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

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

Dataset: Num of genes in input gene set: 8 Total number of genes: 16493

CLIC PDF output has three sections:

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

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

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

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

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

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

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

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

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

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

Bottom panel shows the background distribution and the expression profile for CEM genes in this dataset. Ldlrap1 Dlgap2 Num ofGenesinQueryGeneset:8.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Nrp1 Prph Nefh Gan Nefl Ina

Nefl Nefh Ina Prph Dlgap2 Nrp1 Ldlrap1 Gan Singletons CEM 1(128datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 2900011O08Rik Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page1 Tmem130 Zfp804a Arhgef7 Slc6a15 Slc7a14 Mapk10 Snap25 Spock3 Snap91 Resp18 Sult4a1 Pcsk1n Ctnna2 Dlgap2 Nap1l2 Tagln3 Crmp1 Gdap1 Stmn3 Stmn2 Cadps Unc80 Tubb3 Elavl3 Elavl4 Elavl2 Gpr22 Nrsn1 Disp2 Cplx1 Grm7 Myt1l Gng3 Add2 Napb Nefm Hpca Scg5 Scg3 Vat1l Jph3 Prph Rtn1 Nefh Bai3 Syt4 Nefl Syp Ina 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE12499 [10] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE56236 [12] GSE33770 [8] GSE17797 [19] GSE40261 [8] GSE8715 [6] GSE43779 [6] GSE53951 [10] GSE35396 [24] GSE17739 [24] GSE11110 [11] GSE5128 [18] GSE24628 [16] GSE54678 [6] GSE4816 [12] GSE39621 [51] GSE30865 [68] GSE28559 [30] GSE32937 [8] GSE31004 [8] GSE48369 [36] GSE13432 [12] GSE38672 [6] GSE40286 [10] GSE17096 [20] GSE7831 [14] GSE7020 [8] GSE9338 [42] GSE38335 [9] GSE32529 [224] GSE15069 [15] GSE21193 [10] GSE20636 [35] GSE26076 [12] GSE21687 [192] GSE51213 [16] GSE6223 [13] GSE10587 [6] GSE15914 [9] GSE9566 [38] GSE51365 [28] GSE6134 [7] GSE15729 [15] GSE30138 [51] GSE11343 [19] GSE9954 [70] GSE6933 [15] GSE26822 [8] GSE1986 [17] GSE31106 [18] GSE6196 [9] GSE29458 [23] GSE11291 [60] GSE51483 [45] GSE8249 [46] GSE5296 [96] GSE24207 [73] GSE4774 [15] GSE10246 [182] GSE30863 [20] GSE49128 [17] GSE27546 [51] GSE51108 [6] GSE18597 [42] GSE10871 [32] GSE8024 [8] GSE46211 [18] GSE14012 [24] GSE51080 [18] GSE16496 [102] GSE37301 [20] GSE11165 [6] GSE38693 [8] GSE19925 [6] GSE17745 [6] GSE9977 [24] GSE19709 [168] GSE26024 [20] GSE7707 [18] GSE8434 [6] GSE54774 [12] GSE37975 [8] GSE11918 [9] GSE13149 [25] GSE43261 [38] GSE14354 [6] GSE13421 [8] GSE7809 [8] GSE16994 [12] GSE20426 [35] GSE11149 [8] GSE11400 [8] GSE18704 [9] GSE24489 [14] GSE44923 [16] GSE32020 [26] GSE14843 [6] GSE19753 [29] GSE58915 [21] GSE50123 [6] GSE21594 [12] GSE32681 [61] GSE15794 [6] GSE23081 [6] GSE41759 [14] GSE59437 [30] GSE30744 [6] GSE15760 [6] GSE45229 [20] GSE17097 [20] GSE10182 [7] GSE4928 [8] GSE8407 [17] GSE23600 [10] GSE55738 [6] GSE22291 [16] GSE53299 [6] GSE20645 [8] GSE35160 [6] GSE16585 [31] GSE31570 [6] GSE10192 [24] GSE29632 [42] GSE26616 [6] GSE27114 [6] GSE10478 [6] GSE27987 [31] GSE48397 [10] GSE8091 [16] GSE9743 [12] GSE36814 [20] GSE52118 [9] GSE30561 [6] GSE30498 [12] GSE10904 [6] GSE19793 [32] GSE11859 [27] GSE4658 [6] GSE11818 [6] GSE24614 [6] GSE11333 [6] GSE9913 [9] GSE42548 [29] GSE8488 [15] GSE25286 [10] GSE30852 [6] GSE27630 [8] GSE48811 [20] GSE15401 [18] GSE9975 [36] GSE20008 [6] GSE46443 [12] CEM+ CEM GSE28417 [12] GSE16675 [72] GSE19338 [24] GSE50122 [10] GSE8726 [7] GSE12333 [6] 0.0 GSE51422 [6] GSE41746 [18]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 54.04 54.38 54.44 54.44 54.54 54.59 54.89 55.58 56.16 56.50 56.62 56.86 58.11 58.68 58.93 60.12 60.80 63.14 63.20 63.76 64.18 64.25 65.11 66.65 67.53 68.87 68.90 70.36 71.50 78.92 79.67 84.02 86.29 86.29 87.37 91.92 96.32 97.32 102.23 105.65 106.22 110.31 111.07 123.66 165.98 1.0 Notes Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page2 Mapk8ip2 Gm16532 Fam155a Rundc3a Zcchc12 Jakmip2 Ppp2r2c Dync1i1 Map7d2 Phactr3 Camta1 Spock1 Cyp4x1 N28178 Syngr3 Kcnip4 Pnma2 Sh3gl2 Rimkla Nap1l5 Lsamp Iqsec3 Gap43 Slitrk1 Rph3a Cend1 Stmn4 Soga3 Scn3b Ppfia2 Rims3 Lhfpl5 Scn8a Fxyd7 Ndrg4 Nrsn2 Uchl1 Vsnl1 Ttc9b Chgb Chd5 Chga Nsg2 Kif3c Syn1 Syn2 Sv2a Dner Ttc9 Vgf 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 40.22 40.46 40.58 40.89 40.96 41.19 41.19 41.20 41.27 41.40 41.72 41.93 42.11 42.48 43.32 43.32 43.52 43.57 43.64 43.77 44.01 44.33 44.99 45.05 45.06 45.31 46.32 46.57 47.43 47.94 47.98 48.61 48.80 48.92 49.33 49.43 49.73 49.83 50.01 50.80 51.00 51.32 51.34 51.63 52.67 53.05 53.12 53.19 53.89 53.97 1.0 Notes 3110047P20Rik Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page3 Tmem179 Ankrd34b AI593442 Tmem59l Cacna1b Zcchc18 Pacsin1 Slc17a6 Dusp26 Unc13a Rab33a Tubb4a St8sia3 Chrna7 Cadm2 Hpcal4 Vstm2l Dpysl5 Sez6l2 Lonrf2 Celsr3 Dpp10 Pgbd5 Rab6b Rab9b Rims1 Panx2 Fbxo2 Prmt8 Amph Car10 Astn1 Stx1b Fgf12 Gria2 Lrfn5 Eno2 Ache Rgs7 Celf6 Sncg Scg2 Nrg3 Clgn Syt9 Klc1 Lgi1 Tub Vip 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 30.87 30.92 31.10 31.22 31.47 31.66 31.83 32.19 32.30 32.31 32.74 33.11 33.24 33.28 33.54 33.57 33.64 33.64 33.85 34.07 34.07 34.53 34.60 34.62 34.76 34.84 35.25 35.32 35.55 35.69 35.79 36.06 36.49 36.90 37.29 37.32 37.67 37.71 37.75 37.85 38.08 38.12 38.21 38.65 38.72 38.81 39.29 39.39 39.62 40.04 1.0 Notes A730017C20Rik D130043K22Rik Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page4 Tmem151b Cacna2d3 Fam19a2 Gdap1l1 Tram1l1 Slc4a10 Prkar1b Rimbp2 Snhg11 Gabra5 Syngr1 Rnf165 Trim67 Camkv Plcxd3 Lamp5 Fbxl16 Amer3 Bend6 Actl6b Apba2 Rgs17 Pcdh9 Dock3 Lhfpl4 Zmat4 Cartpt Pcsk2 Igsf21 Vwc2l Synpr Cntn2 Sgip1 Atcay Nfasc Htr3a Map6 Snph Cux2 Celf5 Rell2 Fsd1 Fstl5 Jph4 Gnal Plp1 Syt1 Dcx 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 24.41 24.48 24.52 24.74 24.74 24.80 24.89 25.03 25.16 25.19 25.29 25.30 25.56 25.76 25.76 25.84 25.89 26.03 26.04 26.43 26.45 26.48 27.00 27.01 27.16 27.17 27.27 27.28 27.46 27.52 27.61 27.70 27.78 27.83 27.87 28.00 28.35 28.38 28.51 28.62 28.81 29.25 29.43 29.44 29.47 29.92 30.29 30.34 30.56 30.65 1.0 Notes Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page5 Camk2n2 AI836003 Fam169a Zdhhc22 March11 Neurod1 Cntnap4 Slc32a1 Slc24a2 Vwa5b2 Stxbp5l Rab39b Necab1 Gabrb2 Dzank1 Rbfox3 Atp2b2 Rnf112 Vamp1 Hs3st4 Crtac1 Nrcam Slitrk5 Lrrc4c Cdh10 Cabp1 Unc5d Kndc1 Cpne4 Sgpp2 Usp29 Pcdh8 Rims2 Akap6 Kcnc2 Cntn1 Cbln2 Calb2 Clvs2 Ttyh1 Grin1 Celf4 Rgs8 Nell1 Ralyl Psd2 Pak7 Tac1 Erc2 Pclo 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 19.20 19.32 19.32 19.62 19.62 19.69 19.74 19.87 19.91 20.24 20.35 20.42 20.46 20.52 20.73 20.76 21.39 21.41 21.52 21.53 21.58 21.65 21.71 21.74 21.75 21.83 21.90 22.10 22.20 22.43 22.48 22.58 22.85 22.96 23.16 23.29 23.40 23.46 23.50 23.54 23.55 23.61 23.66 23.78 23.94 24.10 24.15 24.20 24.23 24.27 1.0 Notes 6330403K07Rik Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page6 St6galnac5 Fam163a Fam19a1 Adcyap1 Cntnap2 Rps6kl1 Slc18a3 Rasgrf1 Dbndd1 Elmod1 Cacnb4 St6gal2 Fkbp1b Il1rapl1 Slc35f1 Slc35f3 Scn2a1 Gabrg2 Maneal Rbfox1 Dlgap1 Slc6a1 Brinp1 Ap3b2 Kcna1 Scn1a Mrap2 Synrg Cbln4 Ptpn5 Trim9 Caln1 Syt11 Asic2 Acsl6 Lmo3 Ptprn Gria1 Efr3b Celf3 Svop Sv2b Ly6h Ptprt Myt1 Xkr4 Pirt Sst Th 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 14.30 14.32 14.45 14.63 14.69 14.70 14.73 14.79 15.06 15.14 15.21 15.48 15.49 15.55 15.69 15.72 15.72 16.08 16.15 16.16 16.29 16.32 16.33 16.56 16.61 17.09 17.15 17.22 17.23 17.31 17.33 17.33 17.59 17.76 17.88 17.95 18.13 18.23 18.26 18.27 18.28 18.55 18.62 18.63 18.64 18.76 18.80 18.81 18.93 19.04 1.0 Notes D430019H16Rik D430041D05Rik D10Bwg1379e Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page7 Tmem169 Syndig1 Adam22 Fam57b Slc17a7 Slc29a4 Zfyve28 Phyhipl Epha10 Vstm2a Pip5kl1 Mgat5b Sertm1 Sptbn4 Prima1 Grin3a Lrrtm3 Lrrtm4 Cpne9 Cpne6 Abcg4 Adcy1 Rab3a Crhbp Snrpn Nrxn2 Cntn4 Brsk1 Nhlh2 Lrp11 Sept3 Nalcn Syt16 Glra2 Gad1 Dpp6 Cdh8 Sncb Nat8l Gnaz Pcp4 Bex2 Ggt7 Mcf2 Syt5 Fat3 Npy 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 9.98 10.00 10.13 10.37 10.37 10.40 10.43 10.47 10.56 10.81 10.95 10.97 10.99 11.16 11.19 11.22 11.24 11.31 11.32 11.35 11.64 11.70 11.72 11.84 11.99 12.06 12.25 12.28 12.33 12.68 12.87 12.95 13.01 13.02 13.02 13.07 13.11 13.24 13.38 13.43 13.60 13.64 13.70 13.78 13.88 13.92 14.06 14.08 14.11 14.23 1.0 Notes 6330403A02Rik 9330159F19Rik D3Bwg0562e Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page8 Ankrd34a Pcdh11x Gprasp2 Jakmip3 Golga7b Rasl10b Arhgdig Arhgef9 Slc6a17 Galnt13 March4 Fbxo41 Pou4f2 Kcnip2 Tspyl4 Gng13 Map1a Slitrk4 Frmd3 Wdr17 Ptprz1 Ppfia3 Bean1 Pcsk1 Faim2 Gpr61 Gpr17 Spry3 Frrs1l Ctxn2 Trhde Calcb Calb1 Zdbf2 Lin7b Wnk3 Fgf13 Sez6l Htr2c Prrt3 Omg Lgi2 Mbp Atl1 Crh Isl1 Tro 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 4.94 4.95 5.13 5.16 5.18 5.21 5.24 5.29 5.40 5.43 5.52 5.53 5.55 5.68 5.77 5.96 6.01 6.02 6.42 6.55 6.73 6.80 6.83 7.01 7.09 7.11 7.53 7.62 7.69 7.71 7.71 7.82 8.01 8.09 8.14 8.44 8.46 8.50 8.59 8.59 8.98 9.01 9.20 9.24 9.24 9.43 9.57 9.61 9.68 9.87 1.0 Notes A830018L16Rik LOC101055948 Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page9 Tmem151a Atp6v1g2 Fam163b Fam196b Neurod6 Kcnmb2 Gm4988 Kcnma1 Plekhd1 Mpped1 Rgs7bp Asphd2 Cacng2 Cacng3 Cacng4 Phox2a Necab2 Gabra1 Cnnm1 Rnf208 Pou4f1 Ptchd1 Bzrap1 Nkain2 Ppm1e Gprin1 Galnt9 Slitrk2 Clstn2 Kcnd2 Mmd2 Kcnt1 Nptx2 Ttbk1 Lin7a Grm3 Grik2 Ermn Cdh9 Chn1 Rgs4 Ints6 Fez1 Caly Trhr Ntm Psd Alk 0.0 1.0

GSE45487 [9] GSE9441 [36]

GSE26355 [6] Scale ofaveragePearsoncorrelations GSE24276 [6] GSE41095 [6] GSE40939 [10] GSE35260 [21] GSE20260 [48] GSE17404 [9] 0.2 GSE6957 [12] GSE12772 [8] GSE47811 [12] GSE48203 [9] GSE35357 [12] GSE10806 [11] GSE26461 [6] GSE32103 [6] GSE56492 [12] 0.4 GSE3595 [6] GSE4260 [6] GSE35436 [6] GSE6275 [36] GSE14499 [26] GSE14395 [24] GSE33134 [31] GSE23923 [8] GSE52357 [8] 0.6 GSE54056 [12] GSE10965 [8] GSE45028 [22] GSE29382 [36] GSE22448 [6] GSE38797 [16] GSE9123 [8] GSE13103 [8] GSE32330 [12] 0.8 GSE11443 [6] GSE31208 [8] GSE43381 [26] GSE37431 [6] Score 1.61 1.64 1.76 1.99 2.03 2.08 2.09 2.17 2.17 2.27 2.31 2.32 2.42 2.44 2.47 2.51 2.53 2.62 2.71 2.73 2.74 2.75 2.85 2.86 2.87 3.02 3.05 3.30 3.30 3.53 3.56 3.56 3.65 3.80 3.82 3.86 3.88 3.88 3.99 4.21 4.56 4.56 4.59 4.59 4.67 4.68 4.69 4.73 4.81 4.91 1.0 Notes E130309D14Rik Symbol Num ofCEMGenes:5.Predicted466.SelectedDatasets:128.Strength:0.9 CEM 1,Geneset"[G]neurofilament",Page10 Rundc3b Ccdc177 Vstm2b Kcnab1 Ncam2 Hs3st2 L1cam Mdga2 Krt222 Lrrc24 Rab3b Syne1 Cxxc4 Mllt11 Negr1 Rufy3 Trpc3 Nrip3 Kifc2 Ptprr 0.0 1.0

GSE45487 [9] GSE9441 [36]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45487 Status: Public on Mar 26 2013 Title: Identification of genes responsive to low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 preosteoblast cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24252911 Summary & Design: Summary: Although LIPUS has been shown to enhance fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells using a GeneChipÂ® system.

Overall design: The mouse preosteoblast MC3T3-E1cells were treated with LIPUS (30 mW/cm2) for 20 min followed by culturing for 6 and 24 h at 37C. Mock-treated cells were served as control. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was monitored by an Affymetrix GeneChip system with a Mouse Genome 430 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer's instructions.

Background corr dist: KL-Divergence = 0.0154, L1-Distance = 0.0176, L2-Distance = 0.0004, Normal std = 0.7802

0.511 Kernel fit Pairwise Correlations Normal fit

Density 0.256

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

MC3T3-E1MC3T3-E1 (control-1)MC3T3-E1 (control-2) (0.14925)MC3T3-E1 (control-3) (0.0385276)MC3T3-E1 LIPUS-24 (0.185456)MC3T3-E1 LIPUS-24 h MC3T3-E11 (0.0878663) LIPUS-24 h MC3T3-E12 (0.0191493) LIPUS-6 h MC3T3-E13 (0.150707) LIPUS-6 h 1 (0.159347) LIPUS-6 h 2 (0.0573518) h 3 (0.152345)[ min ] [ medium ] [ max ] CEM 1 Nefl 11.0 13.5 19.7 P ( S | Z, I ) = 1.00 Nefh 11.9 15.9 25.0 Mean Corr = 0.93436 Ina 15.1 24.8 47.6 Prph 18.4 24.4 42.1 Dlgap2 12.3 15.1 18.4 Nefm 11.5 11.9 16.7 Snap25 9.2 10.1 11.4 Elavl2 8.3 9.2 11.7 Gng3 40.0 58.5 78.8 Cadps 10.8 13.5 14.3 CEM 1 + Cplx1 65.2 83.3 105.8 Top 10 Genes Stmn2 45.6 50.4 106.0 Sult4a1 14.2 18.5 28.8 Nrsn1 11.1 12.3 56.4 Elavl4 11.8 15.9 18.9

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE9441" 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=GSE9441 Status: Public on Dec 07 2007 Title: The effect of sleep deprivation on gene expression in the brain and the liver of three inbred mouse strains Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18077435 Summary & Design: Summary: These studies adress differential changes in gene expression between 6h sleep deprived and control mice in the brain and the liver. We profiled gene expression in three different inbred strains to understand the influence of genetic background.

Keywords: brain, genetic background, sleep deprivation

Overall design: Experiments were performed on male mice (C57BL/6J (B6), AKR/J (AK), DBA/2J (D2)), 12-13 weeks of aged, purchased from Jackson Laboratory. Animals were housed in a light/dark cycle of 24 hrs with water and food available ad libitum. Mice of the 3 inbred strains were sleep deprived for 6h starting at light onset (ZT0) and sacrificed together with their home-cage controls at ZT6 (n=9 / strain =3 / condition =2 / tissues =2; total = 108 mice).

