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: 10 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. Tmem138 Slc22a17 Atp6v0b Atp6ap1 Atp6v0c Slc3a1 Abcb6 Vps4b Mtmr2 Num ofGenesinQueryGeneset:10.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Sbf2

Slc22a17 Atp6v0c Atp6v0b Sbf2 Slc3a1 Mtmr2 Atp6ap1 Abcb6 Tmem138 Vps4b CEM 1(6datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page1 BC022687 Rab11fip3 Tmem138 Ankrd13c Fam188b Slc22a17 Zcchc14 Atp6ap1 Atp6v0b Trappc3 Atp6v0c Rasl11a Slc35b4 Slc17a5 Rundc1 Pgpep1 Mtmr11 Fahd2a Adhfe1 Chmp6 Kcnj16 Tmco3 Tmed4 Slc3a1 Ndfip1 Ctdspl Abcb6 Usp20 Abca3 Vps4b Mtmr2 Timp3 Fahd1 Mark3 Mtch1 Erlin2 Mertk Glis3 Aspa Dab2 Sod3 Pccb Tbx2 Purg Rtn3 Sbf2 Itfg1 Ift80 Bad Npl 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE32529 [224] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE18042 [18] GSE34423 [40] GSE10806 [11] GSE7069 [8] GSE41925 [8] GSE26668 [6] GSE7596 [6] GSE13805 [7] GSE23833 [12] GSE12073 [12] GSE39030 [6] GSE27630 [8] GSE48790 [8] GSE43825 [31] GSE41759 [14] GSE27932 [14] GSE27114 [6] GSE53951 [10] GSE14406 [54] GSE38409 [16] GSE9803 [9] GSE46970 [15] GSE22073 [6] GSE12950 [6] GSE23895 [18] GSE24614 [6] GSE22371 [6] GSE14211 [6] GSE6589 [11] GSE12499 [10] GSE45043 [12] GSE55028 [6] GSE11291 [60] GSE27038 [12] GSE46724 [6] GSE17553 [16] GSE43381 [26] GSE40513 [6] GSE59437 [30] GSE48204 [6] GSE33121 [10] GSE17709 [18] GSE38754 [40] GSE43928 [12] GSE18858 [242] GSE12454 [13] GSE50122 [10] GSE11333 [6] GSE55809 [8] GSE7683 [12] GSE9743 [12] GSE8156 [6] GSE29045 [12] GSE4765 [6] GSE1435 [27] GSE16675 [72] GSE8024 [8] GSE27546 [51] GSE7764 [10] GSE39916 [6] GSE23925 [6] GSE29648 [10] GSE26355 [6] GSE21156 [6] GSE28093 [6] GSE32334 [19] GSE35366 [78] GSE27975 [6] GSE9247 [15] GSE20100 [15] GSE15767 [6] GSE13707 [20] GSE46091 [8] GSE13227 [6] GSE23781 [6] GSE28025 [18] GSE21996 [14] GSE11343 [19] GSE14354 [6] GSE19684 [14] GSE5763 [9] GSE20987 [12] GSE45487 [9] GSE14891 [8] GSE20152 [8] GSE46443 [12] GSE38031 [8] GSE13235 [9] GSE48935 [12] GSE56482 [8] GSE27987 [31] GSE13223 [6] GSE44175 [18] GSE48884 [12] GSE54581 [21] GSE43635 [9] GSE32422 [6] GSE8683 [11] GSE10478 [6] GSE46871 [6] GSE15872 [18] GSE45820 [6] GSE8684 [10] GSE19355 [6] GSE33891 [19] GSE32330 [12] GSE16707 [6] GSE11870 [6] GSE44363 [16] GSE36415 [14] GSE15433 [9] GSE50794 [60] GSE45143 [6] GSE28895 [6] GSE9312 [6] GSE26151 [20] GSE10556 [6] GSE41260 [6] GSE7111 [6] GSE7863 [16] GSE50824 [19] GSE5333 [16] GSE9441 [36] GSE11165 [6] GSE15772 [8] GSE7767 [6] GSE16874 [12] GSE13103 [8] GSE13563 [6] GSE9130 [6] GSE34729 [6] GSE46500 [6] GSE10202 [8] GSE51213 [16] GSE12618 [6] GSE19997 [9] GSE41807 [6] GSE24121 [9] GSE24078 [6] GSE42883 [12] GSE42688 [8] GSE12693 [6] GSE38538 [6] GSE5298 [8] GSE8681 [25] GSE31199 [12] GSE50426 [6] GSE18395 [8] GSE24276 [6] GSE43899 [12] GSE35219 [6] CEM+ CEM GSE23724 [8] GSE12518 [6] GSE8065 [18] GSE37975 [8] GSE19925 [6] GSE42565 [6] 0.0 GSE48338 [8] GSE31099 [24]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 2.93 2.94 2.97 2.98 2.98 2.99 3.00 3.02 3.02 3.02 3.02 3.02 3.02 3.03 3.04 3.05 3.08 3.10 3.11 3.12 3.15 3.26 3.26 3.34 3.36 3.36 3.46 3.48 3.48 3.52 3.52 3.57 3.67 3.69 3.71 3.74 3.79 3.81 3.87 3.93 1.0 Notes 1810043G02Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page2 Tmem229a BC017158 Fam134a Tgfbrap1 Rap1gap Ppapdc2 Ralgapb Atp6ap2 Rapgef3 Fam20b Slc13a3 Slc36a1 Slc37a3 Papss1 Lman2l Tmem9 Pdzd11 Osbpl8 Clptm1 Phlpp2 Rnf215 Lrpap1 Ahcyl1 Cx3cl1 Slc1a4 Armc5 Erlec1 Asna1 Mroh1 Mrps6 Dzip1l Tanc2 Dstyk Rabl5 Trpc1 Stk30 Bicc1 Plvap Lmo4 Pi4ka Myo6 Blvra Gde1 Cml1 Vps8 Tpp1 Arsb Ddr1 Fzd1 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 2.47 2.47 2.49 2.51 2.51 2.52 2.52 2.52 2.53 2.55 2.57 2.57 2.58 2.58 2.59 2.59 2.60 2.62 2.63 2.63 2.64 2.64 2.65 2.65 2.65 2.66 2.68 2.70 2.70 2.70 2.72 2.75 2.76 2.76 2.80 2.81 2.82 2.82 2.82 2.83 2.85 2.85 2.85 2.87 2.87 2.89 2.91 2.92 2.92 2.93 1.0 Notes Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page3 BC034090 Atp6v1b2 Pafah1b1 Dennd1a Ccdc107 Zkscan1 Zc3h12c Atp6v1a Plekhb2 Slc18b1 Slc17a3 Nudt19 Akr1e1 Sptan1 Dcbld1 Cluap1 Ptpdc1 Rnf103 Kcnj10 Sh3tc2 Zbtb41 Zfp704 Ttc30b Olfml3 Glt8d1 Cnbd2 Hook2 Wdr90 Clstn1 Susd2 Ap1s1 Morn2 Bcl2l2 Snx25 Fkbp2 Rogdi Fras1 Synj1 Tmx2 Krt10 Rce1 Pkd2 Ppil6 Pcca Npnt Pigq Ildr2 Mvk Dll1 Evc 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 2.16 2.16 2.18 2.19 2.19 2.20 2.20 2.20 2.20 2.21 2.22 2.22 2.22 2.22 2.23 2.24 2.24 2.24 2.24 2.27 2.28 2.29 2.29 2.29 2.30 2.30 2.30 2.31 2.31 2.31 2.33 2.38 2.38 2.39 2.40 2.40 2.41 2.42 2.43 2.43 2.43 2.43 2.44 2.44 2.44 2.45 2.45 2.45 2.45 2.47 1.0 Notes 3110057O12Rik 2300009A05Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page4 Tmem115 Tmem14a Atp6v0d1 Fam211b Fam195b Kbtbd11 Slc22a6 Slc33a1 Slc30a9 Neurl1b Fbxw17 Galnt18 Ddrgk1 Rhbdf1 Gpm6a Tardbp Smpd1 Aamdc Zfp672 Slc9a6 Slc1a1 Abhd3 Enpp5 Cspg4 Plscr2 Nceh1 Rab34 Acox1 Igfbp7 Snx13 Fads3 Jmjd8 Rnf14 Lgmn Pcyt2 Fbln7 Taf9b Vwa1 Ip6k2 Lzts3 Bbs1 Palm Itgb8 Wasl Rtkn Fgf1 Gls Ivd 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.94 1.96 1.96 1.96 1.97 1.98 1.98 1.98 1.98 1.98 1.99 2.00 2.00 2.01 2.01 2.02 2.02 2.02 2.03 2.03 2.03 2.03 2.04 2.04 2.05 2.05 2.05 2.05 2.05 2.06 2.06 2.06 2.07 2.08 2.09 2.10 2.10 2.10 2.11 2.11 2.13 2.14 2.14 2.14 2.14 2.14 2.14 2.15 2.15 2.16 1.0 Notes 2310067B10Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page5 Ppp1r16a Atp6v1c1 Txndc15 Tmem64 Ankrd29 Hmg20a Cables1 Vipas39 Cttnbp2 Phyhipl Fbxo10 Cnnm2 Sdhaf1 Atp1a1 Cldn16 Fgfbp3 Vamp4 Vamp2 Sgsm2 Emc10 Jkamp Rbbp6 Mccc1 Ap2b1 Spsb4 Ube2a Kank4 Igfbp3 Ndrg3 Car12 Dctn3 Sugct Mpzl1 Parva Nicn1 Tfcp2 Tctn3 Wsb2 Nprl2 Gatm Cdipt Arl8a Hint2 Bdh2 Cml5 Cys1 Pdk2 Eea1 Prnp 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.77 1.77 1.78 1.78 1.78 1.78 1.78 1.78 1.79 1.79 1.79 1.80 1.80 1.80 1.81 1.81 1.81 1.82 1.82 1.83 1.83 1.84 1.85 1.85 1.85 1.86 1.86 1.86 1.87 1.88 1.88 1.89 1.89 1.89 1.89 1.90 1.90 1.90 1.90 1.92 1.92 1.92 1.93 1.93 1.93 1.93 1.93 1.93 1.94 1.94 1.0 Notes D430042O09Rik 2610034B18Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page6 Tmem175 Ralgapa1 Slc25a11 Fam173a Commd3 Nudt16l1 L3hypdh Ccdc104 Ccdc173 Tbc1d19 Stard3nl Ppp1r1b Mettl7a2 Scamp5 Slc37a4 Slc22a2 Slc26a4 Fam65a Lmbrd1 Fbxo28 Mpv17l Apmap Cadm4 Slc7a8 Cgref1 Neurl4 Nphp1 Celsr2 Rgag4 Klhl17 Asb13 Snx14 Lmtk2 Mgat5 Atraid Mef2a Chpt1 Prosc Bcl7a Cryl1 Cbx6 Sytl2 Acy3 Inadl Dlg5 Dlst Wls Abr 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.58 1.59 1.60 1.61 1.61 1.62 1.62 1.63 1.64 1.64 1.64 1.65 1.65 1.65 1.65 1.66 1.66 1.67 1.67 1.67 1.67 1.67 1.68 1.68 1.68 1.68 1.69 1.69 1.69 1.69 1.70 1.70 1.71 1.71 1.71 1.71 1.71 1.72 1.72 1.72 1.73 1.73 1.73 1.74 1.74 1.74 1.74 1.75 1.76 1.77 1.0 Notes 0610011F06Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page7 Tmem252 Fam101a Fam149a Ankdd1b Map3k10 Smarca2 Dync2h1 Tmem65 Sema3b Slc5a12 Nudcd3 Ccdc25 Scube3 Pnmal2 Thsd7a Minpp1 Srgap3 Prkag2 Kctd17 Slc4a4 Stard8 Myo9a Lrrc45 Pomt2 Reps2 Mtmr6 Syde1 Vps29 Gnptg Pdzk1 Bpnt1 Oxct1 Gnai1 Kctd6 Ncald Trpv4 Fmo1 Arnt2 Pth1r Comt Rhob Agrn Smo Pigg Scai Ier5l Irgq Dak Htt 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.46 1.46 1.46 1.47 1.47 1.47 1.47 1.47 1.48 1.48 1.49 1.49 1.49 1.49 1.49 1.49 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.51 1.51 1.51 1.51 1.51 1.52 1.52 1.53 1.53 1.54 1.54 1.54 1.55 1.55 1.55 1.55 1.55 1.55 1.56 1.57 1.57 1.57 1.57 1.58 1.58 1.58 1.58 1.0 Notes Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page8 Gabarapl1 BC023829 Tmem135 Laptm4b Irak1bp1 S100a16 Osbpl10 Atp6v1h Efcab12 Dnajc12 Slc47a1 Afap1l2 Cmtm4 Ndufc1 Ptpn23 Smim8 Zfp810 Tm2d2 Dhdds Ubxn4 Cpeb2 Hsbp1 Ap3d1 Ap1b1 Npdc1 Pebp1 Cryzl1 Frem2 Degs2 Pcbp3 Vdac1 Exoc7 Igsf11 Otub1 Crocc Gstz1 Nme5 Dclk3 Hnmt Gpc4 Glis2 Scoc Gbf1 Xpr1 Ntn4 Alad Nxt2 Ctsf Bok Sri 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.32 1.32 1.33 1.33 1.33 1.33 1.34 1.34 1.34 1.34 1.34 1.34 1.35 1.36 1.36 1.36 1.36 1.37 1.37 1.37 1.38 1.38 1.38 1.38 1.38 1.38 1.38 1.39 1.39 1.39 1.40 1.40 1.40 1.40 1.41 1.41 1.41 1.41 1.42 1.42 1.42 1.43 1.43 1.43 1.44 1.44 1.44 1.45 1.45 1.46 1.0 Notes 4933427D14Rik 8430419L09Rik 1700029J07Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page9 Fam171a1 Secisbp2l Tmem117 Tmem136 Atxn7l3b Ccdc160 Ankrd12 Atp6v1d Aldh5a1 Pip4k2c March6 Gpr124 Adra2b Nudt18 Ptpn13 Cldn12 Ptges2 Plxnb1 Trim37 Lamb2 Lmcd1 Wdr34 Cd200 Wdfy3 Vps4a Mcfd2 Atrnl1 Carkd Bmp7 Tprkb Stx12 Emx1 Gpx6 Opa3 Cdh6 Gas6 Acy1 Pkp4 Dgkz Mfn1 Itpr1 Fkrp Sbf1 Gzf1 Stx6 Fat1 Ak3 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.19 1.19 1.19 1.20 1.21 1.21 1.21 1.21 1.21 1.21 1.21 1.21 1.21 1.21 1.22 1.22 1.22 1.22 1.23 1.23 1.23 1.24 1.24 1.24 1.25 1.25 1.25 1.26 1.26 1.26 1.26 1.26 1.27 1.27 1.27 1.28 1.29 1.29 1.29 1.30 1.30 1.31 1.31 1.31 1.31 1.32 1.32 1.32 1.32 1.32 1.0 Notes 2310030G06Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page10 Tmem151b AW549877 Tmem178 AI429214 Slc25a16 Adamts5 Ppp1r37 Sema3g Arhgef2 Slc16a4 Galnt14 Dnmt3a Dusp14 Nckap5 Tspan5 Gpr155 Col4a5 Gkap1 Abcb8 Enpp2 Rab6b Reep5 Vstm4 Pde8b Mtmr4 Igfbp2 Slain1 Nrbp2 Prr15l Mink1 Hnf1b Srpx2 Srek1 Zbtb4 Gcdh Sfrp1 Dmtn Tyw3 Cog7 Chd3 Sdhc Egfl6 Kifc3 Scd2 Sdc2 Grlf1 Cbr1 Sirt3 Tle2 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 1.09 1.09 1.09 1.10 1.10 1.10 1.11 1.11 1.11 1.11 1.11 1.12 1.12 1.12 1.13 1.13 1.13 1.13 1.13 1.13 1.13 1.14 1.14 1.14 1.15 1.15 1.15 1.15 1.15 1.16 1.16 1.16 1.16 1.16 1.16 1.16 1.17 1.17 1.17 1.17 1.17 1.17 1.18 1.18 1.18 1.18 1.18 1.18 1.19 1.19 1.0 Notes 2610008E11Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page11 Atp6v0a1 Slc25a14 Fam184a Serpinh1 Aldh6a1 Klhdc7a Ankmy2 Plekhg5 Dnajc18 Cd164l2 Slc39a8 Slc38a3 Rhbdd2 Cachd1 Pcyox1 Tspan4 Fbxo18 Gpr137 Manbal Agpat3 Katnb1 Sestd1 Spink8 Sepw1 Gstm5 Nphs2 Cdh16 Kcng1 Dmxl2 Syvn1 Josd2 Arfip2 Mien1 Appl2 Ptpn9 Rabl6 Eme2 Fbln5 Ift122 Napg Aco1 Bbs2 B9d1 Snx1 Mid2 Abat Adm Pfkp Fjx1 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.99 0.99 0.99 0.99 1.00 1.00 1.00 1.00 1.00 1.01 1.01 1.01 1.01 1.01 1.02 1.02 1.02 1.02 1.02 1.02 1.02 1.03 1.03 1.03 1.04 1.04 1.04 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.06 1.06 1.06 1.06 1.07 1.07 1.07 1.07 1.07 1.07 1.08 1.08 1.08 1.08 1.09 1.09 1.0 Notes E130309F12Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page12 Tmem127 Arhgap24 Slc6a20b Slc39a13 B3galnt1 Tspan31 Trabd2b Slc6a17 Slc22a8 Slc15a2 Myo18a Cyb561 Vps13a Minos1 Angpt2 Akr7a5 Rnf186 Acot13 Steap2 Pgam1 Zfand1 Slc9a2 Lamc3 Lama1 Fbxw5 Pomt1 Klhl42 Acad8 Cxxc5 Mxra8 Oxgr1 Strip1 Car15 C1ql3 Nipa1 Scyl1 Map7 Men1 Coq9 Sun1 Cds1 Ace2 Gtf2i Guf1 Pura Amn Atn1 Fpgt Fut9 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.89 0.89 0.89 0.89 0.90 0.90 0.90 0.90 0.90 0.90 0.90 0.91 0.92 0.92 0.92 0.92 0.93 0.93 0.93 0.93 0.93 0.93 0.93 0.93 0.93 0.94 0.94 0.94 0.94 0.94 0.94 0.94 0.94 0.94 0.95 0.96 0.96 0.96 0.96 0.96 0.97 0.97 0.97 0.97 0.97 0.98 0.98 0.98 0.98 0.98 1.0 Notes Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page13 Camsap3 Camsap2 AI317395 Fam210a Sdccag3 Tspan15 Slc39a5 Efemp2 Nckap1 Cc2d1a Fkbp1b Fbxo25 Mgat4b Gprc5c Mfsd7c Osbpl3 Ndufv1 Ndufs8 Rab3ip Sppl2b Ube2j1 Col9a3 Slc5a6 Enpp6 Eif4g3 Kcnk1 C2cd5 Mgrn1 Fbxo3 Lclat1 Mfsd4 Myef2 Dgcr2 Cers5 Dctn5 Aifm3 Trim3 Lpar3 Zfp61 Pias2 Mpc1 Rhcg Kif3b Fgfr3 Canx Clip4 Itga3 Fzd8 Sars Kat5 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.80 0.80 0.81 0.81 0.81 0.81 0.81 0.82 0.82 0.82 0.82 0.82 0.82 0.83 0.83 0.83 0.83 0.83 0.83 0.83 0.83 0.83 0.83 0.84 0.84 0.84 0.84 0.84 0.85 0.85 0.85 0.85 0.85 0.85 0.85 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.87 0.87 0.87 0.88 0.89 0.89 0.89 1.0 Notes 0610007P14Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page14 Tmem132a Cdc42bpb Fam195a Fam217a Hsd11b2 Trappc2l Ccdc176 Adam15 Pip5k1c Bahcc1 Slc35f1 Dtnbp1 Ankib1 Ramp3 Ahcyl2 Samd8 Zfp579 Zfp426 Slc7a9 Scarf2 Hdac8 Ap2s1 Ap2a2 Akap9 Tpcn1 Megf8 Ggact Aldob Nsdhl Atg9a Cyth2 Efhd1 Sin3b Ssfa2 Stk25 Tldc1 Nr2f6 Gpc1 Dgkh Chn2 Dkk2 Selm Ybx2 Pex5 Rgl1 Tecr Sqle Ckb Ddt 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.71 0.71 0.72 0.72 0.72 0.72 0.72 0.73 0.73 0.73 0.73 0.73 0.74 0.74 0.74 0.74 0.74 0.75 0.75 0.75 0.75 0.75 0.75 0.76 0.76 0.76 0.76 0.76 0.77 0.77 0.77 0.77 0.77 0.77 0.77 0.77 0.78 0.78 0.78 0.78 0.79 0.79 0.79 0.79 0.80 0.80 0.80 0.80 0.80 0.80 1.0 Notes D10Bwg1379e Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page15 Tmem176b Gm13889 Camk2n1 Arhgef28 Slc22a19 Fam109a Ccdc157 Tmem9b Tmem70 Rmnd5b Sostdc1 Samd10 Plekha3 Slc39a3 Uqcrfs1 Map2k5 Anapc7 Acad11 March9 Tex264 Spryd3 Higd2a Rnf208 Trim47 Zbtb20 Thnsl2 Zfp358 Tceal8 Oplah Wwc2 Ugt8a Chst8 Egln1 Emc7 Zfp40 Arel1 Aqp2 Elfn1 Mib2 Car4 Rnf6 Xylb E2f5 Pter Dlat Vil1 Flt1 Fah Tst 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.63 0.63 0.63 0.63 0.64 0.64 0.64 0.64 0.65 0.65 0.65 0.65 0.65 0.65 0.66 0.66 0.66 0.66 0.66 0.66 0.67 0.67 0.67 0.67 0.68 0.68 0.68 0.68 0.68 0.68 0.68 0.69 0.69 0.69 0.69 0.69 0.69 0.70 0.70 0.70 0.70 0.70 0.70 0.71 0.71 0.71 0.71 0.71 0.71 0.71 1.0 Notes 1700066M21Rik 1700040L02Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page16 Tmem150a Tmem218 Tmem147 Tmem30a Tmem246 Slc25a40 Slc22a23 Tmem35 Prkcdbp Sdr39u1 Col16a1 Slc7a12 Map2k1 Cadps2 Clcn4-2 Sec22b Vps33a Gpr125 Lyplal1 Dhrs13 Osbpl5 Nudt12 Kdm4c Slc4a3 Cpeb4 Ckmt1 Enkd1 Mmab Erbb2 Rragc Deaf1 Plod2 Stk19 Ift172 Gnaq Ghdc Dag1 Pnkd Clybl Usp2 Eogt Ppt2 Mtor Klc1 Ext1 Boc Ak4 Ttl 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.56 0.56 0.56 0.56 0.56 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.57 0.58 0.58 0.58 0.58 0.59 0.59 0.59 0.59 0.59 0.59 0.59 0.59 0.59 0.60 0.60 0.60 0.60 0.60 0.60 0.60 0.61 0.61 0.61 0.61 0.61 0.61 0.61 0.61 0.62 0.62 0.62 0.62 0.62 0.63 0.63 1.0 Notes Mettl7a2Higd1c 2310022B05Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page17 Gramd1b Abhd14b Dync1h1 Ugt2b38 Plekha1 Plekha7 Slc35d1 Slc13a4 Slc16a2 C78339 Zmym3 Tysnd1 Morc2a Tfcp2l1 Rnf217 B3gat3 Plxdc2 Zfp523 Myo5b Iqsec2 Dalrd3 Mpv17 Amacr Enpep Rsph9 Usp11 Reep2 Hdac6 Usp40 Frem1 Uqcc1 Akap2 Wwtr1 Cgrrf1 Gipc1 Nhsl1 Syt17 Crip2 Trpt1 Rgcc Hykk Tcn2 Ptprf Rfng Nenf Dtx3 Gns Hgd 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.49 0.49 0.49 0.49 0.49 0.49 0.49 0.49 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.51 0.51 0.51 0.51 0.51 0.51 0.51 0.51 0.52 0.52 0.52 0.52 0.52 0.52 0.52 0.52 0.53 0.53 0.54 0.54 0.54 0.54 0.54 0.55 0.55 0.55 0.55 0.55 0.56 0.56 0.56 0.56 1.0 Notes 3632451O06Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page18 Commd10 Adamts15 C1galt1c1 Tmem174 Tmem107 Fam102b Cyp27b1 Pcdhgc4 Khdrbs3 Ranbp3l Dpy19l4 Slc12a1 Galnt11 Clptm1l Capn10 B3galt5 Leprel1 Gpr180 Akr1a1 Rnf152 Pmp22 Rbbp9 Wdr78 Cyfip2 Hoxd4 Pgap3 Snx17 Pdzd3 Zmat3 Matn2 Gulp1 Strip2 Stub1 Clcn2 Acpl2 Trak1 Mrpl4 Tctn2 Chdh Klhl7 Rac3 Cav2 Sall2 Alg1 Cryz Flnb Prr3 Cpe Tef 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.41 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.42 0.43 0.43 0.43 0.43 0.44 0.44 0.44 0.44 0.44 0.44 0.44 0.45 0.45 0.46 0.46 0.46 0.46 0.46 0.47 0.47 0.47 0.47 0.47 0.47 0.47 0.47 0.47 0.48 0.48 0.48 0.48 0.48 0.48 0.49 0.49 0.49 0.49 1.0 Notes 2010315B03Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page19 Ppargc1a Zmynd10 Slc25a12 Fam207a Abhd14a Slc9a3r2 Ankrd50 Flywch1 Slc17a1 C1qtnf2 Armcx1 Ndufs7 Ptpmt1 Hspa4l Sh3gl2 Tm2d3 Fbxw8 Mus81 Abcg2 Acyp1 Rcan3 Rab36 Sycp3 Atg10 Aadat Atg4c Sept8 Ndel1 Acat1 Farp1 Metrn Vwa8 Aqp4 Bag2 Ehd3 Eml2 Pkd1 Pbx4 Ppa2 Mtx3 Galc Pfn2 Nat8 Dvl1 Pclo Fbf1 Tln2 Cck Src 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.34 0.34 0.35 0.35 0.35 0.35 0.35 0.35 0.36 0.36 0.36 0.36 0.36 0.36 0.36 0.36 0.36 0.37 0.37 0.37 0.37 0.37 0.37 0.37 0.37 0.38 0.38 0.38 0.39 0.39 0.39 0.39 0.39 0.39 0.39 0.39 0.39 0.39 0.39 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.41 0.41 0.41 1.0 Notes 3830406C13Rik 1700011H14Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page20 Rab11fip4 Tmem129 Map1lc3a Epb4.1l1 Tbc1d25 Nckipsd Dnajc16 Plekha6 Slc38a6 Zfyve16 Man2c1 Mesdc2 Sacm1l March8 Coro2b Gpr126 Uqcr10 Rnf128 Pou6f1 Ubiad1 Prss12 Hpcal1 Zfp772 Slc7a4 Med28 Soga2 Msto1 Cdip1 Prkca Acsf3 Spef1 Bcam Trpv6 Clock Htra3 Suox Eif1b Ldhb Nrep Sirt2 Lgr4 Cyld Sdsl Pls3 Ift88 Ilvbl St7l Nf2 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.27 0.27 0.27 0.27 0.27 0.28 0.28 0.28 0.28 0.28 0.29 0.29 0.29 0.29 0.29 0.29 0.29 0.29 0.30 0.30 0.30 0.30 0.30 0.30 0.30 0.30 0.31 0.31 0.31 0.31 0.31 0.31 0.31 0.31 0.31 0.32 0.32 0.32 0.32 0.32 0.32 0.33 0.33 0.33 0.33 0.33 0.33 0.34 0.34 0.34 1.0 Notes 1810010H24Rik 1110001J03Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page21 Tmem206 Fam117b Ivns1abp Slc22a22 Slc25a23 Map3k12 Dync2li1 Tspan12 Tmem68 Ankrd46 Hmgcs1 Col12a1 Dnajc30 Rwdd4a Slc19a1 Slc46a1 Slc31a1 Cyp1b1 Kcnab3 Cacng4 Zdhhc1 Ogfod3 Pea15a Gyltl1b Akt1s1 Stk32b Kdelc2 Cndp1 Renbp Agap1 Retsat Ddah2 Vps11 Cckar Vegfb Sfxn5 Nrarp Gphn Strn4 Nox4 Hexb Ldhd Snx7 Pak4 Tns1 Glo1 Hk1 Nsf 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.20 0.20 0.21 0.21 0.21 0.21 0.21 0.21 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.23 0.23 0.23 0.23 0.23 0.23 0.23 0.23 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.24 0.25 0.25 0.25 0.26 0.26 0.26 0.26 0.26 0.26 0.27 0.27 0.27 0.27 0.27 1.0 Notes 2700081O15Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page22 Tmem119 Pomgnt1 Cyp24a1 Ccdc181 Ugt2b37 Pmepa1 Slc27a1 Slc12a4 Map4k3 Ankhd1 Cacnb2 Necap1 Ccdc39 Crebbp Ctnnd1 Ramp1 B3gat2 Wdpcp Pih1d2 Plcxd1 Zfp580 Slc2a1 Fbxl16 Mocs2 Myo19 Crebzf Qsox2 Vstm5 Rcan1 Casc4 Gpr89 Tesk1 Srp68 Ptov1 Bcl7b Etnk1 Vegfa Ptpru Ptpro Prepl Aco2 Vasn Ldb2 Cbr4 Ttc8 Mgp Os9 Shd Id3 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.13 0.14 0.14 0.14 0.14 0.14 0.15 0.15 0.15 0.15 0.15 0.15 0.16 0.16 0.16 0.16 0.16 0.16 0.16 0.16 0.16 0.16 0.17 0.17 0.17 0.17 0.17 0.17 0.17 0.17 0.18 0.18 0.18 0.18 0.18 0.18 0.18 0.18 0.19 0.19 0.19 0.19 0.19 0.19 0.20 0.20 0.20 0.20 0.20 0.20 1.0 Notes 2610301B20Rik D630045J12Rik 1700088E04Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page23 Fam171a2 Rap1gap2 Cdc42ep1 Tmem50b Fam181b Tmem18 Ppp2r5b Chmp2b Ppp1r26 Arhgdig Mospd2 Slc16a7 Slc34a3 Man1b1 Ndufaf3 Rgs7bp Rb1cc1 Zc3h14 Agpat4 Stxbp1 Prss23 Trim35 Slc9a1 Greb1l Mapk4 Spire1 Acbd5 Plscr4 Pdha1 Mgst3 Dhrs1 Rhot2 Cetn4 Aamp Prkcz Ttc17 Map2 Dpcd Nbea Faah Gjb2 Elp4 Prr5 Syp Pcx Irx1 Nf1 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.07 0.07 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.09 0.09 0.09 0.09 0.09 0.09 0.09 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.11 0.11 0.11 0.11 0.11 0.11 0.12 0.12 0.12 0.12 0.12 0.12 0.12 0.12 0.13 0.13 0.13 0.13 0.13 0.13 0.13 0.13 1.0 Notes Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page24 Tmem126b Tmem106c Kidins220 Fam229b Fam216a Sepsecs Osbpl1a R3hdm2 Pitpnm2 Sowaha Fam73a Pgrmc1 Pgrmc2 Necap2 Brms1l Chmp3 Ampd2 Zbtb45 Lactb2 Fam3a Wdr13 Pik3r2 Cdk18 Kank1 Pkhd1 Coasy Cyp51 Vps18 Msrb2 Gpr85 Fscn1 Oxld1 Prkd1 Brcc3 Grina Mdh2 Jam3 Chd6 Lrfn3 Bdh1 Dad1 Uap1 Speg Tchh Nebl Pigp Nat6 Selo Maf Id4 0.0 1.0

