp1A2lox.mesp1 (dayA2lox.mesp1 3) (0.0696129)(dayA2lox.mesp1 3 + (day dox)A2lox.mesp1 3 (0.0975247) + (day3 DKK1)A2lox.mesp1 + (dayDKK1(0.0774216)A2lox.mesp1 4) + (0.0346513)(day dox)A2lox.mesp1 4 (0.049501)+ (day dox)A2lox.mesp1 4 (0.0580332) + (day DKK1)A2lox.mesp1 4 + (day (0.0454198)DKK1A2lox.mesp1 6) +(0.0876359)(day A2lox.mesp1dox) 6 +(0.0397506) (day dox) 6 (0.181741) + (day DKK1) 6 + (0.0605755)DKK1 + [dox) min (0.198133) ] [ medium ] [ max ] CEM 1 Cpsf3l 1007.6 1913.4 2147.4 P ( S | Z, I ) = 1.00 Polr2b 3226.7 4274.1 4796.2 Mean Corr = 0.68662 Ints3 534.4 713.4 824.1 Ints7 1108.9 1544.3 1765.1 Ints1 561.1 827.9 986.0 Ints4 785.1 1116.9 1225.2 Ints9 566.3 1219.7 1291.1 Ints2 1413.3 1866.1 2197.6 Polr2a 1409.2 1960.9 2433.4 Trim28 6784.3 8498.1 10365.3 Nup133 1218.7 2676.3 3091.4 Gart 1779.0 4904.1 6598.5 Xpo5 723.9 1271.4 1427.6 Ttf2 668.0 1580.4 1900.7 CEM 1 + Eif3l 6357.9 7911.0 9127.3 Top 10 Genes Cpsf3 1736.1 2508.1 2947.6 Ruvbl1 1341.4 3113.9 3762.7 Cpsf1 3078.7 4104.8 4517.5 Msh2 1320.7 3689.0 5003.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE17796" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 39 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

0.502 Kernel fit Pairwise Correlations Normal fit

Density 0.251

0.000 CEM 1

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

Pre-normalization Quantiles

liver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-rep 1 (0.0228062)liver-hypoxia-2hours-rep 2 (0.0248433)liver-hypoxia-2hours-rep 3 (0.0284543)liver-hypoxia-2hours-rep 4 (0.0344018)liver-hypoxia-2hours-rep 1 (0.0289617)liver-hypoxia-2hours-rep 2 (0.026182)liver-hypoxia-2hours-rep 3 (0.0190045)liver-hypoxia-2hours-rep 4 (0.0207933)liver-hypoxia-2hours-rep 5 (0.0372617)liver-vehicle-2hours-rep 6 (0.0284517)liver-vehicle-2hours-rep 7 (0.0287065)liver-vehicle-2hours-rep 8 (0.0251862)liver-vehicle-2hours-rep 5 (0.0249828)bone 6 (0.0362515) marrow-vehicle-2hours-repbone 7 (0.0378876) marrow-vehicle-2hours-repbone 8 (0.0369536) marrow-vehicle-2hours-repbone marrow-hypoxia-2hours-repbone 1 (0.0607678)marrow-hypoxia-2hours-repbone 2 (0.0367406)marrow-hypoxia-2hours-repbone 3 (0.0362292)marrow-hypoxia-2hours-repspleen-vehicle-2hours-rep 1 (0.0304863)spleen-vehicle-2hours-rep 2 (0.0272841)spleen-vehicle-2hours-rep 3 (0.0279562)spleen-vehicle-2hours-rep 41 (0.0315497)(0.0315208)spleen-hypoxia-2hours-rep 2 (0.0194546)spleen-hypoxia-2hours-rep 3 (0.022613)spleen-hypoxia-2hours-rep 4 (0.0136983)spleen-hypoxia-2hours-rep 1 (0.0178318)spleen-vehicle-2hours-rep 2 (0.0195783)spleen-hypoxia-2hours-rep 3 (0.0111163)spleen-hypoxia-2hours-rep 4 (0.0184433)spleen-vehicle-2hours-rep 5 (0.0232924)spleen-vehicle-2hours-rep 7 (0.0195281)spleen-vehicle-2hours-rep 8 (0.0128817)spleen-hypoxia-2hours-rep 6 (0.0126233)spleen-hypoxia-2hours-rep 7 (0.0166202) 8 (0.0177589) 5 (0.0132726) 6 (0.0176233)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 559.2 932.6 1351.2 P ( S | Z, I ) = 1.00 Polr2b 2520.9 3212.5 4087.3 Mean Corr = 0.68805 Ints3 98.4 201.4 334.5 Ints7 786.2 1974.9 2464.1 Ints1 321.3 518.9 788.1 Ints4 382.6 597.9 1023.6 Ints9 375.8 683.6 1097.1 Ints2 137.8 957.2 1203.8 Polr2a 423.6 1099.9 2327.8 Trim28 1301.6 3359.1 4152.8 Nup133 371.9 878.0 1938.8 Gart 757.5 1007.4 1369.4 Xpo5 170.9 628.3 898.4 Ttf2 127.5 298.2 689.8 CEM 1 + Eif3l 3199.2 4266.9 5690.4 Top 10 Genes Cpsf3 1184.6 1710.2 2456.3 Ruvbl1 555.9 764.5 1083.8 Cpsf1 1543.2 2012.3 2690.2 Msh2 281.3 670.0 946.1

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE13408" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.737 Kernel fit Pairwise Correlations Normal fit

Density 0.368

0.000 CEM 1

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

Pre-normalization Quantiles

TKO EBTKO (2-55-2) EBWT (14-14-4) (0.0333006) EB (B21)WT (0.0303509) ESC (0.094497)WT (B21) EB (0.109406)(J1)WT ESC(0.0449168)WT (J1) EB (0.0370997) (R1)WT ESC (0.0522721)TKO (R1) EB (0.0483591)TKO (7-4-1) ESC TKO(0.0838393) (7-4-1) EBTKO (Dutch) (0.142864) ESCTKO (0.031552) (Dutch) EBTKO (Ta1-12) (0.0597196) ESC (0.11697)(Ta1-12) (0.114854) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 929.2 1846.7 2975.8 P ( S | Z, I ) = 1.00 Polr2b 3386.7 5536.9 7180.2 Mean Corr = 0.68561 Ints3 276.2 427.0 622.3 Ints7 915.2 1243.1 3354.6 Ints1 248.0 521.9 755.7 Ints4 538.6 926.0 1502.1 Ints9 533.1 741.2 1418.0 Ints2 1036.4 2180.7 3377.1 Polr2a 1788.4 2373.7 3534.0 Trim28 4169.7 7637.1 11510.4 Nup133 736.1 3260.1 4505.1 Gart 1001.8 4212.0 7741.0 Xpo5 389.4 598.0 982.2 Ttf2 517.9 2730.6 3583.7 CEM 1 + Eif3l 5353.3 7561.1 9154.3 Top 10 Genes Cpsf3 1507.3 2993.9 3702.0 Ruvbl1 1201.1 2622.1 4311.2 Cpsf1 1673.4 3286.4 4000.2 Msh2 1163.4 4977.5 6793.6

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE26355" 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=GSE26355 Status: Public on Jan 01 2011 Title: Expression data from early and late born Atoh1 lineages within the E14.5 rhombomere 1 and isthmus Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21440680 Summary & Design: Summary: Following neural tube closure at around E9.5, the rhombic lip within the rhombomere 1/isthmus region (""upper rhombic lip"") produces a sequence of neuronal lineages that populate the brainstem and cerebellum. The transcription factor Atoh1 (Math1) is required for this specialized neurogenesis, although the genetic programs that delineate the temporal cell fate changes downstream of Atoh1 are not well characterized. We examined the gene expresion changes that take place within Atoh1 lineages

Overall design: We purified early (E10.5) and late (E13.5) born Atoh1 expressing cells from E14.5 embryos using a transgenic labeling strategy, and analyzed differences in gene expression across the two populations using the microarray data shown below.