Background corr dist: KL-Divergence = 0.0092, L1-Distance = 0.0360, L2-Distance = 0.0014, Normal std = 0.9491

0.436 Kernel fit Pairwise Correlations Normal fit

Density 0.218

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

B_AK_Control_ZTB_AK_Control_ZTB_AK_Control_ZT 6_1 B_AK_SleepDep_ZT(0.0223105) 6_2 B_AK_SleepDep_ZT(0.0188679) 6_3 B_AK_SleepDep_ZT(0.0222324) 6_1B_B6_Control_ZT (0.0207531) 6_2B_B6_Control_ZT (0.0238524) 6_3B_B6_Control_ZT (0.0332868) 6_1 B_B6_SleepDep_ZT(0.0286353) 6_2 B_B6_SleepDep_ZT(0.0221545) 6_3 B_B6_SleepDep_ZT(0.029051) 6_1B_D2_Control_ZT (0.0255818) 6_2B_D2_Control_ZT (0.030566) 6_3B_D2_Control_ZT (0.0297623) 6_1 B_D2_SleepDep_ZT(0.0249779) 6_2 B_D2_SleepDep_ZT(0.0254203) 6_3 B_D2_SleepDep_ZT(0.0409407) 6_1L_AK_Control_ZT (0.0278382) 6_2L_AK_Control_ZT (0.0297356) 6_3L_AK_Control_ZT (0.0303308) 6_1 L_AK_SleepDep_ZT(0.0381516) 6_2 L_AK_SleepDep_ZT(0.0421854) 6_3 L_AK_SleepDep_ZT(0.0319151) 6_1L_B6_Control_ZT (0.0499005) 6_2L_B6_Control_ZT (0.0336627) 6_3L_B6_Control_ZT (0.0328363) 6_1 (0.0217648)L_B6_SleepDep_ZT 6_2 (0.0309291)L_B6_SleepDep_ZT 6_3 (0.0238159)L_B6_SleepDep_ZT 6_1L_D2_Control_ZT (0.0378967) 6_2L_D2_Control_ZT (0.0240538) 6_3L_D2_Control_ZT (0.0180981) 6_1 (0.022576)L_D2_SleepDep_ZT 6_2 (0.0215381)L_D2_SleepDep_ZT 6_3 (0.0216686)L_D2_SleepDep_ZT 6_1 (0.0198932) 6_2 (0.02082) 6_3 (0.0219966)[ min ] [ medium ] [ max ] CEM 1 Nefl 37.3 10487.2 13260.7 P ( S | Z, I ) = 1.00 Nefh 69.6 2322.7 3107.9 Mean Corr = 0.92344 Ina 59.6 4012.1 4914.2 Prph 51.2 94.5 175.2 Dlgap2 43.9 151.5 371.5 Nefm 32.9 5791.4 7498.1 Snap25 33.0 33907.1 42134.3 Elavl2 32.0 1626.2 2165.7 Gng3 74.8 9800.5 14323.5 Cadps 37.0 3686.9 5176.8 CEM 1 + Cplx1 97.0 14367.2 17570.3 Top 10 Genes Stmn2 114.4 9659.1 12963.9 Sult4a1 125.3 4214.9 6347.2 Nrsn1 46.1 5918.1 7620.5 Elavl4 46.3 1242.8 1892.7

Null module Nrp1 Ldlrap1 Gan 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) (0.0424054) iPS NSCs cell cell-derivedsample_3stemNeural sample_1(0.0896592) sample_1 NSCs cell stemNeural sample_2(0.0594458) sample_2 NSCs(0.0501137) cell (0.143068) stem sample_3 sample_3 (0.0567689) cell (0.176797) sample_4 (0.0396609) (0.29666) (0.0454211)[ min ] [ medium ] [ max ] CEM 1 Nefl 21.5 36.4 312.0 P ( S | Z, I ) = 1.00 Nefh 21.2 25.1 705.4 Mean Corr = 0.89696 Ina 107.8 143.0 772.9 Prph 26.5 37.9 196.5 Dlgap2 17.2 20.6 26.9 Nefm 25.4 34.4 44.4 Snap25 15.8 19.6 23.2 Elavl2 221.1 366.1 527.1 Gng3 62.7 87.8 705.9 Cadps 22.9 32.9 183.8 CEM 1 + Cplx1 166.6 207.8 230.2 Top 10 Genes Stmn2 56.2 72.9 2081.8 Sult4a1 32.6 43.4 243.1 Nrsn1 20.0 21.7 27.0 Elavl4 70.4 92.5 111.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE56236" 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=GSE56236 Status: Public on Jul 14 2014 Title: Glomerular transcriptomic analysis of the influence of Genetic background effect during anti-GBM glomerulonephritis in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We analyzed the impact of the genetic background during experimental passive non-accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) (an equivalent to nephrotoxic nephritis) in two different mouse genetic backgrounds (C57BL6/J vs 129S2svPAS/crl).

Glomerular extracts have been made at an early time point (e.g day 4 of the induction of the glomerulonephritis). RNA have been extracted following standard procedures.

Overall design: 3 mice per group have been compared. 3 Control mice from each background. And 3 anti-GBM-GN challenged mice from each Genetic background, corresponding to 12 samples in total.

Background corr dist: KL-Divergence = 0.0993, L1-Distance = 0.0856, L2-Distance = 0.0127, Normal std = 0.5345

0.830 Kernel fit Pairwise Correlations Normal fit

Density 0.415

0.000 CEM 1

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

Pre-normalization Quantiles

Day_4_anti_GBM_GN_C57BL6JDay_4_anti_GBM_GN_C57BL6JDay_4_anti_GBM_GN_C57BL6JControlControl animal rep1 Control(0.0158184)C57BL6Janimal rep2 Day_4_anti_GBM_GN_129S2SvPAs(0.0184943)C57BL6Janimal rep3rep1 Day_4_anti_GBM_GN_129S2SvPAs(0.0936358)(0.0879277)C57BL6J rep2 Day_4_anti_GBM_GN_129S2SvPAs(0.230568) rep3 Control(0.0471849)Control animal rep1 Control129S2SvPASanimal (0.277226) rep2 129S2SvPASanimal (0.0203977) rep3rep1 129S2SvPAS (0.0456205)(0.0304993) rep2 (0.0360533) rep3[ min (0.0965743) ] [ medium ] [ max ] CEM 1 Nefl 22.5 23.3 24.2 P ( S | Z, I ) = 1.00 Nefh 34.2 35.8 36.9 Mean Corr = 0.89489 Ina 30.4 32.7 33.6 Prph 27.0 27.7 28.7 Dlgap2 25.0 26.0 26.8 Nefm 29.9 31.8 32.9 Snap25 29.3 31.2 32.1 Elavl2 28.9 30.7 31.7 Gng3 21.8 22.5 23.2 Cadps 25.9 27.1 27.9 CEM 1 + Cplx1 31.2 32.3 33.5 Top 10 Genes Stmn2 30.2 35.3 69.0 Sult4a1 28.3 29.4 30.7 Nrsn1 28.7 30.3 31.2 Elavl4 25.4 26.5 27.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE33770" 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=GSE33770 Status: Public on Nov 12 2013 Title: Microarray Studies on the STAT5A MUTANT. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Stat5+/- mice were bred into the C57BL/6 background. Stat5+/- mice were intercrossed and mouse embryonic fibroblasts (MEFs) were isolated from 12.5-13.5-day WT or Stat5-/- fetuses. The retroviral-expression vector carrying a DNA binding domain mutant Stat5A (E437/E438?AA) or tyrosine-phosphorylated Stat5A Y694F mutation based on an MSCV-IRES-GFP backbone (gift from Richard Moriggl, Ludwig-Boltzmann Institute, Vienna, Austria) was infected into Stat5-/- MEFs. FACS was used to select GFP+ cells. After 5 hours starvation in serum free medium with 0.1% of BSA, MEFs were treated with growth hormone for 2 hours. Total cellular RNA from each group of the MEFs was extracted with TRIzol reagent (Invitrogen) according to the manufacturer's instructions. Microarray analyses were performed using Affymetrix Mouse Genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA) (four groups, biological replicates for each group). Expression values were determined with GeneChip Operating Software (GCOS) v1.1.1 software. RMA signals were summarized using GeneSpring GX 10.0.1 (Agilent) and normalized by quantile normalization. All data analysis was performed with GeneSpring software GX 10.01.

Overall design: Total 4 groups (EA, EA_GH, YF, YF_GH), biological duplicate replication for each group

Background corr dist: KL-Divergence = 0.0380, L1-Distance = 0.0916, L2-Distance = 0.0110, Normal std = 0.7913

0.534 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

EA-2 (0.0908289)EA-gh1 EA-gh2(0.0339773) YF1(0.329807) (0.0919436)YF2 (0.0547485)YF-gh1 YF-gh2(0.301152) EA1(0.0452852) (0.0522575) [ min ] [ medium ] [ max ] CEM 1 Nefl 2.8 2.9 3.0 P ( S | Z, I ) = 1.00 Nefh 2.9 3.0 3.3 Mean Corr = 0.88555 Ina 3.2 3.3 3.6 Prph 2.8 3.0 3.1 Dlgap2 2.4 2.5 2.6 Nefm 3.0 3.1 4.2 Snap25 3.3 3.5 3.9 Elavl2 10.9 105.9 221.7 Gng3 2.7 2.8 3.0 Cadps 3.7 4.0 4.6 CEM 1 + Cplx1 3.0 3.2 3.3 Top 10 Genes Stmn2 60.3 783.7 901.5 Sult4a1 2.3 2.4 2.5 Nrsn1 3.7 4.0 4.3 Elavl4 3.5 3.8 4.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE17797" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 19 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17797 Status: Public on Aug 29 2010 Title: UGE and UGM Reveal Novel Signaling Pathways and Ligand-Receptor Interactions in the Primitive Prostate Stem Cell Niche Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20941365 Summary & Design: Summary: We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their global gene expression profiles to define their differentially expressed regulators. To distinguish gene expression patterns that are shared by other developing epithelial/mesenchymal compartments in the embryo from those that pertain to the prostate stem cell niche, we also determine the global gene expression of epidermis and dermis of the same embryos. We identified a distinctive core of transcripts that were differentially regulated in the prostate stem cell niche. Our analysis indicates that several of the key transcriptional components that are likely to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Serbp1) and cell migration (e.g., Areb6 and Rreb1). Several of the promoter binding motifs that are enriched in the profiles are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. We also focused on defining ligand-receptor interactions that may be relevant in controlling signals in the stem cell niche and identified the Wnt/beta-catenin, ephrin, Notch, sonic hedgehog, FGF, TGF-beta and bone morphogenic signaling pathways as being of likely relevance in the prostate stem cell niches. Members of the integrins family including those that bind extracellular matrix proteins such as laminin and activate latent TGF-beta are also expressed in the prostate niche.development.

Keywords: Differential gene expression

Overall design: Six biological replicate experiments were performed for UGE. Five biological replicate experiments were performed for UGM. Four biological replicate experiments were performed for Epidermis. Four biological replicate experiments were performed for Dermis.

Background corr dist: KL-Divergence = 0.0825, L1-Distance = 0.0284, L2-Distance = 0.0013, Normal std = 0.4742

0.841 Kernel fit Pairwise Correlations Normal fit

Density 0.421

0.000 CEM 1

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

Pre-normalization Quantiles

mouse_urogenital_sinus_epithelium_rep1mouse_urogenital_sinus_epithelium_rep2mouse_urogenital_sinus_epithelium_rep3mouse_urogenital_sinus_epithelium_rep4mouse_urogenital_sinus_epithelium_rep5mouse_urogenital_sinus_epithelium_rep6 (0.0233331)mouse_urogenital_sinus_mesenchyme_rep1 (0.0360802)mouse_urogenital_sinus_mesenchyme_rep2 (0.033325)mouse_urogenital_sinus_mesenchyme_rep3 (0.025421)mouse_urogenital_sinus_mesenchyme_rep4 (0.0275606)mouse_urogenital_sinus_mesenchyme_rep5 (0.031815)mouse_epidermis_rep1mouse_epidermis_rep2 (0.120252)mouse_epidermis_rep3 (0.100451)mouse_epidermis_rep4 (0.121425) (0.0284405)mouse_dermis_rep1 (0.0760743) (0.0432653)mouse_dermis_rep2 (0.13937) (0.0582479)mouse_dermis_rep3 (0.0384941) (0.0111899)mouse_dermis_rep4 (0.0308395) (0.0287244) (0.0256917)[ min ] [ medium ] [ max ] CEM 1 Nefl 32.6 100.5 13312.2 P ( S | Z, I ) = 1.00 Nefh 26.7 37.2 216.5 Mean Corr = 0.86931 Ina 57.1 75.7 1546.2 Prph 38.7 58.9 7064.8 Dlgap2 20.2 24.9 39.8 Nefm 27.6 53.5 6018.3 Snap25 16.0 18.0 1394.6 Elavl2 23.0 240.3 4539.7 Gng3 66.1 85.9 427.2 Cadps 22.9 90.8 2067.2 CEM 1 + Cplx1 157.2 187.8 1070.8 Top 10 Genes Stmn2 88.3 448.3 7250.5 Sult4a1 35.6 43.3 244.8 Nrsn1 25.7 31.6 289.3 Elavl4 66.9 83.5 2503.2

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE40261" 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=GSE40261 Status: Public on Aug 22 2012 Title: Hepatic gene expression changes following antisense oligonucleotide-based inhibition of miR-29a Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22167021 Summary & Design: Summary: Adult BALB/c female mice were injected intraperitoneally with a single dose at 20 mg per kg of antisense oligonucleotide either against miR-29a (5-TAACCGATTTCAGATGGTGCTA-3) or against a scrambled sequence (5-TCATTGGCATGTACCATGCAGCT-3 Antisense oligonucleotides contained 2-O-methoxyethyl (2-MOE), 2-flouro (2-F) 2’-alpha-flouro units with a phosphorothioate backbone (Regulus Therapeutics). Six days following the injection, liver was isolated, total RNA was prepared as described above, and the RNA was amplified and biotinylated using the MessageAmp Premier kit (Ambion). Samples (n=4 each experimental and control) were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Arrays in the Childrens Hospital of Philadelphia Nucleic Acids Core Facility´and analyzed with the assistance of the Penn Bioinformatics Core. Probe intensities were normalized using the GCRMA method and the significance of the log2-transformed, GCRMA-normalized signal intensities was determined using SAM

Overall design: Adult mice injected with anti-miR-29a or scrambled control ASO, n=4 per group

Background corr dist: KL-Divergence = 0.0598, L1-Distance = 0.0534, L2-Distance = 0.0053, Normal std = 0.5600

0.739 Kernel fit Pairwise Correlations Normal fit

Density 0.370

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 1 (0.234786)Control 2 (0.0507712)Control 3 (0.0430394)Anti-29a 4 (0.137986)Anti-29a 1 (0.0564938)Anti-29a 2 (0.103963)Anti-29a 3 (0.274951) 4 (0.0980106) [ min ] [ medium ] [ max ] CEM 1 Nefl 14.1 14.9 15.5 P ( S | Z, I ) = 1.00 Nefh 18.8 20.0 20.8 Mean Corr = 0.84760 Ina 26.5 29.2 31.9 Prph 14.2 14.9 15.2 Dlgap2 11.0 11.3 11.6 Nefm 12.7 13.1 13.6 Snap25 20.1 21.3 23.5 Elavl2 17.0 17.9 18.7 Gng3 11.0 11.6 12.0 Cadps 20.8 22.0 23.1 CEM 1 + Cplx1 30.8 32.6 38.5 Top 10 Genes Stmn2 11.1 11.2 11.6 Sult4a1 10.6 10.8 12.0 Nrsn1 17.7 18.6 19.8 Elavl4 17.3 17.9 19.3

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE8715" 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=GSE8715 Status: Public on Aug 09 2007 Title: Transcriptional Profiling of the Megabladder Mouse - A Unique Model of Bladder Dysmorphogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Recent studies in our lab have identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb-/-) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion into chromosome 16 followed by a translocation of this fragment into chromosome 11. In an effort to identify potential gene targets affected in mgb mice, we performed transcriptional profiling on embryonic day 15 (E15) mgb-/- bladders using both a Chromosome 11/16 Custom GeneChip Array and the Affymetrix Mouse Genome 430 2.0 GeneChip. This analysis identified no definitive mis-expressed gene targets on chromosome 11. In contrast, mgb-/- mice significantly over-expressed a cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb-/- bladders. Immunohistochemical studies indicated that the spatial distribution of Urp was altered in mgb-/- bladders, while biochemical studies suggested a potential role for Urp in modifying smooth muscle cell phenotype in vitro. Pathway analysis of mgb microarray data showed dysregulation of at least 60 gene products associated with the differentiation of smooth muscle. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb-/- bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development.

Keywords: mgb mutant bladders

Overall design: Gene expression profiling was performed on two separate study groups. First, total cellular RNA was isolated from wildtype (n=2; 1 female/1 male), mgb+/- (n=2; 1 female/1 male), and mgb-/- (n=2; 1 female/1 male) E15 whole embryos. Second, total cellular RNA was isolated from the bladders of E15 wildtype (n=7; 3 female/4 male), mgb+/- mice (n=7; 3 female/4 male), and mgb-/- mice (n=11; 7 females/4 males).

Background corr dist: KL-Divergence = 0.0433, L1-Distance = 0.0337, L2-Distance = 0.0016, Normal std = 0.6128

0.660 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

mgb -/- mgbfemale, -/- mgbmale,whole +/- whole E15mgb female, embryo +/-E15Wild male,whole embryo (HMF_529)type whole WildE15 female,(HMM_533) embryotype E15 (0.0967748) male,embryowhole (HTF_523) (0.0457872) whole E15 (HTM_532) embryo E15 (0.193033) embryo (WTF_528)(0.0972276)[ min (WTM_525) (0.47412)] (0.0930577)[ medium ] [ max ] CEM 1 Nefl 641.8 1172.9 4382.8 P ( S | Z, I ) = 1.00 Nefh 25.7 52.9 111.2 Mean Corr = 0.82161 Ina 57.8 110.0 1072.4 Prph 165.6 270.3 1114.9 Dlgap2 24.1 32.9 48.5 Nefm 597.5 1101.0 2903.6 Snap25 276.8 472.7 2361.8 Elavl2 627.1 1299.6 3215.1 Gng3 40.4 94.1 412.0 Cadps 51.2 82.2 340.3 CEM 1 + Cplx1 35.5 63.0 109.0 Top 10 Genes Stmn2 466.2 873.6 2771.9 Sult4a1 42.0 93.5 178.1 Nrsn1 33.7 106.7 571.9 Elavl4 65.5 150.7 347.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE43779" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.538 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

control controlbiological controlbiological rep1 2-AA biological(0.187177) rep2 treatment2-AA (0.12906) rep3 treatment2-AA biological(0.146631) treatment biological rep1 biological(0.105104) rep2 (0.0777784) rep3[ (0.35425) min ] [ medium ] [ max ] CEM 1 Nefl 40.3 10599.5 18413.7 P ( S | Z, I ) = 1.00 Nefh 75.2 578.2 1126.3 Mean Corr = 0.81993 Ina 10.9 999.1 2126.0 Prph 34.2 82.9 115.4 Dlgap2 10.2 284.8 433.0 Nefm 8.9 824.5 2548.6 Snap25 3.0 30482.1 50053.7 Elavl2 7.7 1619.7 4822.8 Gng3 37.9 3011.1 3854.3 Cadps 9.6 711.1 1760.9 CEM 1 + Cplx1 11.6 3237.7 5661.1 Top 10 Genes Stmn2 234.1 939.2 2081.1 Sult4a1 11.9 1644.3 2527.9 Nrsn1 6.5 1963.7 4062.0 Elavl4 71.2 775.4 941.9

Null module Nrp1 Ldlrap1 Gan 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 (0.124173)MEFs_mock_sample1 (0.0941103)MEFs_IFNb_sample1 (0.169202)MEFs_mock_sample2 (0.0874465) MEFs_IFNb_sample2(0.0811143) (0.0846581)L929_mock L929_IFNb(0.0544261) (0.114379) (0.0733939) (0.117096) [ min ] [ medium ] [ max ] CEM 1 Nefl 5.0 37.7 4450.5 P ( S | Z, I ) = 1.00 Nefh 6.0 29.1 241.1 Mean Corr = 0.79724 Ina 19.1 49.7 7687.6 Prph 5.0 36.7 227.4 Dlgap2 5.0 88.4 126.6 Nefm 5.0 63.8 1301.9 Snap25 5.0 17.1 14778.0 Elavl2 171.4 599.0 7211.8 Gng3 26.1 53.3 7544.6 Cadps 5.0 35.7 4265.6 CEM 1 + Cplx1 8.5 39.7 4843.2 Top 10 Genes Stmn2 5.0 155.8 17979.7 Sult4a1 22.6 85.9 1506.1 Nrsn1 5.0 48.2 674.8 Elavl4 5.0 138.2 4113.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE35396" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35396 Status: Public on Jul 26 2012 Title: Selective knockout of NeuroD1 in the retina and pineal gland Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22784109 Summary & Design: Summary: NeuroD1 encodes a basic helix-loop-helix transcription factor involved in the development of neural and endocrine structures. NeuroD1 mRNA is highly abundant in the adult mammalian pineal gland and exhibits a developmental expression pattern similar to the retina. This is consistent with the common evolutionary origin of pinealocytes and retinal photoreceptors. Pinealocytes and retinal photoreceptors express a shared set of phototransduction genes and submammalian pinealocytes are photosensitive. In contrast to the retina, the pineal gland is a relatively homogeneous structure, composed 95% of pinealocytes. This makes the pineal gland a particularly useful model for understanding photoreceptor cell biology. The loss of NeuroD1 in the retina results in progressive photoreceptor degeneration and the molecular mechanisms underlying this retinal degeneration phenotype remain unknown. Similarly, the role that NeuroD1 plays in the pineal gland is unknown.

To determine the function of NeuroD1 in the pineal gland and retina, a Cre/loxP recombination strategy was used to selectively target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, a transcription factor selectively expressed in the pineal gland and retina. Pineal and retinal tissues from two-month-old NeuroD1 cKO and control animals were used in microarray studies to identify candidate genes responsible for the photoreceptor degeneration phenotype.

Overall design: The Cre/loxP recombination strategy was used to target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout mice (NeuroD1floxed::Crx-Cre+/-). NeuroD1 floxed mice (NeuroD1floxed::Crx-Cre-/-) served as the controls. Pineal glands and retinas from two-month-old control and conditional knockout mice were collected at ZT6 and ZT20. 3 pools of 6 pineal glands per genotype and respective time of day were collected for each sample. Similarly, 3 pools of 6 retinas each were also collected. RNA from each pool was extracted and hybridized on the Affymetrix Mouse 430 2.0 array.