GSE4230 [8] GSE31561 [36]

GSE41095 [6] Scale ofaveragePearsoncorrelations GSE11443 [6] GSE14059 [6] GSE46090 [12] GSE6030 [6] GSE55356 [6] GSE22506 [12] 0.2 GSE8726 [7] GSE42018 [8] GSE54490 [12] GSE36384 [12] GSE36618 [6] GSE14499 [26] GSE40260 [6] GSE36814 [20] GSE14585 [9] 0.4 GSE24451 [6] GSE22124 [18] GSE47959 [8] GSE3501 [6] GSE46854 [20] GSE16073 [6] GSE13807 [10] GSE21861 [8] GSE13402 [7] 0.6 GSE22448 [6] GSE10989 [6] GSE49346 [6] GSE7810 [9] GSE44260 [10] GSE30746 [16] GSE12993 [6] GSE2527 [6] GSE35299 [8] 0.8 GSE13874 [14] GSE49050 [72] GSE24625 [12] GSE54653 [6] Score 0.01 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.06 0.06 0.06 0.06 0.06 0.06 0.07 0.07 1.0 Notes 2210016L21Rik Symbol Num ofCEMGenes:10.Predicted1206.SelectedDatasets:6.Strength:0.0 CEM 1,Geneset"[G]vacuolarmembrane",Page25 Tmem55b Plekhh1 Sult1d1 Slc35f3 Cabin1 Zfp768 Them4 Spsb3 Hdac3 Dleu7 Heph Ahi1 Stx3 Evi5 Mut 0.0 1.0

GSE4230 [8] GSE31561 [36]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4230 Status: Public on Feb 13 2006 Title: Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16464245 Summary & Design: Summary: BACKGROUND: Lim1 is a homeobox gene that is essential for nephrogenesis. During metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle stage, leading to the production of small, non-functional kidneys that lack nephrons.

METHODS: In the present study, we used Affymetrix probe arrays to screen for nephron-specific genes by comparing the expression profiles of control and Lim1 conditional mutant kidneys. Kidneys from two developmental stages, embryonic day 14.5 (E14.5) and 18.5 (E18.5), were examined.

RESULTS: Comparison of E18.5 kidney expression profiles generated a list of 465 nephron-specific gene candidates that showed a more than 2-fold increase in their expression level in control kidney versus the Lim1 conditional mutant kidney. Computational analysis confirmed that this screen enriched for kidney-specific genes. Furthermore, at least twenty-eight of the top fifty (56%) candidates (or their vertebrate orthologs) were previously reported to have a nephron-specific expression pattern. Our analysis of E14.5 expression data yielded 41 candidate genes that are up-regulated in the control kidneys compared to the conditional mutants. Three of them are related to the Notch signaling pathway that is known to be important in cell fate determination and nephron patterning.

CONCLUSIONS: Therefore, we demonstrate that Lim1 conditional mutant kidneys serve as a novel tissue source for comprehensive expression studies and provide a means to identify nephron-specific genes.

Keywords: tissue specificity, time course, development, kidney, metanephric mesenchyme, nephron, Lim1, knockout mice, conditional knockout

Overall design: Normalized data were exported in a tab delimited text format. Fold changes of each transcript from different samples were calculated and sorted using Microsoft Excel 5.0 software. Signal obtained from control kidney samples were used as an experiment to compare to the signal obtained from Lim1 conditional mutant kidneys that was designated as a baseline. A 2-fold change in the means of signal obtained from experimental duplicates and those from baseline duplicates was used as the criterion to identify differentially expressed transcripts. To ensure the quality of the data, probe sets that showed a fold change between duplicates greater than between the experimental mean and baseline mean were removed. To study only genes that showed consistent expression on experimental chips, probe sets that did not show consistent present calls in the experimental duplicates were removed. To focus on genes with a significant fold change between the experiment and the baseline, only probe sets that the product of their experimental mean and fold change were more than 100 were retained. To produce a compact differentially expressed gene list, the probe set list was sorted within Microsoft Excel based on Locus Link number and redundant entries were removed. Our experimental design description and the data format provided in the Additional files fulfill the MIAME (minimum information about a microarray experiment) standards.

Background corr dist: KL-Divergence = 0.0369, L1-Distance = 0.0151, L2-Distance = 0.0003, Normal std = 0.6203

0.643 Kernel fit Pairwise Correlations Normal fit

Density 0.322

0.000 CEM 1

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

Pre-normalization Quantiles

E14.5_Control_Kidney_array1E14.5_Control_Kidney_array2E14.5_Mutant_Kidney_array1E14.5_Mutant_Kidney_array2E18.5_Control_Kidney_array1 (0.0731443)E18.5_Control_Kidney_array2 (0.111067) E18.5_Mutant_Kidney_array1(0.109844) E18.5_Mutant_Kidney_array2(0.0596178) (0.185539) (0.190142) (0.147468) (0.123177)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 1028.2 1125.8 1392.0 P ( S | Z, I ) = 1.00 Atp6v0c 2867.2 4700.2 6508.0 Mean Corr = 0.60132Atp6v0b 988.3 1533.8 2322.7 Sbf2 650.9 736.2 802.9 Slc3a1 138.9 191.3 2439.5 Mtmr2 404.9 489.9 707.1 Atp6ap1 1038.7 1597.7 1940.6 Abcb6 225.0 264.5 403.3 Tmem138 438.3 505.9 623.7 Vps4b 165.2 195.3 261.0 Trappc3 1025.0 1132.3 1250.9 BC022687 153.9 218.3 308.4 Ankrd13c 609.7 764.6 1372.1 Mtmr11 208.6 344.6 574.0 Fahd1 265.4 302.7 504.4 CEM 1 + Pccb 429.9 470.9 683.2 Top 10 Genes Bad 619.8 877.0 925.4 Npl 234.3 309.6 733.4 Abca3 207.2 353.1 753.2 Rtn3 1632.6 2028.8 2928.2

Null module GEO Series "GSE31561" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31561 Status: Public on Feb 19 2013 Title: Transcriptional analysis of organ-specific toxicity induced by a panPPAR agonist in mice: Identification of organ-specific toxicity biomarkers Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23272042 Summary & Design: Summary: In this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified.

Overall design: Nine wild type mice (strain: C57BL/6J) were randomly divided into three groups - Group-I, II and III. PPM-201 in the vehicle base was administered daily for 14 days at 6 mg/kg body weight dose rate to each mouse in Group-II and at 20mg/kg body weight dose rate to each mouse in Group-III while the mice in Group-I received only the vehicle base. On 15th day, the mice were sacrificed to harvest blood, heart, skeletal muscle, liver and kidney tissues for clinical chemistry, microarray and histopathology analysis. In the clinical chemistry analysis, alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), creatinine kinase (CK, U/L), blood urea nitrogen (BUN, mmol/L), creatinine (umol/L) and lactate dehydrogenase (LDH, U/L) were measured from the blood of each mouse. Two sections of liver, two sections of kidney, one or two sections of skeletal muscle, and one section of heart were prepared from each mouse, stained with hematoxylin and eosin (H&E), and examined by a veterinary pathologist. RNA was extracted and processed as per the established protocol from heart, skeletal muscle, liver and kidney tissue samples of all the 9 mice for profiling with Affymetrix Mouse Genome 430 2.0 Array and in total 36 chips were prepared. Using various quality control measures, the data was analysed for its quality. As it was found to be good in quality, the data from all the 36 chips were used for further analysis. The results from histopathology and clinical chemistry analysis were compared with the gene expression to determine if the dosages selected for the study were associated with findings in target organs.

