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: 21 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. Mrps12 Mrps22 Mrps14 Mrpl35 Mrpl51 Mrpl32 Mrpl49 Mrpl48 Mrpl37 Mrpl43 Mrpl39 Mrpl20 Mrpl47 Mrpl34 Mrpl13 Mrpl28 Mrpl11 Mrpl18 Mrpl40 Mrpl9 Num ofGenesinQueryGeneset:21.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Dap3

Mrpl40 Mrpl18 Mrps22 Mrpl11 Mrpl28 Mrpl13 Mrpl34 Mrps12 Mrpl47 Mrpl20 Mrpl39 Mrpl43 Mrpl37 Mrpl48 Mrpl49 Mrpl32 Dap3 Mrpl9 Mrpl51 Mrpl35 Mrps14 Singletons CEM 1(448datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page1 Timm17a Mrps18a Timm8b Timm13 Chchd1 Ccdc58 Mrps16 Mrps17 Mrps10 Mrps35 Mrps28 Mrps12 Mrps22 Sssca1 Ndufv2 Atp5g1 Stoml2 Psmb3 Psmg1 Mrpl36 Mrpl16 Mrpl55 Mrpl42 Mrpl22 Mrpl46 Mrpl12 Mrpl32 Mrpl49 Mrpl48 Mrpl37 Mrpl43 Mrpl39 Mrpl20 Mrpl47 Mrpl34 Mrpl13 Mrpl28 Mrpl11 Mrpl18 Mrpl40 Grpel1 Dpy30 Naa10 Mrps7 Polr2j Mrpl2 Mrpl9 Dap3 Slirp Clpp 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE38031 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE14004 [9] GSE18907 [12] GSE48397 [10] GSE21944 [6] GSE23833 [12] GSE20954 [14] GSE51080 [18] GSE13302 [30] GSE46496 [9] GSE56135 [8] GSE46606 [30] GSE41942 [6] GSE30160 [6] GSE11973 [6] GSE19885 [9] GSE15729 [15] GSE13611 [8] GSE31313 [22] GSE12498 [12] GSE45619 [6] GSE8555 [8] GSE22824 [24] GSE52474 [154] GSE31004 [8] GSE13693 [9] GSE46723 [6] GSE31940 [8] GSE26616 [6] GSE11333 [6] GSE10989 [6] GSE37191 [12] GSE47872 [6] GSE10273 [9] GSE20391 [11] GSE12518 [6] GSE55607 [18] GSE38754 [40] GSE13044 [59] GSE52542 [9] GSE46094 [10] GSE27114 [6] GSE55356 [6] GSE13432 [12] GSE48884 [12] GSE28389 [20] GSE15155 [12] GSE28417 [12] GSE51608 [6] GSE44923 [16] GSE59437 [30] GSE6998 [32] GSE27379 [6] GSE6674 [15] GSE13547 [12] GSE48811 [20] GSE21063 [24] GSE35226 [12] GSE41759 [14] GSE18587 [9] GSE20152 [8] GSE23009 [16] GSE46090 [12] GSE18135 [18] GSE5891 [6] GSE41907 [7] GSE32330 [12] GSE22180 [60] GSE33101 [8] GSE11220 [44] GSE10192 [24] GSE15624 [12] GSE15741 [6] GSE26096 [10] GSE9652 [11] GSE24291 [6] GSE8407 [17] GSE16454 [24] GSE31244 [6] GSE6875 [8] GSE38304 [8] GSE56755 [13] GSE7275 [8] GSE19338 [24] GSE17497 [10] GSE39449 [6] GSE13149 [25] GSE31028 [6] GSE34961 [9] GSE19954 [8] GSE17923 [6] GSE10210 [16] GSE7759 [112] GSE20523 [17] GSE27816 [14] GSE39233 [40] GSE40230 [15] GSE5035 [12] GSE51075 [12] GSE42299 [8] GSE23101 [20] GSE11110 [11] GSE11222 [42] GSE35396 [24] GSE15541 [12] GSE9975 [36] GSE23408 [39] GSE36665 [6] GSE27848 [16] GSE5332 [12] GSE37907 [24] GSE33471 [12] GSE33121 [10] GSE24061 [88] GSE22039 [9] GSE12430 [21] GSE26671 [12] GSE13421 [8] GSE4535 [6] GSE26299 [108] GSE18396 [6] GSE14308 [12] GSE20696 [8] GSE15267 [8] GSE31570 [6] GSE16994 [12] GSE14395 [24] GSE54207 [9] GSE40368 [10] GSE6030 [6] GSE3313 [24] GSE23923 [8] GSE56777 [8] GSE44260 [10] GSE47414 [18] GSE7948 [13] GSE32034 [14] GSE17373 [24] GSE13753 [10] GSE21549 [6] GSE24789 [9] GSE27811 [9] GSE57543 [6] GSE23040 [6] GSE25295 [25] GSE12049 [6] GSE53951 [10] GSE28559 [30] GSE24210 [16] GSE10912 [6] GSE53077 [8] GSE11291 [60] CEM+ CEM GSE11759 [6] GSE36392 [9] GSE32277 [33] GSE45744 [12] GSE7694 [12] GSE21041 [6] 0.0 GSE16679 [8] GSE7050 [18]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 349.71 352.53 357.44 357.92 358.57 359.80 361.86 365.23 367.43 367.63 369.18 373.11 375.18 375.69 379.69 380.04 380.93 386.40 389.20 389.81 392.80 394.36 395.18 399.13 403.51 405.21 416.82 434.19 434.56 441.10 454.39 457.26 1.0 Notes Gadd45gip1 Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page2 Aurkaip1 Tomm22 Mrps18b Mrps18c Timm23 Timm10 Ndufaf2 Ndufaf6 Exosc4 Mrps34 Mrps23 Mrps26 Mrps33 H2-Ke2 Ndufb7 Ndufb5 Ndufb6 Uqcr11 Ndufa5 Ndufa8 Ndufs7 Dctpp1 Ndufs8 Psmb5 Psmb6 Mrpl41 Mrpl27 Gtf2h5 Atp5f1 C1qbp Polr2c Atp5j2 Hspe1 Znhit3 Naa38 Mrp63 Polr2f Yars2 Emg1 Sf3b5 Emc6 Nhp2 Sdhd Coq7 Phb2 Cyc1 Mtx1 Fxn Uxt 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 296.88 297.01 297.21 298.05 298.11 298.97 299.87 300.12 300.81 301.66 301.85 307.59 308.09 308.20 309.37 309.55 310.53 310.71 311.43 312.58 314.48 316.33 316.42 317.43 317.45 317.75 317.77 317.78 318.39 322.47 323.40 324.11 325.50 328.92 329.12 333.81 334.00 334.50 334.89 335.17 337.98 338.84 341.95 342.04 343.55 343.75 345.56 345.78 349.18 349.47 1.0 Notes Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page3 BC003965 Rps19bp1 Samm50 Ndufb10 Dnajc15 Psmd12 Timm22 Uqcrfs1 Ndufaf5 N6amt2 Mrps30 Mrps31 Ndufb3 Aarsd1 Malsu1 Ndufa9 Ndufc1 Ndufs3 Pmpcb Psmg3 Psmb4 Psmc4 Mrpl50 Mrpl44 Mrpl45 Polr1d Cops3 Cops6 Nop10 Wdr18 Aimp2 Rpp30 Cops5 Uqcc2 Eif2b1 Atp5h Nudt1 Nudt2 Pfdn4 Banf1 Park7 Bola3 Phf5a Cisd1 Nme1 Lsm4 Glrx3 Pno1 Txn2 Adsl 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 260.15 260.33 260.34 260.56 260.79 260.84 261.87 262.12 262.17 262.40 262.74 263.58 263.83 264.02 264.61 265.48 266.06 266.26 267.11 267.46 268.83 270.17 271.71 272.18 272.34 273.82 274.05 274.92 276.00 276.08 276.60 277.05 278.75 278.95 279.38 281.10 282.54 284.25 286.81 287.63 289.97 290.04 291.52 291.92 292.85 293.29 294.32 295.13 295.74 296.53 1.0 Notes 9430016H08Rik 1810009A15Rik 1700021F05Rik 1110001J03Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page4 Ccdc124 Tomm20 Cox7a2 Tomm7 Mrps21 Mrps27 Mrps36 Dhrs7b Ndufb9 Atp5c1 Cmss1 Suclg1 Psmb2 Psmd6 Psma6 Psma2 Psmc3 Psma4 Psma7 Mrpl54 Rangrf Stra13 Nop16 Cdc34 Cox5a Jagn1 Snrpc Gins4 Polr2i Atp5k l7Rn6 Mrpl4 Lsm6 Lsm3 Apoo Ccnh Hint1 Pycrl Pop7 Ppa2 Eif3i Taf9 Lias Parl Itpa Fh1 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 223.50 223.56 226.54 226.82 227.34 228.10 229.28 229.75 230.12 231.30 232.05 233.29 233.46 233.84 234.39 234.66 236.15 236.50 237.73 238.05 238.58 239.13 240.75 242.82 244.10 244.88 245.50 246.84 247.56 247.67 247.92 248.32 248.81 249.12 249.38 250.84 251.05 251.25 251.40 251.76 252.66 253.87 255.91 256.36 257.59 257.70 257.89 257.90 258.84 259.98 1.0 Notes 1110004E09Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page5 Ebna1bp2 Tmem261 Tmem147 Fam195a Tomm40 Tamm41 Tmem11 Cdc123 Mrps24 Uqcrc2 Atp5g2 Ndufv1 Atp5a1 Alkbh7 Psmb7 Psmc2 Psmc1 Psma1 Mrpl10 Aimp1 Wdr74 Nedd8 Rpl7l1 Eif2b4 Eif2b3 Haus1 Lage3 Mettl5 Atp5d Hmbs Bccip Emc4 Bcs1l Siva1 Mdh2 Glrx5 Coq6 Coq3 Acn9 Coa7 Coa3 Elof1 Rpa3 Ecsit Hax1 Mtx2 Ubl4 Elp5 Pdf 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 197.01 197.54 197.84 197.94 198.55 199.02 200.57 200.86 201.80 202.43 202.50 202.84 203.17 203.36 203.58 203.89 204.20 204.27 204.33 204.97 205.17 205.95 206.16 206.47 207.46 207.60 207.71 208.29 208.65 209.47 209.55 210.18 211.31 211.54 212.80 212.90 213.32 213.68 214.33 215.35 215.47 217.25 217.54 218.10 219.32 221.03 221.07 221.08 222.12 223.31 1.0 Notes 2810428I15Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page6 Tmem126a Xrcc6bp1 Wbscr22 Snrnp25 Timm44 Ndufaf1 Chchd4 Csnk2b Exosc3 Prkrip1 Snrpd3 Arl6ip4 Uqcrc1 Ndufa4 Ndufs1 Nudt19 Ptpmt1 Ruvbl2 Rps27l Eef1e1 Psmc5 Magoh Ptrhd1 Polr2h Atpaf2 Cops4 Ahsa1 Eif1ad Tubg1 Prdx3 Pfdn1 Pomp Nme6 Ptcd2 Dus1l Trap1 Ptcd3 Nif3l1 Mrpl3 Gtf3a Atp5j Pdhx Tufm Ppil1 Mecr Imp4 Rfc4 Snf8 Mrrf 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 175.96 176.16 176.97 177.22 177.74 177.82 178.61 179.17 179.69 179.95 180.15 181.04 181.72 181.93 182.00 182.04 182.57 183.33 183.55 183.80 184.92 185.16 185.24 185.77 185.89 186.73 186.80 186.87 187.17 187.98 188.21 188.38 188.57 188.95 189.50 189.65 189.74 190.14 190.29 191.70 192.40 192.43 192.60 193.53 194.17 194.31 194.63 195.01 195.25 196.06 1.0 Notes Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page7 Tmem14c Commd1 Anapc15 Dnajc11 Ranbp1 Cox6b1 Exosc7 Exosc5 Apopt1 Ppp1r7 Pradc1 Psmd9 Mrpl23 Nubp1 Wdr55 Cdc26 Spag7 Cox19 Apex1 Slmo2 Eif2b5 Mrps9 Fkbp3 Thoc6 Snrpg Mipep Gmnn Dars2 Bnip1 Xrcc6 Pold2 Asf1a Bola2 Idh3g Taf12 Lsm2 Mbd3 Myg1 Pyurf Mkks Atp5l Dcps Kti12 Deb1 Ppa1 Cycs Tefm Ftsj1 Drg1 Eif3l 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 151.68 152.89 152.92 153.07 153.16 153.47 153.56 153.77 154.85 154.89 155.21 155.40 155.41 155.83 156.04 156.44 156.90 157.69 157.97 158.61 159.42 159.86 160.39 160.83 161.67 161.86 162.18 162.29 162.38 162.75 163.07 164.12 164.36 165.54 165.57 167.11 167.66 170.23 170.57 170.94 171.39 171.46 171.83 172.74 173.13 173.37 173.38 174.97 174.99 175.74 1.0 Notes 2010107E04Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page8 Rnaseh2c Rnaseh2a Commd2 Mmachc Poldip2 Immp1l Arpp19 Rnmtl1 Gm561 Higd1a Rpp25l Ptges2 Psmd4 Mrpl14 Cwc15 Polr2g Nup35 Hddc2 Ddx56 Ddx49 Ddx39 Ube2k Sec13 Tceb2 Snrpb Gtf2f2 Gmps Apool Gins1 Uchl5 Tsta3 Taf10 Txnl1 Lsm1 Strap Ngdn Crls1 Pdhb Eif3g Ppil3 Ece2 Tcp1 Nip7 Cct5 Bysl Dnlz Tbl3 Gart Cs 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 132.38 132.56 132.65 132.82 133.07 133.24 133.67 133.85 133.87 134.16 134.74 135.24 136.35 137.43 138.33 138.43 138.69 138.80 138.91 139.29 139.44 139.95 140.12 140.17 140.47 140.63 140.84 141.48 141.68 141.83 142.12 142.15 142.42 145.84 146.17 146.25 147.79 148.14 148.43 148.99 149.02 149.22 149.29 149.71 149.89 150.12 150.16 150.80 150.95 151.59 1.0 Notes A430005L14Rik 2700094K13Rik D17Wsu104e Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page9 Hsd17b10 Tmem242 Tmem97 Tmem70 Lamtor5 Timm21 Fam96a Ndufaf4 Prpf38a U2af1l4 Tbc1d7 Ndufa2 Ruvbl1 Usmg5 Pmpca Psmg4 Mthfd1 Pam16 Polr2d Prpf31 Med21 Atpaf1 Nubp2 Polr1c Polr1e Dtymk Asna1 Dynll2 Znhit1 Ssna1 Thoc3 Uqcrb Nubpl Srp19 Nol12 Gpn1 Dohh Guk1 Aven Lap3 Mtg1 Clpb Ufc1 Nxt1 Lyar Faf1 Nit2 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 112.99 113.11 113.12 113.36 114.85 114.94 115.36 115.65 115.70 116.05 116.31 116.79 116.79 117.72 118.78 119.18 119.25 120.35 120.58 120.63 120.87 121.21 121.92 122.39 122.69 123.07 123.39 123.58 123.74 124.00 125.72 126.16 126.20 126.24 126.45 126.62 127.45 127.71 127.71 128.48 128.50 128.98 129.01 129.75 130.06 130.13 130.25 130.41 130.59 131.13 1.0 Notes 0610009D07Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page10 Trnau1ap Zmynd19 Psmc3ip Rabggtb Snrnp40 Fastkd5 Oxnad1 Sac3d1 Mrps25 Spryd4 Ndufs2 Nudt21 Ndufa7 Rbm8a Atad3a Rsl1d1 Pdcd2l Cenpw Grwd1 Nup43 Cpsf3l Rpp40 Cks1b Cox6c Naa20 Rrp15 Prmt1 Atp5b Gins2 Abcf2 Aifm1 Mtfp1 Paics Snrpf Coq4 Psph Ddx1 Tfam Pes1 Mars Mto1 Drg2 Mzt2 Apip Nfu1 Abt1 Rfc3 Dlat Mif 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 92.69 93.16 93.28 93.28 93.72 94.75 94.96 94.97 95.43 95.52 96.04 96.05 96.97 97.32 97.92 98.52 98.80 98.90 99.90 100.01 100.40 100.43 101.08 101.45 102.29 102.61 103.06 103.45 103.60 103.91 104.36 104.80 105.14 105.23 106.48 107.49 107.52 107.88 109.53 110.15 110.51 110.53 110.57 110.61 111.03 111.27 111.79 111.83 112.60 112.72 1.0 Notes 2700060E02Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page11 Tmem208 Nsmce4a Timm17b Ccdc101 Snrnp27 Ndufb11 Trappc1 Dnajc24 Psmd14 Magohb Fam58b Fam96b Ndufaf7 Abhd11 Cacybp Tsen15 Chrac1 Atp5g3 Dnph1 Apitd1 Smdt1 Pebp1 Cd320 Pbdc1 Cdc37 Pdap1 Ubac1 Vdac2 Prmt5 Nme2 Cct6a Eif3m Sf3a3 Gps1 Plrg1 Ufm1 Sdhc Stip1 Noa1 Sod2 Pus1 Tipin Hat1 Cct7 Pstk Tpi1 Gfer Etfb Nifk 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 74.06 74.34 74.84 75.06 75.23 75.94 77.41 77.88 78.16 78.44 78.56 79.79 79.88 79.99 80.43 80.68 81.18 81.70 82.01 82.05 82.28 82.43 82.98 83.04 83.07 83.11 83.39 83.59 83.80 83.98 84.17 84.43 85.33 85.40 86.16 86.87 87.04 87.68 87.79 87.86 88.16 88.41 88.55 88.84 89.21 89.67 89.85 91.09 91.53 92.41 1.0 Notes 1110008F13Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page12 Rnaseh2b Mmadhc Babam1 Smim11 Hspbp1 Cops7a Exosc2 Metap2 Uqcr10 Akr1b3 Romo1 Tarbp2 Psmd5 Psmd8 Pgam5 Mrpl52 Adrm1 Med30 Hdhd2 Ppp5c Pdcd2 Actl6a Spc24 Vdac3 Echs1 Pa2g4 Gpr89 Tsen2 Mcts2 Gspt1 Rars2 Phpt1 Trmt5 Smu1 U2af1 Szrd1 Cse1l Tars2 Nop9 Eif3d Rpa2 Ldha Imp3 Dars Ifrd2 Rtca Srm Ppif Etfa 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 58.94 59.15 59.35 59.75 59.85 60.16 60.22 60.37 60.49 60.53 60.97 61.34 61.45 61.59 61.64 61.83 62.84 63.15 63.18 63.29 63.55 63.94 64.23 65.00 65.26 65.91 66.38 67.01 67.03 67.20 67.33 67.35 67.61 67.66 67.84 68.14 68.38 68.98 69.01 69.20 69.73 70.23 70.82 71.28 71.67 71.81 72.80 73.06 73.10 73.32 1.0 Notes 2700029M09Rik 9130401M01Rik 1110004F10Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page13 Tmem199 Ndufaf3 Gemin2 Mterfd2 Zc3hc1 Cbwd1 Gtf2h2 Osgep Endog Nup85 Nup88 Ncbp1 Cox18 Tfb1m Vdac1 Mcts1 Nudt9 Prdx2 Prim1 Pfdn2 Cnih4 Grhpr Galk1 Noc4l Ciao1 Mnd1 Gpn3 Gfm2 Nob1 Coq9 Nmt1 Nelfe Rae1 Lipt2 Qdpr Urod Orc3 Orc6 Rrp9 Mcat Cct2 Alg3 Rfc5 Eci1 Isy1 Tk1 Mpi 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 40.91 41.32 41.35 41.68 41.83 42.72 43.06 43.18 43.30 43.34 43.81 43.93 44.17 44.38 44.40 44.51 44.87 45.38 45.47 45.51 45.87 45.89 45.98 46.02 46.11 46.36 46.70 47.29 47.52 48.49 48.95 50.82 51.38 51.41 51.63 51.76 52.40 52.61 53.21 53.88 54.62 55.61 56.01 56.12 56.19 57.00 57.08 57.65 57.74 57.83 1.0 Notes 1110058L19Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page14 Tomm40l Cdk2ap1 Foxred1 Slc25a5 Ctnnbl1 Zswim7 Ncaph2 Tubb4b Pdzd11 Sdhaf1 Psmd3 Psmd1 Psmd2 Smim8 Dcaf13 Cox4i1 Bri3bp Lrpprc Dhodh Cirh1a Med27 Gtf2e2 Cenpv Shmt2 Rpp21 Nop56 Wdr83 Cox11 Usp39 Mcm7 Rrp36 Snrpe Adat2 Elac2 Taf11 Gpn2 Dpcd Coq5 Nans Eif3k Pcna Qtrt1 Cbr4 Rars Rfc2 Pgls Mri1 Ak2 Ddt 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 21.28 21.44 21.67 22.30 22.42 23.24 23.56 23.58 24.22 24.59 24.61 24.64 25.11 25.35 26.05 26.66 27.70 27.85 29.08 30.27 30.31 30.61 30.92 31.66 31.79 32.62 32.74 32.82 32.86 33.08 33.50 33.56 34.18 34.31 34.41 34.42 35.05 35.74 37.03 37.13 37.38 37.53 38.05 38.24 38.60 39.32 39.41 39.69 39.84 40.02 1.0 Notes 0610009B22Rik 2310009B15Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page15 Tmem223 Lamtor2 Trmt10c Chchd6 Bckdhb Yae1d1 Otud6b Snrpa1 Sdhaf2 Dnaaf2 Dmap1 Mrpl24 Med11 Polr3h Cenpp Diablo Nsun2 Cox10 Ap4s1 Nsfl1c Cdc45 Arfrp1 Poc1a Vps29 Zmat5 Lcmt1 Msto1 Ube2t Pycr2 Wipi2 Ttc27 Gcdh Tyw3 Bop1 Pop4 Yif1b Dkc1 Rcc1 Yif1a Tdp1 Ftsj2 Fen1 Hdgf Utp6 Cuta Cct4 Ppie Ltv1 0.0 1.0