Background corr dist: KL-Divergence = 0.0411, L1-Distance = 0.0557, L2-Distance = 0.0049, Normal std = 0.6303

0.710 Kernel fit Pairwise Correlations Normal fit

Density 0.355

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

Pineal glandPineal from glandPineal control from glandPineal controlmouse from glandPineal controlatmouse fromZT6, glandPineal controlbiologicalatmouse fromZT6, glandPineal controlbiologicalatmouse from ZT6, repglandPineal 1controlbiologicalatmouse (0.0320768) from ZT20, repglandPineal 2NeuroD1atmouse (0.0278723)biological from ZT20, repglandPineal 3NeuroD1at (0.0480041)biological cKO fromZT20, gland Pinealrep mouse NeuroD1 1 biological cKOfrom(0.0400081) gland Pinealrep atmouse NeuroD1 2 ZT6,cKOfrom(0.04672) gland Retinarep biologicalatmouse NeuroD1 3 ZT6,cKOfrom(0.0411471) fromRetina biologicalatmouse NeuroD1 control ZT6,cKOrep fromRetina 1 biologicalatmouse (0.0489621) control mouseZT20,cKOrep fromRetina 2 atmouse (0.0506828)biological control atmouseZT20,rep fromRetinaZT6, 3 at (0.0317962)biological controlbiologicalatmouseZT20, rep fromRetinaZT6, 1 biological control(0.0232471)biologicalatmouse rep from RetinaZT6,rep 2 1control(0.0358027)biologicalatmouse (0.0337114) rep from RetinaZT20,rep 3 2NeuroD1(0.0311822)atmouse (0.0559603)biological from RetinaZT20,rep 3NeuroD1at (0.0182109)biological cKO fromRetinaZT20, rep mouse NeuroD1 1 biological cKOfrom(0.0487009)Retina rep atmouse NeuroD1 2 ZT6,cKOfrom(0.0441973)Retina rep biologicalatmouse NeuroD1 3 ZT6,cKOfrom(0.0370845) biologicalatmouse NeuroD1 ZT6,cKOrep 1 biologicalatmouse (0.0415798) ZT20,cKOrep 2 atmouse (0.0584381)biological ZT20,rep[ min 3 at (0.0386822)biological ZT20, rep ]1 biological (0.0694343) rep 2 (0.0333156) rep[ 3medium (0.0631832) ] [ max ] CEM 1 Nefl 3.1 4223.4 4983.7 P ( S | Z, I ) = 1.00 Nefh 536.8 1689.4 3429.7 Mean Corr = 0.78980 Ina 1094.3 2392.2 3959.1 Prph 0.7 56.3 217.9 Dlgap2 0.7 6.7 18.1 Nefm 10.5 648.2 1207.8 Snap25 8476.6 9792.4 12419.1 Elavl2 140.7 1370.1 1835.0 Gng3 39.5 5138.2 6366.8 Cadps 183.1 4195.5 5233.1 CEM 1 + Cplx1 714.0 2513.8 3388.8 Top 10 Genes Stmn2 25.8 1187.6 1868.8 Sult4a1 913.0 2053.8 2477.0 Nrsn1 2242.7 4074.5 5504.9 Elavl4 21.5 284.5 569.1

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE17739" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17739 Status: Public on Oct 22 2009 Title: Circadian gene profiling in the distal nephron and collecting ducts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19805330 Summary & Design: Summary: Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.

Keywords: time course

Overall design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.

Background corr dist: KL-Divergence = 0.0374, L1-Distance = 0.0298, L2-Distance = 0.0014, Normal std = 0.6138

0.650 Kernel fit Pairwise Correlations Normal fit

Density 0.325

0.000 CEM 1

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

Pre-normalization Quantiles

DCT/CNT_ZT0_pool1DCT/CNT_ZT0_pool2DCT/CNT_ZT4_pool1 (0.0315113)DCT/CNT_ZT4_pool2 (0.037949)DCT/CNT_ZT8_pool1 (0.024426)DCT/CNT_ZT8_pool2 (0.0494146)DCT/CNT_ZT12_pool1 (0.0504281)DCT/CNT_ZT12_pool2 (0.0678914)DCT/CNT_ZT16_pool1 DCT/CNT_ZT16_pool2(0.0269742) DCT/CNT_ZT20_pool1(0.0579507) DCT/CNT_ZT20_pool2(0.0527605) CCD_ZT0_pool1(0.0636211) CCD_ZT0_pool2(0.0810228) CCD_ZT4_pool1(0.0630866) (0.0266659)CCD_ZT4_pool2 (0.0489991)CCD_ZT8_pool1 (0.0296847)CCD_ZT8_pool2 (0.0286491)CCD_ZT12_pool1 (0.0372252)CCD_ZT12_pool2 (0.0203814)CCD_ZT16_pool1 (0.0452304)CCD_ZT16_pool2 (0.039001)CCD_ZT20_pool1 (0.0331279)CCD_ZT20_pool2 (0.030679) (0.0252672) (0.0280528) [ min ] [ medium ] [ max ] CEM 1 Nefl 225.9 1597.9 3741.4 P ( S | Z, I ) = 1.00 Nefh 23.7 36.7 51.0 Mean Corr = 0.78783 Ina 12.2 21.2 49.9 Prph 13.9 27.0 49.8 Dlgap2 16.0 21.6 46.8 Nefm 8.6 16.0 27.4 Snap25 8.4 13.5 55.5 Elavl2 12.3 32.3 61.2 Gng3 77.8 116.0 156.8 Cadps 9.1 12.0 16.8 CEM 1 + Cplx1 72.0 158.6 201.6 Top 10 Genes Stmn2 53.7 97.1 121.4 Sult4a1 39.6 49.4 73.5 Nrsn1 10.5 15.5 42.4 Elavl4 14.5 42.7 72.9

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE11110" 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=GSE11110 Status: Public on Jun 29 2008 Title: Expression data from bone marrow CLP and B-cell progenitor subfractions. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Expression profiling of CLP subfractions (with different potential to develop into T-cells) and B-cell progenitors.

Keywords: cell type comparison, B-cell progenitor, common lymphoid progenitor cells (CLP)

Overall design: CLP and B-cell progenitor subpopulations were FACS sorted. Subsequently RNA was extracted, labelled and hybridized to Affymetrix microarrays. The CLP subfractions were the target of investigation (B-cell progenitors subpopulations served as references of expression levels for B-cell related transcripts) as we sought to identify expression changes potentially explaining difference in function between the hCD25 positiv and negativ subsets.

Background corr dist: KL-Divergence = 0.0563, L1-Distance = 0.0827, L2-Distance = 0.0115, Normal std = 0.6124

0.651 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

Adult murineAdult murineBM,Adult hCD25- murineBM,Adult hCD25-CLP murineBM,Adult (LIN-B220-CD19-IL7R+FLT3+SCA1lowKITlowhCD25-) hCD25-CLP murineBM,Adult (LIN-B220-CD19-IL7R+FLT3+SCA1lowKITlowhCD25-) hCD25-CLP murineBM,Adult (LIN-B220-CD19-IL7R+FLT3+SCA1lowKITlowhCD25-) hCD25+CLP murineBM,Adult (LIN-B220-CD19-IL7R+FLT3+SCA1lowKITlowhCD25+) pro-B CLP murineBM,Adult (LIN-B220-CD19-IL7R+FLT3+SCA1lowKITlowhCD25+)cells pro-B murineBM, (CD19+AA4.1+CD43low)Adult cells pro-B murineBM, (CD19+AA4.1+CD43low)Adult cells pro-B murinespleen, (CD19+B220+CD43-IgM-) cells#1 (0.0201427) spleen,Mature (CD19+B220+CD43-IgM-) #1#2 (0.0266995)(0.0352971) MatureB cells #2#3 (0.0396732)(0.0663818) (CD19+IgM+)B[ cells #1min (0.0553908)(0.245067) (CD19+IgM+) #2 #2 ] #1(0.106538) (0.318913) (0.0447129) #2 (0.0411844)[ medium ] [ max ] CEM 1 Nefl 34.8 44.0 104.4 P ( S | Z, I ) = 1.00 Nefh 88.8 299.0 673.5 Mean Corr = 0.78041 Ina 51.4 62.7 168.7 Prph 59.3 77.4 290.5 Dlgap2 35.7 45.8 110.5 Nefm 32.9 42.7 55.1 Snap25 31.0 44.8 81.4 Elavl2 30.8 42.5 67.3 Gng3 60.5 131.3 577.5 Cadps 33.2 42.4 95.7 CEM 1 + Cplx1 135.0 173.0 396.1 Top 10 Genes Stmn2 73.8 98.8 169.1 Sult4a1 54.3 66.1 182.0 Nrsn1 40.3 47.2 62.8 Elavl4 44.8 65.4 134.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE5128" 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=GSE5128 Status: Public on Sep 01 2006 Title: Gene Expression Biomarkers for Predicting Liver Tumors in Two-Year Rodent Bioassays Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17114358 Summary & Design: Summary: Two-year rodent bioassays play a central role in evaluating both the carcinogenic potential of a chemical and generating quantitative information on the dose-response behavior for chemical risk assessments. The bioassays involved are expensive and time-consuming, requiring nearly lifetime exposures (two years) in mice and rats and costing $2 to $4 million per chemical. Since there are approximately 80,000 chemicals registered for commercial use in the United States and 2,000 more are added each year, applying animal bioassays to all chemicals of concern is clearly impossible. To efficiently and economically identify carcinogens prior to widespread use and human exposure, alternatives to the two-year rodent bioassay must be developed. In this study, animals were exposed for 13 weeks to two chemicals that were positive for liver tumors in the two-year rodent bioassay, two chemicals that were negative for liver tumors, and two vehicle controls. Gene expression analysis was performed on the livers of the animals to assess the potential for identifying gene expression biomarkers that can predict tumor formation in a two-year bioassay following a 13 week exposure.

Keywords: toxicology, chemical carcinogenesis, liver

Overall design: Five week old female B6C3F1 mice were exposed for 13 weeks to the following treatments: 1) 1,5-Naphthalenediamine, CAS No. 2243-62-1, feed, 2000 ppm, positive liver carcinogen; 2) 2,3-Benzofuran, CAS No. 271-89-6, gavage, 240 mg/kg, positive liver carcinogen; 3) N-(1-naphthyl)ethylenediamine dihydrochloride, CAS No. 1465-25-4, feed, 2000 ppm, negative liver carcinogen; 4) Pentachloronitrobenzene, CAS No. 82-68-8, feed, 8187 ppm, negative liver carcinogen; 5) Feed control; 6) Corn oil gavage control. Feed animals were exposed 7 days/week and gavage animals were exposed 5 days/week (5 ml/kg). Microarray analysis was performed on the livers of three mice per treatment group.

Background corr dist: KL-Divergence = 0.0940, L1-Distance = 0.0565, L2-Distance = 0.0073, Normal std = 0.4505

0.886 Kernel fit Pairwise Correlations Normal fit

Density 0.443

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

LiverTissue_GavageTreatment_2,3-Benzofuran_Animal10LiverTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal12LiverTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal14LiverTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal15LiverTissue_FeedTreatment_Pentachloronitrobenzene_Animal16LiverTissue_FeedTreatment_Pentachloronitrobenzene_Animal18LiverTissue_FeedTreatment_Pentachloronitrobenzene_Animal20LiverTissue_GavageTreatment_CornOil_Control_Animal22 (0.0353903)LiverTissue_GavageTreatment_CornOil_Control_Animal24LiverTissue_GavageTreatment_CornOil_Control_Animal25LiverTissue_FeedTreatment_RodentLiverTissue_FeedTreatment_RodentLiverTissue_FeedTreatment_Rodent (0.0532797) (0.0144354)LiverTissue_FeedTreatment_1,5-Naphthalenediamine_Animal2 (0.052341) (0.0275013)LiverTissue_FeedTreatment_1,5-Naphthalenediamine_Animal4 (0.014882) (0.0283142) Chow_Control_Animal27(0.0259788)LiverTissue_FeedTreatment_1,5-Naphthalenediamine_Animal5 Chow_Control_Animal28(0.0358637)LiverTissue_GavageTreatment_2,3-Benzofuran_Animal6 Chow_Control_Animal29(0.0930018)LiverTissue_GavageTreatment_2,3-Benzofuran_Animal8 (0.0532306) (0.0340429) (0.288796)[ min (0.0282773) (0.0562427)] (0.0303615) (0.0538727)[ (0.0741882)medium ] [ max ] CEM 1 Nefl 32.8 36.7 48.7 P ( S | Z, I ) = 1.00 Nefh 51.6 61.6 100.5 Mean Corr = 0.77181 Ina 38.8 51.1 74.6 Prph 43.5 52.8 69.8 Dlgap2 34.3 39.5 47.1 Nefm 28.5 32.9 42.3 Snap25 27.3 31.5 37.9 Elavl2 28.9 33.5 41.1 Gng3 74.9 97.2 233.3 Cadps 31.7 36.6 51.1 CEM 1 + Cplx1 87.3 103.5 147.1 Top 10 Genes Stmn2 61.4 74.2 89.9 Sult4a1 103.5 131.8 187.3 Nrsn1 36.4 40.5 50.5 Elavl4 39.7 47.3 61.5

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE24628" 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=GSE24628 Status: Public on Nov 01 2010 Title: Subtypes of medulloblastoma have distinct developmental origins Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21150899 Summary & Design: Summary: Medulloblastoma encompasses a collection of clinically and molecularly diverse tumor subtypes that together comprise the most common malignant childhood brain tumor. These tumors are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) following aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH-subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here, we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT-subtype), arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, while SHH-subtype tumors are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem that included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice and in 15% of cases in which Tp53 was concurrently deleted, progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.

Overall design: A total of 16 samples are analyzed, repsresenting 4 experimental groups: Ctnnb1 medulloblastoma (3 samples); Ptch1 medulloblastoma (6 samples); embryonic dorsal brainstem (4 samples); and postnatal granule neuron precursor cells (3 samples). Every sample was prepared from a different mouse.

Background corr dist: KL-Divergence = 0.1173, L1-Distance = 0.0431, L2-Distance = 0.0036, Normal std = 0.4305

0.963 Kernel fit Pairwise Correlations Normal fit

Density 0.482

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

pgr003 pgr006(0.163919) pgr010(0.0219762) pgr011(0.0264901) pgr012(0.0323969) pgr013(0.0262469) pgr014(0.0240889) pgr016(0.0318356) pgr029(0.0315237) pgr033(0.0294319) pgr035(0.0212999) pgr049(0.041593) pgr051(0.115788) pgr053(0.0572623) pgr055(0.146255) pgr066(0.094744) (0.135147) [ min ] [ medium ] [ max ] CEM 1 Nefl 2.0 472.3 12902.6 P ( S | Z, I ) = 1.00 Nefh 12.1 209.3 1889.7 Mean Corr = 0.76968 Ina 79.0 1409.9 2575.3 Prph 2.3 27.0 1655.6 Dlgap2 1.4 36.3 285.6 Nefm 9.3 472.2 9659.0 Snap25 26.5 8385.9 12610.2 Elavl2 249.7 5964.8 10606.9 Gng3 57.3 1640.9 4479.2 Cadps 836.3 4555.9 10376.2 CEM 1 + Cplx1 14.3 2416.5 6829.7 Top 10 Genes Stmn2 73.8 7600.6 19676.3 Sult4a1 12.1 1333.1 2161.6 Nrsn1 4.9 360.4 1964.8 Elavl4 88.2 2481.7 5248.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE54678" 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=GSE54678 Status: Public on Jun 30 2014 Title: A pivotal role of SRC-2 in Metastatic and Castration Resistant Prostate Cancer Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: SRC-2 is frequently amplified or overexpressed in metastatic prostate cancer patients. In this study, we used genetically engineered mice, overexpressing SRC-2 specifically in the prostate epithelium as a mouse model to examine the role of SRC-2 in prostate tumorigenesis. Over-expression of SRC-2 in PTEN heterozygous mice accelerates PTEN mutation induced tumor progression and develops a metastasis-prone cancer.

We used microarrays to examine the molecular profile of prostate-specific SRC-2 overexpression adult dorsal-lateral prostate in comparison with that of control PTENF/+ heterozygous deletion mice.

Overall design: total RNA was extracted from dorsal-lateral prostate of 7 months old-PTEN flox/+ control and PTEN flox/+; Rosa26-SRC-2 OE/+ adult mice, followed by gene expression profiling using Affymetrix microarrays. Each sample contains pooled prostate RNA from 3 mice.

Background corr dist: KL-Divergence = 0.0300, L1-Distance = 0.0202, L2-Distance = 0.0004, Normal std = 0.6761

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

Control,Control, biologicalControl, biological replicateSRC-2OE, biological replicate 1 SRC-2OE,(0.302147) biological replicate 2 SRC-2OE,(0.148751) biological 3replicate (0.207726) biological replicate 1 (0.050435) replicate 2 (0.185561) [3 (0.105381)min ] [ medium ] [ max ] CEM 1 Nefl 237.7 954.9 1693.6 P ( S | Z, I ) = 1.00 Nefh 199.0 314.9 581.3 Mean Corr = 0.76894 Ina 54.2 111.6 207.9 Prph 131.7 430.8 1243.0 Dlgap2 1.0 14.7 20.4 Nefm 72.7 373.1 820.3 Snap25 370.1 1107.6 2910.0 Elavl2 65.9 240.5 638.9 Gng3 47.6 140.2 267.5 Cadps 467.3 650.2 830.5 CEM 1 + Cplx1 61.3 202.8 460.9 Top 10 Genes Stmn2 288.6 575.9 1453.1 Sult4a1 73.2 112.5 217.8 Nrsn1 29.7 76.3 174.8 Elavl4 125.9 186.4 357.8

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE4816" 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=GSE4816 Status: Public on May 12 2006 Title: Gene expression profiles of the P1 bladder isolated from SMAA or SMAGA (Acta2 or Actg2) transgenic and wild type mice. (GUDMAP Series ID: 2) 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 bladder. 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 bladder. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in laser capture microdissected components of the developing bladder. 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. As a first step we sought to determine if expression of the reporter gene (EGFP or EYFP) used to identify smooth muscle cells altered the gene expression profile of the bladder.

Keywords: Comparison of postnatal day 1 bladders.

Overall design: Postnatal day 1 bladders were isolated from transgenic and wild-type mice to determine the effects of transgene expression on the gene expression profile in the bladder.

Background corr dist: KL-Divergence = 0.1519, L1-Distance = 0.0383, L2-Distance = 0.0029, Normal std = 0.3705

1.077 Kernel fit Pairwise Correlations Normal fit

Density 0.538

0.000 CEM 1

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

Pre-normalization Quantiles

13B (0.044102)15B (0.0652135)40B (0.012933)43B (0.293351)45B (0.0444326)61B (0.0307864)23B (0.0815106)27B (0.0556723)32B (0.0752841)24B (0.0542299)25B (0.0934207)26B (0.149064) [ min ] [ medium ] [ max ] CEM 1 Nefl 112.2 2582.7 6401.0 P ( S | Z, I ) = 1.00 Nefh 7.5 95.6 270.3 Mean Corr = 0.73411 Ina 28.3 106.2 411.2 Prph 70.5 654.1 1437.7 Dlgap2 23.2 56.7 66.1 Nefm 306.6 1663.8 3965.2 Snap25 42.7 665.7 2254.3 Elavl2 52.0 876.1 1922.3 Gng3 32.4 126.2 411.7 Cadps 66.5 419.1 758.8 CEM 1 + Cplx1 16.8 110.2 262.8 Top 10 Genes Stmn2 206.7 1537.6 4258.6 Sult4a1 41.7 86.2 151.5 Nrsn1 21.6 73.4 213.4 Elavl4 62.5 223.3 627.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE39621" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39621 Status: Public on Dec 27 2012 Title: Expression data from brain, liver and spleen of Npc1-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23094108 Summary & Design: Summary: Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional neurological, lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1-/- mice (Npc1nih)relative to Npc1+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates for the neurological disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gauchers disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1-/- as well as Balb/c Npc1nmf164 mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry.

We used microarrays on the diseased organs, brain, liver and spleen of the Npc1-/- mice to unserstand the molecular changes occur during the progression of NPC diseases. From the data, we have identified 12 potential genes which can be potentially developed as blood-based biomarker. We have also discovered up regulation of innate iimunity genes in all three organs of Npc1-/- mice and functionally validated them in liver and spleen.

Overall design: Brain from 11 female Npc1/ and 16 control female mice (Npc1+/+ and Npc1+/) from 6 age groups (20-25, 37-40, 54-55, 59-62, 67-71 and 81-84 days) were surgically harvested. Liver and spleen from 6 Npc1-/- and 6 Npc1+/- female mice from three age group ( 20-25, 54-55 and 67-71 days) were surgically harvested. Organs were kept in RNA later and stored at -20 ´C until used. RNA was isolated and Affymetrix mouse 430 2.0 array hybridizations were performed by UCLA Clinical Microarray Core, UCLA, Los Angeles, CA, USA. Subsequent raw data were analyzed using DNA-Chip Analyzer (D-Chip) with the .CEL files obtained from AGCC. Data from Npc1-/- mice from all age groups were compared to control mice (Npc1+/- and/or Npc1-/- mice) from all age groups separately for brain, liver and spleen. 'Matrix Table1' corrsponds for brain, 'Matrix Table2' corresponds for liver and 'Matrix Table3' corresponds for spleen. Thresholds for selecting significant genes were set at a relative difference Â³1.5-fold, absolute difference Â³100 signal intensity units and p<0.05. Genes that met all three criteria simultaneously were considered as significant change.