Background corr dist: KL-Divergence = 0.0965, L1-Distance = 0.0540, L2-Distance = 0.0060, Normal std = 0.4768

0.888 Kernel fit Pairwise Correlations Normal fit

Density 0.444

0.000 CEM 1

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

Pre-normalization Quantiles

Heart vehicleHeart vehiclerep1Heart (0.0191418) vehiclerep2Heart (0.0166403) 6mgkg-1rep3Heart (0.0150715) 6mgkg-1 Heartrep1 (0.0108074) 6mgkg-1 Heartrep2 (0.0104837) 20mgkg-1 Heartrep3 (0.0106172) 20mgkg-1Heart rep1 20mgkg-1(0.00865561)Kidney rep2 (0.00744927) Kidneyvehicle rep3 (0.0125807) Kidneyvehiclerep1 (0.0569613) Kidneyvehiclerep2 (0.0471088) Kidney6mgkg-1rep3 (0.0418676) Kidney6mgkg-1 rep1 (0.0580429) Kidney6mgkg-1 rep2 (0.101516) Kidney20mgkg-1 rep3 (0.0371293) Kidney20mgkg-1 rep1 Liver 20mgkg-1(0.0391734) rep2 vehicleLiver (0.0412808) rep3 vehiclerep1Liver (0.0492379) (0.0310413) vehiclerep2Liver (0.0322923) 6mgkg-1rep3Liver (0.0386734) 6mgkg-1 rep1Liver (0.0272462) 6mgkg-1 rep2Liver (0.0100519) 20mgkg-1 rep3Liver (0.0428841) 20mgkg-1Liver rep1 20mgkg-1(0.018529)Skeletal rep2 (0.0186576)Skeletal Musclerep3 (0.0193581)Skeletal MusclevehicleSkeletal Musclevehiclerep1 (0.0284436)Skeletal Musclevehiclerep2 (0.0263257)Skeletal Muscle6mgkg-1rep3 (0.0233183)Skeletal Muscle6mgkg-1 rep1Skeletal (0.0164276)Muscle6mgkg-1 rep2Skeletal (0.0207228)Muscle20mgkg-1 rep3 (0.0192585)Muscle20mgkg-1 rep1 20mgkg-1(0.0167334) rep2 (0.0169501) rep3[ (0.00932081)min ] [ medium ] [ max ] CEM 1 Slc22a17 91.8 167.0 641.1 P ( S | Z, I ) = 1.00 Atp6v0c 3950.4 4806.7 7002.9 Mean Corr = 0.43970Atp6v0b 1330.9 1641.5 2684.4 Sbf2 143.9 275.5 373.0 Slc3a1 105.0 712.7 8465.5 Mtmr2 68.1 102.9 176.9 Atp6ap1 2409.7 3331.0 3832.5 Abcb6 651.3 1032.3 2751.3 Tmem138 54.4 77.2 202.0 Vps4b 35.1 89.9 213.3 Trappc3 841.1 1387.9 1641.6 BC022687 14.1 26.6 158.6 Ankrd13c 2793.5 3834.3 9651.4 Mtmr11 172.2 396.8 2835.3 Fahd1 452.3 1287.7 1981.0 CEM 1 + Pccb 1206.4 1766.4 2758.1 Top 10 Genes Bad 293.5 440.0 599.4 Npl 101.9 206.9 1886.5 Abca3 94.0 214.8 1091.7 Rtn3 2191.2 2986.5 5435.1

Null module GEO Series "GSE32529" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 224 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

Details of this dataset are not shown due to large number of samples and the page size limit. Find details in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32529

Background corr dist: KL-Divergence = 0.0225, L1-Distance = 0.0447, L2-Distance = 0.0023, Normal std = 0.7763 GEO Series "GSE18042" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.884 Kernel fit Pairwise Correlations Normal fit

Density 0.442

0.000 CEM 1

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

Pre-normalization Quantiles

pre-estradiol,pre-estradiol, biologicalpre-estradiol, biological3 hrep1 post-estradiol,biological biological(0.0684776)3 hrep2 post-estradiol,biological (0.0628073)3 hrep3 post-estradiol,biological (0.0532038)7 h post-estradiol,biological rep17 h post-estradiol,biological(0.038658) rep27 h post-estradiol,biological(0.031711) rep314 h (0.0400994) post-estradiol,biological rep114 h (0.0124612) post-estradiol,biological rep214 h (0.0138503) post-estradiol,biological rep321 h (0.0501975) post-estradiol,biological rep121 h post-estradiol,biological(0.0246967) rep221 h post-estradiol,biological(0.00889869) rep330 h post-estradiol,biological(0.0430277) rep130 h post-estradiol,biological(0.0459365) rep230 h post-estradiol,biological(0.0287025) rep3 (0.0705695) rep1 (0.114964) rep2 (0.151234) rep3[ min (0.140504) ] [ medium ] [ max ] CEM 1 Slc22a17 28.3 42.5 62.4 P ( S | Z, I ) = 1.00 Atp6v0c 3604.9 5293.4 8477.4 Mean Corr = 0.31566Atp6v0b 1171.2 2733.8 6251.4 Sbf2 18.2 25.5 35.8 Slc3a1 118.3 154.2 219.6 Mtmr2 60.6 81.8 96.7 Atp6ap1 1765.6 3450.5 7358.0 Abcb6 3050.5 7980.8 10424.0 Tmem138 99.7 161.9 248.4 Vps4b 101.7 125.5 162.2 Trappc3 1241.8 1473.9 2442.8 BC022687 17.7 25.2 43.0 Ankrd13c 6454.8 6829.8 8371.8 Mtmr11 50.9 69.9 123.5 Fahd1 94.4 337.9 605.3 CEM 1 + Pccb 261.4 405.4 497.3 Top 10 Genes Bad 631.6 863.9 1365.5 Npl 373.9 459.6 1032.6 Abca3 155.1 255.7 325.5 Rtn3 2642.3 3066.9 4155.6

Null module GEO Series "GSE34423" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 40 -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=GSE34423 Status: Public on Dec 14 2011 Title: Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice [Expression array]. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21455306 Summary & Design: Summary: Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.

Overall design: 2932 days old male B6C3F1/Crl (C57BL/6 x C3H/He ) mice were obtained from Charles River Laboratories (Germany). Animals were allowed to acclimatise for 5 days prior to being randomly divided into two treatment groups (n = 10) and phenobarbital (Sigma 04710, 0.05% (w/v) in drinking water) was administered to one group through ad libitum access to drinking water for 28 days. Mice were checked daily for activity and behavior and sacrificed on the last day of dosing (day 28). Blood was withdrawn for PK analysis and target (liver) and non-target (kidney) tissues removed, split into several sections, frozen in liquid nitrogen and stored at 80´C for subsequent analyses. Total RNA from liver and kidney was purified and processed for Affymetrix gene expression profiling while genomic DNA was prepared for promoter array based methylome analysis using the Methylated DNA immunoprecipitation (MeDIP) procedure. Remaining tissue material was used for chromatin immunoprecipitation (ChIP) to analyze histone modifications at individual promoters. Plasma samples were also collected to evaluate phenobarbital exposure in individual animals by LC-MS.

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0729, L2-Distance = 0.0087, Normal std = 0.5583

0.829 Kernel fit Pairwise Correlations Normal fit

Density 0.415

0.000 CEM 1

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

Pre-normalization Quantiles

PB_Kidney_Control_5PB_Kidney_Control_1PB_Kidney_Control_9 PB_Kidney_Control_4(0.02779) PB_Kidney_Control_10(0.0235104) PB_Kidney_Control_8(0.0163724) PB_Kidney_Control_3(0.0309729)PB_Kidney_Control_7 (0.0273754) PB_Kidney_Control_2(0.0200469) PB_Kidney_Control_6(0.0294157) PB_Liver_Control_10(0.0187198) PB_Liver_Control_9(0.0278129) PB_Liver_Control_2(0.0216974) (0.0290769)PB_Liver_Control_3 (0.0154211)PB_Liver_Control_6 (0.0162621)PB_Liver_Control_5 (0.0320862)PB_Liver_Control_4 (0.0279472)PB_Liver_Control_8 (0.0342567)PB_Liver_Control_1 (0.0353222)PB_Liver_Control_7 (0.0136301)PB_Kidney_treated_20 (0.018067)PB_Kidney_treated_18 (0.0195268)PB_Kidney_treated_12PB_Kidney_treated_11 (0.0221878)PB_Kidney_treated_17 (0.0181286)PB_Kidney_treated_16 (0.0138519)PB_Kidney_treated_14 (0.0273031)PB_Kidney_treated_15 (0.0176543)PB_Kidney_treated_13 (0.0289297)PB_Kidney_treated_19 (0.026061)PB_Liver_treated_12 (0.0168299)PB_Liver_treated_13 (0.0243838)PB_Liver_treated_14 (0.0145014) (0.0178214)PB_Liver_treated_15 (0.0303753)PB_Liver_treated_11 (0.0393725)PB_Liver_treated_16 (0.0268134)PB_Liver_treated_18 (0.0195053)PB_Liver_treated_19 (0.0339593)PB_Liver_treated_20 (0.0401934)PB_Liver_treated_17 (0.0447684) (0.0215639) (0.0304854)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 97.3 355.1 694.9 P ( S | Z, I ) = 1.00 Atp6v0c 11288.6 18022.6 20857.5 Mean Corr = 0.24432Atp6v0b 1723.5 4571.3 6256.9 Sbf2 125.5 229.1 301.4 Slc3a1 1542.3 11116.4 14114.0 Mtmr2 124.5 474.8 770.7 Atp6ap1 1582.1 4907.2 5664.9 Abcb6 826.5 1773.5 2876.2 Tmem138 16.1 148.7 280.8 Vps4b 86.8 134.2 218.4 Trappc3 1481.6 2246.1 2602.2 BC022687 48.0 681.7 1124.2 Ankrd13c 927.3 8794.1 11994.5 Mtmr11 19.8 899.3 1458.2 Fahd1 767.7 1819.1 2412.2 CEM 1 + Pccb 1975.3 2642.0 3694.6 Top 10 Genes Bad 227.8 394.1 595.4 Npl 48.3 575.8 1357.5 Abca3 546.7 2951.5 3741.0 Rtn3 2721.9 8823.6 10758.4

Null module GEO Series "GSE10806" 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=GSE10806 Status: Public on Jun 28 2008 Title: Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18594515 Summary & Design: Summary: Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc, and Klf4. Considering that ectopic expression of c-Myc causes tumourigenicity in offspring and retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here, we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc are sufficient to generate iPS cells from neural stem cells. These two-factor (2F) iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.

Overall design: - iPS cell_4F_3

Background corr dist: KL-Divergence = 0.0471, L1-Distance = 0.0191, L2-Distance = 0.0004, Normal std = 0.6050

0.659 Kernel fit Pairwise Correlations Normal fit

Density 0.330

0.000 CEM 1

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

Pre-normalization Quantiles

EmbryonicEmbryonic StemEmbryonic cells Stem Inducedsample cells Stem Inducedsample1 pluripotent (0.0266628)cells Neuralsample2 pluripotent (0.0392086) stem stem Neural3 (0.0487646) (iPS) cellsstem StemInduced cells (NSC)(iPS) cells (Oct4,Induced pluripotentcells sample (NSC) Klf4) (Oct4,Induced pluripotent sample2 sample (0.270654) stemKlf4)Induced pluripotent 3 (iPS)sample 2(0.265639) stem(0.038722) pluripotentcells (iPS)3 stem(0.0430591) (Oct4, cells (iPS) stemKlf4) (Oct4, cells (iPS)sample Sox2, (Oct4,[ cells min 1c-Myc, (0.0488123)Sox2, (Oct4, Klf4)c-Myc,] Sox2, sample Klf4)c-Myc, sample1[ (0.112809)Klf4) medium sample2 (0.0393721) 3 (0.066296) ] [ max ] CEM 1 Slc22a17 319.1 365.9 2541.2 P ( S | Z, I ) = 0.99 Atp6v0c 7647.6 10943.9 12437.0 Mean Corr = 0.41277Atp6v0b 1829.9 2600.6 3469.4 Sbf2 274.9 365.7 969.9 Slc3a1 30.7 33.2 45.0 Mtmr2 367.9 485.9 1081.7 Atp6ap1 1266.5 2141.4 3720.9 Abcb6 315.7 414.9 1319.6 Tmem138 192.5 234.9 533.3 Vps4b 24.0 30.1 48.1 Trappc3 1385.8 1515.2 2334.9 BC022687 64.4 103.5 163.6 Ankrd13c 824.7 1602.6 3310.3 Mtmr11 41.7 79.4 537.0 Fahd1 142.2 178.1 385.6 CEM 1 + Pccb 658.8 712.4 1204.7 Top 10 Genes Bad 123.3 228.0 502.9 Npl 503.9 1002.5 2288.6 Abca3 75.2 113.5 423.6 Rtn3 1181.0 1840.0 11718.0

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

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

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

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

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

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

ESC_Zfx-flox_Replicate1ESC_Zfx-flox_Replicate2ESC_Zfx-null_Replicate1ESC_Zfx-null_Replicate2 (0.158022)HSC_Zfx-cko_Replicate1 (0.0910813)HSC_Zfx-cko_Replicate2 (0.168449)HSC_Zfx-flox_Replicate1 (0.0994972)HSC_Zfx-flox_Replicate2 (0.122563) (0.157908) (0.085287) (0.117191)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 95.3 421.9 788.7 P ( S | Z, I ) = 0.03 Atp6v0c 3256.9 9661.7 11915.6 Mean Corr = 0.38100Atp6v0b 283.5 2779.5 3215.9 Sbf2 4.8 299.1 422.3 Slc3a1 2.1 20.3 77.2 Mtmr2 88.3 949.7 1174.0 Atp6ap1 2151.2 3230.5 4497.2 Abcb6 241.3 904.0 1000.7 Tmem138 107.6 223.4 268.5 Vps4b 87.8 125.5 166.6 Trappc3 1050.0 1325.6 1421.0 BC022687 16.6 159.1 356.4 Ankrd13c 820.7 2033.6 2590.6 Mtmr11 25.2 100.6 208.8 Fahd1 56.0 96.4 122.2 CEM 1 + Pccb 229.1 612.3 895.7 Top 10 Genes Bad 169.0 349.9 381.4 Npl 489.2 858.2 2115.0 Abca3 20.1 240.9 289.6 Rtn3 4086.3 5266.1 5699.3

Null module GEO Series "GSE41925" 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=GSE41925 Status: Public on Dec 01 2012 Title: Transcription factor AP-2 gamma is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23136388 Summary & Design: Summary: We characterzised global changes in gene expresseion between 8 cell embryos and blastocysts to identify potential genes required for blastocyst formation.

Overall design: Expression data from mouse 8-cell embryos and blastocysts. Eight-cell embryos and blastocysts were obatained from B6D2F1 female X B6D2F1 male. We analyzed a total of four samples at both stages.

Background corr dist: KL-Divergence = 0.0169, L1-Distance = 0.0482, L2-Distance = 0.0027, Normal std = 0.8501

0.514 Kernel fit Pairwise Correlations Normal fit

Density 0.257

0.000 CEM 1

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

Pre-normalization Quantiles

8-cell staged8-cell mousestaged8-cell wholemousestaged8-cell embryos wholemousestagedBlastocyst embryos wholemouse repBlastocyst 1staged embryos(0.115657) whole repBlastocyst 2mousestaged embryos(0.0681855) repBlastocyst 3wholemousestaged (0.133716) rep embryos 4wholemousestaged (0.166199) embryos wholemouse rep 1 embryos(0.0970524) whole rep[ 2 embryos(0.0856317)min rep 3 (0.127452) ]rep 4 (0.206106)[ medium ] [ max ] CEM 1 Slc22a17 182.3 223.2 309.4 P ( S | Z, I ) = 0.01 Atp6v0c 6940.9 9801.0 11792.3 Mean Corr = 0.57826Atp6v0b 1369.7 2684.0 3344.7 Sbf2 16.1 62.2 87.3 Slc3a1 31.2 72.3 123.1 Mtmr2 116.9 207.5 287.5 Atp6ap1 2808.9 3532.6 3776.4 Abcb6 707.7 933.8 1015.6 Tmem138 90.3 264.0 360.0 Vps4b 22.9 53.6 89.9 Trappc3 2096.8 4435.1 5226.6 BC022687 15.4 89.9 114.1 Ankrd13c 1961.4 2226.8 2583.2 Mtmr11 1.8 6.4 36.5 Fahd1 3.0 62.7 79.7 CEM 1 + Pccb 1058.8 1221.2 1543.3 Top 10 Genes Bad 477.1 971.2 1266.7 Npl 3536.8 8091.8 11784.8 Abca3 57.3 736.3 879.3 Rtn3 116.1 2442.6 2882.8

Null module GEO Series "GSE26668" 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=GSE26668 Status: Public on Mar 23 2011 Title: Expression data from E13.5 Fz4-/-Fz8-/- and Fz4+/+Fz8-/- kidneys Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21343368 Summary & Design: Summary: Fz4 and Fz8 cooperate in regulating the branching morhpogenesis of the developing kidney during mouse embryonic development, hence determines the eventual kidney size.

We used microarrays to study the global gene expression profiles regulated by Fz4 and Fz8 signaling during early kidney development, and to understand the collaboration between the signaling events mediated by Fz4 and Fz8

Overall design: Kidney rudiments were dissected from E13.5 mouse embryos for RNA extraction and hybridization on Affymetrix MOE430.2 arrays. Three biological replicates of each genotype were analyzed.

Background corr dist: KL-Divergence = 0.0193, L1-Distance = 0.0128, L2-Distance = 0.0002, Normal std = 0.7424

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

Fz4Fz8 Fz4Fz8DKO C1 Fz4Fz8DKO (0.162184) C2 Fz4Fz8DKO (0.112449) C3 Fz4Fz8DKO (0.0815385) M1 Fz4Fz8DKO (0.198703) M2 DKO (0.273737) M3 (0.171388) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 502.1 722.8 913.5 P ( S | Z, I ) = 0.00 Atp6v0c 3018.1 3213.8 3984.6 Mean Corr = 0.52214Atp6v0b 611.4 778.8 919.0 Sbf2 217.7 340.2 433.2 Slc3a1 105.7 188.5 192.4 Mtmr2 134.5 178.2 207.3 Atp6ap1 1418.2 1800.7 1863.6 Abcb6 767.2 990.0 1284.7 Tmem138 130.6 221.5 322.2 Vps4b 54.8 98.0 130.3 Trappc3 1015.9 1145.5 1326.4 BC022687 7.6 9.6 11.3 Ankrd13c 3299.3 3697.4 3867.2 Mtmr11 268.9 483.9 486.1 Fahd1 183.2 278.4 331.6 CEM 1 + Pccb 632.2 705.2 866.8 Top 10 Genes Bad 553.7 675.2 881.6 Npl 119.3 137.5 168.8 Abca3 36.8 65.9 76.5 Rtn3 1978.0 2215.1 2342.2

Null module GEO Series "GSE7596" 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=GSE7596 Status: Public on Feb 15 2008 Title: AKT regulates de novo induction of Foxp3 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18283119 Summary & Design: Summary: The CD4+Foxp3+ regulatory T cells play an essential role in maintaining tolerance via their suppressive function on conventional T cells. The intracellular signaling pathways that regulate Foxp3 expression are largely unknown. In this study we describe a novel inhibitory role for AKT in regulating de novo induction of Foxp3 both in vivo and in vitro. A constitutively active allele of AKT significantly diminished TGF-Ã¢ induced Foxp3 induction via a rapamycin-sensitive pathway, establishing a role for the AKT-mTOR axis in Treg cells. Moreover, the observed impairment in Foxp3 induction was paralleled by a selective downmodulation of the imparted Treg transcriptional signature highlighting the importance of the balance of intracellular signals in Treg differentiation . Our results provide a basis for further elucidation of molecular mechanisms that regulate Foxp3 induction and identify AKT as an important negative regulator of this process.

Keywords: Cell population comparison

Overall design: All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and three replicates were generated for all groups. RNA from 0.5-2.5 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.

Background corr dist: KL-Divergence = 0.0197, L1-Distance = 0.0262, L2-Distance = 0.0010, Normal std = 0.7478

0.533 Kernel fit Pairwise Correlations Normal fit

Density 0.267

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

AktTGF,GFPTGF, rep1 (0.122904)AktTGF, rep1 (0.110854)AktTGF, rep2 (0.211986)GFPTGF, rep3 (0.166954)GFPTGF, rep2 (0.190194) rep3 (0.197109) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 266.4 356.0 358.6 P ( S | Z, I ) = 0.00 Atp6v0c 2708.4 4059.0 4309.3 Mean Corr = 0.42869Atp6v0b 989.4 1513.8 1600.1 Sbf2 58.0 66.8 69.4 Slc3a1 90.8 118.7 133.6 Mtmr2 71.5 81.7 98.0 Atp6ap1 4628.6 7344.0 8266.6 Abcb6 116.3 127.2 130.0 Tmem138 172.4 231.5 247.3 Vps4b 155.7 170.7 200.6 Trappc3 1185.5 1382.6 1430.2 BC022687 18.7 21.1 23.2 Ankrd13c 1300.9 1509.0 1624.7 Mtmr11 74.7 86.0 95.7 Fahd1 52.9 56.7 63.2 CEM 1 + Pccb 303.4 347.7 372.7 Top 10 Genes Bad 62.3 68.7 76.8 Npl 47.3 56.9 65.5 Abca3 78.5 89.8 93.2 Rtn3 4575.4 4974.1 5275.4

Null module GEO Series "GSE13805" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13805 Status: Public on Dec 02 2009 Title: Expression data from wild type and calreticulin deficient murine embryonic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20506533 Summary & Design: Summary: Primordial genomic challenge compromises embryonic development and survival, and surveillance of deployed transcriptional programs may provide an early opportunity to forecast phenotype abnormalities. Here, comparisons between wild-type and calreticulin-ablated embryonic stem cells revealed transcriptome shifts precipitated by calreticulin loss. Bioinformatic analysis identified down and up-regulation in 1187 and 418 genes, respectively. Cardiovascular development precedes other organogenic programs, and examination of cardiogenic genes revealed a map of calreticulin-calibrated expression profiles that encompass the developmental regulators, Ccnd1, Ccnd2 and Notch1. Interrogation of primary function in the resolved network forecasted abnormalities during myocardial development. Whole embryo magnetic resonance imaging, verified by pathoanatomical analysis, diagnosed prominent ventricular septal defect. Correlation clustering and network resolution of probesets associated with protein folding/chaperoning and calcium handling demonstrated 14 and 19 genes, respectively, modulated by calreticulin deficiency. Calreticulin deletion provoked ontological re-prioritization of gene expression, molecular transport and protein trafficking that translated into multiple subcellular functional outcomes. Individual stem cell-derived cardiomyocytes lacking calreticulin demonstrated a disorganized contractile apparatus with mitochondrial paucity and architectural aberrations. Thus, bioinformatic deconvolution of primordial embryonic stem cell transcriptomes enables predictive phenotyping of defective developmental networks that coalesce from complex systems biology hierarchies.

Keywords: Comparison of embryonic stem cell genomes between wild type and calreticulin knockouts

Overall design: Stem cells cultured in triplicate (or more) were pooled to provide raw material per sample. Each sample represents material collected from three technical replicates or more. In this manner, two wild type samples, and five derived from calreticulin knockout samples, were obtained. Although sample content contains material from three or more technical replicates harvested contemporaneously, each sample is a distinct biological replicate. Total RNA was extracted from each of the samples and RNA pools were profiled on Affymetrix Mouse 430 2.0 Arrays to identify global gene expression changes invoked by genomic ablation of calreticulin.