GSE16874 [12] GSE8044 [6]

GSE51385 [8] Scale ofaveragePearsoncorrelations GSE44118 [6] GSE21299 [12] GSE7784 [12] GSE6623 [12] GSE12432 [15] GSE12982 [53] 0.2 GSE51213 [16] GSE32199 [6] GSE15610 [12] GSE7707 [18] GSE35785 [10] GSE18500 [35] GSE22774 [6] GSE27092 [6] GSE31208 [8] 0.4 GSE21996 [14] GSE35091 [11] GSE59202 [8] GSE4718 [6] GSE4238 [24] GSE38837 [6] GSE24628 [16] GSE29241 [6] GSE11572 [12] 0.6 GSE43825 [31] GSE49248 [12] GSE19286 [6] GSE13227 [6] GSE46724 [6] GSE48790 [8] GSE23006 [48] GSE39820 [22] GSE8836 [56] 0.8 GSE35160 [6] GSE14406 [54] GSE33199 [64] GSE41095 [6] Score 10.36 10.47 11.13 11.51 11.56 12.27 12.36 12.40 12.48 12.79 13.00 13.33 13.39 13.55 14.31 14.34 14.72 14.90 15.25 15.69 15.76 15.78 15.84 16.06 16.17 16.75 16.82 16.92 17.19 17.47 17.73 17.87 17.93 18.34 18.54 18.54 18.54 18.71 18.75 18.76 19.16 19.47 19.64 19.71 19.73 19.86 20.35 20.60 20.64 20.65 1.0 Notes 2700097O09Rik Symbol Num ofCEMGenes:18.Predicted774.SelectedDatasets:448.Strength:31.7 CEM 1,Geneset"[G]mitochondrialribosome",Page16 Pla2g12a Fam173b Anapc13 Rsl24d1 Nup133 Ndufa3 Acot13 Pet112 Nelfcd Wdr73 Ddx27 Lyrm4 Lonp1 Skp1a Mrps6 Fkbp2 Thoc5 Gnb1l Mcm5 Alyref Rrp12 Cfdp1 Riok2 Rpl14 Smn1 Pole3 Bzw2 Dhps Cdk1 Bag1 Cby1 Eif4e Mrs2 Hars Ssr2 Ppat Tsr2 Tars Aatf Dlst Spr 0.0 1.0

GSE16874 [12] GSE8044 [6]

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

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

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

0.423 Kernel fit Pairwise Correlations Normal fit

Density 0.212

0.000 CEM 1

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

Pre-normalization Quantiles

BCells_WildType_day0_REP1BCells_WildType_day0_REP2BCells_WildType_day0_REP3BCells_Transgenic_day0_REP1 BCells_Transgenic_day0_REP2(0.108316) BCells_Transgenic_day0_REP3(0.0899236) BCells_WildType_day2_REP1(0.0756627)BCells_WildType_day2_REP2 (0.0798958)BCells_WildType_day2_REP3 (0.0630991)BCells_Transgenic_day2_REP1 (0.0881539) BCells_Transgenic_day2_REP2(0.0873736) BCells_Transgenic_day2_REP3(0.0721411) (0.0972302) (0.0807079) (0.0538805)[ (0.103616)min ] [ medium ] [ max ] CEM 1 Mrpl40 1138.8 4657.5 5483.9 P ( S | Z, I ) = 1.00 Mrpl18 850.8 2803.8 3579.0 Mean Corr = 0.96891 Mrps22 549.8 2052.5 2677.0 Mrpl11 1363.7 2516.3 3181.2 Mrpl28 991.4 1974.2 2211.8 Mrpl13 1655.7 4926.6 5694.5 Mrpl34 614.3 1165.8 1601.7 Mrps12 1187.1 2671.0 2811.4 Mrpl47 844.9 3089.5 3422.9 Mrpl20 926.4 3524.4 4026.6 Mrpl39 662.9 1439.1 1655.6 Mrpl43 1624.1 2827.6 3149.7 Mrpl37 691.3 1485.9 1866.8 Mrpl48 851.1 1695.0 2189.5 Mrpl49 322.5 758.5 946.4 Mrpl32 1802.1 3809.4 4142.8 Dap3 1678.9 3034.2 3606.5 Mrpl9 795.2 1859.9 2330.4 Mrpl12 1107.2 4411.6 5738.2 Mrpl46 907.3 2808.0 3295.7 Timm13 1891.7 4827.6 5583.8 Mrpl22 1156.2 4381.1 4755.4 Mrpl42 1274.2 5032.6 6107.6 CEM 1 + Mrps28 678.1 2139.6 2594.0 Top 10 Genes Grpel1 1431.5 3573.6 4200.6 Chchd1 1996.5 5858.8 6476.4 Mrps7 998.3 2984.2 3757.0 Mrps35 1055.2 1839.8 2235.5

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE8044" 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=GSE8044 Status: Public on Jun 08 2007 Title: Brown versus white tissue adipose selective genes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17618855 Summary & Design: Summary: The aim of this study was to identify genes expressed selectively in brown adipose tissue as compared to white adipose tissue from the same animals. This analysis provides a gene set that is brown and white adipose selective.

Keywords: tissue comparison from mice

Overall design: Interscapular brown adipose tissue and epididymal white adipose tissue was carefully dissected from 3 male C57Bl/6 mice. These samples were profiled independently using Affymetrix mouse 430_2 gene arrays, representing 3 biological replicates for each brown and white adipose tissues.

Background corr dist: KL-Divergence = 0.0069, L1-Distance = 0.0138, L2-Distance = 0.0002, Normal std = 0.9444

0.428 Kernel fit Pairwise Correlations Normal fit

Density 0.214

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

White adiposeWhite adipose adultWhite rep1 adipose adultBrown (0.155129) rep2 adiposeadultBrown (0.179639) rep3 adiposeBrown adult (0.169014) rep1 adipose adult (0.168323) rep2 adult (0.175416) rep3 (0.15248)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 2118.2 2867.2 3367.6 P ( S | Z, I ) = 1.00 Mrpl18 515.8 2171.0 2322.8 Mean Corr = 0.94794 Mrps22 673.3 2063.0 2185.9 Mrpl11 2485.7 3738.5 3935.7 Mrpl28 658.7 1888.0 1957.5 Mrpl13 1479.4 3529.2 3988.6 Mrpl34 1564.6 9412.9 9906.8 Mrps12 943.1 1980.3 1985.3 Mrpl47 692.8 2440.2 2819.1 Mrpl20 2619.7 3904.5 4469.5 Mrpl39 676.4 3685.1 3977.1 Mrpl43 1501.5 2420.2 2512.6 Mrpl37 1020.9 2026.2 2186.3 Mrpl48 741.0 2187.6 2293.2 Mrpl49 585.6 1050.0 1064.5 Mrpl32 1238.1 2845.5 2931.9 Dap3 2104.8 2362.2 2652.6 Mrpl9 936.8 3037.7 3543.3 Mrpl12 758.1 3854.3 4398.0 Mrpl46 499.7 1827.4 1931.3 Timm13 2624.0 6282.6 6534.3 Mrpl22 1116.5 2837.7 2950.3 Mrpl42 2745.1 10298.1 11225.4 CEM 1 + Mrps28 742.7 2052.8 2391.6 Top 10 Genes Grpel1 2977.5 9207.7 9660.4 Chchd1 2181.3 4945.6 5059.2 Mrps7 736.2 1794.2 1990.3 Mrps35 597.1 3038.6 3513.0

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE38031" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38031 Status: Public on Jul 25 2013 Title: DNA damage-induced differentiation of NSC Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24052948 Summary & Design: Summary: Murine ES-derived neural stem cells (NSC) were not irradiated (ctrl) or irradiated with 10Gy and cultured for 7 days (irr).

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

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

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

0.456 Kernel fit Pairwise Correlations Normal fit

Density 0.228

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl_rep1ctrl_rep2 (0.130028)ctrl_rep3 (0.0634697)ctrl_rep4 (0.21068)irr_rep1 (0.110868)irr_rep2 (0.157888)irr_rep3 (0.13969)irr_rep4 (0.0683341) (0.119042) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1754.0 2871.9 3255.5 P ( S | Z, I ) = 1.00 Mrpl18 2526.7 4548.3 5184.1 Mean Corr = 0.94662 Mrps22 1578.8 2187.5 2380.5 Mrpl11 1812.7 2864.2 3354.6 Mrpl28 2409.1 3719.5 4132.6 Mrpl13 3304.1 4222.6 4627.8 Mrpl34 2069.0 3493.2 3792.2 Mrps12 1997.1 3290.9 3568.3 Mrpl47 839.2 1251.6 1410.2 Mrpl20 3476.1 4388.0 5054.4 Mrpl39 2019.8 2653.0 2952.9 Mrpl43 3155.7 3570.2 3895.5 Mrpl37 647.4 1120.3 1290.1 Mrpl48 2171.4 2733.4 3104.0 Mrpl49 1156.0 1451.5 1531.6 Mrpl32 2853.4 3323.8 3875.5 Dap3 3434.5 4952.0 5146.7 Mrpl9 1229.8 1437.8 1612.7 Mrpl12 2377.3 5251.9 5750.9 Mrpl46 986.9 1341.3 1496.6 Timm13 5304.9 7898.0 8167.6 Mrpl22 2822.3 4465.3 5017.6 Mrpl42 3487.4 5442.2 5913.8 CEM 1 + Mrps28 1853.5 3367.8 3874.3 Top 10 Genes Grpel1 2754.3 3209.3 3662.8 Chchd1 4263.5 6777.0 7670.6 Mrps7 2064.2 3854.3 4090.1 Mrps35 961.5 1737.7 1963.8

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE14004" 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=GSE14004 Status: Public on Jan 14 2009 Title: Re-expression of GATA2 Cooperates with PPAR gamma Depletion to Revert the Adipocyte Phenotype Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19136559 Summary & Design: Summary: The nuclear receptor PPAR gamma is required for adipocyte differentiation, but its role in mature adipocytes is less clear. Here we report that knockdown of PPAR gamma expression in 3T3-L1 adipocytes returned the expression of most adipocyte genes towards preadipocyte levels. Consistently, down regulated but not up regulated genes showed strong enrichment of PPAR gamma binding. Surprisingly, not all adipocyte genes were reversed and the adipocyte morphology was maintained for an extended period after PPAR gamma depletion. To explain this, we focused on transcriptional regulators whose adipogenic regulation was not reversed upon PPAR gamma depletion. We identified GATA2, a transcription factor whose down-regulation early in adipogenesis is required for preadipocyte differentiation, remaining low after PPAR gamma knockdown. Forced expression of GATA2 in mature adipocytes complemented PPAR gamma depletion and impaired adipocyte functionality with a more preadipocyte- like gene expression profile. Ectopic expression of GATA2 in adipose tissue in vivo had similar effect on adipogenic gene expression. These results suggest that PPAR gamma-independent down regulation of GATA2 prevents reversion of mature adipocytes after PPAR gamma depletion.

Keywords: cell type comparison, Gata2, PPAR gamma, adipocyte, preadipocytes, differentiation

Overall design: Technical replicates: PPAR gamma siRNA 1, PPAR gamma siRNA 2, PPAR gamma siRNA 3

Background corr dist: KL-Divergence = 0.0294, L1-Distance = 0.0232, L2-Distance = 0.0006, Normal std = 0.6966

0.586 Kernel fit Pairwise Correlations Normal fit

Density 0.293

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

preadipocytepreadipocyte rep1preadipocyte (0.100606) rep2control (0.116129) rep3 controlsiRNA (0.1242) rep1controlsiRNA (0.209406) rep2PPARsiRNA (0.169549) gamma rep3PPAR (0.211211) gammasiRNAPPAR rep1gammasiRNA (0.0207109) rep2siRNA (0.0227161) rep3 (0.0254725)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1713.2 2267.2 3359.2 P ( S | Z, I ) = 1.00 Mrpl18 1658.3 1973.3 5143.2 Mean Corr = 0.93498 Mrps22 1103.6 1524.4 2832.5 Mrpl11 2494.3 3652.9 4034.8 Mrpl28 2110.6 3136.6 4567.8 Mrpl13 5638.9 6194.5 7682.0 Mrpl34 1141.8 1823.5 4558.0 Mrps12 1095.8 1597.0 2778.8 Mrpl47 817.9 958.3 1891.4 Mrpl20 1608.6 2417.6 6791.4 Mrpl39 1379.0 2371.4 3749.6 Mrpl43 2590.7 3644.6 5370.8 Mrpl37 614.4 846.5 1688.0 Mrpl48 996.5 1624.6 2825.2 Mrpl49 1088.8 1367.0 2165.4 Mrpl32 2206.2 2606.6 4566.1 Dap3 3356.2 4717.5 7362.2 Mrpl9 1393.0 1594.0 3604.5 Mrpl12 1201.5 1561.7 6131.0 Mrpl46 650.4 934.2 2718.9 Timm13 3532.7 4199.4 7179.6 Mrpl22 1919.3 2990.1 4984.8 Mrpl42 3170.6 4539.2 7459.7 CEM 1 + Mrps28 756.4 1182.6 2304.6 Top 10 Genes Grpel1 2097.0 3608.9 9080.6 Chchd1 2339.2 2789.4 3658.5 Mrps7 1419.7 2051.5 3348.4 Mrps35 1622.2 2493.0 5999.9

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE18907" 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=GSE18907 Status: Public on Mar 19 2011 Title: Gene expression profiling of pregnant and virgin mouse lung and liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21646719 Summary & Design: Summary: Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.

Overall design: Three chips were done per organ (liver/lung) and per condition (virgin/pregnant), with equal amounts of RNA from two mice pooled for one chip.

Background corr dist: KL-Divergence = 0.0162, L1-Distance = 0.0642, L2-Distance = 0.0067, Normal std = 0.9265

0.431 Kernel fit Pairwise Correlations Normal fit

Density 0.215

0.000 CEM 1

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

Pre-normalization Quantiles

Lung VirginLung 1 Virgin (0.0526029)Lung 2 Virgin (0.0589816)Lung 3 Pregnant (0.0930597)Lung Pregnant Lung1 (0.0879586) Pregnant Liver2 (0.0709883) Virgin Liver3 (0.093019) 1 Virgin (0.0806656)Liver 2 Virgin (0.140128)Liver 3 Pregnant (0.117821)Liver Pregnant Liver1 (0.058622) Pregnant 2 (0.0523907) 3 (0.0937635) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1336.6 2053.0 2838.3 P ( S | Z, I ) = 1.00 Mrpl18 1075.8 1883.9 2458.3 Mean Corr = 0.91259 Mrps22 630.6 2087.1 2705.9 Mrpl11 1002.5 1840.1 2419.8 Mrpl28 1161.8 3077.9 3675.4 Mrpl13 2990.2 5050.4 6109.6 Mrpl34 1032.4 2009.7 2383.8 Mrps12 1361.2 3357.8 4007.3 Mrpl47 1001.4 1576.1 2267.5 Mrpl20 1763.8 2385.4 3175.1 Mrpl39 1108.1 2207.3 3045.4 Mrpl43 1907.0 3453.9 4124.7 Mrpl37 464.9 885.6 1031.5 Mrpl48 1312.6 1839.3 2440.0 Mrpl49 609.4 1121.4 1395.4 Mrpl32 1852.8 2503.4 2917.3 Dap3 1697.2 2681.4 3319.4 Mrpl9 660.2 772.9 1226.7 Mrpl12 1409.4 5714.6 7526.3 Mrpl46 933.9 2329.4 2620.6 Timm13 3435.9 7874.0 9051.3 Mrpl22 1548.9 3686.7 4489.2 Mrpl42 2774.1 4215.2 5965.9 CEM 1 + Mrps28 1359.4 3069.5 3656.8 Top 10 Genes Grpel1 2047.2 6077.8 8145.2 Chchd1 2024.6 3134.8 3776.5 Mrps7 1024.9 3209.4 3834.3 Mrps35 661.2 1265.1 1674.9

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE48397" 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=GSE48397 Status: Public on Jul 10 2013 Title: Expression data from (mouse) normal lung fibroblasts and carcinoma-associated fibroblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22962265 Summary & Design: Summary: Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed, including gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs to seek for differentially-expressed secreted proteins.

Gene expression microarrays were used to identify transcriptomic changes between NFs and CAFs that may contribute to their different tumor-enhancing capacity.

Overall design: NFs and CAFs were grown in vitro for RNA extraction and hybridization on mouse 430_2 Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0594, L1-Distance = 0.0233, L2-Distance = 0.0009, Normal std = 0.5290

0.754 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

lung fibroblasts,lung fibroblasts,lung biological fibroblasts,lung biological fibroblasts,replicatelung biological fibroblasts,replicate 1carcinoma-asssociated (0.111845) biological replicate 2carcinoma-asssociated (0.147962) biological replicate 3carcinoma-asssociated (0.349763) replicate 4carcinoma-asssociated (0.230346)fibroblasts, 5carcinoma-asssociated (0.0150397)fibroblasts, biological fibroblasts, biological fibroblasts,replicate biological fibroblasts,replicate 1 (0.0311906) biological[ replicate min2 (0.017967) biological replicate 3 ](0.042939) replicate 4 (0.0395023) [5 (0.0134455)medium ] [ max ] CEM 1 Mrpl40 1161.9 1861.0 4949.1 P ( S | Z, I ) = 1.00 Mrpl18 1236.8 2168.1 4518.0 Mean Corr = 0.90592 Mrps22 776.3 1378.5 1992.5 Mrpl11 1610.5 1980.0 4307.3 Mrpl28 1511.9 1867.8 3227.6 Mrpl13 2533.9 3361.7 5256.4 Mrpl34 1556.9 2246.0 3114.9 Mrps12 986.6 1630.7 2785.4 Mrpl47 335.2 730.7 1165.9 Mrpl20 2574.3 3809.7 7461.0 Mrpl39 1077.9 1474.1 2036.1 Mrpl43 1795.8 2655.7 3058.7 Mrpl37 655.6 943.1 1567.2 Mrpl48 908.1 1259.6 2527.3 Mrpl49 685.7 926.7 1243.4 Mrpl32 1417.9 2128.7 3522.0 Dap3 3049.7 3580.6 4907.1 Mrpl9 688.5 909.9 1440.9 Mrpl12 1283.2 2643.5 8208.8 Mrpl46 627.8 862.8 1865.6 Timm13 4171.3 5514.8 10386.2 Mrpl22 1396.3 2140.5 4058.6 Mrpl42 1601.3 2544.0 3397.5 CEM 1 + Mrps28 993.4 1802.8 3861.5 Top 10 Genes Grpel1 1911.1 3311.0 4821.1 Chchd1 1679.7 2739.9 5622.8 Mrps7 1367.7 2129.0 3321.7 Mrps35 577.0 727.9 1830.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE21944" 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=GSE21944 Status: Public on Jul 02 2010 Title: The orphan nuclear hormone receptor ERRÎ² controls rod photoreceptor survival. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20534447 Summary & Design: Summary: Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERRÎ² as selectively expressed in rod photoreceptors. Overexpression of ERRÎ² induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRÎ² results in dysfunction and degeneration of rods, while inverse agonists of ERRÎ² trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRÎ². ERRÎ² coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRÎ² activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRÎ² is a critical regulator of rod photoreceptor function and survival, and suggest that ERRÎ² agonists may be useful in the treatment of certain retinal dystrophies.