Background corr dist: KL-Divergence = 0.0594, L1-Distance = 0.0598, L2-Distance = 0.0057, Normal std = 0.5712

0.698 Kernel fit Pairwise Correlations Normal fit

Density 0.349

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 BrainWT 20d Brain Mouse1HET 25d Brain Mouse1 HET(0.0123966) 20d Brain NPCMouse1(0.0204902) 25d Brain NPCMouse1 (0.0150473) 20d Brain HETMouse1 (0.0116725) 25d Brain HETMouse1 (0.0418176) 37d Brain NPCMouse1 (0.0110336) 40d Brain NPCMouse1 (0.0161992) 37d Brain HETMouse1 (0.0127347) 40d Brain HETMOuse1 (0.0133559) 54d Brain NPCMouse1 (0.0242479) 55d Brain NPCMouse1 (0.0236213) 54d Brain WTMOuse1 (0.0329659) 55dBrain WTMouse1 (0.0114021) 60d Brain Mouse1HET (0.00522802) 60d Brain Mouse2 HET(0.0324737) 59d Brain NPCMouse1(0.0384892) 62d Brain NPCMouse1 (0.010674) 59d Brain WTMouse1 (0.00985432) 62dBrain HETMouse1 (0.0236936) 67d Brain Mouse1NPC (0.0153195) 67d Brain HETMouse1(0.00941722) 67d Brain HETMouse1 (0.0197078) 81d Brain NPCMouse1 (0.0287018) 82d Brain NPCMouse1 (0.0295644) 82d Brain HETMouse1 (0.00747432) 84d Liver HETMouse1 (0.00834446) 20d Liver Mouse1NPC (0.00577624) 25d Liver Mouse1NPC (0.0175351) 20d Liver Mouse1HET (0.0330007) 25d Liver Mouse1HET (0.0209471) 54 Liver Mouse1NPC (0.0240221) 55d Liver (0.0272474)Mouse1NPC 54d Liver Mouse1HET (0.0239673) 55d Liver Mouse1HET (0.0168486) 67d Liver Mouse1NPC (0.0217127) 67d Liver Mouse2NPC (0.0255262) 67 Liver Mouse1HET (0.0247152) 71d Spleen (0.0162706)Mouse1HET Spleen20dNPC (0.0166773) Mouse1 25dSpleenNPC Mouse1 (0.0155019) Spleen20dHET Mouse1 (0.0111463) Spleen25dHET Mouse1 (0.0130677) Spleen54dNPC Mouse1 (0.0127926) 55dSpleenNPC Mouse1 (0.0116066) Spleen54dHET Mouse1 (0.037423) Spleen55dHET Mouse1 (0.0101195) Spleen67dNPC Mouse1 (0.0156969) 67dSpleenNPC Mouse2 (0.0599412) Spleen67 Mouse1 (0.0121731) 71d (0.0167913)Mouse1 (0.0235665)[ min ] [ medium ] [ max ] CEM 1 Nefl 3.3 4724.0 11352.6 P ( S | Z, I ) = 1.00 Nefh 22.7 1065.6 6677.6 Mean Corr = 0.73359 Ina 46.3 2380.4 4716.9 Prph 3.4 72.9 340.0 Dlgap2 6.1 53.0 241.2 Nefm 3.7 3722.1 10662.3 Snap25 5.4 11445.2 17641.7 Elavl2 3.7 2102.1 3667.0 Gng3 13.7 5642.7 7620.5 Cadps 3.7 3271.6 5860.8 CEM 1 + Cplx1 2.6 6703.3 9131.3 Top 10 Genes Stmn2 28.2 3095.5 7970.3 Sult4a1 8.3 1856.9 4415.9 Nrsn1 6.0 4341.3 7551.8 Elavl4 3.7 848.0 2587.1

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE30865" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 68 -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=GSE30865 Status: Public on Jul 22 2011 Title: Gene expression of polyoma middle T antigen induced mammary tumors [NZB x PyMT] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22308418 Summary & Design: Summary: Mouse genetic crosses were established between the PyMT model of metastatic breast cancer and NZB strain. Tumors were harvested from the animals for gene expression analysis to identify genes and network modules associated with progression to distant metastatic disease.

Overall design: Gene expression of 68 samples from the NZB crosses were assayed on Affymetrix chips

Background corr dist: KL-Divergence = 0.0881, L1-Distance = 0.0712, L2-Distance = 0.0127, Normal std = 0.4866

0.869 Kernel fit Pairwise Correlations Normal fit

Density 0.435

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

NZB BackcrossNZB BackcrossNZB animal BackcrossNZB 2421animal Backcross (0.00878314)NZB 2424animal Backcross (0.00437778)NZB 2426animal Backcross (0.091356)NZB 2703animal Backcross (0.00242706)NZB 3001animal Backcross (0.00389494)NZB 3004animal Backcross (0.00306736)NZB 3039Ranimal Backcross NZB(0.00677543) 3042animal Backcross (0.0197969)NZB 3046animal Backcross (0.00359925)NZB 3053animal Backcross (0.0418862)NZB 3197animal Backcross (0.00264494)NZB 3199animal Backcross (0.00499514)NZB 3289animal Backcross (0.00475904)NZB 3290animal Backcross (0.0126758)NZB 3291animal Backcross (0.0843058)NZB 3295animal Backcross (0.00324399)NZB 3296animal Backcross (0.0109571)NZB 3296Ranimal Backcross NZB(0.0434435) 3299Ranimal Backcross NZB(0.0136851) 3351animal Backcross (0.00865409)NZB 3351Ranimal Backcross NZB(0.0138622) 3353animal Backcross (0.00582828)NZB 3355animal Backcross (0.00625085)NZB 3394animal Backcross (0.00261549)NZB 3397animal Backcross (0.0510169)NZB 3546animal Backcross (0.00145088)NZB 3547animal Backcross (0.00198459)NZB 3548animal Backcross (0.0269966)NZB 3550animal Backcross (0.00384673)NZB 3567animal Backcross (0.0294027)NZB 3568animal Backcross (0.00488946)NZB 3569animal Backcross (0.00235018)NZB 3570animal Backcross (0.00550565)NZB 3572animal Backcross (0.00442321)NZB 3738animal Backcross (0.00248735)NZB 3739animal Backcross (0.00307499)NZB 3769animal Backcross (0.00768411)NZB 3824animal Backcross (0.00752477)NZB 3825animal Backcross (0.00593807)NZB 3827animal Backcross (0.00247469)NZB 3830Ranimal Backcross NZB(0.011106) 3852Ranimal Backcross NZB(0.0113518) 3853animal Backcross (0.0192527)NZB 3854Ranimal Backcross NZB(0.00895742) 3855animal Backcross (0.00359107)NZB 3864animal Backcross (0.00698142)NZB 3867animal Backcross (0.00657664)NZB 3868animal Backcross (0.00617121)NZB 3890Ranimal Backcross NZB(0.0118024) 3891animal Backcross (0.0479296)NZB 4946animal Backcross (0.0394228)NZB 4950animal Backcross (0.0118145)NZB 4955animal Backcross (0.00665495)NZB 4956animal Backcross (0.0198848)NZB 4957Ranimal Backcross NZB(0.0123382) 4958animal Backcross (0.00490199)NZB 4960animal Backcross (0.0126108)NZB 4963animal Backcross (0.0560957)NZB 4966animal Backcross (0.006755)NZB 4967animal Backcross (0.0106138)NZB 4971animal Backcross (0.00454702)NZB 4973animal Backcross (0.0408484)NZB 4975animal Backcross (0.0071793)NZB 4977animal Backcross (0.00840337)NZB 4978animal Backcross (0.00537121) 4979Ranimal (0.0144225) 4980animal (0.0265819) 5000 (0.0128971)[ min ] [ medium ] [ max ] CEM 1 Nefl 20.6 25.5 49.6 P ( S | Z, I ) = 1.00 Nefh 20.0 30.6 106.9 Mean Corr = 0.75330 Ina 40.8 51.4 129.8 Prph 54.4 68.1 171.1 Dlgap2 18.0 22.8 34.0 Nefm 16.2 20.4 32.6 Snap25 11.5 15.2 29.7 Elavl2 14.8 21.2 110.4 Gng3 85.0 116.6 559.4 Cadps 13.3 16.5 32.5 CEM 1 + Cplx1 65.8 85.0 135.7 Top 10 Genes Stmn2 82.0 111.2 269.4 Sult4a1 21.3 26.3 37.8 Nrsn1 16.4 20.7 45.1 Elavl4 19.6 28.2 87.3

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE28559" 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=GSE28559 Status: Public on Jul 15 2011 Title: An expression microarray approach for the identification of candidate metastable epialleles in the mouse genome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the Agouti Expression Fingerprint. We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray.

Using Expression data from tissues of the three germ layers (liver, kidney, brain), high variance in agouti RNA levels among isogenic animals coupled with low variance among tissue types in individual animals is demonstrated. Here, we provide proof of concept for the Agouti Expression Fingerprint; the characterization of epigenetically labile loci in humans will be crucial to the development of novel screening and therapeutic targets for human disease prevention.

Overall design: For expression microarray studies, total RNA was isolated from liver, kidney, and brain tissue from 10 male Avy/a mice (2 per each of the 5 coat color classes) at time of weaning and coat color determination (day 22). Using Affymetrix GeneChip Mouse Genome 2.0 arrays (Santa Clara, CA), we queried the entire mouse genome for candidate metastable epialleles that display the Agouti Fingerprint. Approximately 100 of the greater than 40,000 transcripts on the mouse array displayed an expression pattern characterized as high inter-individual variation coupled with low inter-tissue variation (R-value > 1.5).

Background corr dist: KL-Divergence = 0.0741, L1-Distance = 0.0520, L2-Distance = 0.0050, Normal std = 0.5242

0.825 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

Liver-Yellow1Kidney-Yellow1 (0.0159025)Brain-Yellow1Liver-Slightly_Mottled1 (0.0315393) (0.0622263)Kidney-Slightly_Mottled1Brain-Slightly_Mottled1Liver-Mottled1 (0.0218542)Kidney-Mottled1 (0.032043) Brain-Mottled1(0.0133822) (0.158447)Liver-Heavily_Mottled1 (0.0101452) Kidney-Heavily_Mottled1(0.0453902)Brain-Heavily_Mottled1Liver-Pseudo_Ag1 (0.0158119)Kidney-Pseudo_Ag1 (0.0225614)Brain-Pseudo_Ag1 (0.0594952) (0.0256076)Liver-Yellow2 (0.015483)Kidney-Yellow2 (0.0664919) (0.0149126)Brain-Yellow2Liver-Slightly_Mottled2 (0.0219699) (0.0461208)Kidney-Slightly_Mottled2Brain-Slightly_Mottled2Liver-Mottled2 (0.0115225)Kidney-Mottled2 (0.0163269) Brain-Mottled2(0.00842138) (0.0456507)Liver-Heavily_Mottled2 (0.0146953) Kidney-Heavily_Mottled2(0.0508966)Brain-Heavily_Mottled2Liver-Pseudo_Ag2 (0.0108256)Kidney-Pseudo_Ag2 (0.0119859)Brain-Pseudo_Ag2 (0.0542829) (0.0390692) (0.0193861) (0.0375529)[ min ] [ medium ] [ max ] CEM 1 Nefl 2.0 28.2 11173.8 P ( S | Z, I ) = 1.00 Nefh 12.6 66.9 3072.5 Mean Corr = 0.71571 Ina 37.5 107.9 5914.1 Prph 3.6 12.0 136.8 Dlgap2 1.5 55.4 608.7 Nefm 1.1 4.8 6078.3 Snap25 1.0 14.4 24160.7 Elavl2 1.0 2.7 3889.9 Gng3 103.1 253.0 11293.1 Cadps 1.3 24.3 5903.7 CEM 1 + Cplx1 14.8 92.3 10032.8 Top 10 Genes Stmn2 14.1 78.7 10630.8 Sult4a1 3.7 48.7 4751.8 Nrsn1 5.5 80.3 9181.2 Elavl4 4.0 62.4 2273.2

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE32937" 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=GSE32937 Status: Public on Oct 13 2011 Title: MicroRNA-29 in Aortic Dilation: Implications for Aneurysm Formation Organism: Mus musculus Experiment type: Non-coding RNA profiling by array Platform: GPL1261 Pubmed ID: 21903938 Summary & Design: Summary: We compared the aorta of 6-weeks-old mice (young) with 18-months-old mice (old). Using the publicly available tools Sylamer and DIANA-mirExTra, we identified an enrichment for miR-29 binding sites in the 3'UTR of genes downregulated in the aged aortas. We subsequently showed that inhibition of miR-29 in aged mice prevented dilation of the aorta.

Overall design: aortas of 6 week old and 18 month old mice

Background corr dist: KL-Divergence = 0.0766, L1-Distance = 0.0196, L2-Distance = 0.0005, Normal std = 0.4847

0.823 Kernel fit Pairwise Correlations Normal fit

Density 0.412

0.000 CEM 1

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

Pre-normalization Quantiles

18 month18 oldmonth aorta18 oldmonth 35_old aorta18 oldmonth mRNA36_old aorta6 week old (0.154018)mRNA37_old aorta 6old week aorta(0.0260151)mRNA38_old 6old week45_young aorta(0.198601)mRNA 6old week46_young aorta(0.237825) mRNA old 47_young aorta (0.07178)mRNA 48_young (0.15716)mRNA (0.102345)mRNA[ min (0.0522558) ] [ medium ] [ max ] CEM 1 Nefl 63.2 218.8 374.5 P ( S | Z, I ) = 1.00 Nefh 29.1 78.7 122.3 Mean Corr = 0.71327 Ina 44.0 67.1 125.9 Prph 71.4 171.7 306.7 Dlgap2 2.5 22.8 37.0 Nefm 28.0 83.6 192.2 Snap25 134.9 398.5 749.2 Elavl2 53.7 138.4 223.3 Gng3 102.2 214.5 232.2 Cadps 49.4 125.9 232.1 CEM 1 + Cplx1 113.6 146.1 266.7 Top 10 Genes Stmn2 236.6 427.2 695.1 Sult4a1 12.8 51.2 125.5 Nrsn1 32.8 109.4 129.7 Elavl4 5.7 82.5 101.8

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE31004" 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=GSE31004 Status: Public on Dec 15 2011 Title: Effects of Nicotine on the Fetal Mouse Palate Development and Transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus. To demonstrate the effect of nicotine on craniofacial development, particularly palatogenesis, we delivered three different doses of nicotine (1.5, 3.0 and 4.5 mg/kg/day) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous osmotic mini-pump. We assessed the pups for morphological anomalies, as well as genome-wide mRNA (transcriptome) microarray analysis. Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality in the pups. However, it did not cause obvious cleft palate. The microarray data analysis using IPA identified differential expression of genes involved in various biological pathways, particularly cancer, genetic diseases, and tissue development in response to consistent nicotine exposure. 6232 up-regulated and 6310 down-regulated genes were detected in nicotine-treated groups compared to the control. Moreover, 45% of the genes associated with cleft palate were found to be affected by nicotine. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and RT-PCR. We concluded that consistent nicotine exposure during pregnancy interferes with normal growth and development of the fetus including palatogenesis; however, this interference does not result in cleft palate, rather smaller palate size with persistent MES. To our knowledge, this is the first experiment revealing the impact of nicotine on the fetal palate transcriptome in mice.

Overall design: Total 8 samples were analyzed. Using an osmotic minipump, duplicate samples from palates of either sterile physiological saline or nicotine (1.5 mg/kg/day, 3.0 mg/kg/day, or 4.5 mg/kg/day)-treated newborn pups.

Background corr dist: KL-Divergence = 0.0673, L1-Distance = 0.0308, L2-Distance = 0.0016, Normal std = 0.5256

0.759 Kernel fit Pairwise Correlations Normal fit

Density 0.379

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

Saline control,Saline control, Nicbiological 1.5mg/kg/day, Nicbiological rep1 1.5mg/kg/day,Nic (0.46018) rep2 biological3.0mg/kg/day,Nic (0.0674709) biological3.0mg/kg/day, rep1Nic biological4.5mg/kg/day,(0.0752883) rep2Nic biological4.5mg/kg/day,(0.0366956) rep1 biological(0.0796826) rep2 biological(0.031677) rep1 (0.161048) rep2[ min (0.0879568) ] [ medium ] [ max ] CEM 1 Nefl 64.5 838.3 5827.5 P ( S | Z, I ) = 1.00 Nefh 34.0 119.9 546.5 Mean Corr = 0.71207 Ina 33.7 102.5 756.5 Prph 47.2 144.6 746.3 Dlgap2 11.2 28.2 54.6 Nefm 115.5 1052.4 6345.9 Snap25 14.9 114.7 1199.0 Elavl2 21.7 80.0 861.6 Gng3 28.4 213.2 1367.5 Cadps 15.4 139.3 816.9 CEM 1 + Cplx1 276.4 423.9 691.1 Top 10 Genes Stmn2 179.9 543.3 3147.7 Sult4a1 18.1 44.4 114.8 Nrsn1 43.0 98.7 143.4 Elavl4 13.9 62.4 791.6

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE48369" 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=GSE48369 Status: Public on Aug 20 2013 Title: Expression data of sleeping, waking, and sleep deprived in adult heterozygous Cnp eGFP-L10a mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24005282 Summary & Design: Summary: Transcriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because the previous studies pooled transcripts from all brain cells, including neurons and glia.

In the following experiment, we studied the specific effects of sleep and wake conditions on glia cells of mouse cerebral cortex using the genetically targeted translating ribosome affinity purification (TRAP) methodology. We used bacterial artificial chromosome (BAC) transgenic mice expressing EGFP tagged ribosomal protein L10a in oligodendrocytes which constitute a defined cellular population of the mouse brain. Using this approach, we could extract only the oligodendrocitic mRNAs, and only those already committed to be translated into proteins (L10a is part of the translational machinery).

Overall design: Six mice for each vigilant state group (sleep (S), waking (W), and sleep deprivation (SD)) were considered. For each animal, one forebrain sample was immediately processed. Samples were immunoprecipitated to isolate oligodendrocytes. The precipitated portion formed the bound sample (IP) containing olidodendrocytes and the remaining part formed the unbound sample (UB) containing all the remaining cell types (neurons and other glia cells). Then, both IP and UB samples were processed and RNA was extracted.

Background corr dist: KL-Divergence = 0.0780, L1-Distance = 0.0388, L2-Distance = 0.0022, Normal std = 0.4968

0.851 Kernel fit Pairwise Correlations Normal fit

Density 0.425

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

Bound fractionBound fractionBound Sleep animal,fractionBound Sleep animal,fractionbiologicalBound Sleep animal,fractionbiologicalBound Sleep rep 1 animal,fractionbiologicalBound Sleep(0.00610425) rep 2 animal,fractionbiologicalBound Sleep(0.0199731) rep 3 animal,fractionbiologicalBound Waking(0.0207209) rep 4 fractionbiologicalBound Waking (0.0260295)animal, rep 5 fractionBound Waking (0.0544305) animal,biological rep 6 fractionBound Waking (0.0457126) animal,biological rep fractionBound Waking1 animal,biological (0.0256209) rep fractionBound Waking2 animal,biological (0.0671025) rep fractionBound Sleep3 animal,biological (0.0138974) rep depfractionBound Sleep4 biological (0.0246337) animal, rep depfractionBound Sleep5 (0.0359083) animal, biologicalrep depfractionBound Sleep6 (0.031122) animal,biological deprepfractionUnbound Sleep 6 animal,biological (0.0160152) deprepUnbound Sleep fraction 7 animal,biological (0.00354213) deprepUnbound fraction Sleep8 animal,biological (0.0211631) repUnbound animal,fraction Sleep9 biological (0.0217504) repUnbound animal,fractionUnbiological Sleep10 (0.0256032) repUnbound animal,fractionUnbiological Sleep11 (0.0395074)Unbound rep animal,fractionUnbiological Sleep 1 (0.00837681)Unbound rep animal,fractionUnbiological Sleep 2 (0.0158054)Unbound rep animal,fractionUnbiological Waking 3 (0.0319741)Unbound rep fractionUnbiological Waking animal, 4 (0.0218221)Unbound rep fraction Waking animal, Unbiological5 (0.0246651)Unbound rep fraction Waking animal, Unbiological6 (0.0083018)Unbound fractionrep Waking animal,Unbiological 1Unbound (0.0169091) fractionrep Waking animal,Unbiological 2Unbound (0.0384441) fractionrep Sleep animal,Unbiological 3Unbound (0.0757989) depfractionrep Sleep Unbiological animal,4Unbound (0.0273121) depfractionrep Sleep animal,5UnbiologicalUnbound (0.0159394) depfractionrep Sleep animal,6Unbiological (0.0184381) depfraction Sleep rep animal,Unbiological 6dep (0.038261)Sleep rep animal,Unbiological 7dep (0.0350064) rep animal,Unbiological[ 8 min(0.0222883) rep Unbiological 9 (0.0397149) ]rep 10 (0.0392728) rep 11[ (0.0228325) medium ] [ max ] CEM 1 Nefl 9318.9 14247.8 15833.2 P ( S | Z, I ) = 1.00 Nefh 485.1 976.3 1629.2 Mean Corr = 0.71178 Ina 837.0 2397.2 3879.0 Prph 28.4 67.9 236.1 Dlgap2 650.9 2688.1 4097.8 Nefm 2206.7 4871.7 5947.5 Snap25 19517.5 25284.2 28898.0 Elavl2 807.6 3243.4 4462.1 Gng3 6000.1 15163.3 17304.4 Cadps 354.7 1290.9 2074.5 CEM 1 + Cplx1 3355.0 10002.4 11691.2 Top 10 Genes Stmn2 516.2 2883.6 3522.3 Sult4a1 1448.9 5081.9 7480.1 Nrsn1 260.3 3957.9 5811.8 Elavl4 382.9 923.1 2340.1

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE13432" 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=GSE13432 Status: Public on Feb 01 2009 Title: Adipose tissue exposed to cold Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19117550 Summary & Design: Summary: Cold triggers VEGF dependent but hypoxia independent angiogenesis in adipose tissues and anti-VEGF agents modulate adipose metabolism

The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism remain poorly understood. Here we show that exposure of mice to cold led to conversion of white adipose tissue (WAT) to brown-like adipose tissue, accompanying the switch of an active angiogenic phenotype. Gene expression profile analysis showed VEGF was upregulated via most likely hypoxia-independent PGC-1 transcriptional activation. Intriguingly, VEGFR2 blockage abolished the cold-induced angiogenesis, significantly impaired nonshivering thermogenesis capacity, and markedly reduced adipose metabolism. Unexpectedly, VEGFR1 blockage resulted in opposite effects by increasing adipose vascularity and metabolism. These findings demonstrate that VEGFR2 and VEGFR1 mediate polarized activities in modulating adipose angiogenesis and metabolism. Taken together, our findings have conceptual implications in applying angiogenesis modulators for the treatment of obesity and metabolic disorders.