Background corr dist: KL-Divergence = 0.0370, L1-Distance = 0.0281, L2-Distance = 0.0009, Normal std = 0.6423

0.639 Kernel fit Pairwise Correlations Normal fit

Density 0.320

0.000 CEM 1

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

Pre-normalization Quantiles

Wild typeWild mouse typeCRT embryonicmouse knockoutCRT embryonic knockout stem mouseCRT cell, knockout stem embryonicmouseCRT biological cell, knockout embryonicmouseCRT biological stem rep1knockout embryonicmouse cell,(0.110285) stem rep2 biological embryonicmouse cell,(0.0853002) stem biological embryonic cell,rep1 stem biological(0.182256)[ cell,rep2min stem biological(0.171206) cell,rep3 ] biological(0.199948) rep4 (0.113711) rep5[ medium (0.137294) ] [ max ] CEM 1 Slc22a17 352.6 449.0 729.6 P ( S | Z, I ) = 0.00 Atp6v0c 8586.1 10746.4 12847.5 Mean Corr = 0.35659Atp6v0b 918.2 1703.7 2658.0 Sbf2 195.2 335.6 431.6 Slc3a1 5.6 9.2 29.7 Mtmr2 226.7 327.1 709.8 Atp6ap1 1223.4 1588.5 3877.9 Abcb6 240.6 341.0 1529.7 Tmem138 169.0 313.9 402.3 Vps4b 58.5 87.7 119.9 Trappc3 1195.8 1404.2 1916.9 BC022687 66.2 110.3 170.8 Ankrd13c 994.0 2230.0 2463.3 Mtmr11 11.8 38.4 103.3 Fahd1 94.1 133.6 156.7 CEM 1 + Pccb 491.6 650.4 759.5 Top 10 Genes Bad 114.1 224.6 402.7 Npl 350.2 1108.7 1631.6 Abca3 43.2 103.6 399.1 Rtn3 1593.3 2536.1 5623.2

Null module GEO Series "GSE23833" 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=GSE23833 Status: Public on Sep 01 2010 Title: The Forkhead factor FoxQ1 influences epithelial differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20717954 Summary & Design: Summary: The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration and differentiation.In this study we identified the Forkhead factor FoxQ1 as increased in expression during TGF-beta1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity.The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts and an increased expression of several junction proteins (e.g. E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression.Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells.Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-beta1 induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, e.g. Ets-1, Zeb1 and Zeb2.In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation

Overall design:

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0772, L2-Distance = 0.0080, Normal std = 0.6930

0.668 Kernel fit Pairwise Correlations Normal fit

Density 0.334

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

2h_co._enriched12h_co._enriched22h_co._enriched3 (0.103738)2h_co._total1 (0.0781805)2h_co._total2 (0.0361718) (0.0742679)2h_co._total3 (0.108872)2h_TGFbeta_enriched1 (0.102622)2h_TGFbeta_enriched22h_TGFbeta_enriched32h_TGFbeta_total1 (0.0568535)2h_TGFbeta_total2 (0.116655)2h_TGFbeta_total3 (0.100808) (0.0678673) (0.0791087) (0.0748542)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 116.0 182.0 222.1 P ( S | Z, I ) = 0.00 Atp6v0c 3101.2 7040.5 9155.6 Mean Corr = 0.22063Atp6v0b 559.3 1206.0 1497.4 Sbf2 118.0 171.6 210.6 Slc3a1 66.1 90.3 124.5 Mtmr2 73.1 104.1 141.2 Atp6ap1 1143.0 3511.6 3836.8 Abcb6 213.6 467.6 604.8 Tmem138 558.1 834.9 1278.8 Vps4b 129.1 236.5 383.5 Trappc3 445.2 770.7 979.5 BC022687 88.0 125.2 198.7 Ankrd13c 2164.6 2342.2 2514.2 Mtmr11 677.7 1614.7 1933.2 Fahd1 55.9 91.5 144.7 CEM 1 + Pccb 97.1 261.3 380.7 Top 10 Genes Bad 266.9 790.3 952.3 Npl 27.4 30.3 36.3 Abca3 95.6 308.8 419.1 Rtn3 5171.9 9306.7 10700.0

Null module GEO Series "GSE12073" 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=GSE12073 Status: Public on Aug 20 2008 Title: Expression data from transgenic Aire expressing pancreatic islets Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18780794 Summary & Design: Summary: The aim of this study was to determine the effect of transgenic Aire expression on the transcriptional profile of a tissue that normally does not express Aire: pancreatic islets. The transcriptional profile of transgenic RIP-Aire27 islets was compared to non-transgenic littermate islets as well as to archival NOD thymic medullary epithelial cells (MEC) data. All data were from non-obese diabetic (NOD) mice

Keywords: RIP-Aire transgenic vs non-transgenic comparison

Overall design: 3-wk-old individual male RIP-Aire27 or non-transgenic littermates islets were isolated by gradient purification followed by hanpicking under a microscope for subsequent RNA purification, labeling and hybridization to Affymetrix arrays.

Background corr dist: KL-Divergence = 0.0336, L1-Distance = 0.0527, L2-Distance = 0.0050, Normal std = 0.6590

0.605 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

NOD non-transgenicNOD non-transgenicNOD non-transgenic isletNOD rep1 RIP-Aire27 isletNOD (0.0715618) rep2 RIP-Aire27 isletNOD (0.0666161)islet rep3 RIP-Aire27 rep1NOD (0.101617)islet (0.193621) Aire rep2NOD islet WT (0.0967024) Aire MECrep3NOD WT (0.0688786)rep1 Aire MECNOD (0.09203) WT rep2 Aire MECNOD (0.1013) KO rep3 Aire MECNOD (0.0445592) KO rep1 Aire MEC (0.073295) KO rep2 MEC (0.0535676) rep3 (0.0362518)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 395.3 782.6 1137.0 P ( S | Z, I ) = 0.00 Atp6v0c 3183.7 5497.1 7119.7 Mean Corr = 0.47778Atp6v0b 1402.2 1861.7 2305.0 Sbf2 77.6 127.6 185.7 Slc3a1 175.8 226.1 300.2 Mtmr2 75.4 93.6 142.9 Atp6ap1 4468.1 8362.2 14178.2 Abcb6 181.2 301.5 488.3 Tmem138 187.3 259.6 357.5 Vps4b 104.7 177.6 242.0 Trappc3 1009.2 1663.3 1980.7 BC022687 30.7 64.3 152.9 Ankrd13c 1254.6 1872.7 2220.6 Mtmr11 88.1 146.4 242.2 Fahd1 103.8 151.4 236.2 CEM 1 + Pccb 217.8 330.2 532.7 Top 10 Genes Bad 87.1 115.3 146.6 Npl 130.7 269.8 3413.2 Abca3 88.6 120.1 217.1 Rtn3 3789.2 9868.7 14172.0

Null module GEO Series "GSE39030" 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=GSE39030 Status: Public on Oct 29 2013 Title: Impact of ectopic expression of SNAIL2, ZEB2, ZEB1 or TWIST1 on BRAF-target genes in the murine melanocytic melan-a cell line Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24075834 Summary & Design: Summary: We have demonstrated that the oncogenic activation of B-RAF (using a truncated delta-BRAF-ER version inducible with tamoxifen) in the melan-a melanocyte cell line triggers the activation of Zeb1 and Twist1 at the expanse of Zeb2 and Snail2. Enforced maintenance of Zeb2 or Snail2 expression reduces the B-RAF oncogenic potential while ectopic expression of Zeb1 or Twist1 cooperates with B-RAF in melan-a cell transformation. To get an insight into the properties of these embryonic transcription factors, gene expression profiles of melan-a-derived cell lines either expressing a non-activated B-RAF (- tamoxifen) or an activated BRAF (+ tamoxifen) alone or in combination with Snail2, Zeb2, Twist1 or Zeb1 have been established.

Overall design: Ectopic expression of SNAIL2, ZEB2, ZEB1 or TWIST1 on BRAF-target genes in the murine melanocytic melan-a cell line.

Background corr dist: KL-Divergence = 0.0343, L1-Distance = 0.0304, L2-Distance = 0.0011, Normal std = 0.6606

0.626 Kernel fit Pairwise Correlations Normal fit

Density 0.313

0.000 CEM 1

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

Pre-normalization Quantiles

BRAF nonBRAF activated activatedBRAF in activatedBRAF thein the murine activated BRAF murine + ZEB2 melanocytic activatedBRAF melanocytic +in SNAIL2 the activated murine+ melan-aTWIST1 in melan-athe melanocytic+ murineZEB1 incell the cell line in melanocytic murinelinethe (0.082278) melan-a [ (0.111989)murine minmelanocytic cell melan-amelanocytic line] (0.0878833)melan-a cell linemelan-a cell [(0.367654) medium line cell (0.148319) line (0.201877) ] [ max ] CEM 1 Slc22a17 85.8 146.3 212.2 P ( S | Z, I ) = 0.00 Atp6v0c 12606.6 16284.3 24816.7 Mean Corr = 0.26613Atp6v0b 416.0 795.0 1185.8 Sbf2 227.3 380.1 522.1 Slc3a1 3.0 28.0 35.2 Mtmr2 1302.6 1621.0 1769.8 Atp6ap1 2946.8 3795.9 4474.8 Abcb6 275.3 886.6 1728.3 Tmem138 149.2 168.5 192.1 Vps4b 77.9 105.2 125.5 Trappc3 616.1 709.4 1147.2 BC022687 232.7 354.1 599.0 Ankrd13c 2754.8 3156.9 3360.6 Mtmr11 75.4 101.4 127.1 Fahd1 112.4 188.5 297.0 CEM 1 + Pccb 428.5 584.6 711.7 Top 10 Genes Bad 785.0 1069.4 1656.8 Npl 1.3 17.3 30.7 Abca3 200.9 302.7 409.3 Rtn3 4405.8 5176.3 5729.3

Null module GEO Series "GSE27630" 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=GSE27630 Status: Public on Feb 05 2013 Title: The transcription factor Otx2 regulates choroid plexus development and function Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23364326 Summary & Design: Summary: The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.

Overall design: We performed gene expression microarray analysis of fourth ventricular choroid plexus tissue from Otx2 k.o. mice compared to wildtype mice from the same litters.

Background corr dist: KL-Divergence = 0.0475, L1-Distance = 0.0207, L2-Distance = 0.0005, Normal std = 0.5785

0.695 Kernel fit Pairwise Correlations Normal fit

Density 0.348

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

Fourth ventricularFourth ventricularFourth choroid ventricularFourth choroid plexus ventricularFourth choroid fromplexus ventricularFourth Otx2ko choroid fromplexus ventricularFourth Otx2komice choroid fromplexus ventricular Fourthat Otx2ko miceE13, choroid fromplexus ventricularbiologicalat Otx2ko miceE13, choroid fromplexus biologicalat wildtype mice E13, replicatechoroid fromplexus biologicalat wildtype E13, replicatemice from plexus1 (0.173967) [biological atwildtype min replicate miceE13,from 2 (0.146206) biologicalatwildtype replicate miceE13, ]3 (0.185568) biologicalat mice E13, replicate4 (0.107549) biologicalat[ E13, replicatemedium 1 (0.0425027) biological replicate 2 (0.143682) replicate 3 (0.10607)] 4 (0.0944548)[ max ] CEM 1 Slc22a17 2780.1 4242.0 4641.0 P ( S | Z, I ) = 0.00 Atp6v0c 13684.7 15497.2 16040.4 Mean Corr = 0.34274Atp6v0b 1741.0 2280.8 2432.1 Sbf2 245.1 280.5 328.6 Slc3a1 57.3 69.6 88.0 Mtmr2 278.0 379.5 443.0 Atp6ap1 3135.4 3412.2 3708.8 Abcb6 519.7 679.4 833.7 Tmem138 459.4 674.0 802.2 Vps4b 71.3 89.2 117.3 Trappc3 1747.8 1871.0 2128.5 BC022687 562.7 952.6 1113.4 Ankrd13c 2128.2 2609.6 2689.1 Mtmr11 209.0 271.6 321.2 Fahd1 278.4 302.8 314.1 CEM 1 + Pccb 641.7 678.8 714.0 Top 10 Genes Bad 1115.7 1238.3 1311.5 Npl 1235.9 1495.8 2010.5 Abca3 213.9 230.5 249.5 Rtn3 7476.4 8002.0 9404.8

Null module 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 (0.222007)line, rep2Wild-type, biological (0.228996)line,Wild-type, biological biological rep Gtf2i1 (0.0576603) biological rep Mutant rep1 Gtf2i2 (0.0947992) (0.0867987) Mutantline, rep2 biological (0.145349) line, biological rep 1 (0.0915002) rep[ 2min (0.0728897) ] [ medium ] [ max ] CEM 1 Slc22a17 314.1 354.8 423.2 P ( S | Z, I ) = 0.00 Atp6v0c 10753.3 11780.8 12429.3 Mean Corr = 0.35262Atp6v0b 434.3 539.7 693.6 Sbf2 228.1 245.9 318.4 Slc3a1 25.7 30.2 33.1 Mtmr2 406.8 481.7 635.8 Atp6ap1 2240.3 3115.4 4691.4 Abcb6 372.3 576.2 717.4 Tmem138 156.1 191.0 227.8 Vps4b 32.1 35.0 38.0 Trappc3 1554.4 2001.2 2039.4 BC022687 130.7 386.0 957.3 Ankrd13c 1871.1 2038.0 2835.6 Mtmr11 64.8 260.2 360.7 Fahd1 163.0 279.9 423.3 CEM 1 + Pccb 647.1 693.8 936.9 Top 10 Genes Bad 419.9 689.7 841.3 Npl 578.5 757.2 1224.4 Abca3 103.5 123.9 198.6 Rtn3 2920.4 2998.6 3387.7

Null module GEO Series "GSE43825" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 31 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43825 Status: Public on Dec 31 2013 Title: Gene expression profiles from mammary tissue of control mice, small K5˛N˛†cat hyperplasia, large K5˛N˛†cat hyperplasia and K5˛N˛†cat tumor Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Basal-like breast cancer is a heterogeneous disease characterised by the expression of basal cell markers, no oestrogen or progesterone receptor expression and a lack of HER2 overexpression. Recent studies have linked activation of the Wnt/beta-catenin pathway to basal-like breast cancer. Transgenic mice expressing N-terminally truncated stabilised beta-catenin in the mammary basal/myoepithelial cell layer (K5deltaNbetacat strain) develop mammary hyperplasias that progress to invasive carcinomas. Histological and microarray analyses of these lesions have revealed their high similarity to a subset of basal-like human breast tumours with squamous differentiation. As in human basal-like carcinomas, the Myc pathway was found to be activated in the mammary lesions of K5deltaNbetacat mice. Mammosphere and transplantation assays showed that a basal cell population with stem/progenitor characteristics was amplified in K5deltaNbetacat mouse preneoplastic glands. Myc deletion from the mammary basal layer of K5deltaNbetacat mice abolished both basal cell regenerative capacity and tumorigenesis. These results show that Myc is essential for beta-catenin-induced stem cell amplification and tumorigenesis and that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumours.

Overall design: mammary tissue from K5˛N˛†cat mice were dissected at successive stages of development (small hyperplasia (n=5), large hyperplasia (n=5), tumor (n=11) and control (n=4)) for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0953, L1-Distance = 0.0371, L2-Distance = 0.0022, Normal std = 0.4542

0.902 Kernel fit Pairwise Correlations Normal fit

Density 0.451

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

K5˛N˛†catK5˛N˛†cat miceK5˛N˛†cat tumor miceK5˛N˛†cat 1 tumor (0.0277164) miceK5˛N˛†cat 2 tumor (0.0190426) miceK5˛N˛†cat 3 tumor (0.0167289) miceK5˛N˛†cat 4 tumor (0.0271253) miceK5˛N˛†cat 5 tumor (0.0238567) miceK5˛N˛†cat 6 tumor (0.0153639) miceK5˛N˛†cat 7 tumor (0.0141248) miceK5˛N˛†cat 8 tumor (0.0193904) miceK5˛N˛†cat 9 tumor (0.0278592) miceK5˛N˛†cat 10 tumor (0.0238695)smallK5˛N˛†cat 11 hyperplasia (0.0260625)smallK5˛N˛†cat hyperplasia small 1K5˛N˛†cat (0.0069457) hyperplasia small 2K5˛N˛†cat (0.0125919) hyperplasia small 3K5˛N˛†cat (0.0102457) hyperplasia Large 4K5˛N˛†cat (0.0326768) hyperplasia Large 5K5˛N˛†cat (0.00609997) hyperplasia Large 1K5˛N˛†cat (0.0109518) hyperplasia Large 2Control (0.0089238) hyperplasia Large 3Control mice (0.0128005) hyperplasia 1 4Control (0.0460503)mice (0.00676414) 2 5Control (0.0641727)mice (0.00463855) 3 sorted (0.0140289)mice 4 basal sorted(0.0379343) cells basalsorted Control cells basalsorted Control mice cells basalsorted 1 Control (0.0636051)mice cells basalsorted 2 K5creL/L (0.0871111)mice cells basal 3 K5creL/L(0.134762) micecells K5creL/L1 (0.0660604)mice 2 (0.05616)mice[ min3 (0.0763365) ] [ medium ] [ max ] CEM 1 Slc22a17 68.6 251.4 699.2 P ( S | Z, I ) = 0.00 Atp6v0c 1770.2 9906.3 15754.1 Mean Corr = 0.15332Atp6v0b 283.6 2783.6 4613.3 Sbf2 179.8 413.5 677.6 Slc3a1 5.9 37.8 662.8 Mtmr2 135.9 486.0 731.7 Atp6ap1 958.7 4155.9 5940.2 Abcb6 64.6 213.2 643.1 Tmem138 5.0 115.2 258.9 Vps4b 12.8 128.8 198.9 Trappc3 446.3 2084.4 2980.2 BC022687 28.2 145.6 281.4 Ankrd13c 1124.7 1969.2 2666.4 Mtmr11 75.1 293.8 623.4 Fahd1 42.0 229.6 461.0 CEM 1 + Pccb 249.6 681.7 2450.0 Top 10 Genes Bad 289.4 642.8 981.4 Npl 80.4 687.7 2465.1 Abca3 5.0 215.4 619.0 Rtn3 888.2 4123.5 7014.2

Null module GEO Series "GSE41759" 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=GSE41759 Status: Public on Apr 19 2013 Title: Differential Gene Expression and Mitochondrial Dysfunction in Imprinting center deletion (PWS- IC del) Mouse model of Prader-Willi Syndrome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Prader-Willi syndrome (PWS) is a genetic disorder caused by deficiency of imprinted gene expression from the paternal chromosome 15q11-15q13 and clinically characterized by neonatal hypotonia, short stature, cognitive impairment, hypogonadism, hyperphagia, morbid obesity and diabetes. Previous clinical studies suggest that a defect in energy metabolism may be involved in the pathogenesis of PWS. Assessment of enzyme activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the brain, heart, liver and muscle were assessed.

We used microarrays to detail the global programme of gene expression underlyingthe PWS and identified distinct classes of disregulated genes during this process.

Overall design: Skeletal (quadriceps) muscle Vastus Lateralis and whole brain samples from the mutant mice and their wild-type age-matched littermates were analyzed by microarray technology using the Mouse Genome 430 2.0 arrays (Affymetrix).

Background corr dist: KL-Divergence = 0.0080, L1-Distance = 0.0325, L2-Distance = 0.0010, Normal std = 0.9775

0.408 Kernel fit Pairwise Correlations Normal fit

Density 0.204

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

muscle brainVastus tissue muscleLateralis, sample, brainVastus wild tissuewild muscletypeLateralis, type sample,mice, brainVastusmice, wild biological tissuewild biological muscletypeLateralis, type sample,mice, replica brainVastusmice, replica wild biological tissue wild1biological muscletypeLateralis,(0.0740483) 1 type (0.0969719) sample,mice, replica brainVastusmice, replica wild biological tissue wild2biological muscletypeLateralis,(0.0422723) 2 type (0.0994406) sample,mice, replica brainVastusmice, replica mutant biological tissue mutant3biological muscleLateralis,(0.0906738) 3 mice, (0.0721225) sample, mice,replica brainVastus biological replica mutant biological tissue mutant4 Lateralis,(0.0440058) 4 mice, (0.0535786) replicasample, mice, replica biological mutant 1biological mutant(0.107124) 1 (0.0498871) mice, replica mice, replica[ biological min 2biological (0.0773646) 2 (0.0641322) replica] replica 3 (0.0715237) 3 (0.0568547)[ medium ] [ max ] CEM 1 Slc22a17 242.2 4507.3 5290.2 P ( S | Z, I ) = 0.00 Atp6v0c 5048.3 9500.0 11515.9 Mean Corr = 0.27253Atp6v0b 2430.1 4045.8 4794.4 Sbf2 145.1 243.4 328.1 Slc3a1 43.5 65.7 99.6 Mtmr2 224.8 282.4 385.1 Atp6ap1 3151.5 5266.6 6072.1 Abcb6 560.6 1112.4 1419.3 Tmem138 68.2 151.8 202.6 Vps4b 73.0 117.9 147.3 Trappc3 852.2 1970.5 2315.5 BC022687 51.5 322.6 440.7 Ankrd13c 1293.9 2671.4 3324.2 Mtmr11 69.7 135.3 209.2 Fahd1 203.6 565.4 715.2 CEM 1 + Pccb 1049.4 2361.9 3117.6 Top 10 Genes Bad 271.9 417.7 557.1 Npl 170.9 284.5 437.5 Abca3 142.7 579.7 722.8 Rtn3 2585.2 11338.7 12986.2

Null module GEO Series "GSE27932" 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=GSE27932 Status: Public on Mar 16 2011 Title: FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17254969 Summary & Design: Summary: Activated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis.