Overall design: Affymetrix MOE430 microarrays were used to analyze the expression patterns of P21 mouse retinal tissues. The results were compared across the variable of Genotype, specifically ERRÎ² knockout versus wildtype.

Background corr dist: KL-Divergence = 0.0113, L1-Distance = 0.0143, L2-Distance = 0.0002, Normal std = 0.8473

0.475 Kernel fit Pairwise Correlations Normal fit

Density 0.238

0.000 CEM 1

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

Pre-normalization Quantiles

C57Bl/6C57Bl/6 P21, wildtypeC57Bl/6 P21, wildtype retina,C57Bl/6 x Sv129 1retina,C57Bl/6 x(0.0525956) P21, Sv129 ERRÎ²2C57Bl/6 x(0.0568935) P21, Sv129 -/-ERRÎ² P21, knockoutP21, wildtype -/-ERRÎ² knockout retina, -/- retina, knockout 1retina, (0.146613) 3[ (0.356161) min 2retina, (0.160025) 3 ](0.227712) [ medium ] [ max ] CEM 1 Mrpl40 361.7 1043.4 1296.9 P ( S | Z, I ) = 1.00 Mrpl18 473.3 1497.0 1607.8 Mean Corr = 0.90475 Mrps22 507.6 1099.3 1369.4 Mrpl11 990.8 1280.0 1712.2 Mrpl28 745.2 1322.1 1708.4 Mrpl13 932.3 2677.1 3052.5 Mrpl34 447.6 1106.2 1452.8 Mrps12 411.2 1405.3 1452.9 Mrpl47 461.2 788.7 1090.2 Mrpl20 702.7 1526.5 1907.8 Mrpl39 540.9 1137.3 1222.2 Mrpl43 661.4 2114.7 2633.7 Mrpl37 311.7 610.2 655.4 Mrpl48 852.5 1567.7 1970.6 Mrpl49 718.7 2417.3 2607.3 Mrpl32 695.6 1434.6 1698.6 Dap3 736.2 2172.2 2293.2 Mrpl9 665.6 1435.8 1739.7 Mrpl12 313.8 1110.5 1467.3 Mrpl46 582.9 918.6 1211.1 Timm13 854.8 2534.4 3290.6 Mrpl22 587.4 1517.7 1611.9 Mrpl42 693.4 2475.2 2605.7 CEM 1 + Mrps28 273.1 900.0 1175.0 Top 10 Genes Grpel1 929.2 1536.3 1733.7 Chchd1 1053.6 1925.2 2424.4 Mrps7 377.5 1010.2 1277.6 Mrps35 338.3 708.9 813.1

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE23833" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Overall design:

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

0.668 Kernel fit Pairwise Correlations Normal fit

Density 0.334

0.000 CEM 1

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

Pre-normalization Quantiles

2h_co._enriched12h_co._enriched22h_co._enriched3 (0.0729588)2h_co._total1 (0.0653077)2h_co._total2 (0.0666407) (0.0599004)2h_co._total3 (0.066646)2h_TGFbeta_enriched1 (0.185604)2h_TGFbeta_enriched22h_TGFbeta_enriched32h_TGFbeta_total1 (0.121423)2h_TGFbeta_total2 (0.113719)2h_TGFbeta_total3 (0.0909143) (0.0445931) (0.0395575) (0.0727358)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 760.4 2894.2 3524.5 P ( S | Z, I ) = 1.00 Mrpl18 846.7 1923.5 2522.1 Mean Corr = 0.90244 Mrps22 1088.7 1957.9 2279.8 Mrpl11 1232.4 3999.2 5353.0 Mrpl28 468.5 1973.0 2941.0 Mrpl13 719.2 3881.5 5667.0 Mrpl34 258.7 770.2 1147.3 Mrps12 597.1 1349.9 1847.4 Mrpl47 819.2 1193.0 1466.3 Mrpl20 529.6 1520.7 2108.8 Mrpl39 918.9 2264.6 2522.2 Mrpl43 1117.4 3021.8 4137.8 Mrpl37 196.8 477.5 552.4 Mrpl48 263.0 918.9 1140.3 Mrpl49 393.7 812.1 1013.3 Mrpl32 987.9 1672.6 2352.8 Dap3 869.5 3301.2 3715.4 Mrpl9 914.6 1537.1 1868.6 Mrpl12 642.5 2125.4 2684.6 Mrpl46 778.1 1422.3 2041.3 Timm13 686.6 3417.1 5229.0 Mrpl22 2176.2 3356.8 4727.9 Mrpl42 866.8 4071.9 5033.3 CEM 1 + Mrps28 389.1 1646.6 2015.6 Top 10 Genes Grpel1 1475.4 4556.4 5294.0 Chchd1 715.0 2518.3 4128.3 Mrps7 595.2 1699.5 2381.4 Mrps35 301.0 758.8 1065.8

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE20954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20954 Status: Public on Aug 17 2010 Title: mRNA expression profile in mouse lung development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20520778 Summary & Design: Summary: We performed miRNA and mRNA profiling over a 7-point time course, encompassing all recognized stages of lung development and explore dynamically regulated miRNAs and potential miRNA-mRNA interaction networks specific to mouse lung development

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

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

0.551 Kernel fit Pairwise Correlations Normal fit

Density 0.275

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse lung-embryoMouse lung-embryoMouse day lung-embryoMouse 12-rep1 day lung-embryoMouse 12-rep2 (0.0920106) day lung-embryoMouse 14-rep1 (0.14377) day lung-embryoMouse 14-rep2 (0.102996) day lung-embryoMouse 16-rep1 (0.0793849) day lung-embryoMouse 16-rep2 (0.0666817) day lung-postnatalMouse 18-rep1 (0.0585124) day lung-postnatalMouse 18-rep2 (0.0519392) lung-postnatalMouseday (0.0315564) 2-rep1 lung-postnatalMouseday (0.0341782)2-rep2 lung-postnatalMouseday (0.0454183)10-rep1 lung-postnatalday 10-rep2 (0.0593661) day 30-rep1 (0.0631845) day 30-rep2 (0.080186)[ min (0.0908162) ] [ medium ] [ max ] CEM 1 Mrpl40 951.0 1165.6 2140.8 P ( S | Z, I ) = 1.00 Mrpl18 1029.8 1362.0 3165.7 Mean Corr = 0.89972 Mrps22 475.1 763.0 2612.9 Mrpl11 1153.2 1506.4 3993.7 Mrpl28 1060.3 1350.8 2799.8 Mrpl13 2090.0 2820.9 6176.7 Mrpl34 719.8 1255.7 2931.5 Mrps12 743.0 888.0 1583.6 Mrpl47 528.8 731.1 1558.8 Mrpl20 1312.7 2121.1 3306.4 Mrpl39 619.5 963.8 1333.9 Mrpl43 1354.8 1767.8 2362.2 Mrpl37 617.9 737.3 1449.8 Mrpl48 1256.6 1534.0 2014.3 Mrpl49 759.5 1001.6 1614.1 Mrpl32 1145.1 2020.3 2518.8 Dap3 1445.4 1885.2 2819.9 Mrpl9 1115.2 1554.4 1887.8 Mrpl12 948.4 1179.5 3759.2 Mrpl46 581.9 696.8 1067.5 Timm13 1935.1 2721.6 3979.7 Mrpl22 1123.2 1549.3 3036.2 Mrpl42 1775.4 2214.0 4556.0 CEM 1 + Mrps28 720.7 925.9 1458.3 Top 10 Genes Grpel1 1329.8 1818.8 2424.6 Chchd1 1673.8 2199.8 4866.7 Mrps7 833.0 1027.4 2203.7 Mrps35 628.0 901.9 1609.8

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE51080" 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=GSE51080 Status: Public on Mar 01 2014 Title: Expression data from exposure of BAT and WAT at 6 and 28 degrees C Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We run microarrays from three per group Sv129 female mice, ten weeks old, which were maintained at 28´C (warm conditions) or 6´ C (cold stimulated) for ten days, while standard animal house temperature is 22 ´C.

After ten days, three types of tissue were collected: Brown Adipose Tissue (BAT), Mesenteric (visceral) White Adipose Tissue (MES) and Posterior Subcutaneous White Adipose Tissue (WAT)

Overall design: Different adipose tissue depots were taken for RNA extraction and hybridization on Affymetrix microarrays. We sought to determine the differences between white and brown adipose tissues at different temperatures

Background corr dist: KL-Divergence = 0.0623, L1-Distance = 0.0392, L2-Distance = 0.0026, Normal std = 0.5381

0.741 Kernel fit Pairwise Correlations Normal fit

Density 0.371

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

SubcutaneousMesenteric Brownwhite white adipose adiposeSubcutaneous adipose 6degBrown 6deg 28deg (S0510F001) (S0510F003) adiposeBrownwhite (S0510F002) adipose adiposeSubcutaneous 28deg (0.00863745) (0.121478) 28degSubcutaneous(S0510F005) 28deg(0.0467103) (S0510F004) Subcutaneous(S0510F006)white (0.104199) adipose Subcutaneouswhite (0.0372238) (0.0571708) adipose 6degBrownwhite (S0510F007) adipose adipose28degMesentericwhite adipose(S0510F008) 28degMesenteric 6deg (0.0120431) white (S0510F011)(S0510F009) 6degBrown adipose white(0.0231449) (S0510F010) adiposeMesenteric adipose 28deg(0.13213)(0.0274187)Mesenteric 6deg (S0510F012) (0.0111522) 28degwhite (S0510F014)Brown adipose(S0510F013) white adiposeMesenteric (0.0451782) adipose 6deg(0.14044) 28deg(0.0256742) (S0510F015) 6degwhite (S0510F017) (S0510F016) adipose (0.0453218) 6deg (0.0884516) (0.0439014)[ (S0510F018)min ] (0.0297243)[ medium ] [ max ] CEM 1 Mrpl40 1173.9 1525.9 2795.0 P ( S | Z, I ) = 1.00 Mrpl18 2986.2 3358.4 5614.7 Mean Corr = 0.89915 Mrps22 969.5 1663.4 3019.3 Mrpl11 2289.6 2699.4 4002.2 Mrpl28 1034.9 1340.7 2467.3 Mrpl13 3092.4 3738.5 5476.6 Mrpl34 688.2 1133.5 3461.4 Mrps12 894.8 1159.7 2195.4 Mrpl47 2605.9 3379.1 7104.1 Mrpl20 3111.3 4485.0 7526.8 Mrpl39 687.6 1241.1 2984.2 Mrpl43 1442.5 1867.1 3637.1 Mrpl37 554.4 886.1 2107.9 Mrpl48 2055.7 2476.0 3913.9 Mrpl49 878.9 1182.7 2123.1 Mrpl32 2789.6 3190.4 4206.9 Dap3 2732.0 3231.0 4433.0 Mrpl9 695.3 1084.0 2672.0 Mrpl12 2762.0 5159.9 7061.0 Mrpl46 770.7 1242.3 2870.7 Timm13 2026.8 3466.7 5534.5 Mrpl22 2286.9 2627.4 3727.1 Mrpl42 4846.0 5983.2 8556.5 CEM 1 + Mrps28 2525.4 3320.3 4818.8 Top 10 Genes Grpel1 3614.8 5814.3 8444.6 Chchd1 1419.4 1818.9 3177.7 Mrps7 1359.3 2076.8 3333.0 Mrps35 1153.8 1892.6 4366.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE13302" 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=GSE13302 Status: Public on May 12 2009 Title: Gene expression profiling in the lung and liver of Perfluorooctane sulfonate (PFOS) exposed mouse fetuses Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19429403 Summary & Design: Summary: Most of the transcriptional changes induced by PFOS in the fetal mouse liver and lung were related to activation of PPARalpha. When compared to the transcript profiles induced by PFOA (Pubmed ID 17681415), few remarkable differences were found other than up-regulation of Cyp3a genes. Because PFOS and PFOA have been shown to differ in their mode of action in the murine neonate, these data suggest that changes related to PFOS-induced neonatal toxicity may not be evident in the fetal transcriptome at term.

Overall design: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 5, or 10 mg/kg/day PFOS in 0.5% Tween 20. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for each treatment group using Affymetrix mouse 430_2 microarrays.

Background corr dist: KL-Divergence = 0.0214, L1-Distance = 0.0694, L2-Distance = 0.0077, Normal std = 0.8465

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

0mg/kg/day0mg/kg/day PFOS,0mg/kg/day lungPFOS,0mg/kg/day rep1 liverPFOS, (0.046677)0mg/kg/day rep1 lungPFOS, (0.0329715)0mg/kg/day rep2 liverPFOS, (0.0224052)0mg/kg/day rep2 lungPFOS, (0.032943)0mg/kg/day rep3 liverPFOS, (0.0436824)0mg/kg/day rep3 lungPFOS, (0.0284981)0mg/kg/day rep4 liverPFOS, (0.0294496)5mg/kg/day rep4 lungPFOS, (0.0456281)5mg/kg/day rep5 liverPFOS, (0.0332223)5mg/kg/day rep5 lungPFOS, (0.0413448)5mg/kg/day rep1 liverPFOS, (0.026206)5mg/kg/day rep1 lungPFOS, (0.0238191)5mg/kg/day rep2 liverPFOS, (0.0339909)5mg/kg/day rep2 lungPFOS, (0.0311617)5mg/kg/day rep3 liverPFOS, (0.0384963)5mg/kg/day rep3 lungPFOS, (0.0376431)5mg/kg/day rep4 liverPFOS, (0.0242683)10mg/kg/day rep4 lungPFOS, (0.0504065)10mg/kg/day rep5 liver PFOS, (0.0335348)10mg/kg/day rep5 lungPFOS, (0.0371637)10mg/kg/day rep1 liverPFOS, 10mg/kg/day(0.0320028) rep1 lungPFOS, 10mg/kg/day(0.029555) rep2 liverPFOS, 10mg/kg/day(0.0224449) rep2 lungPFOS, 10mg/kg/day(0.0325779) rep3 liverPFOS, 10mg/kg/day(0.0267606) rep3 lungPFOS, 10mg/kg/day(0.0363776) rep4 liverPFOS, (0.0450561) rep4 lungPFOS, (0.0318656) rep5 liver (0.0314127) rep5 [(0.0184346) min ] [ medium ] [ max ] CEM 1 Mrpl40 822.2 1693.4 2175.6 P ( S | Z, I ) = 1.00 Mrpl18 733.2 1161.2 1656.5 Mean Corr = 0.89197 Mrps22 551.9 1530.6 1898.4 Mrpl11 816.2 1196.6 1442.6 Mrpl28 950.1 1730.5 2003.0 Mrpl13 1925.0 3259.2 3755.9 Mrpl34 884.6 1334.4 1612.3 Mrps12 871.1 1621.4 1942.6 Mrpl47 551.9 1027.6 1376.3 Mrpl20 928.1 1570.8 1967.2 Mrpl39 841.5 1273.0 1626.2 Mrpl43 1507.5 1958.6 2318.2 Mrpl37 532.9 770.4 894.9 Mrpl48 957.9 1204.2 1542.0 Mrpl49 542.7 826.6 1087.2 Mrpl32 1422.9 1709.1 1969.0 Dap3 1614.2 2452.7 3040.0 Mrpl9 892.2 1115.7 1350.7 Mrpl12 934.9 2904.8 3662.9 Mrpl46 597.7 1234.6 1527.5 Timm13 1846.4 3492.8 4011.7 Mrpl22 803.9 1567.3 2013.6 Mrpl42 1375.0 2906.1 3679.3 CEM 1 + Mrps28 685.4 2017.4 2685.3 Top 10 Genes Grpel1 1248.7 3435.5 4466.9 Chchd1 1563.5 2151.6 2744.2 Mrps7 714.9 1490.4 1912.0 Mrps35 828.6 1239.6 1637.6

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE46496" 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=GSE46496 Status: Public on Jun 07 2013 Title: Atrial Identity Is Determined by A COUP-TFII Regulatory Network (RNA) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23725765 Summary & Design: Summary: Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.

We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria.

Overall design: We extracted RNA from mutant right atria, control right atria and control ventricles from 2 months old adult mice, followed by gene expression profiling using Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0268, L1-Distance = 0.0394, L2-Distance = 0.0028, Normal std = 0.6869

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

Atria, Mutant,Atria, Mutant, biologicalAtria, Mutant, biologicalAtria, replicate Control, biologicalAtria, replicate 1 (0.0349988)Control, biologicalAtria, replicate 2 (0.0373579)Control, biologicalVentricles, replicate 3 (0.0395317) biologicalVentricles, replicate Control, 1 (0.11114)Ventricles, replicate Control, 2biological (0.0790951) Control, 3biological (0.0957818) replicate biological replicate 1 (0.255423) [replicate 2min (0.15288) 3 (0.193792)] [ medium ] [ max ] CEM 1 Mrpl40 1064.0 1172.8 1606.0 P ( S | Z, I ) = 1.00 Mrpl18 2620.1 2903.4 4457.0 Mean Corr = 0.87935 Mrps22 1116.2 1230.8 2124.9 Mrpl11 2061.9 2179.7 2991.2 Mrpl28 1858.5 2692.2 4273.9 Mrpl13 3904.7 4737.2 6060.9 Mrpl34 1005.7 1469.1 2101.5 Mrps12 2156.5 2695.7 3299.8 Mrpl47 1541.2 2181.4 4012.4 Mrpl20 1573.2 1895.7 2543.2 Mrpl39 2074.5 2193.5 3590.9 Mrpl43 1460.5 2117.9 2748.2 Mrpl37 359.2 418.9 835.8 Mrpl48 1810.8 2524.8 3107.6 Mrpl49 677.8 888.2 1173.8 Mrpl32 2159.1 2369.9 3421.7 Dap3 3149.9 3779.9 5237.6 Mrpl9 1603.3 1736.7 2794.6 Mrpl12 3738.4 4500.2 7196.5 Mrpl46 1375.6 1608.5 2914.7 Timm13 2090.5 2645.8 3302.8 Mrpl22 2097.5 2396.8 3748.6 Mrpl42 12288.8 13776.6 18856.7 CEM 1 + Mrps28 3243.7 4085.6 5258.0 Top 10 Genes Grpel1 3193.6 3511.8 6638.5 Chchd1 4063.4 4779.9 5669.0 Mrps7 1066.5 1354.8 2040.8 Mrps35 1854.0 2106.7 3902.9

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE56135" 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=GSE56135 Status: Public on Jun 15 2014 Title: Intrinsic differences between oral and skin keratinocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The morphology and the behavior of skin and oral tissue keratinocytes are different. One significant dissimilarity between the two sites is the response to injury. Oral and skin keratinocytes have intrinsic differences in the response to injury and such differences are reflected in gene expression profiles.

We used microarrays to investigate differences in global gene expression patterns between baseline skin and oral epithelium sheets without their underlying connective tissue.

Overall design: Paired skin and oral epithelium was separated from the dermis for RNA extraction and hybridization on Affymetrix microarrays. Skin epidermal tissues were obtained from the tail of mice and oral epidermal tissues were obtained from the hard palate. Enzymatically isolated epithelium was used for analysis.

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0140, L2-Distance = 0.0002, Normal std = 0.7354

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

m1 mousem2 skinmousem4 epithelium skinmousem5 epithelium skinmouse 1 (0.0908585)p1 epithelium mouseskin 2 (0.116738)p2 epithelium palatalmouse 4 (0.120573)p4 epitheliumpalatalmouse 5 (0.153854)p5 epitheliumpalatalmouse 1 (0.132121) epitheliumpalatal 2 (0.189131) epithelium 4 (0.0941189) 5[ (0.102607) min ] [ medium ] [ max ] CEM 1 Mrpl40 1315.0 1967.4 2133.9 P ( S | Z, I ) = 1.00 Mrpl18 1562.6 1876.4 2307.9 Mean Corr = 0.86260 Mrps22 1077.1 1302.4 1474.4 Mrpl11 1229.6 1430.8 1828.8 Mrpl28 1328.7 1694.7 1764.0 Mrpl13 2550.0 2850.5 3222.3 Mrpl34 748.5 1062.5 1292.4 Mrps12 803.2 1016.1 1048.7 Mrpl47 766.8 1024.2 1069.8 Mrpl20 2250.8 2682.3 2963.1 Mrpl39 919.2 1271.5 1555.2 Mrpl43 1875.3 2290.7 2510.9 Mrpl37 613.0 974.3 1095.5 Mrpl48 1648.8 2793.5 3079.8 Mrpl49 697.5 1071.4 1183.3 Mrpl32 1934.3 2314.8 2793.6 Dap3 1876.6 2350.1 2601.2 Mrpl9 1233.2 1452.0 1519.5 Mrpl12 1969.2 2473.7 2623.7 Mrpl46 1103.4 1764.9 1863.6 Timm13 3683.5 4314.5 5601.0 Mrpl22 1328.0 1702.1 1824.1 Mrpl42 3261.8 4417.7 4896.1 CEM 1 + Mrps28 1476.1 1700.9 1911.1 Top 10 Genes Grpel1 2781.3 3124.6 3527.2 Chchd1 2073.7 2783.9 2894.8 Mrps7 1240.8 1493.6 1992.6 Mrps35 986.5 1470.0 1482.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE46606" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 30 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46606 Status: Public on May 04 2013 Title: Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4 (expression) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23684984 Summary & Design: Summary: Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.