Background corr dist: KL-Divergence = 0.0310, L1-Distance = 0.0295, L2-Distance = 0.0010, Normal std = 0.6844

0.601 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

E10 Atoh1E10 cells Atoh1E10 at cellsE14, Atoh1E13 rep1at cellsE14, Atoh1 (0.196805)E13 rep2at cellsE14, Atoh1 (0.177393)E13 rep3at cellsE14, Atoh1 (0.209698) rep1at cellsE14, (0.151185) rep2at E14, (0.124287) rep3 (0.140633)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 959.8 1972.2 2422.3 P ( S | Z, I ) = 1.00 Polr2b 6935.3 10458.1 11251.3 Mean Corr = 0.67944 Ints3 246.3 331.0 534.2 Ints7 1118.6 3015.0 3470.8 Ints1 471.4 912.0 1031.4 Ints4 695.4 918.8 1077.9 Ints9 225.0 504.7 575.2 Ints2 1040.2 2746.5 2932.2 Polr2a 450.5 911.0 989.8 Trim28 7606.2 12112.3 12949.7 Nup133 1093.7 2729.4 3006.2 Gart 673.2 1373.7 2049.8 Xpo5 418.6 801.5 944.7 Ttf2 155.9 719.2 1122.5 CEM 1 + Eif3l 4174.4 7385.8 7813.5 Top 10 Genes Cpsf3 2444.3 4449.3 5877.6 Ruvbl1 960.1 1663.6 2392.8 Cpsf1 2097.5 4382.7 4693.1 Msh2 2313.4 4074.7 4489.9

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE30745" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.795 Kernel fit Pairwise Correlations Normal fit

Density 0.397

0.000 CEM 1

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

Pre-normalization Quantiles

shMyb.2572shMyb.2572 biolshMyb.2572 repl biol 1,shMyb.2652 3 repl d dox,biol 2,shMyb.2652 3 replsorted d dox,biol 3,shMyb.2652 3 repl(0.108352)sorted d dox,biol 1,Rec 3 repl(0.0314794)sorted d vectordox,biol 2,Rec 3 repl(0.0640634)sorted d biol vectordox, 3,Rec repl3 (0.171548)sorted d biol vector dox,1, shRen.7133 repl d(0.0409062)sorted dox,biol 2, shRen.7133 replsorted d(0.0649659) bioldox, 3, shRen.7133repl (0.0629145)sorted d bioldox, 1, 3 repl (0.0346555) sortedd dox,biol 2, 3 repl(0.115788)sorted d dox, 3, 3 (0.137053)sorted d dox, [ (0.0490191)sorted min (0.119254) ] [ medium ] [ max ] CEM 1 Cpsf3l 1335.4 1962.9 2165.9 P ( S | Z, I ) = 1.00 Polr2b 2469.8 3434.8 3961.7 Mean Corr = 0.67289 Ints3 166.1 251.9 297.9 Ints7 790.1 2041.4 2951.4 Ints1 341.1 825.7 1777.0 Ints4 471.9 727.6 1004.2 Ints9 957.0 1136.1 1531.5 Ints2 208.2 690.6 992.1 Polr2a 1047.2 3382.5 4432.1 Trim28 1668.0 6039.2 7479.2 Nup133 325.6 1215.8 1325.4 Gart 577.9 1733.2 2482.0 Xpo5 547.7 1407.7 1813.6 Ttf2 359.3 1133.9 1428.0 CEM 1 + Eif3l 2985.8 4816.4 6322.7 Top 10 Genes Cpsf3 1568.7 2038.9 2324.5 Ruvbl1 600.4 1551.3 2000.1 Cpsf1 1220.4 2696.2 5429.3 Msh2 392.8 1601.5 2025.5

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE38531" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 35 -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=GSE38531 Status: Public on Jun 05 2014 Title: Expression data in Staphylococcus aureus-infected mice with linezolid and vancomycin treatment Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The precise mechanism and effects of antibiotics in host gene expression and immunomodulation in MRSA infection is unknown. Using a well characterized Methicillin Resistant Staphylococcus aureus (MRSA) isolate USA300 in a murine model of infection, we determined that linezolid and vancomycin induced differential production of bacterial toxins and host cytokines, differences in host gene expression, and differences in immunomodulators during MRSA bloodstream infection. A total of 35 A/J mice, categorized into seven groups (no infection; no infection with linezolid; no infection with vancomycin; 2 hour post-infection (hpi) S. aureus; 24 hpi S. aureus; 24 hpi S. aureus with linezolid; and 24 hpi S. aureus with vancomycin), were used in this study. Mice were injected with USA300 (6 x 106 CFU/g via i.p. route), then intravenously treated with linezolid (25 mg/kg) or vancomycin (25 mg/kg) at 2 hpi. Control and S. aureus infected mice were euthanized at each time point (2 h or 24h) following injection. Whole blood RNA was used for microarray; three cytokines and two S. aureus toxins [PantonValentine Leukocidin (PVL) and alpha hemolysin] were quantified in mouse serum by ELISA. S. aureus CFUs were significantly reduced in blood and kidney after linezolid or vancomycin treatment in S. aureus-infected mice. In vivo IL-1Î² in mouse serum was significantly reduced in both linezolid (p=0.001) and vancomycin (p=0.006) treated mice compared to untreated ones. IL-6 was significantly reduced only in linezolid treated (p<0.001) but not in vancomycin treated mice. However, another proinflammatory cytokine, TNF-Î±, did not exhibit altered levels in either linezolid or vancomycin treated mice (p=0.3 and p=0.51 respectively). In vivo level of bacterial toxin, Panton-Valentine leukocidin, in mouse serum was significantly reduced only in linezolid treated mice (p=0.02) but not in vancomycin treated mice. There was no significant effect of either treatment in in vivo level of alpha hemolysin production. Unsupervised hierarchical clustering using the gene expression data from 35 microarrays revealed distinct clustering based on infection status and treatment group. Study of the antibiotic-specific difference in gene expression identified the number of genes uniquely expressed in response to S. aureus infection, infection with linezolid treatment, and infection with vancomycin treatment. Pathway associations study for the differentially expressed genes in each comparison group (Control vs. 24 h S. aureus infection, 24 h S. aureus infection vs. 24 h S. aureus linezolid, and 24 h S. aureus infection vs. 24 h S. aureus vancomycin) in mice using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified toll-like receptor signaling pathway to be common to every comparison groups studied. Glycerolipid metabolism pathway was uniquely associated only with linezolid treatment comparison group. The findings of this study provide the evidence that protein synthesis inhibitor like linezolid does a better job in treating MRSA sepsis compared to cell wall acting antibiotics like vancomycin.

Overall design: To identify differences in host gene expression in a murine sepsis model treated with a) linezolid and b) vancomycin, we used whole blood gene expression (RNA) signatures from A/J inbred mice infected with USA 300 MRSA to evaluate differences in host gene expression among mice treated with linezolid and vancomycin. We used 5 RNA samples from MRSA-infected, linezolid- or vancomycin-treated mice. A total of 7 experimental groups have been employed: 1) Uninfected control group: (negative controls). 2) Uninfected, linezolid-treated group: Uninfected, linezolid-treated mice. 3) Uninfected vancomycin-treated group: Uninfected, vancomycin-treated mice. 4) Infected control group (positive control 2 h) MRSA-infected, untreated mice. 5) Infected control group (positive control 24 h): MRSA-infected, untreated mice. 6) Infected linezolid group: MRSA-infected, linezolid-treated mice. 7) Infected vancomycin group: MRSA-infected, vancomycin-treated mice.

Background corr dist: KL-Divergence = 0.1180, L1-Distance = 0.0518, L2-Distance = 0.0065, Normal std = 0.4105