Overall design: Mice were engineered with negative control (MxCre- Fk1 L/L Fk2 L/L Afx L/L) and experimental (MxCre+ Fk1 L/L Fk2 L/L Afx L/L) genotypes. RNAs were isolated from Lung endothelial cells (2 negative controls, 2 experimental), liver sinusoidal endothelial cells (3 negative controls, 3 experimental) and thymus cells (2 negative controls, 2 experimental), and profiled on Affymetrix Mouse Genome 430 2.0 Array.

Background corr dist: KL-Divergence = 0.0486, L1-Distance = 0.0400, L2-Distance = 0.0023, Normal std = 0.5970

0.712 Kernel fit Pairwise Correlations Normal fit

Density 0.356

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

Lung EC,Lung control, EC,Lung control, rep1 EC,Lung (0.0352914) experimental, rep2 EC,Liver (0.0519653) experimental, sinusoidalLiver rep1 sinusoidal (0.024105)Liver rep2EC, sinusoidalcontrol, (0.0236421)Liver EC, sinusoidalcontrol, rep1Liver EC, (0.035913) sinusoidalcontrol, rep2Liver EC, (0.0588553) sinusoidalexperimental, rep3Thymus, EC, (0.0501477) experimental,Thymus, EC,control, rep1 experimental,Thymus, control, rep1(0.0912042) rep2 Thymus,(0.102104) experimental, rep2(0.123414) rep3 (0.0856579) experimental, (0.0888406) rep1 (0.0744332) rep2 (0.154427)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 836.3 1070.6 1277.0 P ( S | Z, I ) = 0.00 Atp6v0c 4914.5 7874.5 15683.1 Mean Corr = 0.27071Atp6v0b 1956.8 2778.5 4104.5 Sbf2 47.2 669.1 1352.6 Slc3a1 136.5 192.2 292.6 Mtmr2 410.1 516.5 627.6 Atp6ap1 1444.5 2635.8 3782.6 Abcb6 111.8 284.5 416.9 Tmem138 297.1 335.8 447.1 Vps4b 146.1 173.9 257.0 Trappc3 1235.9 1848.5 2553.2 BC022687 207.8 606.4 1461.8 Ankrd13c 1124.1 1339.8 1721.0 Mtmr11 137.5 246.6 511.6 Fahd1 136.5 216.8 313.6 CEM 1 + Pccb 1024.6 1478.2 1875.0 Top 10 Genes Bad 553.6 803.0 1001.9 Npl 149.6 416.3 964.9 Abca3 325.1 562.9 661.3 Rtn3 2673.8 2929.9 3641.5

Null module GEO Series "GSE27114" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.478 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

2_ESwt_a2_ESwt_b (0.165932)2_NPwt_a (0.13822)2_NPwt_b (0.180412)2_TNwt_a (0.0442981)2_TNwt_b (0.210799) (0.26034) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 464.0 894.9 11092.2 P ( S | Z, I ) = 0.00 Atp6v0c 5257.4 6502.3 24371.3 Mean Corr = 0.24316Atp6v0b 2234.6 3245.6 7677.9 Sbf2 749.5 972.7 1202.2 Slc3a1 38.2 43.6 54.3 Mtmr2 286.4 561.7 700.9 Atp6ap1 1656.5 2427.3 10121.8 Abcb6 393.4 954.0 1298.5 Tmem138 244.8 284.7 346.1 Vps4b 31.0 42.4 46.2 Trappc3 1420.4 1856.5 2963.5 BC022687 34.1 44.2 60.3 Ankrd13c 2090.2 2311.4 3631.2 Mtmr11 123.9 211.6 313.6 Fahd1 276.1 404.6 493.1 CEM 1 + Pccb 394.8 658.9 987.5 Top 10 Genes Bad 207.8 491.8 577.0 Npl 85.4 756.1 1482.9 Abca3 111.9 561.2 2606.5 Rtn3 1774.5 5918.5 27549.3

Null module GEO Series "GSE53951" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53951 Status: Public on Jan 10 2014 Title: Gene expression after type-I interferon treatment in primary neurons, primary fibroblasts and L929 cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24453359 Summary & Design: Summary: Microarray expression profilling of mouse primary mixed cortical/hippocampal neurons, primary fibroblasts and L929 cells to compare ISGs signature in disctinct cell types

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

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

0.611 Kernel fit Pairwise Correlations Normal fit

Density 0.305

0.000 CEM 1

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

Pre-normalization Quantiles

neurons_mock_sample1neurons_IFNb_sample1neurons_mock_sample2neurons_IFNb_sample2 (0.0854399)MEFs_mock_sample1 (0.125392)MEFs_IFNb_sample1 (0.181775)MEFs_mock_sample2 (0.118558) MEFs_IFNb_sample2(0.0840013) (0.0587955)L929_mock L929_IFNb(0.0418604) (0.121806) (0.0860995) (0.0962723) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 9.0 233.6 4082.1 P ( S | Z, I ) = 0.00 Atp6v0c 10201.2 12494.1 16165.2 Mean Corr = 0.20711Atp6v0b 1700.1 2254.9 3577.1 Sbf2 206.5 423.1 606.5 Slc3a1 5.0 33.2 53.2 Mtmr2 300.7 646.3 829.2 Atp6ap1 2973.2 3547.8 4129.1 Abcb6 286.4 397.0 690.9 Tmem138 90.4 204.5 391.0 Vps4b 58.3 76.9 127.6 Trappc3 2098.6 2243.7 2605.7 BC022687 277.1 482.4 904.1 Ankrd13c 1351.0 2509.7 2910.0 Mtmr11 45.2 482.3 668.9 Fahd1 199.3 267.6 551.8 CEM 1 + Pccb 409.5 496.9 819.6 Top 10 Genes Bad 742.1 810.8 1279.5 Npl 22.1 128.1 199.3 Abca3 5.0 167.4 692.5 Rtn3 3827.0 4801.8 15866.5

Null module GEO Series "GSE14406" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 54 -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=GSE14406 Status: Public on Jan 31 2009 Title: Oligodendroglial precursor cell line [Oli-neu] undergoing differentiation into myelin basic protein-producing cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19139271 Summary & Design: Summary: Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a specific role in oligodendrocyte differentiation we performed time dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the differentiated state where regulated gene sets overlap maximally.

In order to also gain insight into the functional role of genes that are regulated in this process, we silenced 88 of these genes using siRNA, and identified multiple repressors of spontaneous differentiation of Oli-neu, most of which were confirmed in rat primary oligodendrocyte precursors cells. Among these repressors were CNPase, a well-known myelin constituent, and three phosphatases, each known to negatively control MAP kinase cascades. We show that a novel inhibitor for one of the identified genes, dual-specificity phosphatase DUSP10/MKP5, was also capable of inducing oligodendrocyte differentiation in primary oligodendrocyte precursors. Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition

Keywords: time course

Overall design: triplicates for 3 times points 10h, 24h, 72h in 6 conditions, Forskolin, Insulin, Dexamethasone, Retinoic Acid, PD174265, Untreated. Arrays were done in two distinct experiments 1 and 2. Some replicates are missing because of lab operating issues

Background corr dist: KL-Divergence = 0.3521, L1-Distance = 0.0454, L2-Distance = 0.0041, Normal std = 0.2629

1.518 Kernel fit Pairwise Correlations Normal fit

Density 0.759

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

DexamethasoneDexamethasoneDexamethasone at 10 h,Dexamethasone atbiol. 10 rep1h,Dexamethasone atbiol. 10in rep2Exp1h,Dexamethasone atbiol. 24in (0.00286701) rep3Exp1h,Dexamethasone atbiol. 24in (0.0124458) rep1Exp1h,Dexamethasone atbiol. 24in (0.0144859) rep2Exp1h,Dexamethasone atbiol. 72in (0.0152059) rep3Exp1h,Forskolin atbiol. 72in (0.0172595) rep1Exp1h,Forskolin at biol.at 72 in10(0.0140561) rep2Exp1h, Forskolinh, biol. atbiol. in10(0.0218602) rep3Exp1 Forskolinrep1h, atbiol. in 24(0.0252608)in Exp1 Forskolinrep2Exp2h, atbiol. 24(0.0206277)in (0.0174041) Forskolinrep1Exp2h, atbiol. 72in (0.00975416) Forskolinrep2Exp2h, atbiol. 72in (0.00969428) Insulinrep1Exp2h, atbiol. 72in (0.0141269) atInsulinrep2Exp2h, 10 biol. h,in (0.00875352) atInsulinbiol.rep3Exp2 10 rep1h,in (0.0103401) atInsulinbiol.Exp2 24in rep2Exp2h, (0.0164251) atInsulinbiol. 24in (0.0164473) rep1Exp2h, atInsulinbiol. 72in (0.0410459) rep2Exp2h, atPD174265biol. 72in (0.02248) rep1Exp2h, PD174265biol. in at(0.0233909) rep2Exp210PD174265 h, in at(0.0221565)biol. Exp210PD174265 rep1h, at(0.0190257)biol. 10inPD174265 rep2Exp1h, atbiol. 24in (0.0173436)PD174265 rep3Exp1h, atbiol. 24in (0.0132689)PD174265 rep1Exp1h, atbiol. 24in (0.00867049)PD174265 rep2Exp1h, atbiol. 72in (0.0351338)PD174265 rep3Exp1h, atbiol. 72in (0.0170592)RetinoicAcid rep1Exp1h, atbiol. 72in (0.017289)RetinoicAcid rep2Exp1h, biol. inat (0.0312876)RetinoicAcid rep3Exp110 h, inatbiol.(0.0361045)RetinoicAcid Exp110 rep1h, atbiol.(0.0709336)RetinoicAcid 10in rep2Exp1h, atbiol.RetinoicAcid 24in (0.00854596) rep3Exp1h, atbiol.RetinoicAcid 24in (0.0110703) rep1Exp1h, atbiol.RetinoicAcid 24in (0.030062) rep2Exp1h, atbiol.RetinoicAcid 72in (0.0065312) rep3Exp1h, atbiol.Untreated 72in (0.0139234) rep1Exp1h, atbiol.Untreated 72in (0.00704916) at rep2Exp1h, 10 biol.Untreated h,in (0.00681313) at biol.rep3Exp1 10Untreated rep1 h,in (0.00846539) at biol.Exp1 10inUntreated rep2Exp1h, (0.00639372) atbiol. 10in (0.0363739)Untreated rep1Exp1h, atbiol. 24in (0.0139449)Untreated rep2Exp2h, atbiol. 24in (0.00982427)Untreated rep1Exp2h, atbiol. 24in (0.0279223)Untreated rep2Exp1h, atbiol. 24in (0.0127788)Untreated rep3Exp1h, atbiol. 72in (0.00603449)Untreated rep1Exp1h, atbiol. 72in (0.0101428)Untreated rep1Exp2h, atbiol. 72in (0.0207654)Untreated rep2Exp1h, atbiol. 72in (0.0581919)Untreated rep3Exp1h, atbiol. 72in (0.0229537) rep1Exp1h, atbiol. 72in (0.00801194) rep2Exp2h, biol. in (0.0191442) rep3Exp2 in (0.0296463)[ Exp2 min (0.00320647) ] [ medium ] [ max ] CEM 1 Slc22a17 1392.9 2524.3 4015.3 P ( S | Z, I ) = 0.00 Atp6v0c 8845.8 13185.0 17799.2 Mean Corr = 0.20826Atp6v0b 3439.6 4802.3 8500.8 Sbf2 261.0 426.9 682.2 Slc3a1 3.2 41.2 157.1 Mtmr2 292.1 1051.5 2294.1 Atp6ap1 3926.7 5076.0 7695.5 Abcb6 1.9 3.2 39.8 Tmem138 30.2 120.2 246.5 Vps4b 2.5 80.6 150.3 Trappc3 933.8 2550.9 3130.2 BC022687 122.7 191.5 344.6 Ankrd13c 1399.5 1788.8 2589.8 Mtmr11 1.6 16.9 78.7 Fahd1 229.3 310.6 499.3 CEM 1 + Pccb 627.7 1285.3 1753.2 Top 10 Genes Bad 655.1 1070.8 1733.4 Npl 663.6 1224.3 1710.1 Abca3 458.8 941.6 1512.9 Rtn3 6238.1 7124.1 9576.2

Null module GEO Series "GSE38409" 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=GSE38409 Status: Public on Jun 02 2012 Title: Expression data from mouse lungs, exposed in-utero to second-hand smoke (SHS) and challenged with ovalbumin (OVA) as adults. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23898987 Summary & Design: Summary: SHS exposure during pregnancy has adverse effects on offspring.

We used microarrays to characterize the gene expression changes caused by in-utero SHS exposure and adult (19-23 weeks) OVA challenge in 23-week mouse lungs.

Overall design: Left lungs from Balb/c male and female mice were collected at 23 weeks of age for RNA extraction and hybridization on Affymetrix mouse 430 2.0 microarrays. Based on the gender differences and in-utero exposure status, there are 4 groups of mice, females and males, exposed in-utero to filtered-air or SHS. All were exposure to OVA (19-23 weeks). We extracted RNA from 4 animals from each group for microarray analysis (total N = 16 samples).

Background corr dist: KL-Divergence = 0.0488, L1-Distance = 0.0396, L2-Distance = 0.0021, Normal std = 0.5850

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

Lung_AF_biologicalLung_AF_biologicalLung_AF_biological rep1Lung_AF_biological (0.040294) rep2Lung_AM_biological (0.0621845) rep3Lung_AM_biological (0.103225) rep4Lung_AM_biological (0.0748854) rep1Lung_AM_biological (0.0467676) rep2Lung_EF_biological (0.0855205) rep3Lung_EF_biological (0.068826) rep4Lung_EF_biological (0.0624894) rep1Lung_EF_biological (0.0494846) rep2Lung_EM_biological (0.074848) rep3Lung_EM_biological (0.0402765) rep4Lung_EM_biological (0.0946856) rep1Lung_EM_biological (0.039273) rep2 (0.064662) rep3 (0.0607947) rep4 (0.031783)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 401.2 529.6 592.7 P ( S | Z, I ) = 0.00 Atp6v0c 6429.4 9905.6 11794.5 Mean Corr = 0.13511Atp6v0b 335.9 1905.2 2767.2 Sbf2 265.5 381.0 490.1 Slc3a1 44.2 57.6 76.7 Mtmr2 494.9 676.3 898.7 Atp6ap1 3923.5 4300.2 4849.2 Abcb6 280.4 342.9 416.1 Tmem138 144.7 201.4 261.1 Vps4b 95.4 150.9 191.2 Trappc3 1401.4 1782.5 2287.4 BC022687 150.1 192.1 215.7 Ankrd13c 2020.7 2750.1 2973.6 Mtmr11 149.2 180.3 222.3 Fahd1 183.9 234.4 270.7 CEM 1 + Pccb 574.8 873.0 1118.6 Top 10 Genes Bad 453.2 551.5 668.1 Npl 178.9 298.7 428.9 Abca3 1011.0 1903.7 2703.9 Rtn3 4789.0 5154.9 5602.5

Null module GEO Series "GSE9803" 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=GSE9803 Status: Public on Dec 17 2007 Title: Striatal gene expression data from 12 weeks-old R6/2 mice and control mice (set 1) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17519223 Summary & Design: Summary: To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.

Keywords: genetic modification

Overall design: Striatal samples from 4 R6/2 mutant mice (12 weeks-old) and 5 age-matched wild-type mice.

Background corr dist: KL-Divergence = 0.0775, L1-Distance = 0.0213, L2-Distance = 0.0006, Normal std = 0.4814

0.829 Kernel fit Pairwise Correlations Normal fit

Density 0.414

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

striatum_wildtype_48striatum_wildtype_45striatum_wildtype_42 (0.0552448)striatum_wildtype_54 (0.0993427)striatum_wildtype_63 (0.145737)striatum_R62_64 (0.105686)striatum_R62_65 (0.0543593)striatum_R62_78 (0.105166)striatum_R62_70 (0.110096) (0.0866386) (0.237729) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 6474.3 7609.0 9337.5 P ( S | Z, I ) = 0.00 Atp6v0c 17577.7 18233.9 21892.2 Mean Corr = 0.31998Atp6v0b 3760.8 4346.8 5162.4 Sbf2 241.5 267.0 357.3 Slc3a1 46.8 51.3 54.1 Mtmr2 121.6 184.1 226.2 Atp6ap1 5450.3 6268.8 7993.2 Abcb6 538.2 630.4 690.2 Tmem138 215.1 277.3 307.7 Vps4b 110.6 146.9 180.2 Trappc3 1999.3 2457.8 3360.6 BC022687 91.8 127.5 172.1 Ankrd13c 3311.4 3786.4 4379.3 Mtmr11 106.1 117.2 147.3 Fahd1 136.2 216.3 258.4 CEM 1 + Pccb 637.7 897.9 1083.0 Top 10 Genes Bad 335.8 388.0 456.8 Npl 129.1 158.4 203.1 Abca3 486.2 555.2 661.9 Rtn3 19101.3 20388.6 22440.4

Null module GEO Series "GSE46970" 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=GSE46970 Status: Public on Jun 18 2013 Title: Gene expression of 4, 5, and 6 days differentiated Flk1+ WT ES cells, and of 6 days differentiated Flk1+ Runx1-/- and Tal-1-/- ES cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19265543 Summary & Design: Summary: In order to identify genes that are activated in differentiating WT ESCs, but are missing in Tal-1-/- and Runx1-/- ESCs, and which might be involved in the generation of definitive hematopoietic progenitors and their specification thereafter, we performed microarray analyses on purified Flk-1+ cells, differentiated from these ESCs for 4, 5, and 6 days in vitro.

Overall design: Gene-expression profiling of three biological replicates was performed at days 4, 5, and 6 during the differentiation process of WT J1 ESCs (9 samples), and at day 6 during the differentiation process of either Runx1-/- J1 or Tal-1-/- J1 ESCs (3 samples each). Total RNA was extracted using the RNeasy Mini kit (Qiagen). The integrity and amount of isolated RNA was assessed for each sample using an Agilent 2100 Bioanalyzer (Agilent, Waldbronn, Germany) and a NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE). Complementary DNA was synthesized from 3-5 Î¼g total RNA, using reagents recommended in the technical manual GeneChip Expression Analysis (Affymetrix, Santa Clara, CA). The in vitro transcription, necessary for the synthesis of biotinylated complementary RNA (cRNA) was performed using the Enzo RNA Transcript Labeling kit (Affymetrix). Fifteen micrograms of fragmented cRNA of each sample were hybridized to nine Mouse Genome 430-2 arrays (Affymetrix). Hybridization was performed in a Hybridization Oven 640, and chips were washed and stained in the Fluidics Station 400 (both Affymetrix), according to procedure 2 as described in the technical manual. Finally, the arrays were scanned with a GeneChip Scanner 3000 using the GCOS software, both Affymetrix. All relevant GCOS data of quality checked microarrays were analyzed with High Performance Chip Data Analysis (HPCDA, unpublished), using the BioRetis database (www.bioretis-analysis.de), as described and validated previously (55). Used query parameters for database filtering process was described earlier several times (56). For hierarchical cluster analysis, we used the program Genes@Work (57) with gene vectors for normalization and Pearson w/mean for similarity measure. As cluster type, we used center of mass.