Overall design: Resting mature peripheral primary B cells were enriched from the spleens of Irf4+/+ or Irf4-inducible mice on the Irf4-/- background. We sought to compare gene expression profiles of wild type and Irf4 mutant B cells in response to mitogens that promote the differentiation of the B cells into plasma cells and cells that have undergone class switch recombination. Day 0 samples represent RNA analysis of unstimulated cells, whereas Day 1 and Day 3 samples represent analysis of stimulated cells in culture. For stimulation, cells were cultured with insect cell purified CD40L and IL-2/4/5 cytokines for the indicated days. In the case of doxycycline-mediated rescue of IRF4 expression, doxycycline was added at predefined low and high concentrations that yield low or high numbers of plasma cells, respectively (see Molecular Systems Biology 7:495). Each replicate represents analysis of B cells from an individual mouse. Of the three replicates in each group, two were performed in parallel and one was performed at a different time. All cells were lysed using Trizol and total RNA was purified according to manufacturer's suggestions. The high quality of the RNA was confirmed using Agilent Bioanalyzer 2100 system. 250ng of RNA was then processed into biotinylated cRNA according to standard procedures and used to hybridize to Affymetrix 430 2.0 arrays. Signal intensities were normalized using the D-Chip algorithm (PM-only model) and the output was used to quantify differential gene expression between groups.

Background corr dist: KL-Divergence = 0.0934, L1-Distance = 0.0402, L2-Distance = 0.0024, Normal std = 0.4712

0.897 Kernel fit Pairwise Correlations Normal fit

Density 0.448

0.000 CEM 1

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

Pre-normalization Quantiles

4KO-hiD14KO-hiD3 rep1 4KO-loD1(0.0431473) rep1 4KO-loD3(0.0137504) rep1 4KO-zeroD0(0.0283612) rep1 4KO-zeroD1(0.0114961) rep14KO-zeroD3 (0.0944145) rep14KO-hiD1 (0.0243074) rep14KO-hiD3 rep2(0.00859461) 4KO-loD1(0.035385) rep2 4KO-loD3(0.0086898) rep2 4KO-zeroD0(0.0294798) rep2 4KO-zeroD1(0.0104815) rep24KO-zeroD3 (0.0991302) rep24KO-hiD1 (0.026548) rep24KO-hiD3 rep3(0.0108348) 4KO-loD1(0.0318077) rep3 4KO-loD3(0.00691032) rep3 4KO-zeroD0(0.0223205) rep3 4KO-zeroD1(0.00704664) rep34KO-zeroD3 (0.0912966) rep3WT-D0 (0.0186971) rep3 rep1WT-D1 (0.0110888) (0.073195) rep1WT-D3 (0.032189) rep1WT-D0 (0.0112521) rep2WT-D1 (0.0684398) rep2WT-D3 (0.0359602) rep2WT-D0 (0.0135026) rep3WT-D1 (0.0850819) rep3WT-D3 (0.0348824) rep3 (0.0117088) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 691.3 1932.2 2569.9 P ( S | Z, I ) = 1.00 Mrpl18 1129.9 3350.8 4354.9 Mean Corr = 0.85272 Mrps22 452.4 1649.4 2490.2 Mrpl11 1179.8 2015.4 3294.5 Mrpl28 884.6 1799.8 2258.8 Mrpl13 1269.8 3536.9 4244.1 Mrpl34 779.6 1428.5 1809.0 Mrps12 837.8 2006.3 2396.0 Mrpl47 741.7 2063.8 3013.1 Mrpl20 791.0 2215.0 3096.5 Mrpl39 887.5 1710.7 2151.6 Mrpl43 1315.0 2482.8 2915.4 Mrpl37 1076.7 1830.8 2279.8 Mrpl48 618.6 1255.6 1690.4 Mrpl49 433.0 1517.4 1726.5 Mrpl32 2432.2 3089.6 3632.6 Dap3 1782.3 2510.7 2714.5 Mrpl9 1014.0 2045.4 2332.2 Mrpl12 1068.9 2804.1 5217.8 Mrpl46 720.2 1423.7 1963.0 Timm13 2137.5 4092.2 5349.3 Mrpl22 1060.5 2359.5 2946.9 Mrpl42 1673.9 3325.2 4517.3 CEM 1 + Mrps28 580.4 1715.3 2785.1 Top 10 Genes Grpel1 1527.5 3073.2 3820.6 Chchd1 2133.0 4077.3 4783.6 Mrps7 901.8 2364.3 2969.7 Mrps35 657.2 1257.0 1493.5

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE41942" 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=GSE41942 Status: Public on Nov 01 2012 Title: Overexpression of miR-9 and miR-9* in 32D cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Overexpression of miR-9 and miR-9* in 32D cells, cells grown under IL-3 conditions and miR-9 and miR-9* were introduced with retroviral vectors containing about ~150 bp up and downstream of mmu-mir-9-2.

Expression was determined to find out the effect of miR-9/9*overexpression on the transcriptome level compared to introduction of empty vector control.

Overall design: Transcriptome levels were determined for 32D cells expressing miR-9 and miR-9* and empty vector control. Experiment performed in three independent replicates.

Background corr dist: KL-Divergence = 0.0444, L1-Distance = 0.0310, L2-Distance = 0.0014, Normal std = 0.6092

0.699 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

32D-EV 32D-EVIL-3 #1 32D-EV(0.0728698)IL-3 #2 32D-miR-9/9*(0.209907)IL-3 #3 32D-miR-9/9*(0.359486) IL-332D-miR-9/9* #1 (0.0517731)IL-3 #2 (0.137386)IL-3 #3 (0.168578)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1413.9 2057.1 3014.0 P ( S | Z, I ) = 1.00 Mrpl18 4456.6 5244.5 7665.3 Mean Corr = 0.83558 Mrps22 1615.8 1807.4 2549.9 Mrpl11 1939.3 2150.1 2908.7 Mrpl28 1546.1 1818.6 2098.3 Mrpl13 4525.7 5625.4 6839.0 Mrpl34 1584.9 2073.3 2713.0 Mrps12 2097.2 3130.5 3572.5 Mrpl47 2244.7 2758.5 3634.0 Mrpl20 1861.5 2313.9 3592.8 Mrpl39 1719.1 2079.1 2738.4 Mrpl43 2398.4 2555.5 2963.4 Mrpl37 457.0 644.0 714.7 Mrpl48 1289.4 1330.9 1746.5 Mrpl49 755.5 878.3 1198.7 Mrpl32 2840.6 3145.7 4156.4 Dap3 3745.6 4654.1 5223.8 Mrpl9 1685.5 1994.3 2139.4 Mrpl12 3925.1 5039.6 7149.9 Mrpl46 1379.3 1557.2 1918.0 Timm13 3084.5 3913.9 5098.5 Mrpl22 2187.2 2614.5 3269.0 Mrpl42 3265.2 4465.8 6409.9 CEM 1 + Mrps28 2166.6 2444.0 2710.5 Top 10 Genes Grpel1 2403.2 2926.7 3551.5 Chchd1 4542.5 4914.7 6418.7 Mrps7 1558.9 1816.6 2441.9 Mrps35 1222.7 1530.0 1784.6

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE30160" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.522 Kernel fit Pairwise Correlations Normal fit

Density 0.261

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild replicate typewild replicate 1 type (0.404362)knockin replicate 2 (0.0806951)knockin replicate 3 (0.0756996)knock replicate 1 (0.217084) in replicate 2 (0.111378) 3 (0.110781)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1795.8 2186.5 2766.3 P ( S | Z, I ) = 1.00 Mrpl18 2400.4 3643.5 4264.3 Mean Corr = 0.82038 Mrps22 1110.3 2323.8 3120.0 Mrpl11 2433.3 3468.0 3950.2 Mrpl28 2251.4 2431.9 2525.6 Mrpl13 2726.7 3775.3 4703.2 Mrpl34 1766.3 2369.4 2749.5 Mrps12 1984.3 2191.0 2680.7 Mrpl47 685.9 1305.3 1718.0 Mrpl20 2329.6 3493.7 4263.2 Mrpl39 1303.3 1551.1 1724.2 Mrpl43 2737.6 3193.2 3581.3 Mrpl37 915.8 1286.6 1633.8 Mrpl48 2744.3 3031.9 3255.1 Mrpl49 819.6 1117.6 1321.1 Mrpl32 2707.1 3814.3 4017.7 Dap3 2147.8 2487.2 2778.9 Mrpl9 1984.8 2458.1 2488.0 Mrpl12 2474.1 5156.4 5912.2 Mrpl46 1111.4 1531.7 1840.3 Timm13 4617.3 6911.4 8059.9 Mrpl22 2162.1 2625.0 3060.3 Mrpl42 3356.5 5218.3 6212.0 CEM 1 + Mrps28 1193.6 2971.4 4001.5 Top 10 Genes Grpel1 2300.1 3244.8 3837.0 Chchd1 3517.5 4910.1 5700.2 Mrps7 1526.0 1872.2 2456.1 Mrps35 1045.5 1950.9 2104.5

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE11973" 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=GSE11973 Status: Public on Jul 31 2008 Title: Wild-type cultured neutrophils versus miR-223 null cultured neutrophils Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18668037 Summary & Design: Summary: This array analysis is to study the regulation of target messages expression in in vitro cultured murine neutrophils versus miR-223 null neutrophils. Culture media was SILAC-IMDM for MS analysis.

Overall design: Wild-type cultured neutrophils versus miR-223 null cultured neutrophils

Background corr dist: KL-Divergence = 0.0336, L1-Distance = 0.0241, L2-Distance = 0.0006, Normal std = 0.6585

0.624 Kernel fit Pairwise Correlations Normal fit

Density 0.312

0.000 CEM 1

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

Pre-normalization Quantiles

NeutrophilsNeutrophils culturedNeutrophils cultured fromNeutrophils miR-223 cultured fromNeutrophils miR-223 cultured null fromNeutrophils mouse miR-223 cultured null from bonemouse wild-type cultured null from marrow bonemouse wild-type frommouse marrow - boneRep wild-type bonemouse 1 [marrow -(0.273827) Repmin marrow bonemouse 2 -(0.0812938) Rep marrow] - bone Rep3 (0.165866) 1 marrow -(0.286804) Rep[ 2 -(0.0669851)medium Rep 3 (0.125224) ] [ max ] CEM 1 Mrpl40 1804.1 1852.6 2439.8 P ( S | Z, I ) = 1.00 Mrpl18 2517.9 3222.4 3740.5 Mean Corr = 0.81880 Mrps22 1253.8 1418.7 1650.6 Mrpl11 1032.4 1272.6 1794.4 Mrpl28 1465.0 1531.3 2151.6 Mrpl13 2490.3 2692.3 3575.0 Mrpl34 1188.8 1362.2 1517.8 Mrps12 1056.7 1217.3 1515.0 Mrpl47 584.7 653.2 790.7 Mrpl20 2806.9 3188.3 3723.4 Mrpl39 1140.1 1210.5 1441.3 Mrpl43 2145.2 2450.7 3066.4 Mrpl37 370.5 454.9 541.7 Mrpl48 1617.8 1783.7 2348.0 Mrpl49 716.9 848.0 942.9 Mrpl32 1903.9 2141.6 2885.9 Dap3 2392.6 2599.1 2969.5 Mrpl9 966.3 1050.5 1176.9 Mrpl12 891.1 1163.9 1659.8 Mrpl46 994.3 1144.1 1482.1 Timm13 2908.2 3335.7 4032.2 Mrpl22 1455.2 1692.0 2168.7 Mrpl42 2242.7 2571.4 3449.0 CEM 1 + Mrps28 944.3 1073.4 1295.5 Top 10 Genes Grpel1 2061.9 2298.9 2999.9 Chchd1 1899.8 2227.3 3252.5 Mrps7 829.2 922.0 1113.7 Mrps35 1108.0 1249.5 1708.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE19885" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.719 Kernel fit Pairwise Correlations Normal fit

Density 0.359

0.000 CEM 1

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

Pre-normalization Quantiles

RS_DMSO_rep1RS_DMSO_rep2RS_DMSO_rep3 (0.0327758)RS_Rap_rep1 (0.0222666)RS_Rap_rep2 (0.103173) (0.177921)RS_Rap_rep3 (0.108223)RR_Rap_rep-1 (0.116712)RR_Rap_rep-2 RR_Rap_rep-3(0.127369) (0.120689) (0.190869) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1557.0 2726.0 3260.1 P ( S | Z, I ) = 1.00 Mrpl18 1712.2 3740.1 4161.6 Mean Corr = 0.81181 Mrps22 1558.4 2758.4 3712.9 Mrpl11 2059.4 2538.0 4775.1 Mrpl28 2087.4 3032.8 4514.0 Mrpl13 5152.6 6339.9 19068.8 Mrpl34 1275.7 1692.2 3829.6 Mrps12 2095.0 2516.5 3117.1 Mrpl47 1148.0 2218.0 3783.0 Mrpl20 1765.5 3331.9 5086.1 Mrpl39 1376.3 2338.8 2938.0 Mrpl43 2309.2 2843.3 3696.9 Mrpl37 882.9 1285.2 1654.5 Mrpl48 1456.7 1749.8 2954.1 Mrpl49 643.8 1207.7 1397.1 Mrpl32 1947.4 2452.1 3828.1 Dap3 3211.8 4439.7 5214.2 Mrpl9 2211.3 2608.8 2987.8 Mrpl12 1813.4 4263.3 7422.0 Mrpl46 933.1 1375.8 1985.2 Timm13 3774.6 5969.4 7239.8 Mrpl22 3000.7 4089.7 5761.5 Mrpl42 5937.1 6882.7 11416.0 CEM 1 + Mrps28 2365.1 2827.8 3882.1 Top 10 Genes Grpel1 2253.6 4147.1 4970.6 Chchd1 3092.3 4377.9 10267.0 Mrps7 1436.4 2008.8 2438.2 Mrps35 950.4 1030.3 2663.4

Null module Mrpl51 Mrpl35 Mrps14 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 (0.0667485)APOE_KO_DM_9W_4 (0.0277815)APOE_KO_NODM_9W_5 (0.0912939)APOE_KO_NODM_9W_6 (0.0744158)APOE_KO_NODM_9W_7APOE_KO_NODM_9W_8 (0.0836215)APOE_KO_RAGE_KO_DM_9W_9 (0.0199038)APOE_KO_RAGE_KO_DM_9W_10 (0.00986445)APOE_KO_RAGE_KO_DM_9W_11 (0.0348129)APOE_KO_RAGE_KO_DM_9W_12APOE_KO_RAGE_KO_NODM_9W_13 (0.0808206)APOE_KO_RAGE_KO_NODM_9W_14 (0.0864792)APOE_KO_RAGE_KO_NODM_9W_15 (0.0576371) (0.107034) (0.0137059) [(0.0170173) min (0.228864) ] [ medium ] [ max ] CEM 1 Mrpl40 792.2 1017.1 1380.4 P ( S | Z, I ) = 1.00 Mrpl18 1090.0 1299.1 1660.5 Mean Corr = 0.81127 Mrps22 690.3 815.6 1220.0 Mrpl11 1005.7 1312.7 1606.4 Mrpl28 960.2 1286.8 1689.4 Mrpl13 2983.3 3493.3 4206.1 Mrpl34 999.1 1491.6 2556.0 Mrps12 665.2 811.1 1282.8 Mrpl47 1022.4 1624.3 2347.2 Mrpl20 1815.9 2172.2 2996.7 Mrpl39 1172.6 1833.6 2647.6 Mrpl43 1063.8 1232.9 1536.9 Mrpl37 454.0 592.7 778.9 Mrpl48 1283.0 1543.3 1982.8 Mrpl49 438.1 527.6 648.1 Mrpl32 1425.1 1680.8 2030.7 Dap3 1701.4 1921.5 2240.7 Mrpl9 1075.9 1479.4 1888.5 Mrpl12 1537.0 2347.4 3331.6 Mrpl46 857.3 1096.1 1535.0 Timm13 2749.1 3658.2 5275.8 Mrpl22 1608.4 1987.0 2687.9 Mrpl42 3373.2 5278.1 7354.4 CEM 1 + Mrps28 1422.1 1718.3 2340.5 Top 10 Genes Grpel1 2301.6 3977.2 5570.9 Chchd1 2475.8 2938.9 3733.7 Mrps7 949.6 1263.4 1762.8 Mrps35 898.5 1387.1 1988.5

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE13611" 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=GSE13611 Status: Public on Aug 15 2009 Title: Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19732723 Summary & Design: Summary: Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative

Overall design: Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative

Background corr dist: KL-Divergence = 0.0067, L1-Distance = 0.0275, L2-Distance = 0.0010, Normal std = 0.9603

0.415 Kernel fit Pairwise Correlations Normal fit

Density 0.208

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

BCR-ABL1BCR-ABL1 Aid-GFP-negative(1)BCR-ABL1 Aid-GFP-negative(2)BCR-ABL1 Aid-GFP-positive(1)Aid-GFP (0.0183053) Aid-GFP-positive(2)Aid-GFP negative (0.0549013)Aid-GFP negative(0.0394579) LPS+IL4-stimulatedAid-GFP positive(0.0446292) LPS+IL4-stimulated positive LPS+IL4-stimulated splenic LPS+IL4-stimulated splenicB cells [splenic (1)B min cells (0.299784) splenic B(2) cells (0.302097)] (1)B cells (0.0974535) (2)[ (0.143372) medium ] [ max ] CEM 1 Mrpl40 1289.9 2232.7 2584.5 P ( S | Z, I ) = 1.00 Mrpl18 3254.2 4985.2 5251.4 Mean Corr = 0.81056 Mrps22 533.7 1806.6 2395.8 Mrpl11 1734.9 3061.5 3762.5 Mrpl28 1279.4 1719.9 1916.3 Mrpl13 2281.5 4926.5 5246.7 Mrpl34 255.4 1251.4 1491.5 Mrps12 1606.1 1890.4 2400.2 Mrpl47 3174.6 5021.3 5537.0 Mrpl20 1166.3 2733.3 3368.4 Mrpl39 626.3 1571.5 1736.3 Mrpl43 1838.9 2836.6 3070.7 Mrpl37 370.5 1045.8 1343.4 Mrpl48 1823.4 3157.7 3373.3 Mrpl49 627.3 1433.1 1647.1 Mrpl32 3048.5 3525.0 4464.8 Dap3 3084.4 3515.4 4202.7 Mrpl9 701.6 1261.2 1680.0 Mrpl12 1906.2 4601.3 6227.1 Mrpl46 849.4 1643.1 2335.7 Timm13 1535.9 2961.9 3916.9 Mrpl22 2890.4 3467.2 4291.2 Mrpl42 2803.1 5350.5 5586.7 CEM 1 + Mrps28 1424.6 3621.3 4329.1 Top 10 Genes Grpel1 2493.7 3818.7 4471.8 Chchd1 1283.6 2498.0 3132.4 Mrps7 1241.7 1610.1 3044.4 Mrps35 906.4 2053.1 2381.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE31313" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 22 -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=GSE31313 Status: Public on Aug 08 2012 Title: Expression data from anti-EpCAM treated and untreated SP cells compared to lung tissue Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Targeted therapies against cancer stem cells which are enriched in side populations (SP) involves interruption of Wnt-signalling. Furthermore, EpCAM is a SP marker and modulator of Wnt-signalling. Therefore, the effects of an anti-EpCAM treatment on SP-cells and WNT/Î²-catenin signalling was studied.

SP of the murine lung adenocarcinoma cell line A2C12 was obtained by fluorescence activated cell sorting and whole genome scans helped to define their molecular phenotype after anti-EpCAM antibody treatment.