Keywords: Time course

Overall design: Mice were exposed to cold and white addipose tissue was collected at different time points

Background corr dist: KL-Divergence = 0.0338, L1-Distance = 0.0273, L2-Distance = 0.0009, Normal std = 0.6614

0.603 Kernel fit Pairwise Correlations Normal fit

Density 0.302

0.000 CEM 1

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

Pre-normalization Quantiles

1 week 130 week degrees 130 week degrees rep 1 301 week (0.0912917) degrees rep 1 42 week degrees(0.0597893) repl 14 3weekdegrees (0.0739822)rep 1 54 (0.153941)weeksdegrees rep 25 (0.0530487)30weeks rep degrees 35 (0.201044)30weeks degrees rep5 30weeks1 (0.0806581) degrees rep5 4weeks2 degrees(0.0452702) rep5 4weeks3 degrees(0.0895509) rep 1 4 (0.0717509) degrees rep 2 (0.0467017) rep 3 (0.0329706)[ min ] [ medium ] [ max ] CEM 1 Nefl 11.3 12.4 13.4 P ( S | Z, I ) = 1.00 Nefh 124.9 146.4 185.5 Mean Corr = 0.74032 Ina 12.1 14.2 16.0 Prph 13.5 15.6 17.4 Dlgap2 10.4 11.2 12.4 Nefm 12.9 14.3 16.1 Snap25 11.6 12.8 14.4 Elavl2 12.0 13.4 14.9 Gng3 72.8 85.3 128.0 Cadps 14.3 15.7 17.0 CEM 1 + Cplx1 24.5 27.9 33.1 Top 10 Genes Stmn2 34.9 91.3 168.7 Sult4a1 22.2 28.1 68.6 Nrsn1 11.6 12.7 14.2 Elavl4 12.2 13.6 14.9

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE38672" 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=GSE38672 Status: Public on Nov 16 2012 Title: Deletion of miRNA processing enzyme Dicer in POMC-expressing cells leads to neurodegeneration and development of obesity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The activity of the endoribonuclease Dicer is crucial to produce the mature form of most microRNAs (miRNAs). Recent studies indicate that lack of miRNAs in different neuronal types results in a range of anatomical and behavioural phenotypes. In the present study we aimed to investigate the developmental and metabolic consequences of miRNA ablation in hypothalamic POMC neurons studying mice with a conditional deletion of Dicer in this population of neurons (POMCDicerKO). These mice exhibited a progressive obese phenotype characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism and alterations in the pituitary-adrenal axis. The development of the obese phenotype was paralleled by a POMC neuron degenerative process that was complete by 6 weeks of age. Furthermore, immunohistochemistry and gene expression studies in control C57Bl/6 adult mice showed that Dicer was expressed in relevant hypothalamic areas and neurons implicated in energy balance, and that its expression was regulated by nutrient availability. Collectively, our results highlight a crucial role for miRNAs in POMC neuron survival and the consequent development of neurodegenerative obesity.

Overall design: Total RNA was extracted from hypothalamic microdissections of 2-week old control and POMCDicerKO mice using the RNeasy micro spin columns (Qiagen, Venlo, The Netherlands). Ten micrograms of total RNA were converted into cRNA, biotinylated, fragmented, and hybridized to GeneChip Mouse Genome 430 2.0 (Affymetrix, Santa Clara, CA). Six microarrays were hybridized with three independent samples from control and POMCDicerKO mice.

Background corr dist: KL-Divergence = 0.0435, L1-Distance = 0.0161, L2-Distance = 0.0002, Normal std = 0.5962

0.674 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

ControlControl 1 mouseControl 2 (0.044204)mousePOMCDicerKO 3 (0.126178)mousePOMCDicerKO (0.227014) POMCDicerKO1 mouse 2 (0.354538)mouse 3 (0.0999982)mouse (0.148068)[ min ] [ medium ] [ max ] CEM 1 Nefl 4660.7 5226.9 5892.9 P ( S | Z, I ) = 1.00 Nefh 774.1 860.2 1044.1 Mean Corr = 0.71392 Ina 2394.7 2506.5 2835.0 Prph 127.1 301.9 378.8 Dlgap2 33.8 37.2 41.8 Nefm 1553.4 2277.2 3100.7 Snap25 17886.0 18692.5 19328.2 Elavl2 2286.8 2727.8 3536.3 Gng3 1982.8 2111.3 2279.4 Cadps 4829.1 4995.5 5215.0 CEM 1 + Cplx1 2599.6 3437.3 4371.2 Top 10 Genes Stmn2 9874.7 10308.0 10607.5 Sult4a1 3229.0 3404.6 3714.5 Nrsn1 3523.9 3988.6 4118.0 Elavl4 1680.7 1825.0 1939.5

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE40286" 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=GSE40286 Status: Public on Oct 01 2012 Title: The Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22972934 Summary & Design: Summary: We examined how MED23 regulates SRF-targeted genes by comparing WT and Med23 KO mouse embryonic fibroblasts (MEFs) in the presence or absence of serum-stimulation (for 30 and 90 min). To investigate whether MAL antagonizes MED23 in the adipocyte lineage program, we compared the gene expression changes resulting from Mal overexpression (oxMal) and Med23 deficiency (siMed23) in 10T1/2 cell.

Overall design: In MEF cells, we examined SRF-dependent gene expression in three time points (0, 30, 90min) and two conditions (WT and KO). In 10T1/2 cells, we used three treatment conditions (Mal overexpression, Med23 knockdown, and treatment of both Mal overexpression and Med23 knockdown) with control (no treatment).

Background corr dist: KL-Divergence = 0.0284, L1-Distance = 0.0534, L2-Distance = 0.0049, Normal std = 0.7021

0.568 Kernel fit Pairwise Correlations Normal fit

Density 0.284

0.000 CEM 1

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

Pre-normalization Quantiles

MEF, WT_serum_0minMEF, WT_serum_30minMEF, WT_serum_90minMEF, (0.060068) Med23KO_serum_0minMEF, (0.0919177) Med23KO_serum_30minMEF, (0.145641) Med23KO_serum_90min10T1/2, (0.0395741)10T1/2,control 10T1/2,MAL_overexpression (0.109844)(0.0261906) 10T1/2,Med23_knockdown (0.0843579) both_treatment (0.0743591) (0.145036) (0.223012)[ min ] [ medium ] [ max ] CEM 1 Nefl 24.0 35.3 41.2 P ( S | Z, I ) = 1.00 Nefh 20.6 40.3 46.5 Mean Corr = 0.78377 Ina 33.7 44.4 54.8 Prph 24.1 46.3 56.8 Dlgap2 29.3 38.8 47.6 Nefm 25.3 34.5 38.3 Snap25 21.2 31.5 37.9 Elavl2 30.1 40.6 44.6 Gng3 44.7 58.7 75.5 Cadps 21.3 32.5 41.5 CEM 1 + Cplx1 57.0 77.3 106.0 Top 10 Genes Stmn2 38.4 56.2 103.4 Sult4a1 26.0 42.7 44.5 Nrsn1 29.3 37.2 42.7 Elavl4 25.3 39.3 53.9

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE17096" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17096 Status: Public on Dec 09 2011 Title: mRNA composition of IRP1 mRNPs in mouse tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21940823 Summary & Design: Summary: Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP1 (iron regulatory protein 1).

Overall design: All the microarray procedures were conducted at the EMBL Genomics Core Facility using standard Affymetrix protocols. In brief, approximately 120ng of immunoprecipitated RNA was used as input to a two-step amplification procedure to generate biotin-labeled RNA fragments for hybridization to the Affymetrix GeneChip Mouse Genome 430 2.0 array (Eukaryotic Sample and Array Processing manual 701024 Rev.3). Intensity values for the hybridizations were obtained either using RMA, calculations done in bioconductor (www.bioconductor.org) or MAS5, calculated using Affymetrix GCOS package. MAS5 calculated intensities were further quantile normalized using bioconductor.

Background corr dist: KL-Divergence = 0.0791, L1-Distance = 0.0942, L2-Distance = 0.0182, Normal std = 0.5457

0.753 Kernel fit Pairwise Correlations Normal fit

Density 0.377

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

IRP1 immunoprecipitationIRP1 controlIRP1 immunoprecipitationimmunoprecipitationIRP1 duodenum controlIRP1 immunoprecipitationimmunoprecipitationIRP1 replica duodenumduodenum controlIRP1 1 (0.0306734) immunoprecipitationimmunoprecipitationIRP1 replicareplica liverduodenum controlIRP1 21 replica (0.025117)(0.0135523) immunoprecipitationimmunoprecipitationIRP1 replica 1 (0.0319193) liverliver controlIRP1 2 replicareplica (0.027084) immunoprecipitationimmunoprecipitationIRP1 21 (0.0368318) (0.0444596) spleenliver controlIRP1 replica replica immunoprecipitationimmunoprecipitationIRP1 2 (0.0661512) 1spleenspleen control(0.0135798)IRP1 replicareplica immunoprecipitationimmunoprecipitationIRP1 2bone1spleen control (0.0282798)(0.0313276)IRP1 marrow replica immunoprecipitationimmunoprecipitationIRP1 replica bone2bone control (0.0349672)IRP1 marrow marrow1 (0.0589641) immunoprecipitationimmunoprecipitationIRP1 replicareplica brainbone control replicamarrow 21 (0.0344129) (0.0178764)immunoprecipitation 1 replica (0.120524)brainbrain replica replica2 (0.078394)[ 21min (0.109967)(0.122762)brain replica ] 2 (0.0731562)[ medium ] [ max ] CEM 1 Nefl 28.1 34.8 3787.2 P ( S | Z, I ) = 1.00 Nefh 38.1 80.2 627.4 Mean Corr = 0.66499 Ina 51.6 66.4 613.2 Prph 51.6 87.1 124.7 Dlgap2 25.0 36.9 62.6 Nefm 28.0 39.2 8711.3 Snap25 25.1 36.1 12216.0 Elavl2 21.2 28.2 3132.3 Gng3 272.2 526.3 2066.7 Cadps 35.3 53.0 9692.2 CEM 1 + Cplx1 94.9 135.4 10632.6 Top 10 Genes Stmn2 169.7 283.7 12616.1 Sult4a1 51.1 71.4 3039.0 Nrsn1 35.2 44.5 4411.0 Elavl4 60.1 88.7 728.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE7831" 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=GSE7831 Status: Public on Dec 13 2007 Title: Expression data from immature pDC and pDC activated with CpG 1826 and influenza virus PR8 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18029397 Summary & Design: Summary: CpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC

We used microarrays to detail the global programme of gene expression underlying the maturation process of pDC activated with CpG 1826 and influenza virus PR8. We identified a distinct expression profile of upregulated immunomediators.

Keywords: time course

Overall design: Sorted pDCs were cultured for 1h and 4hs in medium control or with 5 ´g/ml CpG 1826 or 300 HAU/ml purified influenza A/PR/8 virus. The first experiment (e1) included pDC in media and stimulated with CpG for 4h. In two other independent experimental batches (e2 and e3), we obtained samples of sorted pDC cultured in medium alone (med), and with CpG or PR8 (flu) for 1h and 4h. RNA extraction was performed using the RNeasy Kit (Qiagen) and hybridization on Affymetrix microarrays was performed using standard protocols. We sought to obtain homogeneous populations of pDCs at different time points under defined activation conditions in order to decipher the temporal resolution of expression profiles during the process of their maturation.

Background corr dist: KL-Divergence = 0.0526, L1-Distance = 0.0887, L2-Distance = 0.0101, Normal std = 0.7226

0.552 Kernel fit Pairwise Correlations Normal fit

Density 0.276

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

pDC mediumpDC medium 1h,pDC biological CpG 1h,pDC biological1h, CpGrep1 biologicalpDC 1h,(0.0282404) flurep2 biologicalpDC 1h, rep1 (0.0705358) biological flu (0.0439693)pDC 1h, rep2 biological medium (0.225364)rep1pDC (0.0211604)medium 4h, rep2pDC biological (0.0499205)medium 4h,pDC biological CpGrep1 4h,pDC biological4h,(0.0777186) CpGrep2 biologicalpDC 4h,(0.0134893) CpGrep3 biologicalpDC rep1 4h,(0.0942411) flu biological(0.0211086)pDC 4h, rep2 biological flu (0.110859) 4h, rep3 biological (0.166476)rep1 (0.0231028) rep2 (0.0538137)[ min ] [ medium ] [ max ] CEM 1 Nefl 29.0 39.7 45.7 P ( S | Z, I ) = 1.00 Nefh 32.7 38.6 56.5 Mean Corr = 0.82403 Ina 36.9 49.4 64.6 Prph 26.6 38.3 49.9 Dlgap2 15.8 19.5 22.1 Nefm 20.2 28.0 32.8 Snap25 20.9 27.7 33.5 Elavl2 22.6 30.0 37.9 Gng3 38.0 44.9 59.7 Cadps 30.1 39.1 46.9 CEM 1 + Cplx1 24.1 31.2 40.0 Top 10 Genes Stmn2 16.7 19.8 23.7 Sult4a1 30.1 38.1 57.2 Nrsn1 22.3 30.3 37.5 Elavl4 47.5 57.2 92.8

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE7020" 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=GSE7020 Status: Public on Feb 14 2007 Title: The molecular consequences of Nix ablation on apoptosis and erythropoiesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17420462 Summary & Design: Summary: Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.

Keywords: strain comparison

Overall design: In the study, we hybridized RNA from 8 week old spleens of wild type (WT) control and Nix null mice (Nix-/-) to Affymetrix MOE430A GeneChipÂ® arrays containing 45,101 well characterized mouse genes/ESTs.

Background corr dist: KL-Divergence = 0.0316, L1-Distance = 0.0553, L2-Distance = 0.0034, Normal std = 0.7696

0.518 Kernel fit Pairwise Correlations Normal fit

Density 0.259

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

NIXKO10NIXKO2 SPLEENNIXKO3 SPLEEN (0.0132991)NIXKO6 SPLEEN (0.452091)WT3 SPLEEN (0.0464806) SPLEENWT4 (0.174445) SPLEEN (0.0199929)WT5 SPLEEN (0.145719)WT6 SPLEEN (0.0477458) (0.100227) [ min ] [ medium ] [ max ] CEM 1 Nefl 12.5 13.6 19.5 P ( S | Z, I ) = 1.00 Nefh 147.4 206.1 305.0 Mean Corr = 0.69987 Ina 16.8 19.6 34.2 Prph 14.6 15.7 18.3 Dlgap2 10.5 11.3 13.0 Nefm 14.6 16.1 26.5 Snap25 12.7 14.2 21.1 Elavl2 12.3 13.8 27.0 Gng3 102.1 115.5 128.8 Cadps 17.3 19.2 26.8 CEM 1 + Cplx1 34.8 39.6 67.8 Top 10 Genes Stmn2 15.2 16.3 23.0 Sult4a1 21.4 23.9 27.5 Nrsn1 14.4 16.1 23.5 Elavl4 15.5 16.8 23.5

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE9338" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 42 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9338 Status: Public on Jan 19 2008 Title: Expression data from Mus musculus subspecies and their F1 hybrids for 3 tissues (brain, liver, testis) Organism: Mus musculus domesticus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17947435 Summary & Design: Summary: We have studied different subspecies of the house mouse (M. m. musculus, M. m. domesticus and M. m. castaneus) and their reciprocal F1 hybrids to estimate the within-locus mode of inheritance for subspecies differences in gene expression in three tissues (brain, liver, testis) of male mice. This study investigates mode of inheritance in crosses at a larger taxonomic distance than have been previously systematically investigated. We found the vast majority of transcripts to be additively expressed with only a few transcripts showing dominance or overdominance in expression, except for one direction of one cross, which showed large mis-expression in the testis.

Keywords: comparative whole transcripome analysis

Overall design: Wild-derived inbred lines of M. m. musculus, M. m. domesticus and M. m. castaneus were used to generate reciprocal crosses of M. m. musculus x M. m. domesticus and M. m. musculus x M. m. castaeneus. The gene expression profile of 2 males each of the hybrids and the pure parental subspecies were analyzed by using the Affymetrix GeneChip 430 2.0 to obtain evidence about the within-locus mode of inheritance of genes. First, we studied all transcripts that are differentially expressed between the parental subspecies and assessed additivity vs. nonadditivity of expression of these transcripts in the F1 hybrids. Second, we investigated those transcripts which do not differ in expression between the parental lines, but which are expressed differently in the F1 hybrids relative to both of their parents.

Background corr dist: KL-Divergence = 0.0697, L1-Distance = 0.0890, L2-Distance = 0.0131, Normal std = 0.6057

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

domesticusdomesticus malemusculus 1, malebiologicalmusculus 2,male biologicalF1 rep1,1, malehybridbiological brainF1 rep2,2, (musculushybridbiological (0.0477651) rep1,brainF1 (musculushybrid brain(0.030936) rep2,motherF1 (domesticus(0.0190837)hybrid brain motherxcastaneus domesticus (domesticus(0.0243147) xcastaneus motherdomesticus male father)F1 mother x1, musculus hybrid malebiological 1,father) F1biological x2, (musculusmusculushybrid biological 2,father) rep1, F1biological (musculushybridrep1, brain 1, father) motherrep2, F1biological brain (castaneushybrid(0.0288378)rep2, brain2, motherx (0.0314011)domesticus biological castaneusbrain (castaneus(0.0277839)rep1, x mother(0.0309641)domesticus castaneusbrain rep2, father)male motherx(0.105943)musculus musculusbrain 1, 1, father) malebiological biological x(0.0364253)musculus musculus 2,male 2,father biological biologicalF1 rep1,1, rep1, malehybridbiological) father1, liver biologicalF1brain rep2,2, rep2, (musculus hybrid biological)(0.0113831) 2, (0.0595591)rep1,liver biologicalF1brain rep1,(musculushybrid (0.0198904) liver (0.021185)rep2,motherF1 brain (0.0117743) rep2,(domesticushybrid liver mother(0.0205565)xcastaneus braindomesticus (0.0188612) (domesticus (0.0368157)xcastaneus motherdomesticus male father)F1 mother x1, musculus hybrid malebiological 1,father) F1biological x2, (musculusmusculushybrid biological 2,father) rep1, F1biological (musculushybridrep1, liver 1, father) motherrep2, F1biological liver (0.0331779) (castaneushybridrep2, liver2, mother(0.0156082)x domesticus biological castaneusliver (0.044777)(castaneus rep1, (0.0117321)xmotherdomesticus castaneusliver rep2, father)male (0.0204613) motherxmusculus musculusliver 1, 1, father) malebiological biological(0.0186506) xmusculus musculus 2,male 2,father biological biologicalF1 rep1,1, rep1, malehybridbiological) father1, testis biologicalF1liver rep2,2, rep2, (musculus hybridbiological) 2,(0.0119379)(0.0229065) rep1,testis biologicalF1liver rep1,(musculushybrid testis(0.00908055)(0.0324546) rep2,motherF1 liver rep2,(domesticus(0.0170322)hybrid testis (0.0291425) motherxcastaneus liverdomesticus (domesticus(0.0110337) (0.0231179) xcastaneus motherdomesticus male father)F1 mother x1, musculus hybrid malebiological 1,father) F1biological x2, (musculusmusculushybrid biological 2,father) rep1, F1biological (musculushybridrep1, testis 1, father) motherrep2, F1biological testis (castaneus hybridrep2,(0.010043) testis2, motherx (0.0121132) biological castaneustestis (castaneus rep1,(0.0105261) xmother (0.00799553) castaneustestis rep2, father) mother x(0.0090243) musculustestis 1,father) biological x(0.00933563)[ musculus min 2,father biological rep1, ) father1,] biologicaltestis rep2, ) 2, (0.0217541) biologicaltestis rep1,[ medium(0.0111936) testis rep2, (0.0117728) testis (0.0116491) ] [ max ] CEM 1 Nefl 2.0 46.3 8274.1 P ( S | Z, I ) = 1.00 Nefh 13.1 158.6 2377.3 Mean Corr = 0.65310 Ina 34.2 147.7 4695.8 Prph 8.0 29.1 111.6 Dlgap2 5.0 48.2 412.2 Nefm 1.0 42.1 6709.9 Snap25 1.0 16.1 20009.3 Elavl2 2.0 180.7 4304.8 Gng3 144.9 298.9 8043.4 Cadps 3.0 138.4 5375.5 CEM 1 + Cplx1 34.2 190.6 8844.4 Top 10 Genes Stmn2 11.1 62.2 8607.0 Sult4a1 17.1 127.8 4084.3 Nrsn1 15.1 89.5 7288.0 Elavl4 4.0 67.4 2814.6

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE38335" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.542 Kernel fit Pairwise Correlations Normal fit

Density 0.271

0.000 CEM 1

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

Pre-normalization Quantiles

DMSO ControlDMSO Control DMSO1 (0.0675994) Control INCB184242 (0.124946) INCB184243 (0.0350858) AcuteINCB18424 1 Acute (0.0713678)INCB18424 2 Acute (0.0378171)INCB18424 3 Persistent (0.124945)INCB18424 Persistent 1 (0.380599) Persistent 2 (0.0687716) 3 (0.0888684)[ min ] [ medium ] [ max ] CEM 1 Nefl 7.9 8.3 8.7 P ( S | Z, I ) = 1.00 Nefh 8.0 8.2 8.4 Mean Corr = 0.82159 Ina 9.5 10.1 10.6 Prph 7.8 8.0 8.5 Dlgap2 6.3 6.5 6.8 Nefm 8.4 8.9 9.3 Snap25 10.1 10.7 11.3 Elavl2 9.7 9.9 10.3 Gng3 6.7 7.0 7.2 Cadps 10.1 10.6 11.4 CEM 1 + Cplx1 11.4 12.5 13.7 Top 10 Genes Stmn2 6.0 6.2 6.4 Sult4a1 6.5 6.6 6.8 Nrsn1 9.2 9.6 10.0 Elavl4 8.9 9.5 9.7

Null module Nrp1 Ldlrap1 Gan 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 "GSE15069" 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=GSE15069 Status: Public on Apr 30 2009 Title: Inhibitor trials in chondrocytes - MAS 5.0 normalization Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20111593 Summary & Design: Summary: Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways. Goal: To identify and functionally characterize novel targets of these signaling pathways in the context of chondrocyte differentiation.