Background corr dist: KL-Divergence = 0.1350, L1-Distance = 0.0345, L2-Distance = 0.0023, Normal std = 0.3999

1.009 Kernel fit Pairwise Correlations Normal fit

Density 0.505

0.000 CEM 1

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

Pre-normalization Quantiles

129_Sv_1_WT_d4_4302129_Sv_2_WT_d4_4302129_Sv_3_WT_d4_4302129_Sv_1_WT_d5_4302 (0.0908067)129_Sv_2_WT_d5_4302 (0.0509071)129_Sv_3_WT_d5_4302 (0.0838012)129_Sv_1_WT_d6_4302 (0.031334)129_Sv_2_WT_d6_4302 (0.0546177)129_Sv_3_WT_d6_4302 (0.082525)129_Sv_1_Runx1_Ko_d6_4302 (0.0180628)129_Sv_2_Runx1_Ko_d6_4302 (0.0244597)129_Sv_3_Runx1_Ko_d6_4302 (0.0330991)129_Sv_1_Tal1_Ko_d6_4302129_Sv_2_Tal1_Ko_d6_4302 (0.0142048)129_Sv_3_Tal1_Ko_d6_4302 (0.262804) (0.10314) (0.018554) (0.0378385) (0.0938452)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 110.9 259.0 569.1 P ( S | Z, I ) = 0.00 Atp6v0c 8763.7 9895.5 13895.0 Mean Corr = 0.18553Atp6v0b 211.6 291.4 719.5 Sbf2 97.3 198.3 355.0 Slc3a1 5.0 11.7 56.6 Mtmr2 450.1 633.3 894.8 Atp6ap1 1535.4 2135.8 3818.3 Abcb6 374.0 948.3 1159.8 Tmem138 116.2 172.3 285.8 Vps4b 29.4 72.4 118.0 Trappc3 1129.6 1502.2 1776.1 BC022687 107.5 161.7 300.3 Ankrd13c 1492.9 1768.8 2413.2 Mtmr11 34.1 105.4 134.4 Fahd1 227.9 288.2 356.6 CEM 1 + Pccb 380.0 563.3 765.9 Top 10 Genes Bad 290.7 440.2 978.6 Npl 97.5 1170.2 2468.7 Abca3 5.0 40.5 144.9 Rtn3 3014.2 4877.9 6874.6

Null module GEO Series "GSE22073" 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=GSE22073 Status: Public on Jun 02 2010 Title: Testis samples from Alkbh1 wild-type and KO mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21072209 Summary & Design: Summary: The aim of the study was to elucidate the role of Alkbh1 by targeted deletion in C57/BL6 mice.

Alkb deficiency results in sex-ratio distortion of offspring and apoptosis in adult testes, most likely caused by defects in the pachytene stage during spermatogenesis.

Due to the pivotal role of Alkbh1 in mouse survival and potentially in germ cells, we searched for Alkbh1-regulated genes in adult testes.

Overall design: Testes from 12 week old mice were selected for RNA extraction and hybridization on Affymetrix microarrays. We used testes from 3 wild type mice and 3 KO mice

Background corr dist: KL-Divergence = 0.0352, L1-Distance = 0.0146, L2-Distance = 0.0002, Normal std = 0.6347

0.630 Kernel fit Pairwise Correlations Normal fit

Density 0.315

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

Testis, WT,Testis, biological WT,Testis, biological replicateWT,Testis, biological replicateAlkbh1Testis, 1 (0.404741) replicateAlkbh1KO,Testis, 2 (0.235561) biological Alkbh1KO, 3 (0.149226) biological replicateKO, biological replicate 1 (0.0932965) replicate[ 2 min(0.045894) 3 (0.0712811)] [ medium ] [ max ] CEM 1 Slc22a17 476.2 497.6 569.7 P ( S | Z, I ) = 0.00 Atp6v0c 5180.6 5508.6 5790.2 Mean Corr = 0.30253Atp6v0b 849.3 890.3 1000.2 Sbf2 691.4 739.4 773.7 Slc3a1 47.7 61.0 61.3 Mtmr2 707.8 807.0 819.1 Atp6ap1 636.5 687.6 705.9 Abcb6 1305.7 1466.4 1631.8 Tmem138 168.3 182.7 200.2 Vps4b 17.8 23.4 28.1 Trappc3 622.4 651.7 695.6 BC022687 857.3 896.4 940.0 Ankrd13c 484.6 505.7 539.7 Mtmr11 34.0 38.9 42.7 Fahd1 329.1 415.4 428.4 CEM 1 + Pccb 386.5 400.5 486.4 Top 10 Genes Bad 1050.0 1170.9 1237.8 Npl 565.2 674.1 694.9 Abca3 189.1 225.1 233.4 Rtn3 2796.9 2873.5 3195.0

Null module GEO Series "GSE12950" 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=GSE12950 Status: Public on Nov 01 2008 Title: Gene expression profile of testes from three mouse strains, AKR/N, C57BL/6 and MRL/MpJ+/+ Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+.

Overall design: Total RNA of testes from 3 different strains of mice, C57BL/6, AKR/N and MRL/MpJ-+/+, were analyzed using microarray 430.20 chip. All mice were 8 weeks old, 2 mice/strain.

Background corr dist: KL-Divergence = 0.0405, L1-Distance = 0.0184, L2-Distance = 0.0003, Normal std = 0.6139

0.658 Kernel fit Pairwise Correlations Normal fit

Density 0.329

0.000 CEM 1

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

Pre-normalization Quantiles

mtestis_AKR-N_rep1mtestis_C57BL-6_rep1mtestis_C57BL-6_rep2 (0.180912)mtestis_MRL-MPJ_rep1mtestis_MRL-MPJ_rep2 (0.141357)mtestis_AKR-N_rep2 (0.318014) (0.0582955) (0.228085) (0.0733373)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 308.4 422.3 523.7 P ( S | Z, I ) = 0.00 Atp6v0c 4287.1 6373.7 6743.0 Mean Corr = 0.32180Atp6v0b 1205.9 1428.7 1475.6 Sbf2 596.7 899.4 1006.0 Slc3a1 4.7 62.8 82.2 Mtmr2 461.7 670.9 716.4 Atp6ap1 476.7 709.3 739.0 Abcb6 1330.3 1470.1 1754.2 Tmem138 173.5 228.8 305.6 Vps4b 38.5 58.2 79.1 Trappc3 585.0 812.5 898.6 BC022687 462.9 585.0 778.8 Ankrd13c 441.3 511.8 665.3 Mtmr11 4.8 14.9 26.4 Fahd1 214.5 250.2 474.6 CEM 1 + Pccb 534.6 1009.0 1031.9 Top 10 Genes Bad 1097.1 1235.2 1299.0 Npl 353.9 560.0 685.3 Abca3 171.9 246.8 296.1 Rtn3 2125.1 2717.7 3337.6

Null module GEO Series "GSE23895" 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=GSE23895 Status: Public on Jan 19 2011 Title: Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21226930 Summary & Design: Summary: Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency.

Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 ´g Se/g diet.

Overall design: Rats or mice were fed Se-deficient diets supplemented with sodium selenite up to 5 ug Se/g diet for 28 or 35 days. Affymetrix Rat 230 2.0 and Mouse 430 2.0 Genome Arrays were used to analyze gene expression in liver in all studies plus kidney in the mouse study.

Background corr dist: KL-Divergence = 0.0133, L1-Distance = 0.0509, L2-Distance = 0.0031, Normal std = 0.9121

0.437 Kernel fit Pairwise Correlations Normal fit

Density 0.219

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

MouseLiver_SeDef_rep1MouseLiver_SeDef_rep2MouseLiver_SeDef_rep3MouseLiver_0.05ugSe_rep1 (0.068738)MouseLiver_0.05ugSe_rep2 (0.0563595)MouseLiver_0.05ugSe_rep3 (0.060735)MouseLiver_0.2ugSe_rep1 (0.0414231)MouseLiver_0.2ugSe_rep2 (0.0462581)MouseLiver_0.2ugSe_rep3 (0.0430247)MouseKidney_SeDef_rep1 (0.0558138)MouseKidney_SeDef_rep2 (0.0449371)MouseKidney_SeDef_rep3 (0.0362832)MouseKidney_0.05ugSe_rep1 (0.0588915)MouseKidney_0.05ugSe_rep2 (0.0439796)MouseKidney_0.05ugSe_rep3 (0.063605)MouseKidney_0.2ugSe_rep1 MouseKidney_0.2ugSe_rep2(0.0603629) MouseKidney_0.2ugSe_rep3(0.0578143) (0.0374311) (0.0815148) (0.0461679) (0.0966603)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 224.0 743.1 921.0 P ( S | Z, I ) = 0.00 Atp6v0c 9195.5 14839.1 17591.0 Mean Corr = 0.23082Atp6v0b 1385.9 1715.8 3299.2 Sbf2 202.3 270.3 290.1 Slc3a1 333.7 11835.1 13694.0 Mtmr2 329.7 387.2 496.4 Atp6ap1 1335.2 3493.4 4125.6 Abcb6 638.3 2177.3 3129.0 Tmem138 339.4 429.6 531.9 Vps4b 121.7 149.8 176.5 Trappc3 1907.7 2246.5 2628.0 BC022687 23.8 274.2 508.5 Ankrd13c 677.4 5809.1 6703.2 Mtmr11 163.3 1312.0 1870.7 Fahd1 882.5 2027.6 2871.9 CEM 1 + Pccb 2956.5 3832.7 5138.2 Top 10 Genes Bad 251.1 312.3 349.4 Npl 156.7 529.8 989.8 Abca3 561.0 1590.8 1974.7 Rtn3 1854.7 5363.2 7217.3

Null module GEO Series "GSE24614" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.499 Kernel fit Pairwise Correlations Normal fit

Density 0.250

0.000 CEM 1

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

Pre-normalization Quantiles

WT fetalWT liver fetal expressionWT liver fetal expressionhLCR liver replicate knock-inexpressionhLCR replicate 1 knock-in(0.18891) hLCRfetal replicate 2 liver knock-in(0.104974) fetal expression 3 liver (0.23772) fetal expression liver replicate expression replicate[ 1 min(0.109812) replicate 2 (0.14379) ] 3 (0.214793)[ medium ] [ max ] CEM 1 Slc22a17 168.1 235.9 260.9 P ( S | Z, I ) = 0.00 Atp6v0c 11209.4 11712.2 12361.7 Mean Corr = 0.29082Atp6v0b 2165.8 2713.6 3074.5 Sbf2 83.4 188.8 214.8 Slc3a1 104.2 114.2 133.0 Mtmr2 94.5 278.9 434.8 Atp6ap1 2613.0 3235.7 3828.6 Abcb6 2758.5 3249.0 3670.3 Tmem138 192.8 267.8 284.3 Vps4b 46.7 54.8 57.8 Trappc3 1340.8 1512.0 1905.2 BC022687 26.6 28.2 29.7 Ankrd13c 1331.1 1737.2 2144.3 Mtmr11 111.7 137.0 150.0 Fahd1 464.5 912.3 1093.4 CEM 1 + Pccb 795.7 959.2 1071.7 Top 10 Genes Bad 951.5 1076.3 1203.3 Npl 374.1 793.4 1006.0 Abca3 376.5 387.9 426.0 Rtn3 4577.3 5342.1 5952.0

Null module GEO Series "GSE22371" 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=GSE22371 Status: Public on Jul 27 2010 Title: Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20615956 Summary & Design: Summary: Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.

Overall design: Mouse E14.5 neocortices and Postnatal day (P) 0.5 brains: E14.5 neocortices KO, 3; E14.5 neocortices WT, 3; Postnatal day (P) 0.5 brains frontal WT, 4; Postnatal day (P) 0.5 brains frontal KO, 4; Postnatal day (P) 0.5 brains parietal WT, 4; Postnatal day (P) 0.5 brains parietal KO, 4; Postnatal day (P) 0.5 brains occipital WT, 4; Postnatal day (P) 0.5 brains occipital KO, 4.

Background corr dist: KL-Divergence = 0.0236, L1-Distance = 0.0109, L2-Distance = 0.0001, Normal std = 0.7039

0.567 Kernel fit Pairwise Correlations Normal fit

Density 0.283

0.000 CEM 1

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

Pre-normalization Quantiles

E14.5_KO_1E14.5_KO_2 (0.344506)E14.5_KO_3 (0.276081)E14.5_wt_1 (0.0892999)E14.5_wt_2 (0.0386582)E14.5_wt_3 (0.0307542) (0.220701) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 2812.4 4121.2 4221.7 P ( S | Z, I ) = 0.00 Atp6v0c 11073.2 13942.7 17123.7 Mean Corr = 0.29761Atp6v0b 2633.7 3955.2 5980.5 Sbf2 268.3 337.5 435.3 Slc3a1 98.6 109.2 131.5 Mtmr2 137.6 277.8 370.7 Atp6ap1 3024.5 4092.9 5075.2 Abcb6 485.0 576.9 809.2 Tmem138 190.6 222.8 285.7 Vps4b 52.4 58.4 60.3 Trappc3 2969.1 4016.2 4734.4 BC022687 128.2 192.0 282.0 Ankrd13c 94.7 221.6 288.5 Mtmr11 173.8 216.3 323.4 Fahd1 176.5 218.0 225.2 CEM 1 + Pccb 1270.8 1455.2 1969.8 Top 10 Genes Bad 616.9 760.1 1201.1 Npl 170.8 245.3 411.7 Abca3 369.8 450.9 575.1 Rtn3 7907.8 9108.0 11604.7

Null module GEO Series "GSE14211" 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=GSE14211 Status: Public on Oct 01 2011 Title: Expression profiling of Noto-GFP+ notochord progenitor cells sorted from E8.5 mouse embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22008794 Summary & Design: Summary: Using a combination of cell sorting and microarray analysis, we identified almost 200 genes as having a high level of expression in the notochord.

After whole mount in situ hybridization screening, we confirmed approximately one third of these as having a novel notochord expression pattern.

Keywords: cell type comparison - embryonic Noto-GFP+ notochord progenitors versus surrounding GFP- comparator cells

Overall design: 3 biological replicates - each replicate includes an experiment cell population (Noto-GFP positive cell sort) and a comparator population (GFP negative cell sort)

Background corr dist: KL-Divergence = 0.0298, L1-Distance = 0.0329, L2-Distance = 0.0014, Normal std = 0.6893

0.583 Kernel fit Pairwise Correlations Normal fit

Density 0.292

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

Noto-GFP_positive_sort_rep1Noto-GFP_positive_sort_rep2Noto-GFP_positive_sort_rep3Noto-GFP_negative_sort_rep1 Noto-GFP_negative_sort_rep2(0.149677) Noto-GFP_negative_sort_rep3(0.143958) (0.117953) (0.278227) (0.181571)[ (0.128613) min ] [ medium ] [ max ] CEM 1 Slc22a17 201.9 319.7 367.6 P ( S | Z, I ) = 0.00 Atp6v0c 2274.6 5775.4 6633.8 Mean Corr = 0.38212Atp6v0b 834.3 2415.2 2710.3 Sbf2 27.4 71.7 119.4 Slc3a1 3.4 41.6 62.1 Mtmr2 123.0 225.0 302.5 Atp6ap1 1466.8 2419.5 3225.4 Abcb6 304.0 590.3 701.6 Tmem138 75.6 208.1 212.1 Vps4b 45.1 65.9 75.1 Trappc3 904.5 1503.0 2429.5 BC022687 41.8 113.6 139.4 Ankrd13c 621.9 1021.1 1491.4 Mtmr11 41.2 78.4 97.1 Fahd1 76.8 89.8 149.6 CEM 1 + Pccb 232.1 297.7 412.3 Top 10 Genes Bad 124.5 200.0 339.4 Npl 164.1 223.5 324.1 Abca3 11.6 36.6 51.4 Rtn3 7564.0 9892.7 10274.5

Null module GEO Series "GSE6589" 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=GSE6589 Status: Public on Dec 23 2006 Title: Gene expression profiles of components isolated from developing kidney at E15.5 using LCM. (GUDMAP Series ID: 12) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in laser capture microdissected components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone.

Keywords: Comparison of kidney components.

Overall design: At specific developmental time points we isolate discrete elements of the kidney by using laser capture microdissection and then define their gene expression profiles with microarrays.

Background corr dist: KL-Divergence = 0.1337, L1-Distance = 0.0480, L2-Distance = 0.0054, Normal std = 0.3999

0.998 Kernel fit Pairwise Correlations Normal fit

Density 0.499

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

CCD_1_7_07_06CorticalProxtubules Collecting (0.0716073)Proxtubules Duct _1_7_07_06Proxtubules_1_6_13_06 (0.0301357) 2_6_13_06UreteralSmoothmuscle_2_4_11_06 (0.0820265)UreteralSmoothmuscle_2_7_07_06 (0.200621)UreteralSmoothmuscle3_1_6_06 (0.311359)Urothelium_1_4_11_06Urothelium5_1_6_06 (0.0635993)Urothelium6_1_6_06 (0.0536083) (0.0333788) (0.0649622) (0.0493966) (0.0393057)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 308.4 644.2 1981.0 P ( S | Z, I ) = 0.00 Atp6v0c 796.8 1726.9 2962.0 Mean Corr = 0.32843Atp6v0b 141.8 290.0 557.6 Sbf2 6.3 61.5 537.6 Slc3a1 33.4 148.6 4375.7 Mtmr2 86.8 245.8 402.8 Atp6ap1 2705.3 3416.4 5419.8 Abcb6 621.6 1264.2 5381.8 Tmem138 183.6 430.3 851.7 Vps4b 33.2 303.7 803.4 Trappc3 1023.3 1489.3 2366.1 BC022687 8.0 61.4 154.0 Ankrd13c 1174.4 2760.4 3928.3 Mtmr11 150.2 241.3 3587.2 Fahd1 3.7 114.0 225.8 CEM 1 + Pccb 158.0 396.6 815.2 Top 10 Genes Bad 78.2 165.2 513.9 Npl 7.1 214.1 302.2 Abca3 13.7 85.8 290.9 Rtn3 8132.9 10697.3 14470.6

Null module GEO Series "GSE12499" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Overall design: - NSC_4

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

0.465 Kernel fit Pairwise Correlations Normal fit

Density 0.233

0.000 CEM 1

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

Pre-normalization Quantiles

NSCs-derivedNSCs-derived iPSNSCs-derived cells iPSOne-factor by cells one-factor iPSOne-factor by cells (Oct4)one-factor One-factor(Oct4) by iPS (Oct4)one-factor cell-derivedsample_1 Neural(Oct4) iPS (Oct4) cell-derivedsample_2stem Neural(Oct4) (0.0477425) iPS NSCs cell cell-derivedsample_3stemNeural sample_1(0.0286551) sample_1 NSCs cell stemNeural sample_2(0.0772393) sample_2 NSCs(0.0844724) cell (0.135627) stem sample_3 sample_3 (0.0666338) cell (0.186947) sample_4 (0.0595303) (0.163388) (0.149765)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 195.2 1034.9 1707.2 P ( S | Z, I ) = 0.00 Atp6v0c 8687.7 10528.9 12992.0 Mean Corr = 0.26175Atp6v0b 1445.1 2027.6 2282.8 Sbf2 249.4 723.7 869.4 Slc3a1 31.6 43.0 50.7 Mtmr2 483.3 659.0 1101.2 Atp6ap1 1193.4 3784.8 5120.9 Abcb6 611.3 1262.1 1580.3 Tmem138 239.2 461.1 695.2 Vps4b 26.4 44.8 49.3 Trappc3 1717.7 2389.3 2527.5 BC022687 73.8 148.7 274.5 Ankrd13c 1899.2 3810.4 4046.3 Mtmr11 47.6 448.1 752.7 Fahd1 240.4 317.7 390.1 CEM 1 + Pccb 693.1 1133.1 1215.3 Top 10 Genes Bad 336.1 513.7 642.9 Npl 2068.7 2828.4 3896.8 Abca3 51.1 228.8 320.6 Rtn3 1868.6 8019.4 11440.1

Null module GEO Series "GSE45043" 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=GSE45043 Status: Public on May 29 2013 Title: Age-mediated transcriptomic changes in adult mouse substantia nigra Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23638090 Summary & Design: Summary: Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques.

Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice.

Overall design: Three age groups of C57 wild type mice were used in microarray analysis: young (2 months old), middle aged (10 months old), and late-middle aged (18 months old) mice. Four replicates were included in each age group and each replicate was pooled from 4 mice (4 mice/replicate x 4 replicates x 3 age groups). Total RNA was isolated from SNpc for hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0738, L1-Distance = 0.0392, L2-Distance = 0.0021, Normal std = 0.5110

0.826 Kernel fit Pairwise Correlations Normal fit

Density 0.413

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

SNpc_2SNpc_2 monthsSNpc_2 months old_rep1SNpc_2 months old_rep2 (0.0518855)SNpc_10 months old_rep3 (0.0470576)SNpc_10 old_rep4months (0.014489)SNpc_10 months old_rep1 (0.197977)SNpc_10 months old_rep2 (0.144224)SNpc_18 months old_rep3 (0.135033)SNpc_18 months old_rep4 (0.0561307)SNpc_18 months old_rep1 (0.0607135)SNpc_18 months old_rep2 (0.0421224) months old_rep3 (0.144118) old_rep4 (0.0390964) (0.0671524)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 1681.3 2019.6 5184.2 P ( S | Z, I ) = 0.00 Atp6v0c 7575.9 8333.2 10357.1 Mean Corr = 0.07505Atp6v0b 709.4 1110.7 1589.3 Sbf2 79.5 93.7 116.4 Slc3a1 65.2 104.5 136.7 Mtmr2 64.7 98.9 117.2 Atp6ap1 4480.2 4922.6 7320.3 Abcb6 263.8 322.0 431.5 Tmem138 147.1 159.7 203.0 Vps4b 130.5 154.6 178.8 Trappc3 2299.4 2615.5 2879.7 BC022687 62.0 76.4 92.7 Ankrd13c 2365.6 2714.4 3126.8 Mtmr11 143.9 180.6 222.7 Fahd1 76.9 124.2 169.6 CEM 1 + Pccb 268.3 309.6 397.5 Top 10 Genes Bad 92.0 112.2 145.0 Npl 158.0 205.3 230.1 Abca3 335.6 384.5 468.0 Rtn3 23132.6 24012.9 28372.1

Null module GEO Series "GSE55028" 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=GSE55028 Status: Public on Apr 01 2014 Title: CMPF alters expression of genes related to metabolism in isolated mouse islets Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: CMPF is elevated in diabetes and is associated with impaired insulin secretion. We used microarrays to determine the effect of CMPF on gene expression in isolated islets.