Overall design: Anti-EpCAM treated and untreated A2C12 cells were subjected to Hoechst 33342 dye exclusion assay and sorted to SP fractions by FACS. Gene expression of SP cells was compared to non-transgenic lung tissue.

Background corr dist: KL-Divergence = 0.0208, L1-Distance = 0.0491, L2-Distance = 0.0029, Normal std = 0.7902

0.505 Kernel fit Pairwise Correlations Normal fit

Density 0.252

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

A2C12 SPA2C12 cells SPA2C12 biological cells SPA2C12 biological cells replicate anti-EpCAMA2C12 biological replicate 1 anti-EpCAM(0.126815)A2C12 replicate treated 2 anti-EpCAM(0.0908218)Male treatedSP lung,3 (0.0965036)Male cells biological treatedSPlung, biologicalMale cells biological SPlung, biologicalreplicateMale cells replicate biological lung, biologicalreplicateMale 1 replicate (0.0174127) biological1 (0.0977912)lung, replicateMale 2 replicate (0.0496461) biological2 (0.0556906)lung, replicateMale 3 (0.0261025) biological3 (0.167367)lung, replicateMale 4 (0.0234522) biological lung, replicateFemale 5 (0.0125703) biological replicate Female lung,6 (0.0140073) biologicalreplicate Female lung,7 (0.0265384) biological Female lung,8 replicate (0.0224749) biological Femalelung, replicate 1 (0.0315147) biological Femalelung, replicate 2 (0.0319552) biological Femalelung, replicate 3 (0.0422974) biological Femalelung, replicate 4 (0.0189774) biological lung, replicate 5 (0.00935455) biological replicate 6 (0.0120955) replicate 7 (0.0100043)[ min8 (0.0166074) ] [ medium ] [ max ] CEM 1 Mrpl40 665.8 1180.4 2793.5 P ( S | Z, I ) = 1.00 Mrpl18 637.1 994.3 3890.2 Mean Corr = 0.80614 Mrps22 385.0 838.0 2604.8 Mrpl11 566.5 816.2 2380.5 Mrpl28 578.7 802.2 2184.4 Mrpl13 1376.5 1795.3 9228.6 Mrpl34 855.1 1356.8 2211.7 Mrps12 1014.6 1370.5 2735.2 Mrpl47 570.8 822.1 1317.5 Mrpl20 1928.5 2292.6 3887.3 Mrpl39 740.7 1262.9 1890.1 Mrpl43 1356.4 1711.5 3377.9 Mrpl37 699.0 821.2 1221.7 Mrpl48 872.9 1211.2 1488.9 Mrpl49 561.3 686.0 1304.5 Mrpl32 1060.2 1758.8 3542.4 Dap3 1461.8 1797.5 3250.9 Mrpl9 558.8 797.1 1856.7 Mrpl12 917.7 1252.9 5144.0 Mrpl46 428.1 678.6 958.6 Timm13 1721.1 2224.8 6478.3 Mrpl22 1058.9 1430.0 2834.6 Mrpl42 2329.8 3186.7 6551.5 CEM 1 + Mrps28 1047.2 1412.2 1612.1 Top 10 Genes Grpel1 1238.8 1874.5 4048.8 Chchd1 1780.7 2221.9 5575.5 Mrps7 503.7 714.5 3200.4 Mrps35 387.2 689.3 1138.3

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE12498" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

Keywords: Cell density, genetic modification

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

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

0.805 Kernel fit Pairwise Correlations Normal fit

Density 0.402

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl-low-1ctrl-low-2 (0.249731)tead2VP16-conf-1 (0.250961)tead2VP16-conf-2yap-conf-1 (0.0263856)yap-conf-2 (0.0232003)(0.0414082)tead2EnR-low-1 (0.0304906)tead2EnR-low-2ctrl-over-1 (0.02559)ctrl-over-2 (0.0453939) (0.0989614)tead2VP16-over-1 (0.0645093)tead2VP16-over-2 (0.0723581) (0.0710101) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1466.6 1844.2 2355.3 P ( S | Z, I ) = 1.00 Mrpl18 1281.6 1482.0 2908.9 Mean Corr = 0.80482 Mrps22 851.4 1151.5 2121.9 Mrpl11 2267.8 2981.7 3867.4 Mrpl28 2230.6 2500.0 4097.6 Mrpl13 4512.9 5027.9 6979.9 Mrpl34 1186.1 1380.1 2119.1 Mrps12 847.3 1266.9 1380.7 Mrpl47 791.0 882.6 1290.6 Mrpl20 2243.3 3047.8 4634.2 Mrpl39 740.5 938.8 1319.4 Mrpl43 2599.0 2855.6 3414.0 Mrpl37 1360.6 1710.4 2718.4 Mrpl48 1100.3 1562.6 1653.3 Mrpl49 976.0 1169.5 1454.3 Mrpl32 1678.3 1916.4 2669.2 Dap3 2826.4 3447.1 3935.6 Mrpl9 1097.8 1234.5 1899.4 Mrpl12 1885.7 2709.6 5650.7 Mrpl46 568.4 842.4 1444.7 Timm13 3956.9 4804.5 7985.9 Mrpl22 1900.3 2528.5 3742.7 Mrpl42 3132.7 3358.7 4635.4 CEM 1 + Mrps28 922.4 1140.8 1399.1 Top 10 Genes Grpel1 2218.3 2721.7 4131.9 Chchd1 2107.0 2219.3 3486.2 Mrps7 1581.3 2052.1 3723.1 Mrps35 986.1 1125.3 1326.5

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE45619" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

kewywords: Mouse megakaryocyte progenitors

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

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

0.596 Kernel fit Pairwise Correlations Normal fit

Density 0.298

0.000 CEM 1

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

Pre-normalization Quantiles

Gs_MKP_BM_1Gs_MKP_BM_2Gs_MKP_BM_3 (0.160375)Gs_MKP_FL_1 (0.114292)Gs_MKP_FL_2 (0.166898) Gs_MKP_FL_3(0.0801172) (0.30712) (0.171197) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1660.3 2363.8 2595.3 P ( S | Z, I ) = 1.00 Mrpl18 3786.6 4853.6 5377.6 Mean Corr = 0.80315 Mrps22 1136.9 1923.1 2102.6 Mrpl11 2987.1 3897.9 4714.4 Mrpl28 1126.4 1593.7 1807.9 Mrpl13 4113.1 4815.4 5652.1 Mrpl34 551.2 924.9 1017.3 Mrps12 928.4 1506.6 1884.1 Mrpl47 3341.6 4025.1 4915.9 Mrpl20 2893.2 3260.7 5233.7 Mrpl39 1153.0 1364.6 1869.0 Mrpl43 1725.5 2302.0 2723.8 Mrpl37 609.5 953.6 1055.8 Mrpl48 2360.0 2499.7 2648.5 Mrpl49 753.6 982.1 1100.4 Mrpl32 3125.6 3724.9 4169.4 Dap3 3103.5 3618.6 4297.3 Mrpl9 788.2 956.8 1068.2 Mrpl12 3282.7 4262.6 5922.7 Mrpl46 648.3 918.1 1348.4 Timm13 1877.8 2432.3 3385.3 Mrpl22 1576.4 2402.0 3373.7 Mrpl42 4105.7 4729.7 6028.9 CEM 1 + Mrps28 2042.6 2663.5 3507.7 Top 10 Genes Grpel1 3362.1 4179.2 5222.8 Chchd1 1209.7 1630.1 1775.7 Mrps7 1720.1 2290.6 2794.2 Mrps35 1646.2 1922.0 2606.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE8555" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: genetic modification

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

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

0.570 Kernel fit Pairwise Correlations Normal fit

Density 0.285

0.000 CEM 1

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

Pre-normalization Quantiles

Gene expressionGene expressionGene profiling expressionGene profiling of expression PhgdhGene profiling of expression knockoutPhgdhGene profiling of expression knockoutPhgdhGene embryo profiling of expression knockoutPhgdhGene embryo wild1profiling of expression knockoutPhgdh (0.0955495) embryo KO1profiling of knockout Phgdh(0.0971923) embryo wild2profiling of knockoutPhgdh (0.142694) embryo KO2 of knockout Phgdh(0.1749)[ embryo wild3min knockout (0.0706332) embryo KO3 ] (0.11583) embryo wild4 (0.156276) KO4[ medium (0.146925) ] [ max ] CEM 1 Mrpl40 545.2 1006.7 1379.9 P ( S | Z, I ) = 1.00 Mrpl18 881.1 2176.6 2536.9 Mean Corr = 0.79580 Mrps22 1242.6 1844.8 2101.2 Mrpl11 1812.1 2170.0 2336.6 Mrpl28 1067.7 1435.1 1741.4 Mrpl13 1866.2 3310.1 3782.9 Mrpl34 1149.0 1827.7 2516.7 Mrps12 949.6 1419.1 1709.7 Mrpl47 629.2 1367.2 1731.6 Mrpl20 1351.4 1841.4 3263.8 Mrpl39 933.3 1287.5 1601.2 Mrpl43 760.8 2052.8 2517.2 Mrpl37 572.2 770.8 933.5 Mrpl48 332.6 1510.1 1967.9 Mrpl49 540.8 690.3 883.0 Mrpl32 1159.9 1643.2 2000.8 Dap3 1177.3 2649.3 3084.0 Mrpl9 1159.0 1278.5 1485.6 Mrpl12 1389.3 2897.5 3962.3 Mrpl46 668.3 737.0 819.0 Timm13 1673.6 3701.2 3988.6 Mrpl22 923.3 1976.6 2366.9 Mrpl42 1747.9 3597.2 4104.9 CEM 1 + Mrps28 538.6 1005.7 1320.7 Top 10 Genes Grpel1 1604.7 1717.8 1875.1 Chchd1 2513.9 3620.0 4780.4 Mrps7 721.7 1357.5 1615.6 Mrps35 483.8 822.6 1101.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE22824" 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=GSE22824 Status: Public on Jan 01 2011 Title: Gene expression in retina and LGN of wild type and Chrnb2-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21547082 Summary & Design: Summary: Mice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.

Using microarray hybridization, we identified transcripts which are differentially expressed between Chrnb2-/- and wild type animals in these two tissues at these two ages.

Overall design: mRNA was isolated from retina and LGN of three male littermates each of WT and Chrnb2-/- mice at P4. mRNA from retinas of two adult male littermates of each type was also examined.

Background corr dist: KL-Divergence = 0.0272, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6813

0.595 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

PicciottoPicciotto b2 -/- Picciottoretina b2 -/- P4, Xuretina b2 mouseb2 -/- -/-P4, Xuretina retina Amouseb2 (0.0571515) -/-P4, XuP4, retina Bmouseb2 mouse (0.0448579) -/- WildP4, retina C Amouse (0.0689212)type (0.0536453) WildP4, retina Bmouse type (0.0343977)Wild P4, retina C typemouse (0.0455709)Picciotto P4, retina Amouse (0.0366907)Picciotto P4, b2 B-/-LGNmouse (0.0648069)Picciotto b2 P4,C-/- (0.0547485)XuLGN mouse b2 b2 -/-P4, -/- XuLGN BLGNmouse (0.0198981)b2 P4, -/-P4,Xu LGNCmouse mouse b2(0.0678786) -/-P4,Wild LGND Amouse (0.0398052) (0.0294058)type P4,Wild LGNBmouse (0.0217371)type WildP4, LGNC mouse (0.0244634)type PicciottoP4, LGN Amouse (0.0258181) PicciottoP4, b2 Dmouse -/- (0.036986) Xuretina b2 b2E -/- (0.0207943)-/-adult, Xuretina retina b2 mouse -/-adult, Wildadult, retina type1542mouse mouse Wildadult, retina(0.0444634) type1543 77mouse adult, (0.0158966) retina(0.0468521) 78 mouse adult,(0.029987) 748mouse (0.0405164) 763[ min (0.0747074) ] [ medium ] [ max ] CEM 1 Mrpl40 740.1 1191.5 1824.1 P ( S | Z, I ) = 1.00 Mrpl18 1077.8 2096.9 3206.5 Mean Corr = 0.79534 Mrps22 1403.4 2019.3 2934.0 Mrpl11 1584.5 2546.3 3972.5 Mrpl28 989.3 1910.0 2832.3 Mrpl13 1298.4 2013.7 4260.8 Mrpl34 1056.0 1963.5 3646.6 Mrps12 756.2 1777.0 2702.9 Mrpl47 920.8 1568.6 2717.1 Mrpl20 1473.4 2372.2 3604.0 Mrpl39 986.4 1295.4 2317.5 Mrpl43 1524.0 2683.5 3050.7 Mrpl37 518.7 1594.9 1882.4 Mrpl48 745.2 1237.6 1993.5 Mrpl49 166.0 2950.2 3685.2 Mrpl32 1120.0 1874.8 3066.8 Dap3 1966.0 2307.6 2815.9 Mrpl9 610.1 1146.2 1696.6 Mrpl12 1477.8 2609.0 3141.8 Mrpl46 817.4 1488.2 2022.6 Timm13 1835.4 4585.7 5318.2 Mrpl22 723.6 1764.9 2826.0 Mrpl42 1739.8 2728.1 4319.4 CEM 1 + Mrps28 411.8 1198.7 2142.6 Top 10 Genes Grpel1 1727.2 2778.6 4429.9 Chchd1 1099.7 3125.6 4474.4 Mrps7 760.7 1178.3 1851.7 Mrps35 457.8 700.1 1732.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE52474" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 154 -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=GSE52474

Background corr dist: KL-Divergence = 0.1954, L1-Distance = 0.0793, L2-Distance = 0.0167, Normal std = 0.3721 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 (0.129936) rep2 biological3.0mg/kg/day,Nic (0.074923) biological3.0mg/kg/day, rep1Nic biological4.5mg/kg/day,(0.130276) rep2Nic biological4.5mg/kg/day,(0.0258345) rep1 biological(0.0367104) rep2 biological(0.300654) rep1 (0.248077) rep2[ min (0.0535884) ] [ medium ] [ max ] CEM 1 Mrpl40 1037.1 1408.3 1813.2 P ( S | Z, I ) = 1.00 Mrpl18 1881.2 2551.2 3927.7 Mean Corr = 0.79211 Mrps22 1563.5 2158.8 3509.1 Mrpl11 1535.9 1860.0 2414.2 Mrpl28 1238.2 1651.9 2540.4 Mrpl13 2196.6 3308.4 4622.5 Mrpl34 1368.7 2260.4 5276.0 Mrps12 824.4 1095.3 1769.7 Mrpl47 1156.9 2313.1 3060.5 Mrpl20 1513.5 1931.6 4389.0 Mrpl39 1072.8 1883.5 2791.4 Mrpl43 1648.9 2347.8 3018.8 Mrpl37 1359.4 2263.9 3760.4 Mrpl48 1159.0 1529.0 2003.0 Mrpl49 1243.2 1557.1 1943.2 Mrpl32 2182.9 2914.5 3574.2 Dap3 1583.6 1853.2 2696.1 Mrpl9 1207.9 2670.4 3269.3 Mrpl12 2853.0 4172.7 5969.0 Mrpl46 972.7 1177.2 2247.5 Timm13 2945.7 4942.1 7929.3 Mrpl22 1212.3 2096.9 3045.9 Mrpl42 3805.9 6824.5 9358.8 CEM 1 + Mrps28 1785.5 2834.0 3730.4 Top 10 Genes Grpel1 3958.4 6594.7 8894.8 Chchd1 3079.1 3654.8 4692.3 Mrps7 1088.7 1664.9 2371.2 Mrps35 915.1 1842.3 3015.0

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE13693" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13693 Status: Public on Feb 06 2009 Title: Gene expression profiling of normal mouse myeloid cell populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7RÎ±), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.

Overall design: See summary.

Background corr dist: KL-Divergence = 0.0176, L1-Distance = 0.0380, L2-Distance = 0.0018, Normal std = 0.8108

0.500 Kernel fit Pairwise Correlations Normal fit

Density 0.250

0.000 CEM 1

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

Pre-normalization Quantiles

NORMALNORMAL BM NEUTROPHILS_2NORMAL BM NEUTROPHILS_1NORMAL BM NEUTROPHILS_3NORMAL (0.156256)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.241044)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.165237)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.186032) (0.0712586)[ min(0.0538613) (0.0470224)] (0.0379501)[ (0.0413393) medium ] [ max ] CEM 1 Mrpl40 499.1 2089.3 2304.2 P ( S | Z, I ) = 1.00 Mrpl18 620.2 3955.1 4303.3 Mean Corr = 0.78337 Mrps22 80.0 1152.1 1782.8 Mrpl11 38.3 1892.7 3066.9 Mrpl28 325.1 1435.8 2021.6 Mrpl13 153.2 2417.9 3310.1 Mrpl34 803.3 1340.9 1763.1 Mrps12 292.1 1585.1 1958.3 Mrpl47 130.8 1185.4 2059.2 Mrpl20 620.0 1132.3 1394.5 Mrpl39 410.7 2245.4 2922.6 Mrpl43 2061.3 2417.6 2922.6 Mrpl37 36.3 562.2 874.2 Mrpl48 772.4 1167.6 1425.2 Mrpl49 104.8 1561.1 1914.8 Mrpl32 1015.1 2264.8 3103.7 Dap3 2400.3 2878.2 3617.7 Mrpl9 336.8 720.7 1797.7 Mrpl12 60.8 2135.9 3792.8 Mrpl46 109.9 1059.9 1451.6 Timm13 768.4 3733.9 4498.6 Mrpl22 667.6 2351.5 3254.8 Mrpl42 100.0 2165.5 3627.7 CEM 1 + Mrps28 101.1 1768.5 2766.0 Top 10 Genes Grpel1 1299.2 5320.7 6115.6 Chchd1 412.7 2281.3 3380.8 Mrps7 196.7 1200.8 1708.1 Mrps35 155.9 1533.4 1896.3

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE46723" 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=GSE46723 Status: Public on Jul 01 2013 Title: Expression data from adult Myeloerythroid Progenitors (MP) Hes1-GFP positive and adult Myeloerythroid Progenitors (MP) Hes1-GFP negative Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23791481 Summary & Design: Summary: Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).

Overall design: Bone marrow lineage negative, cKit+, Sca1- cells were sorted from Hes-GFP mice for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0189, L1-Distance = 0.0122, L2-Distance = 0.0002, Normal std = 0.7520

0.531 Kernel fit Pairwise Correlations Normal fit

Density 0.265

0.000 CEM 1

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

Pre-normalization Quantiles

adult Myeloerythroidadult Myeloerythroidadult Myeloerythroid Progenitorsadult Myeloerythroid Progenitorsadult (MP) Myeloerythroid Progenitorsadult HES1-GFP (MP) Myeloerythroid Progenitors HES1-GFP (MP) negative Progenitors HES1-GFP (MP) negative Progenitorsreplicate HES1-GFP (MP) negative replicate[ 1HES1-GFP min(0.0591361) (MP) positive replicate 2HES1-GFP (0.210132) ] positive replicate 3 (0.225389) positive replicate 1 (0.26421)[ medium replicate 2 (0.117882) 3 (0.12325) ] [ max ] CEM 1 Mrpl40 1818.2 2412.1 2480.4 P ( S | Z, I ) = 1.00 Mrpl18 5919.7 6688.5 7292.5 Mean Corr = 0.77615 Mrps22 1388.8 2409.8 2779.1 Mrpl11 3243.1 3671.0 4278.3 Mrpl28 1442.0 2256.9 2420.8 Mrpl13 4295.0 4679.1 5060.2 Mrpl34 863.3 1229.2 1598.2 Mrps12 2099.6 2493.8 2804.7 Mrpl47 4403.2 6207.6 6372.3 Mrpl20 2995.2 4333.4 4868.4 Mrpl39 842.5 1131.1 1249.2 Mrpl43 1924.7 2121.6 2286.5 Mrpl37 622.1 932.6 1083.0 Mrpl48 3487.4 3741.3 3996.1 Mrpl49 935.1 1292.8 1324.3 Mrpl32 3307.7 4150.8 4491.0 Dap3 3380.1 4908.4 5210.6 Mrpl9 792.4 1329.2 1531.2 Mrpl12 4329.0 5567.6 6693.5 Mrpl46 988.0 1644.9 1961.8 Timm13 3170.9 3863.3 4933.9 Mrpl22 3182.9 4409.7 4756.0 Mrpl42 5926.8 6227.8 6453.2 CEM 1 + Mrps28 4617.8 6152.7 6950.6 Top 10 Genes Grpel1 4061.2 4768.8 4935.2 Chchd1 2120.5 2589.4 2882.9 Mrps7 1532.7 2162.3 2344.2 Mrps35 1609.3 1971.0 2408.4

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE31940" 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=GSE31940 Status: Public on Mar 01 2012 Title: White adipose tissue from aP2-Pex5 knockout and control mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: These arrays contain data from gonodal adipose tissue of aP2-Pex5 -/- male mice

Overall design: 4 arrays from gonadal adipose tissue from control mice (Swiss background) are compared with 4 arrays from gonadal adipose tissue of aP2-Pex5 knockout mice. The latter lack functional peroxisomes in adipose tissue.