Keywords: Treatment, signaling, one-colour array, signaling pathway comparison

Overall design:

Background corr dist: KL-Divergence = 0.0933, L1-Distance = 0.0484, L2-Distance = 0.0037, Normal std = 0.4765

0.897 Kernel fit Pairwise Correlations Normal fit

Density 0.448

0.000 CEM 1

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

Pre-normalization Quantiles

DMSO1_24HRDMSO2_24HR (0.046089)DMSO3_24HR (0.0955094)LY1_24HR (0.0507841)LY2_24HR (0.0385847)LY3_24HR (0.0187257)UO126_1_24HR (0.0276353)UO126_2_24HRUO126_3_24HR (0.023279)SB202190_1_24HR (0.0200639)SB202190_2_24HR (0.0144398)SB202190_3_24HR (0.0337314)TSA1_24HR (0.0256396)TSA2_24HR (0.0615925)(0.191275)TSA3_24HR (0.200977) (0.151673) [ min ] [ medium ] [ max ] CEM 1 Nefl 6.2 19.9 777.4 P ( S | Z, I ) = 1.00 Nefh 19.7 43.6 85.1 Mean Corr = 0.62670 Ina 3.7 15.3 144.4 Prph 7.2 21.0 437.0 Dlgap2 4.3 27.9 56.6 Nefm 6.1 35.0 819.6 Snap25 3.3 12.6 69.3 Elavl2 3.3 4.4 119.6 Gng3 186.8 360.2 613.3 Cadps 16.1 38.4 59.2 CEM 1 + Cplx1 9.6 61.2 166.6 Top 10 Genes Stmn2 182.3 329.1 1765.2 Sult4a1 13.8 50.4 702.6 Nrsn1 6.9 38.1 81.2 Elavl4 32.6 57.1 115.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE21193" 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=GSE21193 Status: Public on Jul 22 2010 Title: The effects of subchronic arsenate exposure on gene expression in the mouse lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20667999 Summary & Design: Summary: Eight week old female C57BL/6 mice were exposed to arsenate in drinking water (50 ppm) for a period of twelve weeks (n = 5). Control animals received distilled deionized water (n = 5). Lung tissue was dissected and used for RNA isolation and gene expression microarray analysis.

Overall design: Eight week old female C57BL/6 mice were exposed to arsenate in drinking water (50 ppm) for a period of twelve weeks (n = 5). Control animals received distilled deionized water (n = 5). Lung tissue was dissected and used for RNA isolation and gene expression microarray analysis.

Background corr dist: KL-Divergence = 0.0535, L1-Distance = 0.0371, L2-Distance = 0.0023, Normal std = 0.5581

0.715 Kernel fit Pairwise Correlations Normal fit

Density 0.357

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

FB_50_12wk_20-5_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_0_12wk_4-3_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_0_12wk_4-4_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_50_12wk_20-4_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_50_12wk_20-3_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_50_12wk_20-2_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_50_12wk_20-1_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_0_12wk_4-5_AsDW_MusLung_Mouse430_2_HJCENV601_2FB_0_12wk_4-1_AsDW_MusLung_Mouse430_2_HJCENV601_2 (0.321525)FB_0_12wk_4-2_AsDW_MusLung_Mouse430_2_HJCENV601_2 (0.0794588) (0.0903704) (0.0443413) (0.0372505)[ min (0.0646647) ] (0.0436268) (0.116658)[ (0.0779686) medium (0.124136) ] [ max ] CEM 1 Nefl 7.2 7.6 7.7 P ( S | Z, I ) = 1.00 Nefh 8.0 8.5 9.0 Mean Corr = 0.72536 Ina 13.3 15.1 16.7 Prph 7.9 8.4 8.7 Dlgap2 6.1 6.5 6.5 Nefm 7.8 8.3 8.6 Snap25 10.5 11.1 11.4 Elavl2 9.5 10.2 11.0 Gng3 5.3 5.7 6.2 Cadps 8.8 9.1 9.4 CEM 1 + Cplx1 9.6 10.3 11.0 Top 10 Genes Stmn2 663.8 925.5 1074.0 Sult4a1 6.0 6.4 6.6 Nrsn1 7.9 8.4 8.8 Elavl4 6.9 7.4 7.6

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE20636" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 35 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20636 Status: Public on Mar 06 2010 Title: Expression data from OVE26 diabetic mouse kidney Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: OVE26 mouse was chosen to study the progressive changes in renal gene expression because it displays the most advanced albuminuria mouse models that assembles advanced human diabetic nephropathy.

OVE26 mice induce inflammatory gene expression changes consistent with advanced renal disease, associated with severe albuminuria and not reported in any other diabetic models. They provide the first opportunity in a model of diabetic nephropathy to assess the effect of induction of inflammatory proteins that have been implicated in renal injury.

Overall design: Microarray expression was performed on whole kidney from control and diabetic mice at 2, 4 and 8 months of age and validated by rtPCR, in situ hybridization or immunohistochemistry.

Background corr dist: KL-Divergence = 0.0571, L1-Distance = 0.0288, L2-Distance = 0.0013, Normal std = 0.5364

0.744 Kernel fit Pairwise Correlations Normal fit

Density 0.372

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

kidney ofkidney 2 month ofkidney 2 old,month ofkidney diabetic 2 old,month ofkidney diabetic 1 2 (0.0215974) old,month ofkidney diabetic 2 2 (0.0166889) old,month ofkidney diabetic 3 2 (0.0215806) old,month ofkidney diabetic 4 2 (0.019292) old,month ofkidney diabetic 5 2 (0.0132848) old,month ofkidney control 6 2 (0.0139431) old,month ofkidney control1 2(0.0214352) old,month ofkidney control2 2(0.0214027) old,month ofkidney control3 2(0.0199592) old,month ofkidney control4 4(0.0214032) old,month ofkidney control5 4(0.00894175) old,month ofkidney diabetic6 4(0.0549752) old,month ofkidney diabetic 1 4 (0.0303397) old,month ofkidney diabetic 2 4 (0.0141866) old,month ofkidney diabetic 3 4 (0.0209764) old,month ofkidney diabetic 4 4 (0.0233968) old,month ofkidney diabetic 5 4 (0.0244406) old,month ofkidney diabetic 6 4 (0.0174052) old,month ofkidney control 7 4 (0.0168483) old,month ofkidney control1 4(0.0209868) old,month ofkidney control2 8(0.0319341) old,month ofkidney control3 8(0.0300423) old,month ofkidney diabetic4 8(0.0292788) old,month ofkidney diabetic 1 8 (0.0271813) old,month ofkidney diabetic 2 8 (0.0642713) old,month ofkidney diabetic 3 8 (0.04027) old,month ofkidney diabetic 4 8 (0.0271121) old,month ofkidney diabetic 5 8 (0.0195339) old,month ofkidney control 6 8 (0.0218043) old,month ofkidney control1 8(0.0315879) old,month ofkidney control2 8(0.0559842) old,month of control3 8(0.0517074) old,month control4 (0.0550855) old, control5 (0.0394806)[ 6 (0.0516417)min ] [ medium ] [ max ] CEM 1 Nefl 24.3 36.9 84.6 P ( S | Z, I ) = 1.00 Nefh 18.4 28.1 75.7 Mean Corr = 0.60176 Ina 41.3 54.5 96.5 Prph 44.8 58.4 82.9 Dlgap2 21.2 26.5 42.8 Nefm 18.9 28.2 57.2 Snap25 12.8 18.8 38.5 Elavl2 12.5 17.2 26.8 Gng3 47.8 126.5 213.0 Cadps 14.9 21.3 48.0 CEM 1 + Cplx1 62.9 101.5 143.1 Top 10 Genes Stmn2 65.3 82.6 114.5 Sult4a1 15.4 31.2 70.6 Nrsn1 19.2 28.5 68.1 Elavl4 18.1 30.2 80.7

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE26076" 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=GSE26076 Status: Public on Jun 15 2011 Title: Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Kruppel-like factor 4 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21398290 Summary & Design: Summary: Purpose: To identify the changes in postnatal mouse conjunctival forniceal gene expression and their regulation by Klf4 around eye opening stage when the goblet cells first appear.

Methods: Laser-capture-microdissection was used to collect conjunctival forniceal epithelial cells from postnatal-day (PN) 9, PN14 and PN20 wild-type (WT), and PN14 Klf4-conditional null (Klf4CN) mice, where goblet cells are absent, developing, present, and missing, respectively. Microarrays were used to compare gene expression among these four groups. Expression of selected genes was validated by Q-RT-PCR, and spatiotemporal expression assessed by in situ hybridization. Results: We identified 668, 251, 1160 and 139 genes that were upregulated and 492, 377, 1419 and 57 genes that were downregulated between PN9 and PN14, PN14 and PN20, PN9 and PN20, and PN14 WT and Klf4CN conjunctiva, respectively. Transcription factors Spdef, FoxA1 and FoxA3 that regulate goblet cell development in other mucosal epithelia, and epithelial specific Ets (ESE) transcription factor family members were upregulated during conjunctival development. Mesenchymal-epithelial transition (MET) was favored and diverse pathways related to glycoprotein biosynthesis, mucosal immunity, signaling, endocytic and neural regulation were affected during conjunctival development. Conjunctival Klf4-target genes differed significantly from the previously identified corneal Klf4-target genes, implying tissue-dependant regulatory targets for Klf4.

Conclusions: We have identified the changes in gene expression accompanying mouse conjunctival development and the role of Klf4 in this process. These studies provide new probes to study conjunctival epithelial development and function, and reveal that the gene regulatory network required for goblet cell development is conserved across different mucosal epithelia.

Overall design: Three independent samples in each of four developmental groups

Background corr dist: KL-Divergence = 0.1081, L1-Distance = 0.0315, L2-Distance = 0.0019, Normal std = 0.4256

0.937 Kernel fit Pairwise Correlations Normal fit

Density 0.469

0.000 CEM 1

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

Pre-normalization Quantiles

ConjunctivalConjunctival fornix_PN9_sample_1Conjunctival fornix_PN9_sample_2Conjunctival fornix_PN9_sample_3Conjunctival fornix_PN14_sample_1(0.0848949)Conjunctival fornix_PN14_sample_2(0.153765)Conjunctival fornix_PN14_sample_3(0.0312692)Conjunctival fornix_PN20_sample_1 (0.0236418)Conjunctival fornix_PN20_sample_2 (0.036616)Conjunctival fornix_PN20_sample_3 (0.0395169)Conjunctival fornix_PN14_Klf4CN_sample_1 (0.0473949)Conjunctival fornix_PN14_Klf4CN_sample_2 (0.0384359) fornix_PN14_Klf4CN_sample_3 (0.0352493) [(0.0522062) min (0.0636887) ] (0.393321)[ medium ] [ max ] CEM 1 Nefl 7.4 63.7 1167.1 P ( S | Z, I ) = 1.00 Nefh 7.0 57.8 152.4 Mean Corr = 0.60369 Ina 25.8 93.8 310.3 Prph 3.4 22.5 50.7 Dlgap2 4.4 35.0 125.1 Nefm 27.2 82.0 334.3 Snap25 41.0 306.4 1861.6 Elavl2 3.4 54.1 184.5 Gng3 41.3 95.8 313.6 Cadps 3.4 168.3 604.7 CEM 1 + Cplx1 7.4 98.6 330.9 Top 10 Genes Stmn2 52.0 103.8 346.4 Sult4a1 7.8 27.9 106.8 Nrsn1 18.2 87.4 169.6 Elavl4 4.4 91.4 153.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE21687" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 192 -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=GSE21687

Background corr dist: KL-Divergence = 0.4486, L1-Distance = 0.0571, L2-Distance = 0.0084, Normal std = 0.2410 GEO Series "GSE51213" 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=GSE51213 Status: Public on Sep 26 2013 Title: Effect of chronic glucocorticoid (GC) treatment on neonatal mouse whole cerebellum and whole lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Dexamethasone (1ug/g, Dex) or vehicle (saline) injected into postnatal days 0-7 (P0 to P7) of C57BL6J mouse pups every day. Whole organ were harvested at P7.

Overall design: KEYWORDS: cell type comparison, treatment comparison.

Background corr dist: KL-Divergence = 0.0258, L1-Distance = 0.0164, L2-Distance = 0.0003, Normal std = 0.6871

0.581 Kernel fit Pairwise Correlations Normal fit

Density 0.290

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

whole cerebellumwhole cerebellumwhole with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone with cerebellumwhole dexamethasone replicate with cerebellumwhole dexamethasone replicate with B39 cerebellumwhole vehicle(0.26225) replicate with B49 cerebellumwhole vehiclereplicate(0.0312665) replicate with B50 lungwhole vehiclereplicate(0.0679343) B78with B52with lung (0.077258)whole vehicle replicate(0.0259335)dexamethasone B79 with lung (0.0361637)whole replicatedexamethasone B80 with lung (0.0357203)whole dexamethasone B81replicate with lung (0.0379096)whole dexamethasone replicate with B28 lungwhole vehicle(0.0375277) replicate with B31 lungwhole vehiclereplicate(0.0316615) replicate with B40 lung vehiclereplicate(0.0495865) B12with B46 (0.092913) vehiclereplicate(0.0496958) B14 (0.0537081) replicate B19 [(0.046997) min B22 (0.0634743) ] [ medium ] [ max ] CEM 1 Nefl 27.4 6427.8 14698.1 P ( S | Z, I ) = 1.00 Nefh 61.4 810.3 4131.2 Mean Corr = 0.73157 Ina 63.4 5974.0 7516.5 Prph 41.9 78.1 239.6 Dlgap2 22.8 32.6 49.0 Nefm 26.0 3075.0 8109.2 Snap25 28.7 4440.1 7498.3 Elavl2 26.4 4631.0 5893.6 Gng3 90.5 10560.4 13228.3 Cadps 22.0 2439.5 4253.2 CEM 1 + Cplx1 70.2 4729.5 5794.9 Top 10 Genes Stmn2 379.9 13366.8 17397.1 Sult4a1 43.1 937.7 1778.4 Nrsn1 33.0 477.7 1048.1 Elavl4 31.2 2301.5 4139.8

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE6223" 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=GSE6223 Status: Public on Nov 18 2006 Title: Gene expression profiles of E14 bladder, urogenital sinus and urethra isolated from SMGA (Actg2) transgenic mice. (GUDMAP Series ID: 6) 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 bladder. The central thesis is straightforward. The combination of microdissected and 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 urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. 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. The data submitted here represents the gene expression profiles of the embryonic day 14 bladder, urogenital sinus, and urethra.

Keywords: Gene expression comparison from developing regions of the mouse embryonic day 14 urogenital system

Overall design: Bladder, urogenital sinus, and urethra regions from embryonic day 14 SMGA/EGFP animals were microdissected and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.

Background corr dist: KL-Divergence = 0.0992, L1-Distance = 0.0390, L2-Distance = 0.0030, Normal std = 0.4599

0.867 Kernel fit Pairwise Correlations Normal fit

Density 0.434

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

060301_2BLAD060301_6BLADJS_8 (0.0546072) (0.0511598)060301_1UGS (0.0709497)060301_2UGS (0.0580893)060301_6UGS (0.261006)JS_7 (0.0449113) (0.186493)JS_060301_1_UrethraJS_060301_2_UrethraJS_060301_6_Urethra 060301_RefRNA_(0.0542701) JS_5(0.0529092) (0.0328102) JS_RefRNA(0.0114509) (0.050176) (0.0711671) [ min ] [ medium ] [ max ] CEM 1 Nefl 89.9 2234.8 10617.1 P ( S | Z, I ) = 1.00 Nefh 1.1 108.3 342.9 Mean Corr = 0.56717 Ina 13.8 166.9 738.9 Prph 4.2 197.3 5000.5 Dlgap2 1.8 16.2 42.5 Nefm 187.5 761.9 8100.4 Snap25 2.8 228.1 1713.9 Elavl2 112.6 1154.9 9025.9 Gng3 32.7 180.6 429.3 Cadps 85.6 448.0 2669.5 CEM 1 + Cplx1 37.0 261.1 565.3 Top 10 Genes Stmn2 13.6 711.9 5734.3 Sult4a1 8.7 44.0 194.1 Nrsn1 6.9 167.5 943.7 Elavl4 23.8 197.2 2540.4

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE10587" 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=GSE10587 Status: Public on Feb 19 2009 Title: Gene expression in stria vascularis of mice lacking Slc26a4 and heterzygous controls before the onset of hearing. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Determination of differential expression of genes in the stria vascularis of pendrin (Slc26a4) heterozygous and knockout mice before the onset of hearing at postnatal day 10 (P10).

Keywords: differential expression under disease state

Overall design: A total of Six samples of stria vascularis RNA obtained from P10 mice were analyzed. Triplicates from pendrin (Slc26a4) heterozygous and knockout mice were run and analyzed.

Background corr dist: KL-Divergence = 0.0370, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.6322

0.642 Kernel fit Pairwise Correlations Normal fit

Density 0.321

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

PostnatalPostnatal day 10Postnatal (P10)day 10Postnatal stria (P10)day vascularis 10Postnatal stria (P10)day vascularis 10Postnatal stria Slc26a4 (P10)day vascularis 10 stria Slc26a4 (P10)(heterozygote)day vascularis 10 stria Slc26a4 (P10)(knockout) vascularis stria Slc26a4 (heterozygote)mice vascularis mice[ (sample1) Slc26a4 (knockout)min (sample2) Slc26a4 (heterozygote)mice (0.0978488)] mice (0.100943) (sample3) (knockout) (sample4) mice[ (0.152939) medium mice (0.178442) (sample5) (sample6) (0.39308) (0.0767461) ] [ max ] CEM 1 Nefl 3.5 13.1 93.6 P ( S | Z, I ) = 1.00 Nefh 5.8 15.6 33.4 Mean Corr = 0.61285 Ina 2.6 31.1 37.5 Prph 161.2 267.9 339.7 Dlgap2 3.3 4.7 29.6 Nefm 1.0 8.6 36.4 Snap25 14.1 32.8 213.0 Elavl2 6.8 21.0 35.3 Gng3 2.1 25.3 63.3 Cadps 1.0 10.9 31.0 CEM 1 + Cplx1 23.0 28.1 82.8 Top 10 Genes Stmn2 2.8 16.5 24.4 Sult4a1 3.5 18.9 32.1 Nrsn1 1.0 10.6 28.4 Elavl4 2.3 9.4 18.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE15914" 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=GSE15914 Status: Public on Oct 01 2009 Title: Interleukin-7 promotes monocyte/macrophage arrest on endothelial cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21804111 Summary & Design: Summary: Background: It is recognized that atherosclerosis can regresses at least in animal models. However, little is known about the mechanisms. We induced regression of advanced atherosclerosis in apolipoprotein E deficient (APOEÂ/Â) mice and studied underlying mechanisms. Unexpectedly, our study led to the role of interleukin-7 (IL-7) in atherogenesis.