Overall design: Isolated islets from male CD1 mice were treated for 24h with vehicle control or 200uM CMPF.

Background corr dist: KL-Divergence = 0.0294, L1-Distance = 0.0116, L2-Distance = 0.0001, Normal std = 0.6652

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

ControlControl Islets 1Control Islets(0.126747) 2CMPF Islets(0.190745) Islets3CMPF (0.0390907) 1 Islets(0.332329)CMPF 2 Islets(0.207082) 3 (0.104006) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 563.1 589.7 670.9 P ( S | Z, I ) = 0.00 Atp6v0c 13949.8 15002.4 16000.5 Mean Corr = 0.23678Atp6v0b 1027.6 1294.3 1594.4 Sbf2 105.7 132.9 156.3 Slc3a1 44.0 61.3 68.4 Mtmr2 733.2 782.9 911.4 Atp6ap1 11313.5 12665.4 14149.2 Abcb6 507.8 623.5 677.8 Tmem138 145.1 156.7 185.1 Vps4b 158.4 176.5 192.5 Trappc3 2396.3 2644.4 2806.7 BC022687 438.2 506.4 532.7 Ankrd13c 3193.4 3414.8 3657.2 Mtmr11 385.4 476.4 571.6 Fahd1 519.4 553.4 627.1 CEM 1 + Pccb 1061.3 1165.4 1194.3 Top 10 Genes Bad 495.3 562.1 586.6 Npl 91.8 127.7 146.7 Abca3 781.1 839.9 965.9 Rtn3 6709.8 7546.1 8028.3

Null module GEO Series "GSE11291" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 60 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11291 Status: Public on Jun 10 2008 Title: Effect of age, calorie restriction and resveratrol on gene expression in mouse heart, brain, and skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18523577 Summary & Design: Summary: Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles.

We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

Keywords: aging intervention study

Overall design: Heart, neocortex tissue, and gastrocnemius muscle was collected from young and old mice at 5 and 30 months of age, respectively; mice were subjected to either a calorie restricted diet or a control diet supplemented with resveratrol

Background corr dist: KL-Divergence = 0.0995, L1-Distance = 0.0458, L2-Distance = 0.0038, Normal std = 0.4744

0.888 Kernel fit Pairwise Correlations Normal fit

Density 0.444

0.000 CEM 1

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

Pre-normalization Quantiles

heart-5 heart-5months heart-5months of age-control heart-5months of age-control heart-5 months diet-biologicalof age-control heart-30 months diet-biologicalof age-controlheart-30 replicate1diet-biological ofmonths age-controlheart-30 replicate2diet-biological months of (0.00881921) age-controlheart-30 replicate3diet-biological months of (0.0134799) age-controlheart-30 replicate4 months diet-biologicalof (0.0224699) age-controlheart-30 replicate5 months diet-biologicalof (0.0108941) age-controlheart-30 months replicate1diet-biologicalof (0.0116687) age-controlheart-30 months replicate2diet-biologicalof age-CR(0.0136467)heart-30 months replicate3diet-biologicalof age-CR(0.01444)diet-biologicalheart-30 months replicate4of age-CR(0.00953351)diet-biologicalheart-30 months replicate5of age-CR(0.0134489)replicate1diet-biologicalheart-30 months of age-CR(0.00737757)replicate2diet-biologicalheart-30 (0.0115568) months of age-resveratrolreplicate3diet-biologicalheart-30 (0.0358827) months of age-resveratrolreplicate4heart-30 (0.0132454) months of age-resveratrol replicate5diet-biologicalgastrocnemius-5 (0.023193) months of age-resveratrol diet-biologicalgastrocnemius-5 (0.0161178) of age, replicate1diet-biologicalgastrocnemius-5 resveratrolmonths replicate2diet-biologicalgastrocnemius-5 (0.00984697) months of replicate3age-controldiet-biologicalgastrocnemius-5 (0.00693626) months of replicate4age-controlgastrocnemius-30 (0.00870622) months diet-biologicalof age-controlreplicate5gastrocnemius-30 (0.00955154) months diet-biologicalof age-controlgastrocnemius-30 (0.0195519) replicate1diet-biological ofmonths age-controlgastrocnemius-30 replicate2diet-biological months of (0.0112705) age-controlgastrocnemius-30 replicate3diet-biological months of (0.0102866) age-controlgastrocnemius-30 replicate4 months diet-biologicalof (0.0141153) age-controlgastrocnemius-30 replicate5 months diet-biologicalof (0.016642) age-controlgastrocnemius-30 months replicate1diet-biologicalof (0.00700463) age-controlgastrocnemius-30 months replicate2diet-biologicalof age-CR(0.0161472)gastrocnemius-30 months replicate3diet-biologicalof age-CR(0.010954)gastrocnemius-30diet-biological months replicate4of age-CR(0.0143179)gastrocnemius-30diet-biological months replicate5of age-CR(0.0122145)gastrocnemius-30replicate1diet-biological months of age-CR(0.00949099)gastrocnemius-30replicate2diet-biological (0.0174892) months of age-resveratrolgastrocnemius-30replicate3diet-biological (0.0256724) months of age-resveratrolneocortex-5replicate4 (0.015349) months of age-resveratrol neocortex-5replicate5diet-biological (0.0154198) months of months age-resveratrol neocortex-5diet-biological (0.0244952) of months of age, neocortex-5 replicate1diet-biologicalage-control resveratrol months of neocortex-5 replicate2diet-biologicalage-control (0.0131342) months diet-biologicalof neocortex-30 replicate3age-controldiet-biological (0.0140347) months diet-biologicalof neocortex-30 replicate4age-control (0.0139512) replicate1diet-biological ofmonthsneocortex-30 replicate5age-control (0.00980052) replicate2diet-biological months ofneocortex-30 (0.0281298) age-control (0.0166299) replicate3diet-biological months ofneocortex-30 (0.023125) age-control replicate4 months diet-biologicalofneocortex-30 (0.0225873) age-control replicate5 months diet-biologicalofneocortex-30 (0.0283023) age-control months replicate1diet-biologicalofneocortex-30 (0.0269609) age-control months replicate2diet-biologicalofneocortex-30 age-CR(0.0238316) months replicate3diet-biologicalofneocortex-30 age-CR(0.0232534)diet-biological months replicate4ofneocortex-30 age-CR(0.0253952)diet-biological months replicate5ofneocortex-30 age-CR(0.025706)replicate1diet-biological months ofneocortex-30 age-CR(0.0239074)replicate2diet-biological (0.0188559) months ofneocortex-30 age-resveratrolreplicate3diet-biological (0.0229668) months ofneocortex-30 age-resveratrolreplicate4 (0.0181992) months of age-resveratrol replicate5diet-biological (0.0214397) months of age-resveratrol diet-biological (0.0176243) of age, replicate1diet-biological resveratrol[ minreplicate2diet-biological (0.0122858) replicate3 diet-biological] (0.0165293) replicate4 (0.0176396) [replicate5 medium(0.0139551) (0.0205188) ] [ max ] CEM 1 Slc22a17 121.4 373.7 6843.6 P ( S | Z, I ) = 0.00 Atp6v0c 5008.9 9677.8 18246.5 Mean Corr = 0.17760Atp6v0b 1755.5 3290.0 8046.1 Sbf2 9.5 257.1 618.8 Slc3a1 3.0 75.3 193.8 Mtmr2 141.5 416.5 750.7 Atp6ap1 2530.7 3847.5 8775.3 Abcb6 257.1 592.7 1143.5 Tmem138 18.1 146.4 285.3 Vps4b 4.2 98.5 187.5 Trappc3 1310.7 2465.5 4977.2 BC022687 25.9 119.6 482.4 Ankrd13c 501.7 1990.1 2975.4 Mtmr11 13.4 138.5 301.0 Fahd1 316.1 953.0 1774.7 CEM 1 + Pccb 758.1 1593.6 2827.1 Top 10 Genes Bad 5.0 302.6 738.7 Npl 39.7 217.9 344.8 Abca3 21.3 190.4 489.4 Rtn3 1582.0 5445.3 20343.0

Null module GEO Series "GSE27038" 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=GSE27038 Status: Public on Feb 03 2011 Title: Expression data from the Ire1Î± null and control murine livers in the absence or presence of ER stress Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21407177 Summary & Design: Summary: Ire1Î± conditional null or control mice of 3-months old were injected intraperitoneally with TM or vehicle.

At 8 hours after the injection, total RNA was isolated from murine liver tissue and subjected to Affymetrix microarray analysis.

Overall design: We used microarrays to profile the global programme of gene expression in the livers of Ire1Î± null and control mice in the absence or presence of ER stress.

Background corr dist: KL-Divergence = 0.1000, L1-Distance = 0.0233, L2-Distance = 0.0009, Normal std = 0.4442

0.898 Kernel fit Pairwise Correlations Normal fit

Density 0.449

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

Fe+CRE+Tm,Fe+CRE+Tm, BiologicalFe+CRE+Tm, BiologicalFe-CRE+Tm, Rep Biological1Fe-CRE+Tm, (0.126065) Rep Biological 2Fe-CRE+Tm, (0.0685496) Rep Biological 3Fe+CRE+, (0.0328792) Rep Biological1 Fe+CRE+,(0.046872) Rep Biological 2 Fe+CRE+,(0.27788) Rep Biological 3Rep Fe-CRE+,(0.0790364) Biological1 (0.0388181) RepFe-CRE+, Biological 2 (0.0446091) RepFe-CRE+, Biological 3 (0.0822191) Rep Biological1 (0.116934) Rep 2 (0.0408451) Rep 3 (0.0452916)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 34.9 85.9 121.0 P ( S | Z, I ) = 0.00 Atp6v0c 6055.1 6973.9 8893.9 Mean Corr = 0.34183Atp6v0b 1342.6 2008.4 2584.8 Sbf2 276.2 354.2 460.7 Slc3a1 1179.8 2738.7 7915.5 Mtmr2 92.9 131.7 181.9 Atp6ap1 1968.5 2202.1 2700.4 Abcb6 2723.8 4605.7 5512.7 Tmem138 73.4 195.5 231.2 Vps4b 68.3 134.2 189.3 Trappc3 822.3 991.3 1450.9 BC022687 46.0 77.2 207.4 Ankrd13c 1827.2 2561.8 4805.5 Mtmr11 52.5 142.7 743.2 Fahd1 259.1 762.0 1529.1 CEM 1 + Pccb 971.1 1465.6 1781.7 Top 10 Genes Bad 405.8 564.6 770.5 Npl 80.3 129.3 208.9 Abca3 308.7 624.2 2201.2 Rtn3 4145.4 4929.5 7613.6

Null module GEO Series "GSE46724" 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=GSE46724 Status: Public on Jul 01 2013 Title: Expression data from adult Myeloerythroid Progenitors (MP) ICN2 positive and adult Myeloerythroid Progenitors (MP) ICN2 negative Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23791481 Summary & Design: Summary: Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).

Overall design: Bone marrow lineage negative, cKit+, Sca1- cells were sorted from Rosa-lsl-ICN2 Mx1-cre+ mice or Mx1-cre+ littermates for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0317, L1-Distance = 0.0230, L2-Distance = 0.0005, Normal std = 0.6657

0.617 Kernel fit Pairwise Correlations Normal fit

Density 0.308

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 Myeloerythroidadult Myeloerythroidadult Myeloerythroid Progenitorsadult Myeloerythroid Progenitorsadult (MP) Myeloerythroid Progenitorsadult ICN2 (MP) Myeloerythroid Progenitors negative ICN2 (MP) Progenitors negative replicateICN2 (MP) Progenitors negative replicateICN2 1 (MP) (0.0647923) positive[ replicateICN2 min2 (MP) (0.186097) positive replicate ICN2 3 ](0.208719) positive replicate 1 (0.240481) replicate 2[ (0.16677) medium 3 (0.13314) ] [ max ] CEM 1 Slc22a17 43.8 49.5 56.8 P ( S | Z, I ) = 0.00 Atp6v0c 3791.2 4893.5 5449.5 Mean Corr = 0.19298Atp6v0b 844.7 1097.8 1306.9 Sbf2 56.2 67.8 76.9 Slc3a1 274.1 318.8 334.7 Mtmr2 42.5 56.3 61.8 Atp6ap1 2835.4 3856.1 4152.1 Abcb6 1935.4 2700.5 2811.0 Tmem138 163.7 195.4 224.5 Vps4b 106.0 142.2 167.6 Trappc3 1576.3 1775.9 1807.8 BC022687 9.5 10.2 10.7 Ankrd13c 4121.0 4316.6 4575.4 Mtmr11 55.8 63.8 78.4 Fahd1 252.2 304.0 392.1 CEM 1 + Pccb 751.0 1208.9 1327.7 Top 10 Genes Bad 796.8 996.7 1032.3 Npl 133.0 329.7 426.4 Abca3 147.4 155.7 175.3 Rtn3 1803.8 2248.7 2332.1

Null module GEO Series "GSE17553" 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=GSE17553 Status: Public on Dec 31 2009 Title: Estradiol or Testosterone treated efferent duct and caput epididymis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19553595 Summary & Design: Summary: The role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract.

Overall design: Adult animals were castrated or sham-castrated, allowed to recover for 14 days, and then treated with 0.015 mg estradiol (castrated), 0.015 mg testosterone propionate (castrated), or vehicle (castrated and sham-castrated as biological controls) in duplicate. Efferent duct and caput epididymis was collected from each sample and analyzed. Duplicates are included in the provided data and numbered 1 or 2 for each treatment regimen.

Background corr dist: KL-Divergence = 0.0449, L1-Distance = 0.0261, L2-Distance = 0.0011, Normal std = 0.5797

0.688 Kernel fit Pairwise Correlations Normal fit

Density 0.344

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

EfferentCaput duct castratedepididymisCaput epididymisCaput 1 (0.0759384)castrated epididymisCaput castrated 1 epididymis Caput(0.0370322) sham-castrated 2 epididymis Caput(0.0603221) sham-castrated epididymisCaput TP 1 (0.0922562)treatedepididymisEfferent TP 2 (0.084085)treated1Efferent (0.0370414)duct E2 sham-castratedtreated2Efferent (0.0306938)duct sham-castrated1Efferent (0.0618887)duct castrated 1Efferent duct (0.0822974) TP 2Efferent duct 2(0.0796525)treated (0.10177) TPEfferent duct treated1 (0.041721) E2Caput duct treated2 (0.133296) E2epididymis treated1 (0.025815) 2 E2(0.0341537) treated 2[ (0.0220369) min ] [ medium ] [ max ] CEM 1 Slc22a17 293.0 638.3 1129.3 P ( S | Z, I ) = 0.00 Atp6v0c 1622.2 9300.2 13925.8 Mean Corr = 0.07978Atp6v0b 355.0 2196.2 3164.7 Sbf2 4.0 430.4 647.5 Slc3a1 4.0 254.4 461.9 Mtmr2 32.6 244.3 450.2 Atp6ap1 3250.5 4383.5 6228.2 Abcb6 387.0 976.9 1553.4 Tmem138 56.5 157.5 400.4 Vps4b 107.5 167.7 262.2 Trappc3 587.3 2232.9 3899.2 BC022687 152.5 261.5 451.1 Ankrd13c 2418.0 3381.3 9618.7 Mtmr11 152.1 598.8 1100.3 Fahd1 54.5 332.4 520.6 CEM 1 + Pccb 211.0 1049.1 1445.8 Top 10 Genes Bad 219.2 564.7 937.8 Npl 338.7 685.7 3375.6 Abca3 20.0 779.2 2274.4 Rtn3 3033.8 6912.1 9453.9

Null module GEO Series "GSE43381" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 26 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43381 Status: Public on Jan 15 2013 Title: Expression profiling across mouse epithelial tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24142692 Summary & Design: Summary: To characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea.

Overall design: Total RNA was purified from esophagus, lung, proximal small intestine, skin, stomach, and trachea. Data from previous studies in the lab (cornea, GSE43155; bladder, GSE15770; and E18.5 skin, GSE15772) were utilized in the comparison.

Background corr dist: KL-Divergence = 0.0408, L1-Distance = 0.0400, L2-Distance = 0.0029, Normal std = 0.6123

0.652 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

E14.5 WTE14.5 Bladder WTE16.5 Bladder 1-3 WT (0.0235045)E16.5 Bladder 1-6 WT (0.0207521)E16.5 Bladder 1-1 WT (0.0155773)E18.5 Bladder 1-2 Get1 (0.0269841)E18.5 1-3+/- Get1 Bladder(0.0381382)E18.5 +/- Get1 Bladder Eso1-4 +/-(0.0175382)E18_5 Bladder Eso2-5 WT1(0.0191992)E18_5 Eso2-6 (0.0277928) WT2(0.0341119)E18_5SI (0.0206203) E18_5 WT4SI (0.0229541)WT1_3 E18_5SI (0.131471)WT3 E18_5 (0.138221)Skin WT4 E14_5 (0.0311676)Skin 1-2_5 E14_5E14.5 (0.017579) 1-2_re WTE16.5 Dorsal (0.00927308) WTE16.5 SkinDorsal WT 1-3E16.5 SkinDorsal (0.0141671) WT 6E18.5 (0.0466017) SkinDorsal WT 7E18.5 (0.0414182) SkinDorsal WT 8E18.5 (0.0453722) SkinDorsal WT 1-4Sto SkinDorsal (0.045866)E18_5 5-5Sto Skin WT1 (0.0778348)E18_5 6-4Sto (0.0167063) WT2 (0.0566107)E18_5 (0.0311592) WT4 (0.0293793) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 230.7 482.2 796.4 P ( S | Z, I ) = 0.00 Atp6v0c 2091.2 2945.5 16583.7 Mean Corr = 0.10525Atp6v0b 452.9 1120.5 4905.3 Sbf2 2.8 33.9 445.1 Slc3a1 24.4 174.2 6852.8 Mtmr2 8.5 44.6 507.1 Atp6ap1 3325.9 4073.5 7452.8 Abcb6 123.8 474.4 753.3 Tmem138 6.9 49.8 119.7 Vps4b 23.9 295.6 507.6 Trappc3 523.8 718.5 2086.1 BC022687 69.1 119.9 245.0 Ankrd13c 1250.4 2635.9 4217.2 Mtmr11 136.9 254.8 573.2 Fahd1 21.5 118.1 2292.9 CEM 1 + Pccb 238.8 393.5 2668.6 Top 10 Genes Bad 483.2 824.4 1642.2 Npl 96.1 278.1 45220.8 Abca3 6.8 87.2 2707.3 Rtn3 3857.4 6925.8 8545.3

Null module 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 (0.213811)V720_PD0332991_rep1 (0.140678)V720_PD0332991_rep2 (0.18829)V720_PD0332991_rep3 (0.197222) (0.155631) (0.104369)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 214.7 238.4 265.6 P ( S | Z, I ) = 0.00 Atp6v0c 5349.6 5963.4 6034.8 Mean Corr = 0.21940Atp6v0b 415.0 478.5 492.4 Sbf2 249.1 271.2 300.6 Slc3a1 20.0 46.5 49.9 Mtmr2 687.8 763.1 763.6 Atp6ap1 4031.2 4997.4 5216.5 Abcb6 1292.8 1385.8 1463.5 Tmem138 163.8 198.5 239.0 Vps4b 155.6 183.1 187.3 Trappc3 838.7 961.0 991.5 BC022687 362.5 512.7 538.9 Ankrd13c 3408.7 3439.9 3675.7 Mtmr11 105.3 109.6 118.5 Fahd1 241.3 275.4 297.3 CEM 1 + Pccb 352.8 368.8 380.2 Top 10 Genes Bad 986.2 1019.8 1111.2 Npl 13.5 19.8 22.4 Abca3 703.9 781.0 830.1 Rtn3 8327.6 9052.2 9344.0

Null module GEO Series "GSE59437" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 30 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59437 Status: Public on Jul 16 2014 Title: Expression data from mouse tissue Angiotensin II treated for 0,1,3,7days Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Angiotensin II (Ang II) mediated signaling plays a key role in the development of hypertension associated target organ damages. However, the gene expression changes regulated by Ang II in the early stage of acute cerebral, cardiac, renal, vascular injury remain unclear.

we investigated Ang IImediated gene expression alteration associated with the development of early cerebral, cardiac, renal, vascular injury by microarray assay in a mouse model.