Background corr dist: KL-Divergence = 0.0585, L1-Distance = 0.0201, L2-Distance = 0.0006, Normal std = 0.5314

0.751 Kernel fit Pairwise Correlations Normal fit

Density 0.375

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

WAT1-ctWAT6-ko (0.197857)WAT2-ct (0.0336563)WAT8-ko (0.236846)WAT3-ctr (0.023883)WAT9-ko (0.113116)WAT4-ct (0.0335769)WAT10-ko (0.248368) (0.112697) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 1625.2 2111.3 2494.0 P ( S | Z, I ) = 1.00 Mrpl18 1361.0 1781.6 2156.3 Mean Corr = 0.77420 Mrps22 898.3 1311.0 1743.9 Mrpl11 1820.5 2077.7 2166.4 Mrpl28 1366.1 1614.6 1708.9 Mrpl13 2199.6 2407.2 2681.6 Mrpl34 1014.2 1353.0 1579.2 Mrps12 1333.2 1526.1 1642.1 Mrpl47 651.9 754.9 986.5 Mrpl20 2518.8 3231.8 4067.8 Mrpl39 1062.7 1235.6 1393.4 Mrpl43 1227.1 1517.8 1665.9 Mrpl37 698.8 874.0 952.6 Mrpl48 1288.4 1486.2 1894.5 Mrpl49 837.6 973.5 1120.8 Mrpl32 1448.2 1667.1 1953.6 Dap3 1564.6 1823.0 2267.4 Mrpl9 1034.7 1151.7 1438.4 Mrpl12 1329.1 2049.2 2870.9 Mrpl46 637.8 747.6 936.2 Timm13 2533.4 3821.7 4097.7 Mrpl22 1378.3 1538.0 1868.4 Mrpl42 2846.3 3457.0 4111.2 CEM 1 + Mrps28 1074.7 1337.6 1624.1 Top 10 Genes Grpel1 1851.1 2399.0 2722.2 Chchd1 2404.4 2649.1 2955.7 Mrps7 1466.3 2004.0 2291.5 Mrps35 791.6 957.5 1152.9

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE26616" 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=GSE26616 Status: Public on Jun 09 2011 Title: EZH1 and EZH2 Co-Govern Histone H3-K27 Trimethylation and Are Essential for Hair Follicle Homeostasis and Wound Repair Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21317239 Summary & Design: Summary: Polycomb protein group (PcG)-dependent trimethylation on H3-K27(H3K27me3) regulates identity of embryonic stem cells (SCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3-K27-methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly-targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA-microarray studies reveal that despite these striking phenotypic differences, similar genes are upregulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are a) PcG-controlled non-skin lineage genes, whose expression is still significantly lower than in native tissues, and b) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they only partially so in epidermal-progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing towards the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3.

Overall design: RNAs from FACS-purified WT and Ezh1/2 2KO ORS, matrix and epidermal cells (Rendl et al., 2005) were provided to the Genomics Core Facility, MSKCC for quality control, quantification, reverse transcription, labeling and hybridization to MOE430A 2.0 microarray chips (Affymetrix). Arrays were scanned per the manufacturers specifications for the Affymetrix MOE430v2 chip. Images were background-subtracted. Probesets were identified as differentially expressed when the absolute fold change was ¥2. Probesets selected for visualization were log2 transformed and were analyzed with hierarchical clustering (Pearson correlation, average linkage), and visualized with heatmaps to assist in interpretation.

Background corr dist: KL-Divergence = 0.0410, L1-Distance = 0.0331, L2-Distance = 0.0015, Normal std = 0.6238

0.652 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

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

Pre-normalization Quantiles

Ezh1/2 2KOEzh1/2 FACS 2KOEzh1/2 purified FACS 2KOEzh1/2 purified basalFACS WTEzh1/2 epidermal purifiedFACS matrix WTEzh1/2 purified FACS cellsORS cells WT (0.0624018) cellspurified basalFACS(0.0795988) (0.238278) epidermal purified matrix cellsORS cells [ (0.472348)cells (0.0769114)min (0.0704625) ] [ medium ] [ max ] CEM 1 Mrpl40 726.5 1225.8 1759.6 P ( S | Z, I ) = 1.00 Mrpl18 1280.6 2097.9 3996.2 Mean Corr = 0.77133 Mrps22 1004.2 1654.8 2418.9 Mrpl11 1130.2 1756.6 3193.9 Mrpl28 970.6 1627.9 2155.8 Mrpl13 2705.5 3547.2 4241.6 Mrpl34 940.9 1511.4 2362.3 Mrps12 1333.8 2130.3 3024.5 Mrpl47 571.1 877.1 1539.3 Mrpl20 1281.2 1941.0 2937.4 Mrpl39 831.8 1466.3 2050.2 Mrpl43 1040.3 2036.2 2748.6 Mrpl37 720.3 788.8 1158.7 Mrpl48 1367.3 1712.0 1722.8 Mrpl49 485.3 618.1 1157.4 Mrpl32 1936.4 3257.7 3524.1 Dap3 2318.6 2900.1 3380.9 Mrpl9 1261.3 2343.0 3038.7 Mrpl12 2271.0 4165.2 5682.9 Mrpl46 585.1 832.5 1243.5 Timm13 2666.7 3908.4 5233.0 Mrpl22 1011.3 1591.4 2696.7 Mrpl42 2575.8 3628.1 5467.8 CEM 1 + Mrps28 1649.3 2239.5 2917.6 Top 10 Genes Grpel1 1682.5 2799.5 3525.0 Chchd1 2174.0 3728.1 4530.8 Mrps7 1063.6 1573.7 2202.6 Mrps35 712.1 1159.9 1503.0

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE11333" 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=GSE11333 Status: Public on May 06 2008 Title: ELAV-like protein HuD overexpression and pulldown (perro-affy-mouse-482241) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Post-transcriptional mechanisms play an important role in the control of gene expression. RNA-binding proteins are key players in the post-transcriptional control of many neural genes and they participate in multiple processes, from RNA splicing and mRNA transport to mRNA stability and translation. Our laboratory has developed the first mouse model overexpressing a RNA-binding protein, the ELAV-like protein HuD, in the CNS under the control of the CaMKinII alpha promoter. Initial behavioral characterization of the mice revealed that they had significant learning deficits together with abnormalities in prepulse inhibition (PPI). At the molecular level, we found that the expression of the growth-associated protein GAP-43, one of the targets of HuD, was increased in the hippocampus of HuD transgenic mice.

Besides binding and stabilizing the GAP-43 mRNA, HuD was shown to bind in vitro or in vivo the mRNAs of acetylcholinesterase, tau, p21, neuroserpin, and MARCKS among others. To identify additional targets of HuD, we propose to pull down the RNAs bound to myc-tagged HuD in vivo in the brains of HuD transgenic mice, to isolate these bound RNAs and use these to probe DNA microarrays. We will use pull downs using non-immune IgGs as controls.

To test our hypothesis we propose 2 specific aims:

1) To identify the targets of HuD in HuD overexpressor mice and

2) To compare these target mRNAs to those we identified previously as having increased levels of expression in the hippocampus of HuD transgenic mice (see protocol # Perrone-Bizzozero-5R01NS030255-12) and/or those that show increased expression in dentate granule cells of HuD transgenic mice ( protocol # perro-affy-mouse-309741)

Based upon the role of the RNA-binding HuD in neuronal development and synaptic plasticity, we expect that HuD targets will include mRNAs for proteins involved in these processes.

All mice are in C57BL/6 background and are male approximately 60 days old. To identify target of HuD in our transgenic mice, we will homogenize the homogenize the hippocampi (2 per animal) of 3 transgenic mice and use these protein extracts for immunoprecipitation assays. Briefly, transgenic myc-tagged HuD protein will be immunoprecipitated using myc-tag antibodies and protein-G agarose beads and samples will be sent to T-Gen for RNA isolation, single round amplification and probing of DNA microarrays. We will use non-immune IgG as a negative control.

Conditions:

Pooled Extracts from 3 transgenic mice IP with myc-tag antibodies: Triplicates

Pooled extract from 3 transgenic mice IP with non-immune IgGs (negative control): duplicates

Keywords: dose response

Overall design:

Background corr dist: KL-Divergence = 0.0289, L1-Distance = 0.0352, L2-Distance = 0.0016, Normal std = 0.7007

0.580 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

hippocampus:hippocampus: hippocampus:HuD RNA1_le1 hippocampus:IgG RNA hippocampus:_le1(0.121006) 1_le1 (0.240555) hippocampus:HuDpulldown(0.115411) HuDpulldown #1_e1_le1 Control #2_e1_le1 IP (0.1169) #2_e1_le1[ (0.151741)min (0.254388) ] [ medium ] [ max ] CEM 1 Mrpl40 393.3 720.7 1562.6 P ( S | Z, I ) = 1.00 Mrpl18 256.4 1119.0 1406.7 Mean Corr = 0.77015 Mrps22 146.1 389.0 718.4 Mrpl11 615.1 989.8 2183.1 Mrpl28 303.3 973.7 1653.2 Mrpl13 1213.7 1697.9 4324.7 Mrpl34 204.1 423.8 770.0 Mrps12 1015.6 2095.7 3256.9 Mrpl47 307.0 835.4 1276.0 Mrpl20 316.9 954.5 1074.8 Mrpl39 230.0 872.2 1137.0 Mrpl43 515.3 1377.7 2908.6 Mrpl37 5.8 130.7 335.6 Mrpl48 215.2 826.4 1769.7 Mrpl49 260.9 685.9 939.8 Mrpl32 333.8 401.3 1329.7 Dap3 508.8 1075.6 2802.8 Mrpl9 131.5 412.5 1154.1 Mrpl12 391.0 1388.0 1920.6 Mrpl46 368.2 1122.2 2038.3 Timm13 928.3 3072.1 5552.2 Mrpl22 1747.4 3223.9 5748.1 Mrpl42 859.4 1429.1 3638.7 CEM 1 + Mrps28 258.9 487.3 1233.8 Top 10 Genes Grpel1 872.5 1530.8 3847.1 Chchd1 707.4 1252.9 3298.5 Mrps7 307.9 889.5 1046.9 Mrps35 103.8 401.3 525.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE10989" 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=GSE10989 Status: Public on Dec 22 2010 Title: Expression data of cystic renal epithelial tissue from mice deficient for fumarate hydratase. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Fumarate hydratase (FH) mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC). We have conditionally inactivated the murine ortholog (Fh1) in renal tubular epithelial cells in order to generate an in vivo model of HLRCC. Fh1 knockout mice recapitulates important aspects of HLRCC including the development of renal cysts that overexpress hypoxia inducible factor alpha (Hifa) and Hif-target genes.

We used microarrays to detail the global programme of gene expression underlying cyst development in Fh1 knockout mice and identified distinct classes of up-regulated genes during this process.

Keywords: gene expression, comparison (wild-type n=3 vs knockout n=3)

Overall design: Renal epithelial tissue was macro-dissected from Fh1 knockout mice and sex-matched litter mate control disease-free animals for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0186, L1-Distance = 0.0758, L2-Distance = 0.0076, Normal std = 0.9701

0.411 Kernel fit Pairwise Correlations Normal fit

Density 0.206

0.000 CEM 1

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

Pre-normalization Quantiles

wild-typewild-type mousewild-type kidneymouseknockout -kidneymouse 1 (0.257392)knockout -kidneymouse 2 (0.175572)knockout -kidneymouse 3 (0.109215) -kidneymouse 1 (0.19397) -kidney 2 (0.111536) - 3 (0.152316)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1789.9 2029.0 2108.1 P ( S | Z, I ) = 1.00 Mrpl18 1148.3 1462.8 1771.5 Mean Corr = 0.76410 Mrps22 1354.2 1705.0 1981.7 Mrpl11 1487.8 1866.0 2009.7 Mrpl28 1629.7 2220.8 2403.6 Mrpl13 3681.1 4477.3 4542.8 Mrpl34 1380.2 2046.2 2221.8 Mrps12 1558.0 1866.7 1990.5 Mrpl47 1489.0 1531.4 1918.9 Mrpl20 2344.4 2792.2 3151.8 Mrpl39 1160.0 1520.6 1789.4 Mrpl43 1890.9 2315.6 2372.5 Mrpl37 770.5 1044.2 1117.1 Mrpl48 1673.1 2331.4 2618.6 Mrpl49 730.5 1088.0 1263.2 Mrpl32 1913.6 2113.8 2476.1 Dap3 2307.1 2528.1 3014.4 Mrpl9 1097.2 1322.2 1419.6 Mrpl12 2922.2 4250.8 4960.6 Mrpl46 1351.2 1972.2 2320.7 Timm13 4105.8 4541.5 4658.6 Mrpl22 2027.1 2550.1 2753.5 Mrpl42 5576.5 7280.6 8320.0 CEM 1 + Mrps28 1424.8 1766.2 1898.2 Top 10 Genes Grpel1 2818.1 3412.0 4005.4 Chchd1 2323.7 3273.4 3433.4 Mrps7 1229.6 1835.6 1866.0 Mrps35 1325.5 2192.2 2236.8

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE37191" 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=GSE37191 Status: Public on Jan 01 2013 Title: Gene expression profiling reveals mast cell-dependent inflammation in the meninges in early EAE. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23267561 Summary & Design: Summary: The meninges are generally considered relatively inert tissues that house the CSF and provide protection for the brain and spinal cord. However, our previous studies using Kit mutant (Kit W/Wv) mast cell-deficient mice demonstrated that mast cells residing in the dura mater and pia mater exacerbate the severity of experimental autoimmune encephalomyelitis (EAE), the rodent model of the CNS demyelinating disease, multiple sclerosis. These data suggest that the meninges are sites of active immune responses in disease. Gene expression profiles of meningeal tissue from wild type and mast cell deficient mice prior to and at day 6 post-EAE induction were found highly distinct. Increases in both mast cell- and neutrophil-associated transcripts were among the notable disease-related changes observed in wild type mice. Kinetic analyses show that meningeal mast cells are activated within 24 hours of disease induction to express multiple mediators including IL-1b and TNF as well as the neutrophil chemoattractant, CXCL2, an observation corresponding with an influx of neutrophils to the meninges. Neutrophil recruitment as well as the disease-related loss of BBB integrity is dependent on mast cell-derived TNF. These data provide unequivocal evidence that the meninges are sites of early inflammatory events in EAE. Mast cells residing within these tissues promote disease by orchestrating an early and efficient immune cell co-localization resulting in a robust local inflammatory response and a breach of the proximal BBB. We hypothesize that these events reflect an aberrant manifestation of the normal immune surveillance role of the meninges in infection settings.

Overall design: Immunized WT and Kit W/Wv mice were sacrificed on Day 6 post-immunization and perfused with PBS as were naÃ¯ve littermate control mice. The dura mater was immediately removed from the calvarium of the skull and pooled (10 mice/group, 4 groups). RNA was isolated using SV Total RNA Isolation System (Promega). Each pool was analyzed in technical triplicates. Briefly, cRNA was synthesized and amplified/labeled using the Affymetrix Express Kit, then fragmented and hybridized to the The GeneChipÂ® Mouse Genome 430 2.0 Array in accordance to the Affymetrix GeneChip expression analysis technical manual (Affymetrix, Santa Clara, CA). After hybridization, arrays were washed and stained with Affymetrix fluidics protocol FS450_0001 and scanned with a 7G Affymetrix GeneChip Scanner. Image data were analyzed with Affymetrix Expression Console¢ software and normalized with Robust Multichip Analysis (RMA; www.bioconductor.org/) to determine signal log ratios (CITE: Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5, R80.). The mean fold change was calculated from 3 independent technical replicates for each of the four experimental conditions and assessed by a non-parametric rank product test (CITE: Hong, F., Breitling, R., McEntee, C.W., Wittner, B.S., Nemhauser, J.L., and Chory, J. (2006). RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22, 2825-2827). Heat maps were generated with Genesis (Cite: Sturn, A., Quackenbush, J. and Trajanoski, Z. (2002) Genesis: cluster analysis of microarray data. Bioinformatics, 18, 207-208).

Background corr dist: KL-Divergence = 0.1081, L1-Distance = 0.0249, L2-Distance = 0.0009, 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

WT mouseWT duramouseWT mater, duramouseWT EAE,mater, duramouse technicalWT EAE,mater, duramouse technicalWT EAE,replicatemater, duramouse technicalKit naÃ¯vereplicatemater, 1 W/Wvdura (0.104958)Kit control,naÃ¯vereplicatemater, mouse 2W/Wv (0.0284268)Kit control,naÃ¯ve technicalduramouse 3W/Wv (0.0559547) mater,Kit control, technicalduramouse W/Wv replicate EAE,mater,Kit technicalduramouse W/Wv replicate technical 1 EAE,mater,Kit(0.135543) duramouse W/Wv replicate technical 2 EAE, replicatemater,(0.172864) duramouse technical 3 naÃ¯ve replicatemater,(0.248913) 1 dura (0.0157434) control,naÃ¯vereplicatemater, 2 (0.0412295) control,naÃ¯ve technical[ 3 min(0.0416779) control, technical replicate ] technical replicate 1 (0.0483437) replicate[ 2 medium(0.0530224) 3 (0.0533227) ] [ max ] CEM 1 Mrpl40 938.8 1195.0 1322.8 P ( S | Z, I ) = 1.00 Mrpl18 1083.6 1325.7 1466.9 Mean Corr = 0.76281 Mrps22 594.5 769.1 853.6 Mrpl11 1317.2 1738.6 1797.4 Mrpl28 1283.8 1680.9 1889.0 Mrpl13 2337.1 3103.4 3342.6 Mrpl34 1399.8 1916.9 2142.9 Mrps12 1365.5 1771.3 1845.1 Mrpl47 729.0 855.6 900.7 Mrpl20 1811.6 2534.8 2883.0 Mrpl39 927.0 1094.9 1193.1 Mrpl43 1301.3 1428.7 1648.5 Mrpl37 1021.5 1220.6 1448.5 Mrpl48 1144.5 1442.0 1593.4 Mrpl49 1080.1 1314.1 1435.2 Mrpl32 1392.4 1806.6 1898.5 Dap3 1323.1 1525.6 1657.5 Mrpl9 805.8 883.5 942.1 Mrpl12 1376.4 1602.7 1863.8 Mrpl46 611.1 753.3 802.4 Timm13 2100.3 2626.6 2867.6 Mrpl22 1321.5 1595.6 1776.4 Mrpl42 2889.8 3543.0 3950.9 CEM 1 + Mrps28 1151.6 1276.2 1442.1 Top 10 Genes Grpel1 1497.8 1846.8 1940.2 Chchd1 1882.3 2326.9 2668.8 Mrps7 1352.2 1579.9 1679.6 Mrps35 374.5 421.6 468.4

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE47872" 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=GSE47872 Status: Public on Mar 26 2014 Title: Integrated analysis identifies key determinants of embryonic stem cell identity and homeostasis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24711389 Summary & Design: Summary: Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators.

Overall design: Microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Ncl siRNA #1 (Invitrogen, 17975-MSS206961) Ncl siRNA #2 (Invitrogen, 17975-MSS275939), and Control siRNA duplex targeting firefly luciferase.