Methods and Results: We treated APOEÂ/Â mice fed a high cholesterol diet for 30 weeks to induce advanced lesions with a helper-dependent adenoviral vector expressing human apoE3 (HDAd-gE3), and analyzed the regression of atherosclerosis after 41 weeks. Using microarray analysis, we identified IL-7 as one of most significantly affected genes by lowering cholesterol. To answer why IL-7 is downregulated by reduced cholesterol, we studied effects of IL-7 on endothelial cells (ECs). Our major findings were (1) long-term lowering cholesterol induced regression of advanced atherosclerosis. (2) Microarray analysis identified multiple signaling pathways affected by lowering cholesterol. (3) Correction for multiple testing revealed that IL-7 expression was downregulated, whereas gamma-sarcoglycan and ˆ´–-actin were upregulated. (4) Oxidized LDL upregulated IL-7 expression in macrophages but not in aorta ECs or smooth muscle cells. (5) IL-7 increased the expression of cell adhesion molecules and chemokine in ECs and promoted monocyte adhesion to ECs. (6) Systemic elevation of IL-7 induced inflammatory response and recruited monocyte/macrophage to the lesions without increasing plasma cholesterol.

Conclusion: Our finding suggest that IL-7 inflames endothelium and triggers the adhesion/recruitment of monocyte/macrophages to the atherosclerotic lesions and thus plays a direct role in development of atherosclerosis.

Key Words: arteriosclerosis, gene therapy, hypercholesterolemia, interleukins, cell adhesion molecules

Overall design: 12039: E3: vector control

Background corr dist: KL-Divergence = 0.0908, L1-Distance = 0.0240, L2-Distance = 0.0008, Normal std = 0.4532

0.880 Kernel fit Pairwise Correlations Normal fit

Density 0.440

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

Baylor/Oka/LiBaylor/Oka/Li etBaylor/Oka/Li al/12031 etBaylor/Oka/Li al/12039 (0.0939139) etBaylor/Oka/Li al/12043 (0.0616085) etBaylor/Oka/Li al/12046 (0.417832) etBaylor/Oka/Li al/12047 (0.0743485) etBaylor/Oka/Li al/12048 (0.0394566) etBaylor/Oka/Li al/12051 (0.119572) et al/12053 (0.0158092) et al/12054 (0.028676) (0.148783)[ min ] [ medium ] [ max ] CEM 1 Nefl 24.1 52.7 226.1 P ( S | Z, I ) = 1.00 Nefh 11.9 17.5 41.1 Mean Corr = 0.53887 Ina 8.2 11.2 41.4 Prph 40.3 63.5 215.8 Dlgap2 10.8 14.1 15.1 Nefm 6.9 8.0 30.1 Snap25 29.9 80.6 493.7 Elavl2 17.2 30.8 171.1 Gng3 32.9 56.3 216.7 Cadps 7.7 13.9 37.9 CEM 1 + Cplx1 32.1 53.0 115.9 Top 10 Genes Stmn2 163.2 186.6 420.5 Sult4a1 26.2 37.9 159.0 Nrsn1 10.1 17.7 69.9 Elavl4 7.4 8.7 20.2

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE9566" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 38 -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=GSE9566 Status: Public on Dec 31 2007 Title: A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18171944 Summary & Design: Summary: A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function

Understanding the cell-cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate astrocytes, neurons, and oligodendrocytes. Here we describe the first method for the isolation and purification of developing and mature astrocytes from mouse forebrain. This method takes advantage of the expression of S100Î² by astrocytes. We used fluorescent activated cell sorting (FACS) to isolate EGFP positive cells from transgenic mice that express EGFP under the control of an S100Î² promoter. By depletion of astrocytes and oligodendrocytes we obtained purified populations of neurons, while by panning with oligodendrocyte-specific antibodies we obtained purified populations of oligodendrocytes. Using GeneChip Arrays we then created a transcriptome database of the expression levels of over 20,000 genes by gene profiling these three main CNS neural cell types at postnatal ages day 1 to 30. This database provides the first global characterization of the genes expressed by mammalian astrocytes in vivo and is the first direct comparison between the astrocyte, neuron, and oligodendrocyte transcriptomes. We demonstrate that Aldh1L1, a highly expressed astrocyte gene, is a highly specific antigenic marker for astrocytes with a substantially broader, and therefore potentially more useful, pattern of astrocyte expression than the traditional astrocyte marker GFAP. This transcriptome database of acutely isolated and highly pure populations of astrocytes, neurons and oligodendrocytes provides a resource to the neuroscience community by providing improved cell type specific markers and for better understanding of neural development, function, and disease.

We acutely purified mouse astrocytes from early postnatal ages (P1) to later postnatal ages (P30), when astrocyte differentiation is morphologically complete (Bushong et al., 2004), and acutely purified mouse OL-lineage cells from stages ranging from OPCs to newly differentiated OLs to myelinating OLs. We extracted RNA from each of these highly purified, acutely isolated cell types and used GeneChip Arrays to determine the expression levels of over 20,000 genes and construct a comprehensive database of cell type specific gene expression in the mouse forebrain. Analysis of this database confirms cell type specific expression of many well characterized and functionally important genes. In addition, we have identified thousands of new cell type enriched genes, thereby providing important new information about astrocyte, OL, and neuron interactions, metabolism, development, and function. This database provides a comparison of the genome-wide transcriptional profiles of the main CNS cell types and is a resource to the neuroscience community for better understanding the development, physiology, and pathology of the CNS.

Keywords: Developmental CNS Cell type comparision

Overall design: FACS purification of astrocytes: Dissociated forebrains from S100Î²-EGFP mice were resuspended in panning buffer (DBPS containing 0.02% BSA and 12.5 U/ml DNase) and sequentially incubated on the following panning plates: secondary antibody only plate to deplete microglia, O4 plate to deplete OLs, PDGFRÎ± plate to deplete OPCs, and a second O4 plate to deplete any remaining OLs. This procedure was sufficient to deplete all OL-lineage cells from animals P8 and younger, however, in older animals that had begun to myelinate, additional depletion of OLs and myelin debris was accomplished as follows. The nonadherent cells from the last O4 dish were harvested by centrifugation, and the cells were resuspended in panning buffer containing GalC, MOG, and O1 supernatant and incubated for 15 minutes at room temperature. The cell suspension was washed and then resuspended in panning buffer containing 20 Î¼g donkey anti-mouse APC for 15 minutes. The cells were washed and resuspended in panning buffer containing propidium iodide (PI). EGFP+ astrocytes were then purified by fluorescence activated cell sorting (FACS). Dead cells were gated out using high PI staining and forward light scatter. Astrocytes were identified based on high EGFP fluorescence and negative APC fluorescence from indirect immunostaining for OL markers GalC, MOG, and O1. Cells were sorted twice and routinely yielded >99.5% purity based on reanalysis of double sorted cells.; FACS purification of neurons: EGFP- cells were the remaining forebrain cells after microglia, OLs, and astrocytes had been removed, and were primarily composed of neurons, and to a lesser extent, endothelial cells (we estimate < 4% endothelial cells at P7 and < 20% endothelial cells at P17). EGFP- cells from S100Î²-EGFP dissociated forebrain were FACS purified in parallel with astrocyte purification and were sorted based on their negative EGFP fluorescence immunofluorescence. Cells were sorted twice and routinely yielded >99.9% purity. In independent preparations, the EGFP- cell population was additionally depleted of endothelial cells and pericytes by sequentially labeling with biotin-BSL1 lectin and streptavidin-APC while also labeling for OL markers as described above. Cells were sorted twice and routinely yielded >99.9% purity.; Panning purification of oligodendrocyte lineage cells: Dissociated mouse forebrains were resuspended in panning buffer. In order to deplete microglia, the single-cell suspension was sequentially panned on four BSL1 panning plates. The cell suspension was then sequentially incubated on two PDGFRÎ± plates (to purify and deplete OPCs), one A2B5 plate (to deplete any remaining OPCs), two MOG plates (to purify and deplete myelinating OLs), and one GalC plate (to purify the remaining PDGFRÎ±-, MOG-, OLs). The adherent cells on the first PDGFRÎ±, MOG, and GalC plates were washed to remove all antigen-negative nonadherent cells. The cells were then lysed while still attached to the panning plate with Qiagen RLT lysis buffer, and total RNA was purified. Purified OPCs were >95% NG2 positive and 0% MOG positive. Purified Myelin OLs were 100% MOG positive, >95% MBP positive, and 0% NG2 positive. Purified GalC OLs depleted of OPCs and Myelin OLs were <10% MOG positive and ~50% weakly NG2 positive, a reflection of their recent development as early OLs.; Data normalization and analysis: Raw image files were processed using Affymetrix GCOS and the MAS 5.0 algorithm. Intensity data was normalized per chip to a target intensity TGT value of 500, and expression data and absent/present calls for individual probe sets were determined. Gene expression values were normalized and modeled across arrays using the dChip software package with invariant-set normalization and a PM model. (www.dchip.org, Li and Wong, 2001). The 29 samples were grouped into 9 sample types: Astros P7-P8, Astros P17, Astros P17-gray matter (P17g), Neurons P7, Neurons P17, Neurons-endothelial cell depleted (P7n, P17n), OPCs, GalC-OLs, and MOG-OLs. Gene filtering was performed to select probe sets that were consistently expressed in at least one cell type, where consistently expressed was defined as being called present and having a MAS 5.0 intensity level greater than 200 in at least two-thirds of the samples in the cell type. We identified 20,932 of the 45,037 probe sets that were consistently expressed in at least one of the nine cell types. The Significance Analysis of Microarrays (SAM) method (Tusher et al., 2001) was used to determine genes that were significantly differentially expressed between different cell types (see Supplemental Table S2 for SAM cell type groupings). Clustering was performed using the hclust method with complete linkage in R. Expression values were transformed for clustering by computing a mean expression value for the gene using those samples in the corresponding SAM statistical analysis, and then subtracting the mean from expression intensities. In order to preserve the log2 scale of the data, unless otherwise indicated, no normalization by variance was performed. Plots were created using the gplots package in R. The Bioconductor software package (Gentleman et al., 2004) was used throughout the expression analyses. Functional analyses were performed through the use of Ingenuity Pathways Analysis (IngenuityÂ® Systems, www.ingenuity.com).

Background corr dist: KL-Divergence = 0.1819, L1-Distance = 0.0468, L2-Distance = 0.0051, Normal std = 0.3520

1.133 Kernel fit Pairwise Correlations Normal fit

Density 0.567

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

OLs (GC_b)Myelin (0.0116067) OLsOLs (MOG_b)(GC_a3)OLs (GC_c) (0.0267837)(0.0210367)Myelin (0.0397169) OLsMyelin (MOG_a2) OLsOPCs (MOG_c) (PDGF_c) Neurons(0.0280955) (0.0357664)Neurons (0.00965545)P16 (10d)Astros P16n (0.0545339) P7(11d)Neurons (5a) (0.079957) (0.0139878)Astros P7 (5b) P7Neurons (0.0375797) (6a) (0.0127633)Astros P7 (6b) P8Neurons (0.0316609) (7a) (0.0110716)Neurons P7 (8b)Cultured P16(0.0349739) (13b)Cultured FACS (0.0578623)Cultured Pos FACS (14c)Neurons All Astroglia (0.00970901) (14d)Cultured P26(0.0124698) (14f) (18b)Cultured (0.00748684)FACS (0.0513738)Cultured Pos FACS (19c)Astros All Astroglia (0.00958599) (19d) P17Cultured (0.00788841) (19e)(22a)Astros Astroglia(0.0061368)(0.00693596) P17Astros (23e)(24a) P17gOPCs (0.00704987)(0.00770994) (25g) (30o)OLs (0.00889921) (0.0119737)(30p)Myelin (0.0566023) OLsAstros (30q) P30Astros (0.0458627) (33a) P1Forebrain (0.00946933) (34a)Neurons (0.00624289) P17 (35h)Cultured P7n (0.111528) (38B)RGCm Astroglia (0.0672557) 8dAstros Astroglia (41FCS) P17gAstros (41NB)(0.00684069)(36g) P17 (0.0163665)(32a) (0.00963851) (0.0159219) [ min ] [ medium ] [ max ] CEM 1 Nefl 51.4 212.3 6539.4 P ( S | Z, I ) = 1.00 Nefh 39.3 73.4 1622.9 Mean Corr = 0.52948 Ina 97.0 292.0 2984.1 Prph 84.9 180.7 465.6 Dlgap2 102.3 183.2 604.0 Nefm 53.5 163.5 7391.9 Snap25 27.2 258.8 11207.8 Elavl2 37.1 168.8 3386.1 Gng3 194.3 1246.8 6563.3 Cadps 209.0 909.6 5324.8 CEM 1 + Cplx1 273.2 578.7 8276.0 Top 10 Genes Stmn2 131.8 865.4 16775.8 Sult4a1 139.9 304.8 4720.1 Nrsn1 99.7 398.4 5817.7 Elavl4 66.2 473.8 3963.9

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE51365" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 28 -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=GSE51365 Status: Public on Oct 18 2013 Title: Latent gammaherpesvirus 68 infection induces distinct transcriptional changes in different organs Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24155394 Summary & Design: Summary: Previous studies identified a role for latent herpesvirus infection in cross-protection to infection and exacerbation of chronic inflammatory diseases. Here, we compared the gene expression signature from livers, spleens and brains of mice infected with wild-type gammaherpesvirus 68 (MHV68), a mutant virus defective in the establishment of latency (ORF73.stop) or mockulum. We identified over 600 genes differentially expressed in organs of mice latently infected with MHV68 and found distinct sets of genes linked to different pathways were altered in spleen compared to liver. Several of the most differentially expressed latency-specific genes (e.g. IFNÎ³, Cxcl9, Ccl5) are associated with known latency-specific phenotypes.

Overall design: RNA was extracted from livers, spleens and brains of 7-9 week old male C57Bl/6 mice infected with gammaherpesvirus 68 (MHV68), a virus defective in establishment of latency (ORF73.stop) or mockulum. RNA from 3-4 mice per treatment was pooled and analyzed by M430 2.0 Affymetrix Gene Chip. Three biologic replicates were analyzed for all conditions, except mock livers, for which four biologic replicates were analyzed.

Background corr dist: KL-Divergence = 0.0674, L1-Distance = 0.0734, L2-Distance = 0.0082, Normal std = 0.6075

0.657 Kernel fit Pairwise Correlations Normal fit

Density 0.328

0.000 CEM 1

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

Pre-normalization Quantiles

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE6134" 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=GSE6134 Status: Public on Aug 08 2007 Title: Offsprings of crosses between hypercholesterolemic and normocholesterolemic parents LUMC-HKG-ApoE-Atherosclerosis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17656671 Summary & Design: Summary: Enhanced prenatal fatty streak formation in human fetuses has been associated with maternal hypercholesterolemia. However, the possible roles of maternal genetic background and in utero environment on development of atherosclerosis in adult life have not been unraveled. We generated genetically identical heterozygous apoE-deficient mice offspring with a different maternal background to study the intrauterine effect of maternal genotype and associated hypercholesterolemia on the developing vascular system. As read out for increased atherosclerosis development in adult life, a constrictive collar was placed around the carotid artery to induce lesion formation. A significant increase in endothelial cell activation and damage was detected in the carotid arteries of heterozygous apoE-deficient fetuses with apoE-deficient mothers compared with offspring from wild type mothers, but no fatty streak formation was observed. Postnatally, all carotid arteries revealed normal morphology. In adult offspring with maternal apoE-deficiency, the constrictive collar resulted in severe lesion (9/10) development compared with no to only minor lesions (2/10) in offspring of wild type mothers. Microarray analysis showed no effect of maternal apoE-deficiency on gene expression in adult offspring. We conclude that maternal apoE-deficiency not only affects fetal arteries, but also increases the susceptibility for development of collar-induced atherosclerosis in adult life.

Keywords: Atheroslcersosis development

Overall design: Crossing of hypercholesterolemic female with normocholesterolemic male and vice versa, determination of susceptabilioty to atherosclerosis in offspring

Background corr dist: KL-Divergence = 0.0638, L1-Distance = 0.0198, L2-Distance = 0.0006, Normal std = 0.5205

0.766 Kernel fit Pairwise Correlations Normal fit

Density 0.383

0.000 CEM 1

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

Pre-normalization Quantiles

ApoE-/+,ApoE-/+, offspringApoE-/+, offspring normocholesterolemicApoE-/+, offspring normocholesterolemicApoE-/+, offspring normocholesterolemicApoE-/+, offspring hypercholesterolemic wt ApoE-/+,mother, offspring hypercholesterolemic wt mother, Apo-/-offspring hypercholesterolemic wt mother,father ApoE-/- hypercholesterolemicApoE-/- LUMC_HKG_MOUSE_430_2 ApoE-/- father ApoE-/- mother,[ LUMC_HKG_MOUSE_430_2-2 fathermin ApoE-/- mother, wt LUMC_HKG_MOUSE_430_2-3father ApoE-/- ]mother, wt LUMC_HKG_MOUSE_430_2-4 father mother, (0.430923)wt LUMC_HKG_MOUSE_430_2-5 father[ wtmedium LUMC_HKG_MOUSE_430_2-6 father(0.192072) LUMC_HKG_MOUSE_430_2-7 (0.11623) (0.046909) ] (0.0847404)[ (0.0568567) max (0.0722683) ] CEM 1 Nefl 20.8 89.6 1323.5 P ( S | Z, I ) = 1.00 Nefh 30.6 70.1 292.8 Mean Corr = 0.51571 Ina 37.7 101.9 228.1 Prph 61.5 123.5 1977.5 Dlgap2 8.0 13.6 26.6 Nefm 5.5 30.9 151.0 Snap25 21.1 116.8 1742.9 Elavl2 17.6 52.5 2042.5 Gng3 60.2 139.6 428.3 Cadps 3.5 39.9 802.6 CEM 1 + Cplx1 43.2 145.5 684.7 Top 10 Genes Stmn2 304.5 490.8 1871.2 Sult4a1 6.5 24.9 238.8 Nrsn1 18.8 99.7 592.4 Elavl4 9.3 66.8 301.1

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE15729" 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=GSE15729 Status: Public on Mar 01 2010 Title: Gene Expression of ApoE Null and ApoE Null/RAGE Diabetic and Non-diabetic Mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20133903 Summary & Design: Summary: The multi-ligand Receptor for AGE (RAGE) contributes to atherosclerosis in apolipoprotein (ApoE) null mice in both the non-diabetic and diabetic states. Previous studies using soluble RAGE, the extracellular ligand-binding domain of RAGE, or homozygous RAGE null mice showed that blockade or deletion of RAGE resulted in marked reduction in atherosclerotic lesion area and complexity compared to control animals. In parallel, significant down-regulation of inflammatory mediators and matrix metalloproteinases was evident in ApoE null mice aortas devoid of RAGE compared to those of ApoE null RAGE-expressing mice. Although these findings suggested that RAGE triggered pro-atherogenic mechanisms via regulation of inflammatory gene expression, these studies did not reveal the broader pathways by which RAGE contributed to atherosclerosis in ApoE null mice.

Therefore, we performed Affymetrix gene expression arrays on aortas of non-diabetic and diabetic ApoE null mice expressing RAGE or devoid of RAGE at nine weeks of age, as this reflected a time point at which frank atherosclerotic lesions were not yet present, but, that we would be able to identify the genes likely involved in diabetes- and RAGE-dependent atherogenesis. The comparisons were as follows: 1. diabetic ApoE null relative to non-diabetic ApoE null; 2. non-diabetic ApoE null / RAGE null relative to non-diabetic ApoE null; 3. diabetic ApoE null / RAGE null relative to non-diabetic ApoE null / RAGE null; and 4. diabetic ApoE null / RAGE null relative to diabetic ApoE null aorta.

Our data reveal that there is very little overlap of the genes which are differentially expressed both in the onset of diabetes in ApoE null mice, and in the effect of RAGE deletion in diabetic ApoE null mice. We next performed a Pathway-Express analysis to determine the pathways that were most associated with the onset of diabetes in ApoE null mice and the effect of RAGE gene deletion in diabetic ApoE null mice. Rigorous statistical analysis was undertaken and revealed that the transforming growth factor-Î² pathway (tgf-Î²) and focal adhesion pathways might be expected to play a significant role in both the mechanism by which diabetes facilitates the formation of atherosclerotic plaques in ApoE null mice, and the mechanism by which deletion of RAGE ameliorates this effect. We focused on three genes of the tgf-Î² family which were found to be up-regulated in diabetic vs. non-diabetic ApoE null aorta, and which were reduced by deletion of RAGE. These included: thrombospondin1 (Thbs1), transforming growth factor-Î²2 (tgf-Î²2) and rho-associated kinase (ROCK1). Real-time quantitative polymerase chain reaction and Western blotting experiments were performed, as well as ROCK1 activity assays in mouse aorta, and validated the findings of the Affymetrix gene array. Further, confocal microscopy revealed that a principal cell type in the ApoE null aorta expressing these factors was the vascular smooth muscle cell. Our data suggest the novel finding that the observed reduction of accelerated atherosclerosis in diabetic ApoE null / RAGE null vs. diabetic ApoE null mice occurs, all or in part, through the ROCK1 branch of the TGF-Î² pathway. We have inferred a detailed mechanism for this process.

Taken together, these data suggest that suppression of ROCK1 activity in the atherosclerosis-vulnerable vessel wall, especially in diabetes, but in non-diabetes as well, may underlie the beneficial effects of RAGE antagonism and genetic deletion in murine models. These findings highlight logical and novel targets for therapeutic intervention in cardiovascular disease and diabetes.