Overall design: All mice were euthanized by an overdose of pentobarbital on days 1, 3 and 7 of Angiotensin II treatment. Total RNA was isolated with TRIzol (Invitrogen) from brains, hearts, kidneys and vessels (n=1-3 per group) at each time point according to manufacturers instructions. Gene expression profiling was performed using Affymetrix GeneChip mouse Genome 430 2.0 array according to the manufacturers instructions (Affymetrix, Inc., Santa Clara, CA). On the GeneChip Mouse Genome 430 2.0 Array, over 45,000 probe sets analyze the expression level of over 39,000 transcripts and variants from over 34,000 well characterized mouse genes.

Background corr dist: KL-Divergence = 0.0645, L1-Distance = 0.0519, L2-Distance = 0.0054, Normal std = 0.5458

0.731 Kernel fit Pairwise Correlations Normal fit

Density 0.365

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

Brain atBrain T0, biological atBrain T0, biological at Brainrep1 T3, biological(0.0440368) at Brainrep2 T3, biological(0.069038) at Brainrep1 T7, biological(0.0861287) at Heartrep2 T7, biological(0.0581954) at Heartrep1 T0, biological(0.0593363) at Heartrep2 T0, biological(0.0856787) at Heartrep1 T0, biological(0.0288697) at Heartrep2 T1, biological(0.0171803) at Heartrep3 T1, biological(0.0231641) at Heartrep1 T1, biological(0.0307906) at Heartrep2 T3, biological(0.0323272) at Heartrep3 T3, biological(0.0275397) at Heartrep1 T3, biological(0.032317) at Heartrep2 T7, biological(0.0207628) at Heartrep3 T7, biological(0.0144515) at Kidneyrep1 T7, biological(0.0202139) Kidneyrep2at T0, (0.0166573) biological Kidneyrep3at T0, (0.0145105) biological Kidneyat rep1 T1, biological(0.0403618) Kidneyat rep2 T1, biological(0.0367138) Kidneyat rep1 T3, biological(0.0286207) Kidneyat rep2 T3, biological(0.0252581) Kidneyat rep1 T7, biological(0.0429146) vesselat rep2 T7, biological(0.014645)atvessel rep1T0, biological (0.0202181)atvessel rep2T1, biological (0.0293041)atvessel rep1 T3, biological(0.0192422) at rep1 T7, biological(0.0251888) rep1 (0.00744764) rep1 (0.0288867)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 358.4 596.1 10592.6 P ( S | Z, I ) = 0.00 Atp6v0c 9910.1 12056.7 28084.7 Mean Corr = 0.23266Atp6v0b 756.3 1202.0 1924.7 Sbf2 125.3 215.9 277.8 Slc3a1 90.0 121.4 25379.6 Mtmr2 158.4 243.8 420.4 Atp6ap1 3529.9 4809.1 8762.0 Abcb6 414.0 813.5 1606.0 Tmem138 134.2 171.8 218.8 Vps4b 36.0 79.2 153.7 Trappc3 1662.1 2118.2 2940.7 BC022687 24.8 56.6 331.8 Ankrd13c 1174.0 2311.6 13286.2 Mtmr11 98.4 191.7 1360.6 Fahd1 439.5 1389.3 3522.3 CEM 1 + Pccb 421.9 1067.4 3597.1 Top 10 Genes Bad 426.9 528.5 733.4 Npl 123.5 281.8 4120.0 Abca3 98.0 199.0 1542.9 Rtn3 4710.2 10252.2 32100.4

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

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

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

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

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

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl NMuMGNMuMG NMuMG cells, NMuMGreplicate cells cells, treated NMuMGreplicate cells 1 (0.171766) treatedbyNMuMG cells 211 (0.144771) days treatedby cells 11 with days treatedby 4ng/ml 11 with days by TGF-Î²,4ng/ml 11 with days [ TGF-Î²,4ng/mlfollowed minwith TGF-Î²,4ng/mlfollowed by ] TGF-Î² TGF-Î²,replicate by withdrawlTGF-Î² replicate 1[ (0.0967288) withdrawlmedium for 2 another(0.138298) for another 13 days,] 13 replicate days, replicate[ 1 max(0.213672) 2 (0.234763) ] CEM 1 Slc22a17 200.1 245.3 296.8 P ( S | Z, I ) = 0.00 Atp6v0c 14053.6 14581.6 21570.0 Mean Corr = 0.20111Atp6v0b 1131.6 1295.1 2953.9 Sbf2 190.9 277.8 308.2 Slc3a1 44.5 53.3 62.9 Mtmr2 547.5 655.6 835.5 Atp6ap1 4742.3 5854.9 10340.0 Abcb6 383.0 434.4 455.2 Tmem138 396.0 472.3 511.8 Vps4b 71.8 113.6 137.6 Trappc3 1284.4 1370.1 1395.7 BC022687 202.0 236.8 401.1 Ankrd13c 1788.6 1993.9 2329.5 Mtmr11 632.6 944.7 986.7 Fahd1 216.6 350.1 822.9 CEM 1 + Pccb 410.4 468.4 786.4 Top 10 Genes Bad 1366.7 1703.5 1920.5 Npl 35.1 39.7 41.7 Abca3 181.6 391.2 503.0 Rtn3 7109.9 9319.2 12078.9

Null module GEO Series "GSE33121" 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=GSE33121 Status: Public on Dec 15 2011 Title: Expression data from ESC and in vitro derived somatic cells and germ cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22194959 Summary & Design: Summary: We performed gene expression profiling on in vitro derived PGCs, undifferentiated ESCs, and somatic cells from the EB to examine germ cell expression in ESC-derived cells

Overall design: All cells were collected using fluorescence activated cell sorting to isolate SSEA1+/cKit+ ESCs, SSEA1+/cKitbright PGCs, Oct4-gfp+/cKitbright PGCs, and SSEA1-/cKit- somatic cells and Oct4-gfp-/cKit- somatic cells.

Background corr dist: KL-Divergence = 0.0409, L1-Distance = 0.0340, L2-Distance = 0.0016, Normal std = 0.6170

0.673 Kernel fit Pairwise Correlations Normal fit

Density 0.337

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

undifferentiatedundifferentiatedcKit+ cKit+ SSEA+ SSEA+cKit+ cKit+ SSEA+iPGC SSEA+cKit+ESC rep rep Oct4+iPGC cKit+ ESC1 1 (0.0697535) (0.112051) rep iPGCrep Oct4+cKit- 2 2 (0.0619259) rep(0.0920996) iPGCSSEA- 1cKit- (0.111882) rep somaticSSEA- 2cKit- (0.0995982) somaticOct4- repcKit- 1 somatic(0.153262) Oct4- rep 2 somatic(0.142732) rep 1 (0.0619098) rep 2 (0.0947856)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 95.9 150.9 314.1 P ( S | Z, I ) = 0.00 Atp6v0c 1956.7 2461.1 3305.1 Mean Corr = 0.35259Atp6v0b 336.5 548.0 1339.9 Sbf2 252.0 435.4 559.9 Slc3a1 88.9 156.9 224.1 Mtmr2 296.2 354.0 428.0 Atp6ap1 975.8 1142.3 1402.3 Abcb6 630.9 829.6 1021.7 Tmem138 87.8 144.7 205.4 Vps4b 15.8 46.3 96.1 Trappc3 886.0 1128.2 1340.6 BC022687 19.6 36.2 55.5 Ankrd13c 1664.6 2060.8 2647.7 Mtmr11 30.9 118.6 167.2 Fahd1 132.8 209.4 292.6 CEM 1 + Pccb 422.4 671.1 842.9 Top 10 Genes Bad 318.9 449.2 638.2 Npl 186.1 453.1 771.2 Abca3 33.1 43.7 57.8 Rtn3 1594.9 2728.2 3386.7

Null module GEO Series "GSE17709" 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=GSE17709 Status: Public on Aug 19 2009 Title: Gene expression analysis of a podocyte specific PTIP deletion in mouse glomerular preparations at 1 month of age Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21060806 Summary & Design: Summary: Glomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.

These mice develop protein urea by 3 months of age. This study was designed to find gene expression differences prior to the onset of the phenotype.

Overall design: Kidneys were excised at 1 month of age. Glomeruli enriched fractions were generated by sieving of the tissue homogenates. RNA was prepared from glomerular enriched fractions.

Background corr dist: KL-Divergence = 0.0391, L1-Distance = 0.0385, L2-Distance = 0.0021, Normal std = 0.6195

0.644 Kernel fit Pairwise Correlations Normal fit

Density 0.322

0.000 CEM 1

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

Pre-normalization Quantiles

wild-type,wild-type, PTIP+,wild-type, rep1PTIP+, wild-type,(0.00849615) rep2PTIP+, wild-type,(0.0561799) rep3PTIP+, wild-type,(0.0206893) rep4PTIP+, wild-type,(0.0999999) rep5PTIP+, wild-type,(0.0696781) rep6PTIP+, Pod-Cre,(0.027526) rep7PTIP+, Pod-Cre,(0.0579551) PTIP-,rep8 Pod-Cre,(0.0420597) rep1 PTIP-, (0.0372399)Pod-Cre, rep2 PTIP-, (0.0330071)Pod-Cre, rep3 PTIP-, (0.0287584)Pod-Cre, rep4 PTIP-, (0.0197898)Pod-Cre, rep5 PTIP-, (0.201108)Pod-Cre, rep6 PTIP-, (0.0996307)Pod-Cre, rep7 PTIP-, (0.0435529)Pod-Cre, rep8 PTIP-, (0.042657) rep9 PTIP-, (0.0446332) rep10 (0.0670384)[ min ] [ medium ] [ max ] CEM 1 Slc22a17 222.2 345.0 518.4 P ( S | Z, I ) = 0.00 Atp6v0c 4930.8 6270.5 6680.9 Mean Corr = 0.33377Atp6v0b 1449.4 2397.2 2778.3 Sbf2 115.5 270.4 416.5 Slc3a1 4056.4 5511.3 7546.8 Mtmr2 31.1 101.4 184.3 Atp6ap1 4210.1 4855.0 5831.5 Abcb6 1500.4 2128.9 2496.0 Tmem138 42.3 104.3 144.9 Vps4b 92.8 149.6 213.5 Trappc3 1072.0 1675.5 2200.8 BC022687 20.0 45.6 69.1 Ankrd13c 5866.3 7177.7 8589.1 Mtmr11 914.7 1495.1 1994.5 Fahd1 256.8 1069.8 2099.7 CEM 1 + Pccb 1289.4 2265.2 4311.0 Top 10 Genes Bad 323.2 752.6 1024.9 Npl 667.2 1391.2 2061.6 Abca3 201.4 826.6 1611.0 Rtn3 3274.9 3708.2 4873.7

Null module GEO Series "GSE38754" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 40 -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=GSE38754 Status: Public on Jun 16 2012 Title: Temporal changes of gene expression in mouse heart, kidney and lung during juvenile growth Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19036884 Summary & Design: Summary: Temporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size.

Overall design: To compare gene expression between fast-growing animals and more slowly growing animals, we extracted total mRNA from kidney and lung in 1-wk, 4-wk, and 8-wk-old mice (5 animals each).

Background corr dist: KL-Divergence = 0.1315, L1-Distance = 0.0443, L2-Distance = 0.0038, Normal std = 0.4135

1.014 Kernel fit Pairwise Correlations Normal fit

Density 0.507

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

1wk Kidney1wk Kidney1 (0.0353145)1wk Kidney2 (0.0086655)1wk Kidney3 (0.0163901)1wk Kidney4 (0.0260175)1wk Heart5 (0.0363729)1wk 1 Heart(0.0220119)1wk 2 Heart(0.0373611)1wk 3 Heart(0.0203382)1wk 4 Heart(0.0256204)1wk 5 Lung(0.0191724)1wk 1 Lung(0.0256352)1wk 2 Lung(0.0252206)1wk 3 Lung(0.0164949)1wk 4 Lung(0.0190994)4wk 5 Kidney(0.0243353)4wk Kidney1 (0.0310841)4wk Kidney2 (0.0463926)4wk Kidney3 (0.04058)4wk Kidney4 (0.0302855)4wk Heart5 (0.0480126)4wk 1 Heart(0.0333374)4wk 2 Heart(0.0176826)4wk 3 Heart(0.0223216)4wk 4 Heart(0.0161838)4wk 5 Lung(0.029995)4wk 1 Lung(0.0224381)4wk 2 Lung(0.0211149)4wk 3 Lung(0.0128769)4wk 4 Lung(0.0119823)8wk 5 Kidney(0.00875439)8wk Kidney1 (0.0348908)8wk Kidney2 (0.0229824)8wk Kidney3 (0.0277927)8wk Kidney4 (0.0479625)8wk Lung5 (0.0535583)8wk 1 Lung(0.013471)8wk 2 Lung(0.0122625)8wk 3 Lung(0.0094607)8wk 4 Lung(0.0159442) 5 (0.0105833) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 277.0 601.6 1117.7 P ( S | Z, I ) = 0.00 Atp6v0c 7966.6 11405.9 19398.4 Mean Corr = 0.32593Atp6v0b 1206.8 2467.3 4749.7 Sbf2 201.3 350.2 661.2 Slc3a1 46.1 134.4 15197.1 Mtmr2 273.2 376.6 530.8 Atp6ap1 2002.3 3596.3 4807.8 Abcb6 204.0 456.0 1064.9 Tmem138 89.1 235.7 369.1 Vps4b 69.4 175.7 255.3 Trappc3 1836.6 2234.8 3255.7 BC022687 65.3 276.0 627.2 Ankrd13c 1199.9 1801.5 9195.2 Mtmr11 152.1 294.9 1446.5 Fahd1 84.2 757.1 2115.6 CEM 1 + Pccb 867.6 2693.5 5409.8 Top 10 Genes Bad 235.8 508.4 693.2 Npl 115.5 226.4 5277.1 Abca3 169.4 1948.7 3203.4 Rtn3 3080.3 4189.4 8116.8

Null module GEO Series "GSE43928" 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=GSE43928 Status: Public on Sep 11 2013 Title: Expression data from TNF-stimulated mouse glomeruli Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23869211 Summary & Design: Summary: The specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.

To examine Tnfr-specific inflammatory responses in intrinsic glomerular cells but not infiltrating leukocytes we performed microarray gene expression profiling on intact glomeruli isolated from wild-type and Tnfr-deficient mice following TNF exposure in vitro.

Overall design: Glomeruli were isolated from male C57BL/6J wild-type and Tnfr-deficient mice applying a magnetic bead-based isolation technique. Isolated intact glomeruli were stimulated with TNF for 12 hours in vitro for subsequent RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0686, L1-Distance = 0.0204, L2-Distance = 0.0006, Normal std = 0.5034

0.792 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

Wild-typeWild-type glomeruli,Wild-type glomeruli, TNF-stimulated,Tnfr1/Tnfr2-deficient glomeruli, TNF-stimulated,Tnfr1/Tnfr2-deficient TNF-stimulated, rep1Tnfr1/Tnfr2-deficient (0.0393008) glomeruli, rep2Tnfr1-deficient (0.0545826) glomeruli, rep3Tnfr1-deficient TNF-stimulated, (0.101921) glomeruli, Tnfr1-deficientglomeruli, TNF-stimulated, Tnfr2-deficientglomeruli, TNF-stimulated, TNF-stimulated,rep1 Tnfr2-deficientglomeruli, (0.0747213) TNF-stimulated,rep2 Tnfr2-deficientglomeruli, (0.0346389) TNF-stimulated,rep3 rep1 glomeruli, (0.169236) (0.0818613) TNF-stimulated, rep2 glomeruli, (0.157692) TNF-stimulated, rep3 (0.105898) TNF-stimulated, rep1[ (0.0507939)min rep2 (0.0598415) ]rep3 (0.0695123)[ medium ] [ max ] CEM 1 Slc22a17 182.5 221.2 327.0 P ( S | Z, I ) = 0.00 Atp6v0c 9930.6 13852.4 16144.6 Mean Corr = 0.20017Atp6v0b 1789.9 4954.6 5673.0 Sbf2 274.0 683.3 947.1 Slc3a1 50.2 63.3 69.5 Mtmr2 251.1 893.0 1350.9 Atp6ap1 3029.2 4383.4 4888.6 Abcb6 182.0 282.8 325.4 Tmem138 230.8 279.4 324.3 Vps4b 89.4 121.7 177.9 Trappc3 1189.4 1770.3 2477.9 BC022687 136.5 214.7 240.3 Ankrd13c 2191.6 2749.9 3507.6 Mtmr11 318.5 491.6 745.6 Fahd1 233.4 283.4 501.8 CEM 1 + Pccb 328.0 546.1 758.4 Top 10 Genes Bad 253.3 761.8 1109.7 Npl 298.2 2790.1 4360.6 Abca3 97.4 285.9 441.9 Rtn3 3520.6 4512.6 5981.4

Null module GEO Series "GSE18858" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 242 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

Details of this dataset are not shown due to large number of samples and the page size limit. Find details in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18858

Background corr dist: KL-Divergence = 0.6578, L1-Distance = 0.0680, L2-Distance = 0.0123, Normal std = 0.2032 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(0.157658) wildE13.5 #2 type(0.0796184) Atrx-nullE13.5 #3 (0.120802) Atrx-null E13.5#1 (0.110233) Atrx-null P0.5#2 (0.0486961) wild P0.5#3 type (0.0424459) wild #1P0.5 type(0.0732225) wild #2P0.5 type(0.0615348) Atrx-null #3P0.5 (0.12863) Atrx-null #1P0.5 (0.0654315) Atrx-null #2AP0.5 (0.0521844) Atrx-null #2B (0.0276118) #3 (0.031931) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 2089.2 3431.2 3912.1 P ( S | Z, I ) = 0.00 Atp6v0c 6628.7 8826.7 10978.1 Mean Corr = 0.24217Atp6v0b 1623.3 2577.3 3306.8 Sbf2 386.2 579.9 884.0 Slc3a1 36.8 89.9 127.3 Mtmr2 315.9 432.0 634.0 Atp6ap1 1728.3 3834.5 4375.5 Abcb6 354.6 549.2 761.8 Tmem138 302.3 408.0 497.5 Vps4b 103.4 147.4 178.7 Trappc3 2443.1 3162.9 3763.4 BC022687 293.9 429.0 668.8 Ankrd13c 1490.0 1816.5 2739.0 Mtmr11 78.0 115.5 132.9 Fahd1 114.7 195.2 244.5 CEM 1 + Pccb 784.6 978.5 1171.8 Top 10 Genes Bad 422.8 529.4 665.0 Npl 200.4 344.3 507.0 Abca3 283.7 540.9 672.3 Rtn3 5662.4 8175.0 9238.9

Null module GEO Series "GSE50122" 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=GSE50122 Status: Public on Nov 18 2013 Title: Runx3 function in splenic NK cells (IL-2 or IL-15) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24236182 Summary & Design: Summary: NK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.

Overall design: To identify Runx3 responsive genes, NK cells were isolated from spleen of WT and Runx3-/- mice . Ten samples (5 WT and 5 Runx3-/-) of freshly isolated NK cells were separately obtained from individual mice. Cells were cultured for 7 days with IL-2 or IL-15.

Background corr dist: KL-Divergence = 0.0244, L1-Distance = 0.0693, L2-Distance = 0.0057, Normal std = 0.8495

0.470 Kernel fit Pairwise Correlations Normal fit

Density 0.235

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

NK_IL2_wt1NK_IL2_wt2 (0.194291)NK_IL2_wt3 (0.0181328)NK_IL2_ko1 (0.126971)NK_IL2_ko2 (0.157926)NK_IL2_ko3 (0.126097)NK_IL15_wt1 (0.0224807)NK_IL15_wt2 (0.080533)NK_IL15_ko1 (0.12344)NK_IL15_ko2 (0.0919199) (0.0582089) [ min ] [ medium ] [ max ] CEM 1 Slc22a17 4.4 5.1 6.5 P ( S | Z, I ) = 0.00 Atp6v0c 5904.2 8995.2 11360.7 Mean Corr = 0.35482Atp6v0b 1581.4 2775.5 5727.8 Sbf2 5.4 6.4 7.2 Slc3a1 4.5 4.8 5.6 Mtmr2 4.7 7.2 12.4 Atp6ap1 4669.7 7113.4 10839.8 Abcb6 95.2 167.1 548.9 Tmem138 36.5 82.9 141.4 Vps4b 7.1 7.7 8.8 Trappc3 982.8 1968.1 3349.3 BC022687 49.3 80.5 151.4 Ankrd13c 747.8 1333.7 1914.3 Mtmr11 3.7 4.0 4.4 Fahd1 13.3 16.7 19.4 CEM 1 + Pccb 157.9 339.7 453.7 Top 10 Genes Bad 428.3 488.4 571.2 Npl 3.9 8.9 26.2 Abca3 4.9 5.4 5.8 Rtn3 7768.4 9051.5 9822.4

Null module