Background corr dist: KL-Divergence = 0.0151, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.8200

0.498 Kernel fit Pairwise Correlations Normal fit

Density 0.249

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 ES cellsNcl-KD ES 96hr, cells Ncl-KDrep1ES 96hr, cells (0.219844) Ncl-KDrep2ES siRNA cells (0.288296) Ncl-KDES #1siRNA cells96hr, ES #1 siRNArep1 cells96hr, (0.0656598) #2 siRNArep2 96hr, (0.112522) #2 rep1 96hr, (0.17668)[ rep2min (0.136998) ] [ medium ] [ max ] CEM 1 Mrpl40 3748.6 4196.5 5463.3 P ( S | Z, I ) = 1.00 Mrpl18 6121.1 6289.3 8677.2 Mean Corr = 0.76226 Mrps22 2111.2 2404.1 3076.8 Mrpl11 3117.4 3497.8 4415.0 Mrpl28 2405.4 2977.2 3072.7 Mrpl13 2623.6 2785.4 3629.7 Mrpl34 3657.4 4425.1 6114.7 Mrps12 2045.2 2449.5 4006.3 Mrpl47 3430.6 3683.8 4562.1 Mrpl20 3060.5 3389.2 5068.5 Mrpl39 3038.4 3310.4 3703.2 Mrpl43 2312.8 2640.1 2795.8 Mrpl37 1190.6 1307.6 1394.9 Mrpl48 933.5 1102.9 1391.2 Mrpl49 1458.8 1757.5 2400.4 Mrpl32 2951.9 3074.7 3744.3 Dap3 3058.2 3377.5 3589.1 Mrpl9 843.6 999.9 1142.5 Mrpl12 3468.1 4184.6 5469.6 Mrpl46 1691.8 1849.2 2195.9 Timm13 5454.5 5934.0 6300.7 Mrpl22 4674.4 5349.6 6260.1 Mrpl42 6173.3 6855.7 8757.4 CEM 1 + Mrps28 2942.5 3200.5 3505.7 Top 10 Genes Grpel1 4335.0 4412.8 4431.1 Chchd1 5997.0 6458.1 7488.6 Mrps7 1927.8 2249.5 2355.8 Mrps35 1476.0 1804.7 2325.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE10273" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

Keywords: growth conditions and rescue

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

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

0.703 Kernel fit Pairwise Correlations Normal fit

Density 0.351

0.000 CEM 1

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

Pre-normalization Quantiles

IRF4,8 null_IL7hi_rep1IRF4,8 null_IL7lo_rep1IRF4,8 null_+IRF4_rep1IRF4,8 (0.0886388) null_IL7hi_rep2IRF4,8 (0.12035) null_IL7lo_rep2IRF4,8 (0.0205448) null_+IRF4_rep2IRF4,8 (0.0459243) null_IL7hi_rep3IRF4,8 (0.211088) null_IL7lo_rep3IRF4,8 (0.0991639) null_+IRF4_rep3 (0.105896) (0.207952) (0.100442)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1337.5 2352.3 2687.3 P ( S | Z, I ) = 1.00 Mrpl18 2689.5 3985.8 4964.4 Mean Corr = 0.76146 Mrps22 876.3 1639.4 1927.3 Mrpl11 1269.9 2313.4 2540.9 Mrpl28 1252.9 1874.7 2078.3 Mrpl13 2077.3 3143.1 3399.5 Mrpl34 1241.6 1899.3 2262.5 Mrps12 901.1 1297.6 1457.4 Mrpl47 1097.4 1956.0 2346.6 Mrpl20 2543.7 2997.4 3550.6 Mrpl39 1076.9 1530.3 1800.7 Mrpl43 2354.7 2707.4 3004.4 Mrpl37 1362.7 1944.8 2287.9 Mrpl48 1178.8 1343.4 1536.5 Mrpl49 654.9 729.4 864.2 Mrpl32 2224.1 2954.1 3177.4 Dap3 1538.3 2201.6 2505.5 Mrpl9 2472.8 2702.5 3074.1 Mrpl12 795.7 2473.7 3162.4 Mrpl46 770.5 1336.6 1614.4 Timm13 2139.9 3580.0 3909.2 Mrpl22 1865.6 2826.1 3310.8 Mrpl42 3499.5 5636.7 6363.9 CEM 1 + Mrps28 702.3 1615.7 1786.4 Top 10 Genes Grpel1 2169.8 3501.3 3928.3 Chchd1 2969.2 4431.5 4801.5 Mrps7 776.6 1223.5 1330.9 Mrps35 836.4 1349.9 1605.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE20391" 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=GSE20391 Status: Public on Jun 16 2010 Title: Comprehensive expression profiling across primary fetal liver terminal erythroid differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20231426 Summary & Design: Summary: Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).

Overall design: Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationexplained in part by impaired cell cycle progression as well as increased apoptosisand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesissuch as alpha-globin and mitoferrin 1demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

Background corr dist: KL-Divergence = 0.0629, L1-Distance = 0.0458, L2-Distance = 0.0040, Normal std = 0.5380

0.745 Kernel fit Pairwise Correlations Normal fit

Density 0.373

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

sorted-R1sorted-R2 cells,sorted-R3 repl cells, 1 sorted-R5(0.0690938) repl cells, 1 sorted-R1(0.245264) repl cells, 1 sorted-R2(0.0420503) repl cells, 1 sorted-R3(0.0404946) repl cells, 2 sorted-R4(0.072379) repl cells, 2 sorted-R5(0.0230467) repl cells, 2 sorted-R2(0.0931882) repl cells, 1 sorted-R3(0.02643) repl cells, 2 (0.204919) repl cells, 3 (0.168869) repl 3 (0.014265)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1203.3 3113.0 4795.0 P ( S | Z, I ) = 1.00 Mrpl18 329.0 2976.6 7863.1 Mean Corr = 0.75542 Mrps22 721.9 2784.6 5499.8 Mrpl11 452.0 2065.0 4450.3 Mrpl28 525.7 1693.3 3795.8 Mrpl13 1678.7 4767.0 8409.5 Mrpl34 1568.0 2861.2 4759.7 Mrps12 871.4 2397.3 3802.5 Mrpl47 402.6 1243.5 4955.0 Mrpl20 1572.6 3557.9 5612.9 Mrpl39 543.6 1510.2 3467.2 Mrpl43 769.9 2290.4 3885.8 Mrpl37 404.5 847.6 1710.2 Mrpl48 699.7 2037.5 3725.9 Mrpl49 249.2 1303.9 1936.6 Mrpl32 2229.6 3674.8 4487.8 Dap3 984.6 4379.0 7202.4 Mrpl9 676.6 1720.0 3070.1 Mrpl12 549.4 3536.1 11718.9 Mrpl46 625.4 1732.3 2860.2 Timm13 1697.5 4434.8 8389.7 Mrpl22 279.9 2117.4 6579.6 Mrpl42 1271.4 5421.5 8836.8 CEM 1 + Mrps28 653.2 3277.6 5370.8 Top 10 Genes Grpel1 2025.0 3742.1 5302.8 Chchd1 864.0 3837.4 6163.3 Mrps7 494.5 1737.6 2869.8 Mrps35 227.2 1034.5 3306.3

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE12518" 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=GSE12518 Status: Public on Apr 15 2009 Title: Differential expression profile between MNV-1 infected and mock-infected RAW 264.7 cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19211757 Summary & Design: Summary: Noroviruses have been widely recognized for their importance as causative agents of non-bacterial gastroenteritis. Mouse norovirus is the only representative of the norovirus genus, family Caliciviridae, able to grow in cell culture. The aim of this study is to describe the differences in the expression profiles of MNV-1 and mock-infected macrophages (RAW 264.7 cells), in order to better understand the response of the host cell to norovirus infection.

Overall design: This study compares two type of samples (MNV-infected and mock-infected RAW cells) in biological triplicates respectively. The MNV stock used for infection was obtained in the same cell line, and purified with a sucrose cushion in order to account for expression changes caused by virus infection only.

Background corr dist: KL-Divergence = 0.0217, L1-Distance = 0.0741, L2-Distance = 0.0057, Normal std = 0.9739

0.425 Kernel fit Pairwise Correlations Normal fit

Density 0.213

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

Macrophages_MNVinfected_12h_rep1Macrophages_MNVinfected_12h_rep2Macrophages_MNVinfected_12h_rep3Macrophages_mock-infected_12h_rep1Macrophages_mock-infected_12h_rep2Macrophages_mock-infected_12h_rep3 (0.420779) (0.067863) (0.0729841) (0.171618)[ (0.221955)min (0.0448014) ] [ medium ] [ max ] CEM 1 Mrpl40 863.7 2243.1 2727.4 P ( S | Z, I ) = 1.00 Mrpl18 842.4 1926.5 3142.0 Mean Corr = 0.75333 Mrps22 1009.2 2102.1 2552.9 Mrpl11 870.4 1688.5 2443.2 Mrpl28 774.3 1578.1 2078.2 Mrpl13 2393.1 4413.9 5398.6 Mrpl34 647.4 1169.0 1862.6 Mrps12 1048.5 1304.5 1727.9 Mrpl47 1197.2 1754.1 2751.6 Mrpl20 1624.8 2008.7 2698.7 Mrpl39 1373.3 2651.8 2867.0 Mrpl43 1474.8 3926.5 4487.7 Mrpl37 91.7 1109.6 1319.5 Mrpl48 553.2 1511.9 1789.5 Mrpl49 310.8 525.9 1067.5 Mrpl32 1950.5 2984.7 3178.8 Dap3 696.5 3300.7 3814.8 Mrpl9 1640.7 2672.1 3380.1 Mrpl12 1727.7 4373.0 7083.8 Mrpl46 680.8 1300.9 1484.0 Timm13 2331.5 4761.0 6591.8 Mrpl22 1373.2 2993.3 3272.1 Mrpl42 1545.0 4132.9 5283.5 CEM 1 + Mrps28 685.3 1781.7 2208.7 Top 10 Genes Grpel1 1483.5 3056.4 3263.3 Chchd1 1587.6 4890.4 5132.6 Mrps7 843.8 1132.5 1902.1 Mrps35 456.8 1407.6 1643.2

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE55607" 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=GSE55607 Status: Public on Mar 06 2014 Title: A mouse model of HIES reveals pro and anti-inflammatory functions of STAT3 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24632714 Summary & Design: Summary: Mutations of STAT3 underlie the autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in non-hematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and non-hematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.

Overall design: The effect of IL-6 and IL-10 on BM-DC gene expression was investigated in cell derived from wild type or mut-Stat3 mice

Background corr dist: KL-Divergence = 0.0380, L1-Distance = 0.0921, L2-Distance = 0.0112, Normal std = 0.7946

0.502 Kernel fit Pairwise Correlations Normal fit

Density 0.251

0.000 CEM 1

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

Pre-normalization Quantiles

02-16-2012_J_Oshea1_AK_Mouse430_2_1_WT_LPS02-16-2012_J_Oshea2_AK_Mouse430_2_2_WT_LPS_IL602-16-2012_J_Oshea3_AK_Mouse430_2_3_WT_LPS_IL1002-16-2012_J_Oshea4_AK_Mouse430_2_4_HIES_LPS02-16-2012_J_Oshea5_AK_Mouse430_2_5_HIES_LPS_IL602-16-2012_J_Oshea6_AK_Mouse430_2_6_HIES_LPS_IL1004-25-2012_J_Oshea1_AK_Mouse430_2_1_WT_LPS 04-25-2012_J_Oshea2_AK_Mouse430_2_2_WT+LPS(0.0492366)04-25-2012_J_Oshea3_AK_Mouse430_2_3_WT+LPS+IL10 (0.032189)04-25-2012_J_Oshea4_AK_Mouse430_2_4_HIES-LPS (0.0842918)04-25-2012_J_Oshea5_AK_Mouse430_2_5_HIES+LPS (0.0436681)04-25-2012_J_Oshea6_AK_Mouse430_2_6_HIES+LPS+IL10 (0.0428197)06-05-2012_J_Oshea1_AK_Mouse430_2_1_WT-LPS (0.0364672)06-05-2012_J_Oshea2_AK_Mouse430_2_2_WT+LPS(0.0263507) 06-05-2012_J_Oshea3_AK_Mouse430_2_3_WT+LPS+IL10(0.00957086)06-05-2012_J_Oshea4_AK_Mouse430_2_4_HIES-LPS (0.019685)06-05-2012_J_Oshea5_AK_Mouse430_2_5_HIES+LPS (0.0496279)06-05-2012_J_Oshea6_AK_Mouse430_2_6_HIES+LPS+IL10 (0.0132083) (0.0342776)(0.0212785) (0.0518327)[ min (0.03232) (0.15294) ] (0.0898429)[ medium (0.210394) ] [ max ] CEM 1 Mrpl40 859.7 1868.2 2715.6 P ( S | Z, I ) = 1.00 Mrpl18 673.2 2413.8 2965.3 Mean Corr = 0.75209 Mrps22 702.4 1900.1 2525.9 Mrpl11 1115.5 2392.2 2990.6 Mrpl28 986.6 1619.3 2309.9 Mrpl13 1649.1 5368.8 7016.7 Mrpl34 654.2 1800.0 2629.6 Mrps12 753.3 1576.1 1995.2 Mrpl47 843.0 1537.3 2357.8 Mrpl20 1197.2 2230.2 3653.6 Mrpl39 746.0 1637.5 1908.8 Mrpl43 1214.6 1837.9 2716.8 Mrpl37 262.4 1038.0 1253.4 Mrpl48 520.7 1372.9 2183.2 Mrpl49 485.2 801.6 1383.6 Mrpl32 1401.7 2481.3 3694.1 Dap3 987.4 2378.0 3224.9 Mrpl9 1456.9 1845.7 2157.0 Mrpl12 888.5 2883.7 4233.7 Mrpl46 855.1 1369.9 1884.7 Timm13 2497.8 4775.4 7587.6 Mrpl22 1397.8 2530.5 4240.1 Mrpl42 766.8 3116.1 4701.6 CEM 1 + Mrps28 364.5 1653.5 2319.5 Top 10 Genes Grpel1 1692.3 2784.4 3793.2 Chchd1 1178.7 2747.7 3436.0 Mrps7 1158.2 2971.4 3656.4 Mrps35 239.7 808.5 1062.9

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE38754" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 40 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

1.014 Kernel fit Pairwise Correlations Normal fit

Density 0.507

0.000 CEM 1

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

Pre-normalization Quantiles

1wk Kidney1wk Kidney1 (0.0123038)1wk Kidney2 (0.00651267)1wk Kidney3 (0.0060231)1wk Kidney4 (0.00547852)1wk Heart5 (0.00723735)1wk 1 Heart(0.0625179)1wk 2 Heart(0.00996487)1wk 3 Heart(0.0170813)1wk 4 Heart(0.0238061)1wk 5 Lung(0.0200807)1wk 1 Lung(0.0204394)1wk 2 Lung(0.0237793)1wk 3 Lung(0.0243945)1wk 4 Lung(0.0260252)4wk 5 Kidney(0.0215459)4wk Kidney1 (0.0105642)4wk Kidney2 (0.0128356)4wk Kidney3 (0.0158369)4wk Kidney4 (0.0120714)4wk Heart5 (0.0122308)4wk 1 Heart(0.078414)4wk 2 Heart(0.0664686)4wk 3 Heart(0.0666415)4wk 4 Heart(0.06256)4wk 5 Lung(0.0670344)4wk 1 Lung(0.0289085)4wk 2 Lung(0.0240241)4wk 3 Lung(0.0265282)4wk 4 Lung(0.0219491)8wk 5 Kidney(0.0275338)8wk Kidney1 (0.00864238)8wk Kidney2 (0.010961)8wk Kidney3 (0.0145353)8wk Kidney4 (0.00620045)8wk Lung5 (0.0159793)8wk 1 Lung(0.0263949)8wk 2 Lung(0.020945)8wk 3 Lung(0.0217066)8wk 4 Lung(0.0300004) 5 (0.0238431) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 490.9 916.9 1667.5 P ( S | Z, I ) = 1.00 Mrpl18 492.1 1090.1 3704.3 Mean Corr = 0.75072 Mrps22 466.8 924.7 1577.6 Mrpl11 914.3 1611.8 2615.3 Mrpl28 646.2 1717.1 2956.6 Mrpl13 1787.3 3304.2 6124.7 Mrpl34 659.2 1867.1 3365.2 Mrps12 854.2 1819.0 2680.7 Mrpl47 308.3 717.6 1651.9 Mrpl20 1149.2 1782.8 3860.7 Mrpl39 629.6 1274.5 2616.1 Mrpl43 967.5 1509.3 2378.7 Mrpl37 411.0 720.2 1234.6 Mrpl48 595.2 1179.2 3044.8 Mrpl49 388.2 710.2 1182.4 Mrpl32 1207.7 1889.0 4035.8 Dap3 645.2 2096.4 3583.9 Mrpl9 917.4 1653.3 3920.0 Mrpl12 612.9 2816.6 5898.9 Mrpl46 679.3 1415.4 2135.5 Timm13 1299.3 2791.4 4222.7 Mrpl22 565.0 1983.1 3666.5 Mrpl42 1180.6 4469.1 16476.9 CEM 1 + Mrps28 563.0 1133.5 3086.1 Top 10 Genes Grpel1 1650.0 3596.0 5962.8 Chchd1 1242.0 2331.2 6326.8 Mrps7 554.8 1409.2 1890.2 Mrps35 522.1 1548.5 3178.8

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE13044" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 59 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13044 Status: Public on Oct 07 2008 Title: Gene expression profiling in the lung and liver of low and high dose Perfluorooctanoic Acid exposed mouse fetuses Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17681415 Summary & Design: Summary: Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well.

Keywords: gene expression, microarray,PFOA, mouse, fetus, liver

Overall design: Please note that each dose experiment had separate concurrent controls.

Background corr dist: KL-Divergence = 0.0397, L1-Distance = 0.0327, L2-Distance = 0.0022, Normal std = 0.6008