Overall design: There were 4 mice in each group initially. However there are only 3 non-diabetic ApoE null / RAGE null mice in the final experimental sample in group 3 due to a failure to generate cRNA from that sample. All samples were normalized to remove chip-dependent regularities using the RMA method. Chips and controls at each combination of genotype and disease sate were normalized together. The statistical significance of differential expression was calculated using the empirical Bayesian LIMMA (LInear Model for MicroArrays) method A cut-off B>0 was used for the statistical significance of gene expression.

Background corr dist: KL-Divergence = 0.1445, L1-Distance = 0.0344, L2-Distance = 0.0024, Normal std = 0.3840

1.039 Kernel fit Pairwise Correlations Normal fit

Density 0.519

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

APOE_KO_DM_9W_1APOE_KO_DM_9W_2APOE_KO_DM_9W_3 (0.0532843)APOE_KO_DM_9W_4 (0.0160807)APOE_KO_NODM_9W_5 (0.0614616)APOE_KO_NODM_9W_6 (0.00969714)APOE_KO_NODM_9W_7APOE_KO_NODM_9W_8 (0.102839)APOE_KO_RAGE_KO_DM_9W_9 (0.0285856)APOE_KO_RAGE_KO_DM_9W_10 (0.0287789)APOE_KO_RAGE_KO_DM_9W_11 (0.0213781)APOE_KO_RAGE_KO_DM_9W_12APOE_KO_RAGE_KO_NODM_9W_13 (0.0386444)APOE_KO_RAGE_KO_NODM_9W_14 (0.051097)APOE_KO_RAGE_KO_NODM_9W_15 (0.144742) (0.0186578) (0.380689) [(0.0186095) min (0.0254546) ] [ medium ] [ max ] CEM 1 Nefl 30.3 48.0 916.1 P ( S | Z, I ) = 1.00 Nefh 23.8 31.0 137.7 Mean Corr = 0.49945 Ina 49.0 68.5 128.7 Prph 46.7 74.5 1050.0 Dlgap2 26.2 28.9 36.7 Nefm 24.3 33.4 609.3 Snap25 26.3 48.9 1429.0 Elavl2 21.3 28.6 661.5 Gng3 64.2 114.4 491.6 Cadps 27.4 37.1 581.8 CEM 1 + Cplx1 111.3 160.7 385.5 Top 10 Genes Stmn2 100.0 160.1 1730.9 Sult4a1 37.1 49.4 168.5 Nrsn1 25.4 31.6 103.0 Elavl4 47.4 63.7 224.8

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE30138" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30138 Status: Public on Dec 31 2011 Title: Global Gene Expression Analysis of Murine Limb Development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22174793 Summary & Design: Summary: Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here, we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature, and nerves are specified and the musculoskeletal system of the limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore-limb and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which tampers off at later time points. Among 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that correlate with functional programs during limb development and are likely to provide new insights into specific tissue patterning processes. Here we provide for the first time, a comprehensve analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.

Overall design: Fifty- one arrays were analyzed, consisting of whole fore-limb and hind-limb bud RNA (experimental) and whole embryo RNA (reference) samples from E9.5 to E13.5 DPC mouse (FVB strain). Embryos were not pooled to generate samples. Each time point has 3 to 5 biological replicates for limb bud samples, duplicates for whole embryos. Comparisons were made between limb bud samples and whole embryo at the same stage, fore-limb samples of different stages, hind-limb samples of different stages, and fore-limb samples compared to hind-limb samples at the same or the next stage.

Background corr dist: KL-Divergence = 0.0710, L1-Distance = 0.0466, L2-Distance = 0.0047, Normal std = 0.4968

0.803 Kernel fit Pairwise Correlations Normal fit

Density 0.402

0.000 CEM 1

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

Pre-normalization Quantiles

Whole EmbryoWhole Embryo WholeE9.5 1 Embryo(0.0103728) WholeE9.5 2 Embryo(0.0370003) WholeE10.5 1Embryo Whole E10.5(0.028271) 2Embryo Whole E11.5(0.0193748) 1Embryo Whole E11.5(0.0447042) 2Embryo Whole E12.5(0.0406224) 1Embryo Whole E12.5(0.109113) 2Embryo Forelimb E13.5(0.0937287) 1 Forelimb E13.5(0.126797) E9.5 21Forelimb (0.149424)(0.0071831) E9.5 2Forelimb (0.00752967) E9.5 3Forelimb (0.0180054) E10.5Forelimb 1 E10.5(0.0114033)Forelimb 2 E10.5(0.0098259)Forelimb 3 E10.5(0.00554543)Hindlimb 4 E10.5(0.011224)Hindlimb 5 E10.5(0.0043683)Hindlimb 1 E10.5(0.00866247)Hindlimb 2 E10.5(0.00736605)Forelimb 3 E10.5(0.00824156)Forelimb 4 E11.5(0.0160159)Forelimb 1 E11.5(0.0149867)Forelimb 2 E11.5(0.00947656)Hindlimb 3 E11.5(0.0141768)Hindlimb 4 E11.5(0.00570696)Hindlimb 1 E11.5(0.00672789)Hindlimb 2 E11.5(0.0110792)Hindlimb 3 E11.5(0.00736966)Forelimb 4 E11.5(0.00918752)Forelimb 5 E12.5(0.00479474)Forelimb 1 E12.5(0.00319302)Forelimb 2 E12.5(0.00792094)Forelimb 3 E12.5(0.00595526)Hindlimb 4 E12.5(0.0138941)Hindlimb 5 E12.5(0.0103051)Hindlimb 1 E12.5(0.00692362)Hindlimb 2 E12.5(0.0108554)Hindlimb 3 E12.5(0.00772881)Forelimb 4 E12.5(0.00424749)Forelimb 5 E13.5(0.0103449)Forelimb 1 E13.5(0.00456126)Forelimb 2 E13.5(0.0126966)Forelimb 3 E13.5(0.00606947)Hindlimb 4 E13.5(0.00650447)Hindlimb 5 E13.5(0.00737885)Hindlimb 1 E13.5(0.00516604)Hindlimb 2 E13.5(0.00435949)Hindlimb 3 E13.5(0.0032154) 4 E13.5(0.00774956) 5 (0.00264473)[ min ] [ medium ] [ max ] CEM 1 Nefl 62.5 285.1 6295.2 P ( S | Z, I ) = 1.00 Nefh 17.6 22.7 52.3 Mean Corr = 0.64064 Ina 26.0 37.9 2164.4 Prph 22.1 32.9 1319.6 Dlgap2 13.8 18.2 24.4 Nefm 40.7 188.2 6541.5 Snap25 12.7 16.7 489.8 Elavl2 78.4 194.0 3170.0 Gng3 137.1 346.5 1579.2 Cadps 20.4 47.7 743.7 CEM 1 + Cplx1 47.8 65.2 426.9 Top 10 Genes Stmn2 78.9 166.7 10405.3 Sult4a1 36.6 51.1 168.8 Nrsn1 19.2 30.4 226.3 Elavl4 59.4 87.7 1338.0

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE11343" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 19 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11343 Status: Public on May 10 2008 Title: Rosiglitazone Treatment Reduces Diabetic Neuropathy in STZ treated DBA/2J mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18583417 Summary & Design: Summary: Diabetic Neuropathy (DN) is a common complication of diabetes. Currently, there is no drug treatment to prevent or slow the development of DN. Rosiglitazone (Rosi) is a potent insulin sensitizer and may also slow the development of DN by a mechanism independent of its effect on hyperglycemia. A two by two design was used to test the effect of Rosi treatment on the development of DN. Streptozotocin-induced diabetic DBA/2J mice were treated with Rosi. DN and oxidative stress were quantified, and gene expression was profiled using the Affymetrix Mouse Genome 430 2.0 microarray platform. An informatics approach identified key regulatory elements activated by Rosi. Diabetic DBA/2J mice developed severe hyperglycemia, DN and elevated oxidative stress. Rosi treatment did not affect hyperglycemia but did reduce oxidative stress and prevented development of thermal hypoalgesia. Two novel transcription factor binding modules were identified that may control genes correlated to changes in DN following Rosi treatment: SP1F_ZBPF and EGRF_EGRF. Rosi treatment reduced oxidative stress and DN independent of its insulin sensitizing effects. Gene expression profiling identified two novel targets activated by Rosi treatment. These targets may be useful in designing drugs with the same efficacy as Rosi in treating DN but with fewer undesirable effects.

Keywords: disease and treatment analysis

Overall design: Affymetrix chips were run on five mice from each group. One chip (in the Control group) failed quality control measures and was excluded.

Background corr dist: KL-Divergence = 0.0893, L1-Distance = 0.0337, L2-Distance = 0.0021, Normal std = 0.4560

0.875 Kernel fit Pairwise Correlations Normal fit

Density 0.437

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

Nerve_Control_Vehicle_702Nerve_Control_Vehicle_703Nerve_Control_Vehicle_704Nerve_Control_Vehicle_705 (0.0125655)Nerve_Diabetic_Vehicle_706 (0.0157781)Nerve_Diabetic_Vehicle_707 (0.0220599)Nerve_Diabetic_Vehicle_708 (0.0215368)Nerve_Diabetic_Vehicle_709 (0.052452)Nerve_Diabetic_Vehicle_710 (0.131459)Nerve_Control_Rosi_711 (0.14814)Nerve_Control_Rosi_712 (0.111626)Nerve_Control_Rosi_713 (0.0111252)Nerve_Control_Rosi_714 (0.0549358)Nerve_Control_Rosi_715 (0.0240063)Nerve_Diabetic_Rosi_716 (0.0234753)Nerve_Diabetic_Rosi_717 (0.0130215)Nerve_Diabetic_Rosi_718 (0.0815851)Nerve_Diabetic_Rosi_719 (0.137505)Nerve_Diabetic_Rosi_720 (0.0357136) (0.0329423) (0.0335012) (0.0365713)[ min ] [ medium ] [ max ] CEM 1 Nefl 309.9 11467.9 14742.1 P ( S | Z, I ) = 1.00 Nefh 175.3 4500.1 6670.3 Mean Corr = 0.48592 Ina 29.4 228.6 1057.8 Prph 174.9 3398.3 7396.2 Dlgap2 7.8 10.3 15.6 Nefm 78.7 3085.2 6199.3 Snap25 287.7 7341.4 10279.7 Elavl2 56.7 1610.3 3077.8 Gng3 249.8 5990.9 9907.4 Cadps 17.1 603.4 1364.2 CEM 1 + Cplx1 136.2 3846.7 8088.6 Top 10 Genes Stmn2 408.0 4285.8 6747.9 Sult4a1 62.7 2286.2 4259.8 Nrsn1 87.9 859.7 1624.7 Elavl4 7.8 243.8 605.5

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE9954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 70 -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=GSE9954 Status: Public on Dec 20 2007 Title: Large-scale analysis of the mouse transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18365009 Summary & Design: Summary: We used microarrays to compare gene expression across different murine tissues.

Keywords: Other

Overall design: Different tissues were dissected from 10-12 week old C57Bl6 mice for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.3484, L1-Distance = 0.0923, L2-Distance = 0.0272, Normal std = 0.2989

1.449 Kernel fit Pairwise Correlations Normal fit

Density 0.724

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse diaphragm,Mouse diaphragm,Mouse biological diaphragm,Mouse biological spleen,replicateMouse biological spleen,replicateMousebiological 1 (0.00371609) spleen,replicateMousebiological 2 replicate(0.00628138) muscle,Mousebiological 3 replicate(0.00232892) 1 (0.0034455)muscle,Mouse biological replicate 2 (0.00322265)muscle,Mouse biological replicate 3 (0.00490496)muscle,Mouse biological replicate 1 liver,(0.0027359)Mouse biological replicate biological2 liver,(0.00841085)Mouse replicate biological3 liver,(0.00535622)Mouse replicate biological4 brain,(0.00359836)Mouse replicate 1 (0.00309907) biological brain,Mouse replicate 2 (0.00356264) biological brain,Mouse replicate 3 (0.00172953) biological lung,Mouse replicate 1 (0.104901)biological lung,Mouse replicate 2 (0.118752)biological lung,Mouse replicate 3 (0.0853843)biological kidney,Mouse replicate 1 (0.024357) kidney,Mousebiological replicate 2 (0.0284025) kidney,Mousebiological 3replicate (0.027319) adrenalMousebiological replicate 1 (0.00328145)adrenal Mousegland, replicate 2 (0.00465562)biologicaladrenal Mousegland, 3 (0.00510964)biologicalbone Mousegland, replicate marrow, biologicalboneMouse replicate 1 marrow, (0.00280185) biologicalboneMouse replicate 2 marrow, (0.00190518) biologicalboneMouse replicate 3 marrow, (0.00918152) biologicaladiposeMouse replicate 1 (0.00998313) biologicaladiposeMouse tissue, replicate 2 (0.00748332) adiposeMouse biologicaltissue, replicate 3 (0.00911134) pituitaryMouse biologicaltissue, replicate4 (0.00668661) pituitaryMouse biologicalgland, replicate 1 (0.013708)pituitaryMouse biological gland, replicate 2 (0.0101121)pituitaryMouse biological gland, replicate 3 (0.0101828)pituitaryMouse biological gland, replicate 1 (0.00533984)salivaryMouse biological gland, replicate 2 (0.00818793)salivaryMouse biologicalgland, replicate 3 (0.00591799)salivaryMousebiological gland, replicate 4 (0.00631542)seminalMousebiological gland, replicate 5 (0.00654986)seminalMousebiological vesicle, replicate 1 (0.00539099) seminalMouse vesicle, biological replicate 2 (0.00303735) thymus,Mouse vesicle, biological replicate3 (0.00255644) thymus,Mouse biologicalbiological replicate 1 thymus,Mouse (0.00394877)biological replicatereplicate 2 testis,Mouse (0.0052193)biological replicate 13biological testis,Mouse (0.00344708)(0.00261949) replicate 2 biological testis,Mouse(0.00320564) replicate 3 biological heart,Mouse(0.00683219) replicate 1 (0.0056019)biological heart,Mouse replicate 2 (0.00596108)biological heart,Mouse replicate 3 (0.00655885)biological smallMouse replicate 1 (0.00583698)intestine, smallMouse replicate 2 (0.0108414)intestine, smallMouse biological 3 (0.00634188)intestine, eye,Mouse biological replicate biological eye,Mouse biological replicate biological 1 (0.00364021)eye,Mousereplicate replicate biological 2 (0.00320436)ESMousereplicate 1 cells,(0.0184012) 3 (0.00214537)ESMousereplicate biological2 cells,(0.0199129) ESMouse biological3 cells,(0.0192083) replicate placenta,Mouse biological replicate 1 placenta,Mouse (0.0253722) biological replicate 2 placenta,Mouse (0.0344354) biological replicate 3 ovary,Mouse (0.0253739) biological replicate biological 1ovary,Mouse (0.0206951) replicate biological 2ovary,Mouse (0.030916) replicate biological 3fetus,Mouse (0.0303813) replicate 1 (0.007877)biological fetus,Mouse replicate 2 (0.00476954)biological fetus, replicate 3 (0.00542446)biological replicate 1 (0.0169627) replicate 2 (0.046171)[ min3 (0.0396884) ] [ medium ] [ max ] CEM 1 Nefl 133.6 190.2 8679.5 P ( S | Z, I ) = 1.00 Nefh 144.2 227.2 954.4 Mean Corr = 0.48667 Ina 172.1 240.0 2590.0 Prph 174.9 231.8 518.2 Dlgap2 140.6 185.8 500.9 Nefm 125.4 181.0 6068.3 Snap25 113.5 161.8 24100.0 Elavl2 123.2 157.6 2065.2 Gng3 228.7 327.6 8189.2 Cadps 128.8 188.4 3910.2 CEM 1 + Cplx1 233.0 317.8 7739.4 Top 10 Genes Stmn2 197.1 339.3 6744.3 Sult4a1 154.6 252.3 3835.4 Nrsn1 138.8 192.6 6059.1 Elavl4 165.3 208.1 1611.2

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE6933" 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=GSE6933 Status: Public on Oct 11 2007 Title: Unique Molecular Signature of Multipotent Adult Progenitor Cells (Affy) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17683608 Summary & Design: Summary: We compare the transcriptome of embryonic stem cells (ESCs), adult stem cells with apparent greater differentiation potential such as multipotent adult progenitor cells (MAPCs), mesenchymal stem cells (MSCs) and neurospheres (NS). Mouse and rat MAPCs were used in this study and two different array platforms (Affymetrix and NIA) were used for mouse samples.

Keywords: mRNA expression profiling, oligonucleotide microarrays, stem cells

Overall design: Three mRNA samples (biological replicates) per cell type taken at different passage number were compared. Cell types include mouse ESCs, mouse MSCs and three clones isolated using mouse MAPC culture condition: mMAPC-1, mMAPC-2 and mClone-3. mMAPC-1 and mClone-3 were obtained from same bone marrow isolation, mMAPC-2 was obtained in a different bone marrow isolation. Two clones derived from same rat bone marrow using rat MAPC culture conditions were compared. Three mRNA samples (biological replicates) per clone were taken at different passage numbers

Background corr dist: KL-Divergence = 0.0852, L1-Distance = 0.0624, L2-Distance = 0.0067, Normal std = 0.5110

0.863 Kernel fit Pairwise Correlations Normal fit

Density 0.432

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

MSC A AffyMSC (0.091414) B AffyMSC (0.0330187) C AffymMAPC-1 (0.04189)mMAPC-1 A AffymMAPC-1 (0.0431559) B AffymMAPC-2 (0.0382676) C AffymMAPC-2 (0.0381066) A AffymMAPC-2 (0.0343592) B AffymClone-3 (0.0319152) C AffymClone-3 (0.0295661)A AffymClone-3 (0.0358523) B AffyESC (0.043725) C AffyA AffyESC (0.0489884) (0.142788) B AffyESC (0.153635) C Affy (0.193318) [ min ] [ medium ] [ max ] CEM 1 Nefl 2.6 19.8 2963.8 P ( S | Z, I ) = 1.00 Nefh 2.6 15.9 1048.7 Mean Corr = 0.48366 Ina 9.0 42.0 1074.1 Prph 4.0 29.8 464.6 Dlgap2 2.8 28.5 56.9 Nefm 3.6 20.4 316.0 Snap25 2.6 3.3 70.0 Elavl2 2.6 28.4 1889.8 Gng3 5.2 58.3 1233.7 Cadps 2.8 5.9 62.7 CEM 1 + Cplx1 3.1 12.6 100.1 Top 10 Genes Stmn2 5.6 95.5 2081.4 Sult4a1 5.8 50.0 480.6 Nrsn1 2.6 5.0 410.9 Elavl4 2.6 8.9 129.7

Null module Nrp1 Ldlrap1 Gan GEO Series "GSE26822" 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=GSE26822 Status: Public on Jan 01 2012 Title: Expression data from postnatal mouse apical and basal organ of Corti from Dicer1 conditional knockout and littermate control cochleae. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21360794 Summary & Design: Summary: Cre recombinase-mediated conditional knockout of floxed Dicer1 alleles causes depletion of small RNAs including microRNAs, which function to repress target mRNA expression by inhibiting translation and/or stimulating mRNA degradation.

We used microarrays to examine gene expression in apical versus basal organ of Corti from the cochleae of control and mutant mice in which Dicer1 was deleted and microRNAs were depleted specifically in sensory hair cells by Atoh1 promoter-driven Cre recombinase expression.

Overall design: Each biological replicate represents the combined apical or combined basal segments of organ of Corti from both cochleae of a single mouse. Two biological replicates for apical and basal organ of Corti from Dicer1 conditonal knockout and littermate controls were collected for RNA extraction and microarray analysis.

Background corr dist: KL-Divergence = 0.0736, L1-Distance = 0.0220, L2-Distance = 0.0008, Normal std = 0.4919

0.811 Kernel fit Pairwise Correlations Normal fit

Density 0.406

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

P16 mutantP16 mutantOCP16 apex, mutantOC biologicalP16 apex, mutantOC biologicalP16 base, rep controlOC 1 biological P16 (0.073962)base, rep controlOC 2 biological P16 (0.0908596)apex, rep controlOC 1 biological P16 (0.054751)apex, rep controlOC 2 biological (0.187472)base, rep OC 1 biological (0.0854665)base, rep 2 biological (0.0541057) rep 1 [(0.17737) repmin 2 (0.276014) ] [ medium ] [ max ] CEM 1 Nefl 7467.0 14826.3 17086.0 P ( S | Z, I ) = 1.00 Nefh 4306.4 11125.6 14272.9 Mean Corr = 0.53122 Ina 821.1 1705.2 2380.1 Prph 8.3 34.9 99.8 Dlgap2 4.0 21.4 24.0 Nefm 2258.2 7333.3 9027.0 Snap25 4972.8 10669.4 17486.7 Elavl2 495.7 1332.8 2686.9 Gng3 483.2 847.5 1439.0 Cadps 965.2 2807.2 5487.3 CEM 1 + Cplx1 4843.1 11690.9 14852.7 Top 10 Genes Stmn2 1128.8 2632.6 4323.2 Sult4a1 333.9 889.6 1874.9 Nrsn1 126.0 219.7 395.5 Elavl4 567.2 2545.0 3232.4

Null module Nrp1 Ldlrap1 Gan