0.972 Kernel fit Pairwise Correlations Normal fit

Density 0.486

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

blood atblood T0, biological atblood T2h, S.at bloodrep1 T0,aureus linezolid(0.0485432) atblood T0,infected, vancomycin attreated,blood T24h, biological at biologicalS.blood T24h, aureustreated, rep1at S.blood T24h, aureusinfected,rep1 biological(0.0498687) at S.blood(0.0173112) T0, aureusinfected, biologicalbiological atrep1blood T2h, infected, (0.017173)linezolid S.at rep1bloodrep2 T0,aureus vancomycin (0.0137458)linezolid (0.0214121) treated,atblood T0,infected, vancomycin attreated,biologicalblood T24h, treated, biological at biologicalS.blood T24h, rep1 aureustreated,biological rep2at (0.0236344)S.blood T24h, aureusinfected,rep2 biological(0.0456953) rep1at S.blood(0.0173486) T0, aureusinfected, (0.0159465) biologicalbiological atrep2blood T2h, infected, (0.0660928)linezolid S.at rep2bloodrep3 T0,aureus vancomycin (0.0600801)linezolid (0.0276759) treated,atblood T0,infected, vancomycin attreated,biologicalblood T24h, treated, biological at biologicalS.blood T24h, rep2 aureustreated,biological rep3at (0.0183398)S.blood T24h, aureusinfected,rep3 biological(0.00696946) rep2at S.blood(0.0564376) T0, aureusinfected, (0.0436525) biologicalbiological atrep3blood T2h, infected, (0.0231853)linezolid S.at rep3bloodrep4 T0,aureus vancomycin (0.0254958)linezolid (0.0306978) treated,atblood T0,infected, vancomycin attreated,biologicalblood T24h, treated, biological at biologicalS.blood T24h, rep3 aureustreated,biological rep4at (0.00923175)S.blood T24h, aureusinfected,rep4 biological(0.00921992) rep3at S.blood(0.0236209) T0, aureusinfected, (0.0110976) biologicalbiological atrep4blood T2h, infected, (0.0758926)linezolid S.at rep4bloodrep5 T0,aureus vancomycin (0.0266667)linezolid (0.0476259) treated,atblood T0,infected, vancomycin attreated,biologicalblood T24h, treated, biological at biologicalS.blood T24h, rep4 aureustreated,biological rep5at (0.0225998)S. T24h, aureusinfected,rep5 biological(0.0308912) rep4 S.(0.0129264) aureusinfected, (0.0140391) biological rep5 infected, (0.0171105)linezolid rep5[ min vancomycin(0.0308319) treated, ] biological treated, rep5 biological[ medium (0.0181873) rep5 (0.0207524) ] [ max ] CEM 1 Cpsf3l 531.8 746.3 947.7 P ( S | Z, I ) = 1.00 Polr2b 666.9 1032.9 1794.8 Mean Corr = 0.67009 Ints3 52.6 68.4 92.0 Ints7 488.8 874.0 1549.0 Ints1 267.4 352.1 508.0 Ints4 274.6 361.0 720.2 Ints9 229.4 305.5 365.2 Ints2 119.5 194.9 431.3 Polr2a 1705.0 3152.1 5264.1 Trim28 981.1 1865.0 3240.1 Nup133 236.8 318.7 410.0 Gart 398.4 709.2 1168.1 Xpo5 220.2 355.7 568.9 Ttf2 240.1 377.9 529.3 CEM 1 + Eif3l 965.0 1515.0 2268.6 Top 10 Genes Cpsf3 574.7 772.9 1233.0 Ruvbl1 135.4 242.0 312.4 Cpsf1 930.8 1416.3 2479.4 Msh2 256.2 381.3 501.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE47959" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.656 Kernel fit Pairwise Correlations Normal fit

Density 0.328

0.000 CEM 1

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

Pre-normalization Quantiles

Ctr_unstim_1Ctr_unstim_2 (0.0997006)Ctr_stim_1 (0.0687654)Ctr_stim_2 (0.12387)Pre_unstim_1 (0.171063)Pre_unstim_2 (0.194873)Pre_stim_1 (0.177999)Pre_stim_2 (0.0406637) (0.123065) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 516.4 684.6 750.4 P ( S | Z, I ) = 1.00 Polr2b 1068.7 1428.6 1576.1 Mean Corr = 0.66064 Ints3 206.3 282.9 398.6 Ints7 4376.5 5629.1 5934.2 Ints1 447.4 550.5 731.0 Ints4 1036.7 1437.6 1639.8 Ints9 471.1 653.8 797.1 Ints2 204.3 317.3 436.2 Polr2a 3226.8 3601.7 4139.4 Trim28 1592.9 1760.7 2560.3 Nup133 506.4 936.0 1139.1 Gart 607.2 825.0 1088.9 Xpo5 131.1 248.3 399.8 Ttf2 198.5 522.8 732.5 CEM 1 + Eif3l 2375.8 2929.2 3360.4 Top 10 Genes Cpsf3 2154.8 2784.5 3138.7 Ruvbl1 794.1 1071.9 1520.5 Cpsf1 575.0 739.1 845.1 Msh2 684.2 1138.9 1463.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE27159" 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=GSE27159 Status: Public on Apr 30 2012 Title: Expression profiling of the murine neural crest precursor cell line, JoMa1 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: JoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.

Overall design: The expression profile of JoMa1 cells was compared to cell lines derived from tumors induced by JoMa1 transfected with MYCN.

Background corr dist: KL-Divergence = 0.0379, L1-Distance = 0.0219, L2-Distance = 0.0005, Normal std = 0.6256

0.653 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

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

Pre-normalization Quantiles

JoMa1_1JoMa1_2 (0.057472)JoMa1_3 (0.125556)JoMa1_GFP (0.0706104)mT3 (0.0903465)(0.202219)mT4 (0.253704)mT5 (0.0790639)mT6 (0.121028) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1392.6 1515.7 1630.3 P ( S | Z, I ) = 1.00 Polr2b 4049.8 5067.2 5833.8 Mean Corr = 0.65448 Ints3 240.0 343.5 385.0 Ints7 1966.0 2279.1 2439.8 Ints1 410.4 801.8 896.5 Ints4 387.8 510.1 552.3 Ints9 659.0 952.1 1046.3 Ints2 1588.4 2088.4 2716.9 Polr2a 1355.7 2042.4 2301.3 Trim28 3799.7 6258.2 7060.6 Nup133 1018.8 1847.7 1970.2 Gart 1021.2 1977.2 2958.5 Xpo5 999.6 1498.5 2157.8 Ttf2 641.9 778.8 824.5 CEM 1 + Eif3l 5685.3 6975.0 7405.4 Top 10 Genes Cpsf3 881.1 1873.8 2219.9 Ruvbl1 2234.8 4255.4 5209.1 Cpsf1 1391.1 1821.0 2035.1 Msh2 857.6 1351.1 1458.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE54653" 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=GSE54653 Status: Public on May 07 2014 Title: Expression data from quiescent and activated neural stem cells from the adult mouse V-SVZ niche Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: RNA was purified from GFAP::GFP+CD133+ and GFAP::GFP+CD133+EGFR+ cells isolated from the adult mouse V-SVZ niche (GFAP::GFP mice, Jackson Mice Stock number 003257)

Overall design: 6 samples consisting of two conditions of three biological replicates each were analyzed

Background corr dist: KL-Divergence = 0.0262, L1-Distance = 0.0342, L2-Distance = 0.0016, Normal std = 0.7186

0.560 Kernel fit Pairwise Correlations Normal fit

Density 0.280

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

adult V-SVZadult qNSCs V-SVZadult qNSCs,biological V-SVZadult qNSCs, biologicalV-SVZ adultreplicate aNSCs, biologicalV-SVZadult replicate 1 (0.220267) aNSCs,biologicalV-SVZ replicate 2 (0.185268) aNSCs,biological replicate 3 (0.139158) biological replicate 1 (0.145672)[ replicate 2min (0.179098) 3 (0.130537)] [ medium ] [ max ] CEM 1 Cpsf3l 307.0 723.2 945.3 P ( S | Z, I ) = 1.00 Polr2b 1518.0 2184.6 3966.8 Mean Corr = 0.65533 Ints3 56.4 281.4 366.8 Ints7 557.3 2537.7 2983.6 Ints1 389.7 779.9 859.1 Ints4 407.6 1535.6 1873.3 Ints9 230.6 643.3 1270.3 Ints2 757.8 1603.3 2002.3 Polr2a 588.4 5427.8 6344.1 Trim28 727.0 5812.4 8326.3 Nup133 446.7 1269.3 2815.2 Gart 380.8 1280.3 1838.7 Xpo5 75.5 384.0 463.3 Ttf2 151.1 720.5 1076.8 CEM 1 + Eif3l 834.0 2311.5 3963.0 Top 10 Genes Cpsf3 588.4 1308.5 1672.6 Ruvbl1 436.9 1463.6 6510.4 Cpsf1 417.3 1399.5 1839.0 Msh2 202.1 1123.8 1769.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE28261" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 72 -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=GSE28261 Status: Public on Mar 30 2011 Title: Whole blood gene expression in female Balb/c mice following 2-week Pb exposure and subsequent 2-week recovery period Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Background: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways.

Methodology/Principal Finding: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern.

Conclusions/Significance: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

Overall design: We isolate total RNA from 72 mouse whole blood samples. These included samples following a 2-week exposure to lead acetate trihydrate (untreated controls = 7; Low Pb 5ug/mL drinking water = 15; High Pb 50ug/mL drinking water = 15) and additional samples following a 2-week recovery period with plain drinking water (untreated controls = 7; Low Pb group = 15; High Pb group = 13).

Background corr dist: KL-Divergence = 0.1437, L1-Distance = 0.0741, L2-Distance = 0.0158, Normal std = 0.3837

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

Blood_Control_Exp_1Blood_Control_Exp_2Blood_Control_Exp_3 Blood_Control_Exp_4(0.00811525) Blood_Control_Exp_5(0.0118584) Blood_Control_Exp_6(0.0049) Blood_Control_Exp_7(0.00747483) Blood_Control_Rec_1(0.0302102) Blood_Control_Rec_2(0.0117496) Blood_Control_Rec_3(0.0278296) Blood_Control_Rec_4(0.00611802) Blood_Control_Rec_5(0.0166489) Blood_Control_Rec_6(0.0267891) Blood_Control_Rec_7(0.0137094) Blood_LowPb_Exp_1(0.0241502) Blood_LowPb_Exp_2(0.00752367) Blood_LowPb_Exp_3(0.0187203) (0.00294549)Blood_LowPb_Exp_4 (0.00981908)Blood_LowPb_Exp_5 (0.00916325)Blood_LowPb_Exp_6 (0.0155597)Blood_LowPb_Exp_7 (0.00581986)Blood_LowPb_Exp_8 (0.0057789)Blood_LowPb_Exp_9 (0.0145891)Blood_LowPb_Exp_10 (0.00816003)Blood_LowPb_Exp_11 (0.00787687)Blood_LowPb_Exp_12Blood_LowPb_Exp_13 (0.00677115)Blood_LowPb_Exp_14 (0.0106603)Blood_LowPb_Exp_15 (0.0238331)Blood_HighPb_Exp_1 (0.00412649)Blood_HighPb_Exp_2 (0.00389294)Blood_HighPb_Exp_3 (0.00494062) Blood_HighPb_Exp_4(0.0304315) Blood_HighPb_Exp_5(0.0100857) Blood_HighPb_Exp_6(0.00404299) Blood_HighPb_Exp_7(0.00732283) Blood_HighPb_Exp_8(0.0144611) Blood_HighPb_Exp_9(0.0209795) Blood_HighPb_Exp_10(0.0214193) Blood_HighPb_Exp_11(0.0402666) Blood_HighPb_Exp_12(0.022243)Blood_HighPb_Exp_13 (0.0139359)Blood_HighPb_Exp_14 (0.0135359)Blood_HighPb_Exp_15 (0.0117929)Blood_LowPb_Rec_1 (0.0132955)Blood_LowPb_Rec_2 (0.0136428)Blood_LowPb_Rec_3 (0.0167478) (0.00764917)Blood_LowPb_Rec_4 (0.00985343)Blood_LowPb_Rec_5 (0.00933148)Blood_LowPb_Rec_6 (0.0199906)Blood_LowPb_Rec_7 (0.032061)Blood_LowPb_Rec_8 (0.0184649)Blood_LowPb_Rec_9 (0.0285427)Blood_LowPb_Rec_10 (0.010625)Blood_LowPb_Rec_11 (0.0110621)Blood_LowPb_Rec_12Blood_LowPb_Rec_13 (0.0141579)Blood_LowPb_Rec_14 (0.00330201)Blood_LowPb_Rec_15 (0.0112435)Blood_HighPb_Rec_1 (0.0123729)Blood_HighPb_Rec_2 (0.0053982)Blood_HighPb_Rec_3 (0.0516361) Blood_HighPb_Rec_4(0.00826122) Blood_HighPb_Rec_5(0.0123861) Blood_HighPb_Rec_6(0.0059994) Blood_HighPb_Rec_7(0.0094918) Blood_HighPb_Rec_8(0.00767477) Blood_HighPb_Rec_9(0.00515446) Blood_HighPb_Rec_10(0.0156444) Blood_HighPb_Rec_11(0.0104469) Blood_HighPb_Rec_12(0.0101597)Blood_HighPb_Rec_13 (0.00456848) (0.0295217) (0.0251725) (0.00588974)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1011.5 1299.8 1706.3 P ( S | Z, I ) = 1.00 Polr2b 1041.9 1594.0 2241.3 Mean Corr = 0.64630 Ints3 67.8 134.2 185.8 Ints7 1139.2 1622.6 2073.9 Ints1 360.0 511.0 843.8 Ints4 429.4 740.8 1192.8 Ints9 371.1 488.4 625.8 Ints2 234.5 327.8 481.4 Polr2a 2383.6 3996.2 5567.7 Trim28 1441.8 2329.3 3768.2 Nup133 367.3 527.0 673.5 Gart 771.1 1132.3 1780.0 Xpo5 331.2 426.7 497.9 Ttf2 218.0 291.9 368.2 CEM 1 + Eif3l 1586.9 2276.2 3405.0 Top 10 Genes Cpsf3 943.6 1441.8 2112.6 Ruvbl1 237.1 320.0 460.4 Cpsf1 944.2 1595.3 2736.4 Msh2 284.6 352.9 421.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE43419" 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=GSE43419 Status: Public on Jan 28 2014 Title: Expression data from MYCN transgenic mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24553121 Summary & Design: Summary: TH-MYCN transgenic (Tg) mice are the model for neuroblastoma. One of the sympathetic ganglia is the origin of neuroblastoma in those mice. The tumor incidences of homozygotes and hemizygotes are 100% and 70-80%, respectively.

The involvement of midkine (Mdk), a tumor-related growth factor, was also examined by knockout mice.

Overall design: Ganglia and tumor tissues were dissected from several genotypes of mice (MYCN Tg homozygote and hemizygote, knockout (KO) of Mdk gene). In some of cases, we cultured neurosphere and tumorsphere. The mRNA extracted from those samples were subjected to Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1213, L1-Distance = 0.0444, L2-Distance = 0.0046, Normal std = 0.4161

0.959 Kernel fit Pairwise Correlations Normal fit

Density 0.479

0.000 CEM 1

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

Pre-normalization Quantiles

MYCN homozygousMYCN homozygousMYCN tumor-1 homozygousMYCN tumor-2 (0.0322365)homozygousWT ganglion-1 Mdk_KO-1 (0.0406821)WT ganglion-2 Mdk_KO-2 MYCN(0.060119) (0.0151063) homozygous MYCN(0.0621328) (0.00908424) homozygousMYCN ganglion-1 hemizygousMYCN ganglion-2 hemizygousMYCN (0.0168686) tumor-1 homozygousMYCN (0.0407775) tumor-2 (0.0324094) homozygousWT ganglion-3 tumor-3(0.0199334)WT ganglion-4 tumor-4 (0.0119163) WT(0.100941) neurosphere-1 (0.0311034) WT(0.0924157) neurosphere-2MYCN (0.0545517) hemizygousMYCN (0.0293138) hemizygousMYCN tumor-3 hemizygousMYCN tumor-4 (0.0636399) hemizygous tumorsphere-1 (0.0474705) tumorsphere-2 (0.121579)[ min (0.117719) ] [ medium ] [ max ] CEM 1 Cpsf3l 143.0 1331.5 2389.2 P ( S | Z, I ) = 1.00 Polr2b 7061.6 9495.1 11385.3 Mean Corr = 0.64239 Ints3 40.5 143.1 357.3 Ints7 561.1 1661.7 2422.6 Ints1 96.4 643.5 2008.1 Ints4 318.2 944.8 1975.0 Ints9 272.8 449.5 739.8 Ints2 453.3 1859.8 2421.9 Polr2a 180.5 626.4 1939.2 Trim28 475.5 5631.9 11230.0 Nup133 318.4 1483.8 3347.0 Gart 729.8 2042.2 3310.8 Xpo5 15.6 862.8 1421.3 Ttf2 439.4 1223.5 1932.2 CEM 1 + Eif3l 1314.7 6133.7 11675.2 Top 10 Genes Cpsf3 1243.2 3137.3 5401.7 Ruvbl1 552.7 2305.6 4433.8 Cpsf1 852.8 2747.5 4754.4 Msh2 547.3 2542.8 4584.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE30868" 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=GSE30868 Status: Public on Feb 23 2013 Title: Parthenogenetic stem cells for tissue-engineered heart repair Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23434590 Summary & Design: Summary: Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.

Overall design: - ESC_3

Background corr dist: KL-Divergence = 0.0306, L1-Distance = 0.0233, L2-Distance = 0.0006, Normal std = 0.6786

0.607 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

ParthenogeneticParthenogeneticParthenogenetic stem Embryoidcells stem sample Embryoidcells stem body sample1 Embryonic(PSC_1)cells (EB) body sample2assays Embryonic(PSC_2) (EB)(0.0671979) stem 3assaysof Embryonic(PSC_3) parthenogenetic(0.0742906) cells stem of sample parthenogenetic(0.0354367) cells stem sample1 (ESC_1)cells stem sample2 cells (ESC_2) (0.237476)stem sample [3 cells (ESC_3) min(0.0682071) sample1 (EB_PSC_1) (0.0608337)] 2 (EB_PSC_2) (0.210303)[ medium (0.246255) ] [ max ] CEM 1 Cpsf3l 599.6 1876.1 2269.6 P ( S | Z, I ) = 1.00 Polr2b 6180.7 7797.0 8992.1 Mean Corr = 0.63989 Ints3 153.2 284.7 650.6 Ints7 778.0 1744.7 2322.4 Ints1 313.7 647.1 949.9 Ints4 1095.6 1927.2 2151.2 Ints9 648.0 1593.2 1743.0 Ints2 2750.5 3040.6 3390.6 Polr2a 617.3 1042.1 1580.8 Trim28 3403.0 16324.7 25017.7 Nup133 1809.1 4994.4 5799.9 Gart 1940.8 9161.9 10238.5 Xpo5 731.7 902.8 1227.5 Ttf2 681.2 1729.1 1998.3 CEM 1 + Eif3l 7066.6 11567.6 13642.3 Top 10 Genes Cpsf3 2459.0 3854.3 4857.2 Ruvbl1 1686.6 4117.3 6220.6 Cpsf1 967.7 3016.2 3295.4 Msh2 2984.5 9711.9 11565.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0445717)technical e9.0, rep2,rep1 biologicalPlacenta (0.0544731)technical e9.0, rep3rep2 biologicalPlacenta (0.0716707)(0.0396565) e9.0, rep1rep2 biologicalPlacenta (0.0267999)(0.0491046) e10.5, rep2 Placenta(0.0324275) biological e10.5, rep3 Placenta(0.0450157) biological e10.5, rep1Placenta biological (0.0550219)e12.0, rep2Placenta biological (0.0311456)e12.0, rep3Placenta biological (0.0206811)e12.0, rep1Placenta biological (0.0202857)e13.5, rep2Placenta biological (0.00951324)e13.5, rep3Placenta biological (0.0137159)e15.0, rep1Placenta biological (0.0040661)e15.0, rep2Placenta biological (0.0172148)e15.0, rep1Placenta biological (0.00988138)e17.0, rep2Placenta biological (0.0110903)e17.0, rep3Placenta biological (0.014101)e17.0, rep1Placenta biological (0.0131306)e19.0, rep2Placenta biological (0.0131271)e19.0, rep3Placenta biological (0.0130644)P0, rep1 biologicalDecidua (0.0145212)P0, rep2 biologicalDecidua rep1e8.5,(0.013488) (0.0242591)biologicalDecidua rep2e8.5, (0.0155216)biologicalDecidua e8.5, rep1, biological Deciduatechnical e8.5, rep2, biological Deciduatechnical e9.0, rep1,rep1 biological Decidua(0.0162039)technical e9.0, rep2,rep1 biological Decidua(0.0172024)technical e10.5, rep1rep2 (0.016873)Decidua(0.0363864)biological e10.5, rep2rep2 (0.0175683)Decidua(0.0179476)biological e12.0, rep1 Decidua biological (0.0168952)e12.0, rep2 Decidua biological (0.0192398)e15.0, rep1 Decidua biological (0.0225048)e15.0, rep2 Decidua biological (0.0186645)e17.0, rep1 Decidua biological (0.0212705)e17.0, rep2 Decidua biological (0.0108418)e19.0, rep1 Decidua biological (0.0194462)e19.0, rep2 Decidua biological (0.013778)P0, rep1 biological (0.0135034)P0, rep2 biological rep1(0.0166483) (0.015461) rep2 (0.0120164)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 529.9 831.9 2092.9 P ( S | Z, I ) = 1.00 Polr2b 657.2 1640.7 2914.4 Mean Corr = 0.63922 Ints3 197.0 371.9 756.2 Ints7 368.9 580.1 1275.1 Ints1 702.9 951.6 1379.2 Ints4 304.6 603.0 882.3 Ints9 299.3 415.8 806.3 Ints2 286.7 720.6 1289.9 Polr2a 1451.6 2270.7 3069.4 Trim28 1146.9 2275.1 6311.9 Nup133 198.5 485.9 1692.1 Gart 358.4 640.4 3237.7 Xpo5 375.1 517.5 990.0 Ttf2 329.5 449.4 1166.0 CEM 1 + Eif3l 3405.0 5114.3 9034.0 Top 10 Genes Cpsf3 464.1 689.5 1613.8 Ruvbl1 216.1 454.9 2430.8 Cpsf1 660.3 1197.0 2143.2 Msh2 277.3 480.8 1099.1

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE14308" 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=GSE14308 Status: Public on Jan 08 2009 Title: Epigenetic Mechanisms Underlie T Cell Plasticity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19144320 Summary & Design: Summary: Multipotential naÃ¯ve CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naÃ¯ve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation.

Overall design: Different T helper subsets are profiled for mRNA expression.

Background corr dist: KL-Divergence = 0.0943, L1-Distance = 0.0377, L2-Distance = 0.0025, Normal std = 0.4622

0.876 Kernel fit Pairwise Correlations Normal fit

Density 0.438

0.000 CEM 1

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

Pre-normalization Quantiles

Th2-1 (0.0462591)Th2-2 (0.0458093)Th1-2 (0.0640198)Th17-1 (0.0331387)Th1-1 (0.0581183)Th17-2 (0.0220349)Naive-1Naive-2 (0.0780152)iTreg-1 (0.0967396) iTreg-2(0.211789) nTreg-1(0.202741)nTreg-2 (0.0368235) (0.104511) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 1424.6 1742.9 3077.9 P ( S | Z, I ) = 1.00 Polr2b 2850.8 3537.7 4648.6 Mean Corr = 0.63850 Ints3 171.6 274.5 391.9 Ints7 1276.4 1643.3 2858.3 Ints1 385.4 545.8 1066.1 Ints4 632.5 952.3 2388.5 Ints9 781.2 890.7 993.3 Ints2 500.3 733.1 921.2 Polr2a 375.8 1570.9 4883.0 Trim28 2476.1 3620.5 8901.8 Nup133 529.7 796.9 2634.6 Gart 1128.4 1495.4 4121.6 Xpo5 347.0 665.5 1122.7 Ttf2 421.7 919.4 2426.6 CEM 1 + Eif3l 5138.1 7277.4 10897.1 Top 10 Genes Cpsf3 2222.3 2774.3 2967.3 Ruvbl1 951.6 1337.5 2783.6 Cpsf1 1135.4 2266.9 2777.9 Msh2 1495.2 1861.0 2477.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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(0.0329113) rep dayHoxa9-ER 2 3,on(0.0356158) rep dayHoxa9-ER 3 4,on(0.0132225) rep dayHoxa9-ER 1 4,on(0.0906805) rep dayHoxa9-ER 2 4,on(0.0125281) rep dayHoxa9-ER 3 5,on(0.0241168) rep dayHoxa9-ER 1 5,on(0.154509) rep dayHoxa9-ER 2 5,on(0.140577) rep dayHoxa9-ER 3 0,on(0.233724) rep day 1 0,on(0.0517335) rep day 2 0,(0.118778) rep 3 (0.0916027)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 810.4 934.8 1027.6 P ( S | Z, I ) = 1.00 Polr2b 1571.8 3158.2 3622.0 Mean Corr = 0.63736 Ints3 201.8 309.2 393.0 Ints7 822.9 1560.4 1820.3 Ints1 375.4 738.3 949.3 Ints4 493.7 741.6 922.2 Ints9 586.1 951.8 1038.5 Ints2 592.4 1265.5 1757.6 Polr2a 1215.3 2946.3 3128.0 Trim28 3020.3 4967.0 6665.2 Nup133 434.3 1314.3 1481.1 Gart 1080.0 2735.8 3352.7 Xpo5 692.4 1146.9 1280.2 Ttf2 402.0 886.6 965.9 CEM 1 + Eif3l 3847.1 5364.9 6179.0 Top 10 Genes Cpsf3 1526.1 1878.9 2177.4 Ruvbl1 625.7 1576.1 1900.1 Cpsf1 1497.5 2693.4 2884.3 Msh2 544.7 1154.8 1541.3

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0396263) 3 (Affymetrix)Tg,Calcineurin biological (0.0409475) 4 (Affymetrix)Tg,Calcineurin biological (0.042067) replicate Tg,Differentiating biological (0.0353572) replicate Tg, 1 (Affymetrix)Differentiating biological replicate 2 P19CL6(Affymetrix)Differentiating replicate (0.0517189) 3 P19CL6(Affymetrix)Differentiating cells (0.0532706) 4at P19CL6(Affymetrix)Differentiating cellsday (0.0610499)6 at afterP19CL6Differentiating cellsday DMSO(0.0563537)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 (0.100406)replicate 3 (Affymetrix) treatment, (0.114912)replicate [1 (Affymetrix)medium (0.24127)replicate 2 (Affymetrix) (0.0450239) 3 (Affymetrix) ] (0.0504957) (0.0675017)[ max ] CEM 1 Cpsf3l 546.6 722.6 1312.6 P ( S | Z, I ) = 1.00 Polr2b 1493.0 1798.4 4878.6 Mean Corr = 0.62300 Ints3 119.1 199.5 687.3 Ints7 313.2 401.3 2833.7 Ints1 277.4 413.5 787.2 Ints4 823.2 1026.2 2435.1 Ints9 348.3 440.3 975.5 Ints2 229.6 371.9 1131.1 Polr2a 1006.4 1241.4 1527.5 Trim28 1222.5 1615.9 10880.4 Nup133 368.5 407.4 2212.0 Gart 754.0 1116.6 3612.0 Xpo5 202.4 297.9 1307.3 Ttf2 150.6 202.0 1602.5 CEM 1 + Eif3l 2969.1 3495.7 12328.3 Top 10 Genes Cpsf3 945.5 1164.6 2744.8 Ruvbl1 414.8 527.3 1963.8 Cpsf1 1396.3 1744.3 3160.1 Msh2 371.4 429.7 2848.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE30873" 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=GSE30873 Status: Public on Jul 23 2011 Title: Effects of caspase-8 deletion in the intestinal epithelium Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21921917 Summary & Design: Summary: Caspase-8 is a cystein protease involved in regulating apoptosis. The function of caspase-8 was studied in the intestinal epithelium, using mice with an intestinal epithelial cell specific deletion of caspase-8.

We used microarrays to investigate the difference of the global programme of gene expression in intestinal epithelial cells of control and caspase-8 deficient mice.

Overall design: Intestinal epithelial cells were isolated from 3 control mice and 3 mice with a conditional deletion of caspase-8 in the intestinal epithelium. RNA was isolated and subjected to Affymetrix gene chip analysis.

Background corr dist: KL-Divergence = 0.0388, L1-Distance = 0.0228, L2-Distance = 0.0006, Normal std = 0.6268

0.649 Kernel fit Pairwise Correlations Normal fit

Density 0.325

0.000 CEM 1

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

Pre-normalization Quantiles

floxed control,floxed control, floxedbiological control, caspase-8biological rep1 caspase-8 biological(0.0978919) rep2deficient,caspase-8 (0.366275) rep3deficient, biological (0.0716704) deficient, biological rep1 biological(0.157619) rep2 (0.141844)[ rep3 min (0.164699) ] [ medium ] [ max ] CEM 1 Cpsf3l 633.6 678.6 728.6 P ( S | Z, I ) = 1.00 Polr2b 1571.7 1994.2 2080.6 Mean Corr = 0.60756 Ints3 174.1 254.5 293.4 Ints7 766.7 1043.5 1635.5 Ints1 454.2 524.9 651.1 Ints4 346.2 404.7 486.4 Ints9 419.7 554.2 790.1 Ints2 418.4 522.7 547.8 Polr2a 1002.4 1181.9 1736.5 Trim28 1206.5 1689.5 2700.9 Nup133 361.8 457.0 603.9 Gart 526.6 689.5 952.7 Xpo5 187.6 274.4 383.0 Ttf2 189.5 229.2 251.2 CEM 1 + Eif3l 2453.9 3089.3 3241.2 Top 10 Genes Cpsf3 933.0 1066.2 1270.8 Ruvbl1 489.8 561.6 638.5 Cpsf1 1356.3 1656.1 2496.8 Msh2 435.3 635.9 813.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE40513" 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=GSE40513 Status: Public on Oct 16 2012 Title: Gene expression profile of mouse breast cancer V720 cells treated with vehicle or PD 0332991 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23079655 Summary & Design: Summary: D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains which allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D associated kinase activity in mice bearing ErbB2-driven mammary carcinomas halted cancer progression and triggered tumor-specific senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing T-cell acute lymphoblastic leukemias (T-ALL) triggered tumorspecific apoptosis. Such selective killing of leukemic cells can be also achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Hence, contrary to what one might expect from ablation of a cell cycle protein, acute shutdown of a D-cyclin leads not only to cell cycle arrest, but it also triggers tumor cell senescence or apoptosis, and it affects different tumor types through distinct cellular mechanisms. Inhibiting cyclin D-activity represents a highly-selective anticancer strategy which specifically targets cancer cells without significantly affecting normal tissues.

Overall design: Mouse breast cancer V720 cells were cultured in the presence of the CDK4/6 inhibitor PD 0332991 (PD; 1 microM) or vehicle (VO) for 24 hrs. Experiment was done in biological triplicate. A total of 6 RNA samples (3 vehicle treated and 3 PD 0332991 treated samples) were used for microarray expression analysis.

Background corr dist: KL-Divergence = 0.0313, L1-Distance = 0.0429, L2-Distance = 0.0022, Normal std = 0.7225

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

V720_vehicle_rep1V720_vehicle_rep2V720_vehicle_rep3 (0.266622)V720_PD0332991_rep1 (0.111445)V720_PD0332991_rep2 (0.158437)V720_PD0332991_rep3 (0.146005) (0.137477) (0.180013)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 771.1 851.4 893.0 P ( S | Z, I ) = 1.00 Polr2b 3016.6 3389.2 3472.3 Mean Corr = 0.59862 Ints3 193.1 217.5 232.0 Ints7 1094.9 1568.4 1583.0 Ints1 330.3 362.3 399.3 Ints4 1386.3 1483.7 1521.0 Ints9 449.5 481.2 501.0 Ints2 1329.4 1400.8 1484.6 Polr2a 2124.0 2486.3 2568.8 Trim28 1400.8 1703.2 1743.5 Nup133 687.3 1046.2 1127.8 Gart 1003.9 1113.0 1147.8 Xpo5 346.6 388.4 429.7 Ttf2 920.9 1346.6 1403.3 CEM 1 + Eif3l 5304.3 5383.2 5487.8 Top 10 Genes Cpsf3 1242.0 1270.2 1286.7 Ruvbl1 1058.7 1339.3 1344.8 Cpsf1 1822.7 1974.4 2012.6 Msh2 800.7 1173.4 1178.8

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE31106" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31106 Status: Public on Aug 02 2012 Title: Expression data for the different phases of ulcerative colitis-associated carcinogenesis in a mouse model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22610167 Summary & Design: Summary: Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains inflammation-dysplasia-cancer sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC.

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

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

0.958 Kernel fit Pairwise Correlations Normal fit

Density 0.479

0.000 CEM 1

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

Pre-normalization Quantiles

normal normalcolorectal normalcolorectal mucosa, inflamedcolorectal mucosa, biologicalinflamed colorectal mucosa, biological inflamedrep1 colorectal mucosa biological(0.033827) lowrep colorectal grade 2mucosa at(0.0542148) low rep2wk, dysplasia grade 3mucosa at(0.0414847)biologicallow 2wk, dysplasia grade atatbiologicalhigh 4wk,2wk, rep dysplasia grade 1 atbiologicalbiological (0.129661)high 4wk, rep dysplasia grade 2atbiological (0.0966408)high 4wk, reprep dysplasia grade1 3biological at (0.0350983)(0.10233)high rep6wk, dysplasia grade2 atbiological(0.126196)high rep6wk, dysplasia grade3 atbiological(0.0465903)high 6wk, rep dysplasia grade 1atbiological adenocarcinoma(0.0333681) 8wk, rep dysplasia 2atbiological adenocarcinoma(0.0419634) 8wk, rep 3atbiological adenocarcinoma(0.00892116) 8wk, repat 20wk, 1 biological (0.0408569) repat biological 20wk, 2 (0.121028) repat biological 20wk, 3rep (0.0112581) 1 biological (0.0233332) rep[ min2 (0.0341934) rep 3 ](0.0190345) [ medium ] [ max ] CEM 1 Cpsf3l 381.9 600.7 875.7 P ( S | Z, I ) = 1.00 Polr2b 2418.6 2924.6 3961.6 Mean Corr = 0.59786 Ints3 81.9 123.1 177.7 Ints7 1023.9 1453.5 2264.4 Ints1 225.9 303.9 373.4 Ints4 372.6 619.6 980.2 Ints9 289.1 405.6 469.6 Ints2 285.6 470.1 605.8 Polr2a 1741.9 2268.2 3327.3 Trim28 1687.9 2753.3 4083.2 Nup133 386.3 512.1 710.3 Gart 619.8 838.6 1266.2 Xpo5 284.9 394.1 607.5 Ttf2 155.5 249.1 329.4 CEM 1 + Eif3l 2143.5 3022.7 3702.8 Top 10 Genes Cpsf3 719.9 967.4 1222.0 Ruvbl1 376.2 517.8 787.7 Cpsf1 873.2 1238.9 1492.8 Msh2 290.6 553.6 904.7

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE17266" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 59 -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=GSE17266 Status: Public on Jan 12 2010 Title: Expression data from B6C3F1 mice treated with baclofen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.

Overall design: Mice were sacrificed by cervical dislocation after either a single dose (1day) or 5 daily doses (5 days) of either baclofen or 0.5% methylcellulose two hours after the last dose. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 59 arrays.

Background corr dist: KL-Divergence = 0.0198, L1-Distance = 0.0483, L2-Distance = 0.0033, Normal std = 0.7864

0.507 Kernel fit Pairwise Correlations Normal fit

Density 0.254

0.000 CEM 1

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

Pre-normalization Quantiles

liver-vehicle-1day-repliver-baclofen-1day-repliver-baclofen-1day-rep 1liver-vehicle-1day-rep (0.0227445)liver-baclofen-1day-rep 1 (0.0216475)liver-vehicle-1day-rep 2 (0.02313) 2liver-baclofen-1day-rep (0.0238773)liver-vehicle-5day-rep 3 (0.0231361) 3liver-baclofen-5day-rep (0.0224628)liver-vehicle-5day-rep 4 (0.026073) 1liver-baclofen-5day-rep (0.0225915)liver-vehicle-5day-rep 1 (0.0266808) 2liver-baclofen-5day-rep (0.0143287)liver-vehicle-5day-rep 2 (0.0258479) 3liver-baclofen-5day-rep (0.0207075)liver-baclofen-5day-rep 3 (0.0313912) 4liver-baclofen-5day-rep (0.0224043)liver-baclofen-5day-rep 4 (0.0245792)liver-baclofen-5day-rep 5 (0.025433)bone 6 (0.0241455) marrow-vehicle-1day-repbone 7 (0.021903) marrow-baclofen-1day-repbone 8 (0.0248381) marrow-vehicle-1day-repbone marrow-baclofen-1day-repbone 1 (0.0251412) marrow-vehicle-1day-repbone 1 (0.013399) marrow-baclofen-1day-repbone 2 (0.0187449) marrow-vehicle-1day-repbone 2 (0.00879344) marrow-baclofen-1day-repbone 3 (0.0135955) marrow-vehicle-5day-repbone 3 (0.0121592) marrow-baclofen-5day-repbone 4 (0.0144978) marrow-vehicle-5day-repbone 4 (0.0113148) marrow-baclofen-5day-repbone 1 (0.0215562) marrow-vehicle-5day-repbone 1 (0.0136434) marrow-baclofen-5day-repbone 2 (0.0217122) marrow-vehicle-5day-repbone 2 (0.011258) marrow-baclofen-5day-repbone 3 (0.0156469) marrow-baclofen-5day-repbone 3 (0.0142287) marrow-baclofen-5day-repbone 4 (0.0145207) marrow-baclofen-5day-repbone 4 (0.0103131) marrow-baclofen-5day-repspleen-vehicle-1day-rep 5 (0.0137113)spleen-baclofen-1day-rep 6 (0.0082947)spleen-vehicle-1day-rep 7 (0.0142052)spleen-baclofen-1day-rep 1 8 (0.0118065) (0.0107375)spleen-vehicle-1day-rep 1 (0.0153631)spleen-baclofen-1day-rep 2 (0.0118156)spleen-vehicle-1day-rep 2 (0.0176246)spleen-baclofen-1day-rep 3 (0.0155136)spleen-vehicle-5day-rep 3 (0.0144613)spleen-baclofen-5day-rep 4 (0.0144763)spleen-vehicle-5day-rep 4 (0.0119786)spleen-baclofen-5day-rep 1 (0.0212122)spleen-vehicle-5day-rep 1 (0.0100486)spleen-baclofen-5day-rep 2 (0.0127692)spleen-vehicle-5day-rep 2 (0.0164143)spleen-baclofen-5day-rep 3 (0.011054)spleen-baclofen-5day-rep 3 (0.00812381)spleen-baclofen-5day-rep 4 (0.00925665)spleen-baclofen-5day-rep 4 (0.0128708)spleen-baclofen-5day-rep 5 (0.0102646) 6 (0.0181819) 7 (0.0130228) 8 (0.00834563)[ min ] [ medium ] [ max ] CEM 1 Cpsf3l 627.8 959.2 1286.3 P ( S | Z, I ) = 1.00 Polr2b 2439.3 3337.3 3853.4 Mean Corr = 0.63299 Ints3 99.2 225.5 372.9 Ints7 812.3 2199.9 2901.3 Ints1 297.8 515.2 843.6 Ints4 422.4 573.9 892.5 Ints9 453.2 727.7 1080.8 Ints2 207.2 1059.9 1375.5 Polr2a 624.3 1164.2 2454.9 Trim28 1816.2 3739.5 4286.8 Nup133 349.3 936.9 1551.1 Gart 676.9 1119.5 1379.9 Xpo5 221.7 705.3 850.0 Ttf2 92.5 341.0 660.4 CEM 1 + Eif3l 3139.5 3935.4 5263.1 Top 10 Genes Cpsf3 1217.4 1516.9 2614.0 Ruvbl1 543.6 761.0 1055.3 Cpsf1 1426.2 2067.4 2629.5 Msh2 189.2 689.2 967.2

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.121851) day lung-embryoMouse 14-rep1 (0.132406) day lung-embryoMouse 14-rep2 (0.123599) day lung-embryoMouse 16-rep1 (0.0884075) day lung-embryoMouse 16-rep2 (0.0451522) day lung-postnatalMouse 18-rep1 (0.0445735) day lung-postnatalMouse 18-rep2 (0.0427068) lung-postnatalMouseday (0.033661) 2-rep1 lung-postnatalMouseday (0.0377702)2-rep2 lung-postnatalMouseday (0.0454987)10-rep1 lung-postnatalday 10-rep2 (0.0560783) day 30-rep1 (0.0781199) day 30-rep2 (0.0831826)[ min (0.066993) ] [ medium ] [ max ] CEM 1 Cpsf3l 664.9 912.4 1585.2 P ( S | Z, I ) = 1.00 Polr2b 2527.2 3093.1 5853.3 Mean Corr = 0.58695 Ints3 129.5 203.4 366.0 Ints7 567.2 899.9 2352.3 Ints1 348.9 440.8 643.6 Ints4 522.6 599.8 1077.0 Ints9 523.6 716.9 1048.0 Ints2 553.1 878.5 2470.9 Polr2a 399.1 634.0 1003.4 Trim28 1813.5 2857.3 7563.0 Nup133 390.0 499.4 1387.4 Gart 594.8 763.9 2397.9 Xpo5 580.6 802.2 1620.5 Ttf2 165.6 300.8 767.6 CEM 1 + Eif3l 2595.7 4909.4 8738.8 Top 10 Genes Cpsf3 901.8 1644.8 2092.5 Ruvbl1 575.6 909.4 2606.2 Cpsf1 1374.4 1551.4 2478.3 Msh2 621.9 847.1 2093.0

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE31028" 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=GSE31028 Status: Public on Sep 02 2011 Title: Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21885018 Summary & Design: Summary: Mouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.

Overall design: Quiescent hair follicle stem cells (qHF-SCs), activated hair follicle stem cells (aHF-SCs) and transient-amplifying matrix cells (HF-TACs) were FACS-purified for RNA extraction and hybridization on Affymetrix microarrays. To obtain homogeneous populations of expression profiles, we applied the FACS technique to purify SC and TACs according to their cell surface markers.

Background corr dist: KL-Divergence = 0.0298, L1-Distance = 0.0230, L2-Distance = 0.0006, Normal std = 0.6841

0.594 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

QuiescentQuiescent hair Activatedfollicle hair Activatedstemfollicle hair cells, follicleTransient-amplifyingstem hair rep1 cells, stemfollicleTransient-amplifying (0.163302) rep2 cells, stem (0.165371) rep1 cells, matrix (0.0870992) rep2 cells,matrix (0.0835153) rep1 cells,[ (0.126504)min rep2 (0.374208) ] [ medium ] [ max ] CEM 1 Cpsf3l 1058.2 1484.8 2000.5 P ( S | Z, I ) = 1.00 Polr2b 3156.6 4121.0 5381.7 Mean Corr = 0.58452 Ints3 197.9 315.8 467.5 Ints7 809.8 1368.7 2827.2 Ints1 358.1 508.6 602.9 Ints4 817.1 938.2 1313.3 Ints9 771.7 1033.7 1204.5 Ints2 276.7 404.7 879.4 Polr2a 1210.5 1427.4 2180.9 Trim28 3240.4 4317.7 6564.9 Nup133 653.8 791.5 2074.4 Gart 599.5 1144.9 1935.5 Xpo5 552.8 687.3 965.5 Ttf2 245.4 373.2 800.3 CEM 1 + Eif3l 6661.1 8022.2 10644.4 Top 10 Genes Cpsf3 1473.6 1670.1 2588.7 Ruvbl1 1105.4 1489.9 2657.8 Cpsf1 1227.1 1545.2 2042.6 Msh2 529.4 689.6 1247.7

Null module Ints5 Ints6 Ints12 Ints8 Ints10 GEO Series "GSE29081" 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=GSE29081 Status: Public on Sep 13 2011 Title: Cerebellar gene expression analysis of Gb5-deficient mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21883221 Summary & Design: Summary: Gb5 is a divergent, evolutionarily-conserved, member of the heterotrimeric G protein b subunit family that is expressed principally in brain and neuronal tissue. Among Gb isoforms, Gb5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling (RGS) proteins that contain G protein-g like (GGL) domains. Previous studies employing Gb5 knockout mice have shown that Gb5 is an essential stabilizer of GGL domain-containing RGS proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. The purpose of this study is to better understand the functions of Gb5 in the brain outside the visual system by employing molecular biology, immunohistochemistry and confocal imaging technologies. We show here that mice lacking Gb5 have a markedly abnormal neurologic phenotype that includes neurobehavioral developmental delay, wide-based gait, motor learning and coordination deficiencies, and hyperactivity. Using immunohistochemical analysis and a green fluorescent reporter of Purkinje cell maturation we show that the phenotype of Gb5-deficient mice includes, in part, delayed development of the cerebellar cortex, an abnormality that likely contributes to the neurobehavioral phenotype. Multiple neuronally-expressed genes are dysregulated in cerebellum of Gb5 KO mice.

Overall design: Brain tissues from WT and KO with three biological replications of mice were collected, frozen in liquid nitrogen, and stored at -70 ´C

Background corr dist: KL-Divergence = 0.0327, L1-Distance = 0.0161, L2-Distance = 0.0003, Normal std = 0.6500

0.619 Kernel fit Pairwise Correlations Normal fit

Density 0.309

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

1-WT (0.241736)2-WT (0.127514)3-WT (0.0757845)4-KO (0.120069)5-KO (0.0593625)6-KO (0.375534) [ min ] [ medium ] [ max ] CEM 1 Cpsf3l 297.7 316.9 393.6 P ( S | Z, I ) = 1.00 Polr2b 2422.3 2662.0 3051.3 Mean Corr = 0.57618 Ints3 176.9 206.8 226.7 Ints7 3957.1 4585.8 5452.1 Ints1 379.1 510.9 700.9 Ints4 1044.6 1087.2 1249.7 Ints9 273.8 332.4 416.6 Ints2 193.7 268.1 276.2 Polr2a 1922.6 2087.3 2679.6 Trim28 1717.8 2236.7 2827.1 Nup133 1590.3 1837.5 1941.0 Gart 437.9 529.0 636.6 Xpo5 149.4 175.1 221.0 Ttf2 49.4 63.1 77.8 CEM 1 + Eif3l 1801.7 2249.0 2659.1 Top 10 Genes Cpsf3 1096.6 1289.2 1402.5 Ruvbl1 171.7 221.8 240.7 Cpsf1 887.3 1101.3 1287.4 Msh2 398.3 441.4 514.6

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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(0.0403601)Day Positive 17 Batch (0.0276895)GFPDay Positive 71Batch GFP(0.030364)Day Negative 1 8Batch (0.0345341)GFPDay Positive 18 Batch (0.0393612)GFPDay Negative 51Batch GFP(0.0291894)Day Negative 15 Batch (0.0369318)GFPDay Positive 61 Batch GFP(0.0514475)Day Negative 62Batch GFP(0.0892147)Day Positive 27 Batch (0.103584)GFPDay Negative 72Batch GFP(0.0569433)Day Positive 28 Batch (0.0354419)GFPDay Negative 82Batch GFP(0.0319179)Mouse Positive2 Batch(0.0317402) embryonicMouse 2Batch (0.0232497) embryonic stem2 (0.069979) cell stem derived cell derived cardiomyocytes[ min cardiomyocytes ] 1 (0.117422) 2 (0.15063)[ medium ] [ max ] CEM 1 Cpsf3l 1217.9 2140.6 2819.2 P ( S | Z, I ) = 1.00 Polr2b 6142.9 9975.4 13777.0 Mean Corr = 0.57568 Ints3 152.2 360.1 423.7 Ints7 444.6 1200.6 1560.4 Ints1 571.4 756.1 1038.4 Ints4 660.3 1013.9 1371.9 Ints9 593.2 1103.7 1513.4 Ints2 691.1 1515.6 1852.1 Polr2a 404.6 514.8 743.1 Trim28 4148.7 7356.7 11437.8 Nup133 761.5 3189.8 3707.7 Gart 2311.8 5569.0 7749.7 Xpo5 400.8 748.2 1505.4 Ttf2 517.4 1313.1 2022.5 CEM 1 + Eif3l 7968.9 11376.2 14245.0 Top 10 Genes Cpsf3 2251.1 4964.1 5825.7 Ruvbl1 1304.7 4274.1 6255.1 Cpsf1 3058.9 4262.7 6247.2 Msh2 765.9 4833.3 9169.1

Null module Ints5 Ints6 Ints12 Ints8 Ints10 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 (0.0211575)T1,lean replicate at2 macrophage (0.0646148)T4,lean replicate at3 macrophage (0.0423248)T4,lean replicate at1 macrophage (0.0577685)T4,lean replicate at2 macrophage (0.0876431)T24,obese replicate at3 (0.0396514)T24, macrophageobese replicateat 1 T24, (0.0545152)macrophageobese replicate 2at (0.067585)macrophage T1,obese replicate 3at (0.0701787)macrophage T1,obese replicate at1 macrophage (0.0373748)T1,obese replicate at2 macrophage (0.0282853)T4,obese replicate at3 macrophage (0.0262553)T4,obese replicate at1 macrophage (0.0674551)T4,obese replicate at2 macrophage (0.0646033)T24, replicate at3 (0.0967255)T24, replicateat 1 T24, (0.062928) replicate 2[ (0.0569538) min 3 (0.0539797) ] [ medium ] [ max ] CEM 1 Cpsf3l 577.4 652.6 1344.7 P ( S | Z, I ) = 1.00 Polr2b 1312.2 1729.7 2138.6 Mean Corr = 0.57502 Ints3 56.4 103.6 167.5 Ints7 280.1 573.5 687.4 Ints1 226.5 326.2 378.4 Ints4 426.8 582.0 831.2 Ints9 621.9 805.5 1061.0 Ints2 260.4 378.8 552.3 Polr2a 435.3 872.7 1197.4 Trim28 1244.8 1395.5 2112.9 Nup133 394.3 589.2 771.7 Gart 619.7 870.4 981.6 Xpo5 253.5 317.3 396.9 Ttf2 161.6 276.1 425.3 CEM 1 + Eif3l 3383.9 3910.6 4425.2 Top 10 Genes Cpsf3 995.7 1679.7 2147.4 Ruvbl1 297.8 371.5 524.3 Cpsf1 1418.4 1815.8 2205.0 Msh2 171.3 369.9 470.1

Null module Ints5 Ints6 Ints12 Ints8 Ints10