0.664 Kernel fit Pairwise Correlations Normal fit

Density 0.332

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

0mg/kg/day0mg/kg/day PFOA,0mg/kg/day RepPFOA,0mg/kg/day 1, Block RepPFOA,0mg/kg/day 1, 2 Block ReplungPFOA,0mg/kg/day 2,(high 2 Block RepliverPFOA, 0mg/kg/daydose) 2,(high 1 Block ReplungPFOA, (0.0134181) 0mg/kg/daydose) 3,(high 1 Block RepliverPFOA, (0.0125156) 0mg/kg/daydose) 3,(high 3 Block ReplungPFOA, (0.0131593) 0mg/kg/daydose) 4,(high 3, Block Rep PFOA,liver (0.012011) 5mg/kg/daydose) 4, (high4, Block Rep PFOA,lung (0.0146919)5mg/kg/day dose) 5, (high4, Block Rep PFOA,liver (0.00825444)5mg/kg/day dose)5, (high5, Block Rep PFOA,lung (0.0139624)5mg/kg/day dose) 1, (high5, Block Rep PFOA,liver (0.00817886)5mg/kg/day dose)1, (high5, Block Rep PFOA,lung (0.0207516)5mg/kg/day dose) 2, (high5, Block Rep PFOA,liver (0.0173519)5mg/kg/day dose)2, (high1, Block Rep PFOA,lung (0.0151728)5mg/kg/day dose) 3, (high1, Block Rep PFOA,liver (0.0204675)5mg/kg/day dose)3, (high2, Block Rep PFOA,lung (0.0096803)5mg/kg/day dose) 4, (high2, Block Rep PFOA,liver (0.0260852)10mg/kg/day dose)4, (high3, Block Rep PFOA,lung (0.0198782)10mg/kg/day dose) 5, (high3, BlockRep liver PFOA, (0.031237)10mg/kg/day dose)5, (high4, Block lung RepPFOA, (0.0156177)10mg/kg/day dose) (high1,4, Blockliver RepPFOA, (0.0191928)10mg/kg/day dose) (high1, 2, Block Rep PFOA,lung (0.0227694)10mg/kg/day dose) 2, (high2, Block Rep PFOA,liver (0.0256513)10mg/kg/day dose)2, (high1, Block Rep PFOA,lung10mg/kg/day (0.0190853) dose) 3, (high1, Block Rep PFOA,liver10mg/kg/day (0.0265091) dose)3, (high3, Block Rep PFOA,lung10mg/kg/day (0.0142232) dose) 4, (high3, Block Rep PFOA,liver0mg/kg/day (0.0246888) dose)4, (high4, Block Rep PFOA,lung0mg/kg/day (0.0284168) dose) 5, (high4, PFOA, BlockRep liver0mg/kg/day (0.0117054) dose)5, (high 5, RepPFOA,Block lung0mg/kg/day (0.0243137) 1,dose) (highBlock5, RepPFOA, liver0mg/kg/day (0.0169562) 1, dose) 5 (high Block ReplungPFOA,0mg/kg/day (0.0231354) 2,dose)(low 5 Block RepliverPFOA, dose)0mg/kg/day (0.0146876) 2,(low 1 Block ReplungPFOA, (0.0149102) dose)0mg/kg/day 3,(low 1 Block RepliverPFOA, (0.00899219) dose)0mg/kg/day 3,(low 2 Block ReplungPFOA, (0.0240394) dose)0mg/kg/day 4,(low 2, Block Rep PFOA, liver(0.00658578) dose)1mg/kg/day 4, (low4, Block Rep PFOA, lung(0.0109342) dose)1mg/kg/day 5, (low4, Block Rep PFOA,liver (0.00790411) dose)1mg/kg/day 5, (low3, Block Rep PFOA,lung (0.0214414) dose)1mg/kg/day 1, (low3, Block Rep PFOA,liver (0.0145509) dose)1mg/kg/day 1, (low5, Block Rep PFOA,liver (0.00985417) dose)1mg/kg/day 1, (low2, Block Rep PFOA,lung (0.0139088) dose)1mg/kg/day 2, (low2, Block Rep PFOA,liver (0.0211146) dose)1mg/kg/day 2, (low3, Block Rep PFOA,lung (0.0201498) dose)1mg/kg/day 3, (low3, Block Rep PFOA,liver (0.0186721) dose)3mg/kg/day 3, (low4, Block Rep PFOA,lung (0.0144019) dose)3mg/kg/day 4, (low4, Block Rep PFOA,liver (0.0235686) dose)3mg/kg/day 4, (low1, Block Rep PFOA,lung (0.0157224) dose)3mg/kg/day 1, (low1, Block Rep PFOA,liver (0.0143057) dose)3mg/kg/day 1, (low3, Block Rep PFOA,lung (0.017891) dose)3mg/kg/day 2, (low3, Block Rep PFOA,liver (0.0141219) dose)3mg/kg/day 2, (low1, Block Rep PFOA,lung (0.0117152) dose)3mg/kg/day 3, (low1, Block Rep PFOA,liver (0.0242708) dose)3mg/kg/day 3, (low5, Block Rep PFOA,lung (0.00954321) dose)3mg/kg/day 4, (low5, Block Rep PFOA,liver (0.0176493) dose) 4, (low4, Block Rep PFOA,lung (0.0107535) dose) 5, (low4, BlockRep liver (0.0177152) dose) 5, (low2, Block lung (0.0107067) dose)[ (low2,min liver (0.03273) dose) (low ] (0.0151302) dose) (0.0129481)[ medium ] [ max ] CEM 1 Mrpl40 1117.4 2085.7 2789.5 P ( S | Z, I ) = 1.00 Mrpl18 830.5 1659.8 2400.9 Mean Corr = 0.74970 Mrps22 642.5 1898.3 2600.8 Mrpl11 805.4 1127.6 1404.8 Mrpl28 874.3 1447.0 2164.6 Mrpl13 2268.5 3858.1 5379.5 Mrpl34 987.7 1651.4 2322.2 Mrps12 965.7 1673.3 2431.7 Mrpl47 608.0 1183.2 1948.0 Mrpl20 1211.1 2018.8 3070.6 Mrpl39 878.9 1343.5 2157.1 Mrpl43 1592.8 2109.4 2898.0 Mrpl37 488.4 907.2 1276.6 Mrpl48 1391.7 1905.6 2257.8 Mrpl49 626.1 994.6 1387.9 Mrpl32 1505.4 1997.0 2510.1 Dap3 1446.6 2407.1 3137.7 Mrpl9 843.9 1118.5 1371.1 Mrpl12 1028.1 3184.4 4550.9 Mrpl46 524.1 1268.8 1622.5 Timm13 1968.1 3293.9 5635.5 Mrpl22 838.0 1882.1 2820.9 Mrpl42 1476.4 2938.8 4975.4 CEM 1 + Mrps28 866.1 3095.3 4223.0 Top 10 Genes Grpel1 1258.8 3292.7 5137.6 Chchd1 1606.9 2244.7 2996.5 Mrps7 1014.2 2023.5 3045.1 Mrps35 831.1 1402.9 2080.1

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE52542" 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=GSE52542 Status: Public on Nov 21 2013 Title: VEGF Isoform Transcriptome Changes in the E9.5 Murine Forebrain Organism: Mus musculus Experiment type: Third-party reanalysis Platform: GPL1261 Pubmed ID: 24124161 Summary & Design: Summary: Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice.

Overall design: This study comprises of new samples and reanalysis of Samples from GSE30767 and GSE8091.

Background corr dist: KL-Divergence = 0.0176, L1-Distance = 0.0390, L2-Distance = 0.0022, Normal std = 0.7805

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

forebrain_Vegf188_1forebrain_Vegf188_2forebrain_Vegf188_3 (0.098621)forebrain_Vegf188_4 (0.147096)forebrain_wildtype_5 (0.0735857)forebrain_wildtype_6 (0.244835)forebrain_Vegf120188_1 (0.0952193)forebrain_Vegf120188_2 (0.127711)forebrain_Vegf120188_3 (0.081178) (0.0348241) (0.0969298)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1069.3 1348.8 2125.0 P ( S | Z, I ) = 1.00 Mrpl18 2642.8 2909.1 4025.5 Mean Corr = 0.74855 Mrps22 2105.2 2324.9 2973.7 Mrpl11 2160.8 2290.2 3656.5 Mrpl28 1198.9 1505.6 2496.4 Mrpl13 2350.4 2839.0 3812.3 Mrpl34 1044.1 1467.9 2173.6 Mrps12 1081.6 1600.1 2527.1 Mrpl47 1669.5 2028.8 2571.3 Mrpl20 1798.5 2116.3 4508.3 Mrpl39 1713.4 1792.0 2030.3 Mrpl43 1025.9 1567.3 2891.2 Mrpl37 753.5 855.4 1354.2 Mrpl48 410.2 560.2 1055.7 Mrpl49 931.6 1091.3 1194.0 Mrpl32 1852.6 2059.2 2773.8 Dap3 1581.2 2085.7 2753.5 Mrpl9 580.1 941.2 1778.3 Mrpl12 3244.9 4121.3 6757.8 Mrpl46 939.1 1042.9 1538.7 Timm13 1698.9 2894.7 5509.8 Mrpl22 1396.4 1518.9 2158.1 Mrpl42 2563.9 3102.4 4471.4 CEM 1 + Mrps28 1425.3 1620.1 2540.5 Top 10 Genes Grpel1 2354.1 2768.4 4043.5 Chchd1 4015.2 4427.2 7452.1 Mrps7 757.1 1184.5 1748.6 Mrps35 739.3 911.9 1380.1

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE46094" 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=GSE46094 Status: Public on May 01 2014 Title: Expression data from PML-RARÎ± transgenic mouse APL(acute promyelocyte leukemia) cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The differentiation of leukemia stem cells (LSCs) is generally regarded as a one-way alterative process to self-renewal. However, how differentiation impacts LSC stemness has largely been unexplored. Here we show that before reaching terminal differentiation (TD), apical LSCs of mouse acute promyelocytic leukemia passed through a partial differentiation (PD) stage, wherein the leukemia cells re-initiated leukemia via de-differentiation albeit at a reduced rate. Notably, while retinoic acid (RA) preferentially drove the transition of LSC to PD, monocytic Irf8 skewed PD cells to terminal maturation over de-differentiation and/or expansion. Remarkably, the combined use of RA and Irf8 induction depleted the total leukemogenic potential, which indicates that discrete stage- or lineage-specific mechanisms elaborate a step-wise LSC differentiation.

We used microarrays to detail the global programme of gene expression indicating the molecular mechanisms unerlying the the process of LSC step-wise differentiation.

Overall design: Retroviral GFP-labled mouse APL cells (bone marrow sample) were repopulated in vivo through transplantation into syngenic recipients. At the proper time points, the GFP positive APL bone marrow cells were collected and sorted for UNSC, UNPD and UNTD samples through FACS. RA-PD and RA-TD cells were sorted from bone marrow tissue treated with ATRA (all trans retinoic acid) for 5 days. The freshly isolated samples were then lysed for RNA extration. Each sample had two biological replicates.

Background corr dist: KL-Divergence = 0.0755, L1-Distance = 0.0335, L2-Distance = 0.0016, Normal std = 0.5022

0.816 Kernel fit Pairwise Correlations Normal fit

Density 0.408

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

APL SCAPL subset, SCAPL subset,biological PDAPL subset,biological rep1PDAPL subset, biological(0.0378574) rep2RAPDAPL biological(0.0498317) subset, rep1RAPDAPL (0.297458) subset, rep2biologicalTDAPL subset, (0.210678) biologicalTD rep1APL subset,biological RATD(0.0615008) rep2APL biological subset, rep1RATD(0.05478) (0.0539212) subset,rep2biological (0.0797927) biological rep1 (0.0206197) rep2[ min (0.133561) ] [ medium ] [ max ] CEM 1 Mrpl40 2135.1 2718.9 4361.9 P ( S | Z, I ) = 1.00 Mrpl18 2315.6 3828.5 5979.8 Mean Corr = 0.74771 Mrps22 939.0 1457.3 2011.2 Mrpl11 1746.3 2905.0 5238.6 Mrpl28 1348.6 1789.6 3101.5 Mrpl13 5450.3 7070.5 9499.0 Mrpl34 1757.9 3285.3 5714.3 Mrps12 1726.0 2699.3 4784.6 Mrpl47 726.1 1217.1 1923.6 Mrpl20 1886.9 2656.2 4803.6 Mrpl39 1307.4 1881.8 3058.3 Mrpl43 2892.1 3757.7 6277.6 Mrpl37 529.9 855.6 1445.8 Mrpl48 1423.0 1994.9 3570.0 Mrpl49 591.2 789.0 1031.1 Mrpl32 2770.1 3899.1 5174.6 Dap3 2414.3 2834.1 4241.5 Mrpl9 783.1 1109.8 1636.3 Mrpl12 1652.7 3784.1 8286.4 Mrpl46 929.8 1245.1 1962.9 Timm13 4428.1 5824.1 10776.8 Mrpl22 2099.9 2933.1 4096.1 Mrpl42 2307.9 3828.8 5625.8 CEM 1 + Mrps28 1719.1 2798.2 5656.1 Top 10 Genes Grpel1 2327.4 3235.3 5470.4 Chchd1 3869.6 5631.1 8931.8 Mrps7 946.0 1490.3 2498.2 Mrps35 906.7 1460.4 2308.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE27114" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.478 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

2_ESwt_a2_ESwt_b (0.171624)2_NPwt_a (0.112101)2_NPwt_b (0.102651)2_TNwt_a (0.0897852)2_TNwt_b (0.280617) (0.243222) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 831.8 2512.0 3669.3 P ( S | Z, I ) = 1.00 Mrpl18 1022.9 2388.3 3479.0 Mean Corr = 0.74632 Mrps22 1607.2 2444.2 2857.2 Mrpl11 1737.5 4131.4 4418.9 Mrpl28 1900.4 4311.1 4853.0 Mrpl13 1205.0 3400.3 4427.1 Mrpl34 1346.3 2418.5 2830.3 Mrps12 1403.7 2266.7 3937.6 Mrpl47 1558.4 3277.1 4250.0 Mrpl20 3429.6 3702.8 3880.7 Mrpl39 873.7 2124.3 2422.3 Mrpl43 2387.5 2611.6 3150.3 Mrpl37 424.4 1198.6 1242.5 Mrpl48 1411.9 2187.9 2369.4 Mrpl49 776.7 1424.5 1696.4 Mrpl32 1652.8 2499.7 2918.5 Dap3 3676.5 5876.2 7478.1 Mrpl9 681.6 1279.1 1372.3 Mrpl12 2127.2 4119.1 4664.1 Mrpl46 986.0 1493.8 1683.7 Timm13 3954.9 6990.2 7401.8 Mrpl22 2002.4 5257.8 6165.2 Mrpl42 3901.0 8040.1 10163.6 CEM 1 + Mrps28 635.3 2385.4 3246.6 Top 10 Genes Grpel1 1338.2 3509.6 4163.2 Chchd1 1960.5 4606.9 5908.1 Mrps7 1081.9 1606.3 1779.1 Mrps35 790.7 1917.9 2313.7

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE55356" 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=GSE55356 Status: Public on Jul 01 2014 Title: p38a-dependent gene expression in the colonic mucosa Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Gene expression in the colonic mucosa of wild-type and p38a-knockout intestinal epithelial cells (IECs) were compared.

C57BL/6 wild-type mice, and intestinal epithelial cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of colonic mucosa

Overall design: Gene expression in each genotype was analyzed in triplicate.

Background corr dist: KL-Divergence = 0.0251, L1-Distance = 0.0199, L2-Distance = 0.0005, Normal std = 0.7025

0.576 Kernel fit Pairwise Correlations Normal fit

Density 0.288

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

KO-A (0.149267)KO-B (0.0821682)KO-C (0.072382)WT-A (0.208512)WT-B (0.184196)WT-C (0.303476) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 904.4 1299.6 1688.1 P ( S | Z, I ) = 1.00 Mrpl18 1377.3 2461.5 3281.0 Mean Corr = 0.74562 Mrps22 672.3 1572.2 1730.5 Mrpl11 1052.9 1610.3 1661.4 Mrpl28 1595.2 1815.6 1908.3 Mrpl13 2331.9 3671.5 3695.1 Mrpl34 971.2 1659.0 1855.5 Mrps12 1746.5 2070.7 2421.2 Mrpl47 1425.0 1832.2 2010.3 Mrpl20 1682.3 2166.3 2241.6 Mrpl39 1017.4 1556.6 2008.0 Mrpl43 1997.2 2526.8 2912.5 Mrpl37 330.4 429.2 594.2 Mrpl48 724.0 1242.0 1357.4 Mrpl49 359.6 646.8 941.9 Mrpl32 1663.6 2218.9 2504.2 Dap3 1431.0 2124.3 2208.7 Mrpl9 1286.5 1745.1 1990.9 Mrpl12 4055.8 5993.5 6346.7 Mrpl46 1313.5 1590.2 1922.3 Timm13 2879.0 3478.2 3786.5 Mrpl22 1146.9 1344.0 1700.7 Mrpl42 3058.9 5041.8 5561.1 CEM 1 + Mrps28 1116.7 2087.7 2802.4 Top 10 Genes Grpel1 2071.1 3506.8 3827.6 Chchd1 2062.2 3162.1 3762.4 Mrps7 659.7 879.5 1209.5 Mrps35 1021.2 1687.9 2247.4

Null module Mrpl51 Mrpl35 Mrps14 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 (0.0299475) degrees rep 1 42 week degrees(0.076579) repl 14 3weekdegrees (0.0674416)rep 1 54 (0.137482)weeksdegrees rep 25 (0.199174)30weeks rep degrees 35 (0.160629)30weeks degrees rep5 30weeks1 (0.0457306) degrees rep5 4weeks2 degrees(0.0523999) rep5 4weeks3 degrees(0.0568434) rep 1 4 (0.0795732) degrees rep 2 (0.0324442) rep 3 (0.0617553)[ min ] [ medium ] [ max ] CEM 1 Mrpl40 1459.4 2049.7 2861.3 P ( S | Z, I ) = 1.00 Mrpl18 2173.0 3011.5 4436.6 Mean Corr = 0.74440 Mrps22 1552.6 2115.3 4024.5 Mrpl11 1365.1 1699.2 2217.4 Mrpl28 851.5 1453.1 2139.9 Mrpl13 2671.9 3409.9 4518.9 Mrpl34 364.2 811.8 2293.7 Mrps12 919.5 1219.6 1690.5 Mrpl47 547.6 1017.4 1472.6 Mrpl20 2323.6 2994.1 6312.2 Mrpl39 1203.6 1863.0 2742.5 Mrpl43 1178.6 1545.8 1881.0 Mrpl37 555.6 717.9 1152.1 Mrpl48 1543.5 1742.0 2529.7 Mrpl49 1077.2 1250.0 1494.5 Mrpl32 2655.7 3460.5 4076.6 Dap3 1603.9 1828.7 2215.8 Mrpl9 1283.5 1592.9 2494.3 Mrpl12 1889.4 2794.6 6121.8 Mrpl46 497.6 890.9 1374.4 Timm13 2322.7 3361.9 6345.9 Mrpl22 1134.6 1588.1 1906.0 Mrpl42 4940.3 7632.6 13030.5 CEM 1 + Mrps28 1023.0 1270.1 1832.5 Top 10 Genes Grpel1 1816.7 3516.4 5392.0 Chchd1 2871.1 3108.5 3590.8 Mrps7 1217.7 1693.7 3085.1 Mrps35 803.2 1504.0 1842.3

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE48884" 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=GSE48884 Status: Public on Jul 16 2013 Title: Cyclin D1 determines estrogen depependent signaling in mouse mammary gland. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23864650 Summary & Design: Summary: Ovariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays.

Overall design: Six separate control Ccnd1+/+ C57BL/6 were compared to six Ccnd1-/- C57BL/6 mice. 3 mice in each group treated with placebo and three mice treated with E2

Background corr dist: KL-Divergence = 0.0851, L1-Distance = 0.0269, L2-Distance = 0.0012, Normal std = 0.4687

0.851 Kernel fit Pairwise Correlations Normal fit

Density 0.426

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 mammaryMouse mammaryMouse gland mammaryMouse Ccnd1+/+ gland mammaryMouse Ccnd1+/+ gland Vehicle mammaryMouse Ccnd1+/+ gland VehicleRep1 mammaryMouse Ccnd1+/+ gland(0.086055) VehicleRep2 mammaryMouse Ccnd1+/+ gland(0.064324) E2Rep3 mammaryRep1Mouse Ccnd1+/+ gland(0.0881477) E2 (0.0725887) mammaryRep2Mouse Ccnd1-/- gland E2 (0.0269761) mammaryRep3Mouse Ccnd1-/- glandVehicle (0.0216225) mammaryMouse Ccnd1-/- gland VehicleRep1 mammary Ccnd1-/-(0.116179) gland VehicleRep2 Ccnd1-/-(0.0356103) gland E2Rep3 Rep1 Ccnd1-/-(0.0337064) E2 (0.335301) Rep2[ minE2 (0.0498287) Rep3 ](0.0696606) [ medium ] [ max ] CEM 1 Mrpl40 1137.6 1532.8 1833.7 P ( S | Z, I ) = 1.00 Mrpl18 657.1 908.8 1291.6 Mean Corr = 0.74308 Mrps22 903.0 1357.7 2198.7 Mrpl11 1836.1 2456.0 3305.3 Mrpl28 2351.0 3143.8 4661.7 Mrpl13 2308.4 3151.9 4382.8 Mrpl34 347.2 511.9 738.1 Mrps12 738.3 910.4 1157.7 Mrpl47 695.1 1092.3 1394.5 Mrpl20 601.5 937.2 1450.0 Mrpl39 662.1 951.3 1517.3 Mrpl43 2606.5 3303.9 4063.2 Mrpl37 656.6 946.9 1845.5 Mrpl48 1407.8 2425.0 4291.5 Mrpl49 503.9 664.8 854.7 Mrpl32 1315.2 1819.1 2179.8 Dap3 3099.9 3557.6 4444.0 Mrpl9 632.8 949.6 1156.7 Mrpl12 1815.5 3454.9 5466.5 Mrpl46 1722.9 2283.0 3411.2 Timm13 2615.4 3725.5 5090.4 Mrpl22 2434.4 2988.7 4086.4 Mrpl42 1679.6 2693.9 4295.8 CEM 1 + Mrps28 965.3 1443.7 2070.1 Top 10 Genes Grpel1 6320.0 8430.5 11020.3 Chchd1 2354.4 3027.8 3676.8 Mrps7 1017.4 1494.1 2328.1 Mrps35 1414.1 1980.7 2891.6

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE28389" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.353

0.000 CEM 1

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

Pre-normalization Quantiles

[E-MTAB-368][E-MTAB-368] Mouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMousestage[E-MTAB-368] E7.5 developmentalMousestage[E-MTAB-368] 1 (0.0864098) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.063909) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.0604124) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0750915) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0185055) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.020554) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0506891) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.0342485) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0192781) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0425465) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0155972) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.022767) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.062146) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0544122) developmentalMousestage 1 E14.5 (0.0697616) developmentalMousestage 2 E16.5 (0.0466813) developmentalstage 1 E16.5(0.0569239) stage[ min 2 E18.5(0.07361) stage 1] E18.5(0.0739553) 2 (0.0525008)[ medium ] [ max ] CEM 1 Mrpl40 997.2 3124.4 5646.2 P ( S | Z, I ) = 1.00 Mrpl18 2152.6 3917.5 6297.7 Mean Corr = 0.73968 Mrps22 1831.1 3198.2 4060.8 Mrpl11 1709.2 4222.9 5244.7 Mrpl28 955.6 2805.7 3576.6 Mrpl13 2808.5 6020.6 8058.0 Mrpl34 1559.5 2265.1 3734.9 Mrps12 1237.9 2616.2 3846.8 Mrpl47 929.2 2567.7 3915.7 Mrpl20 1535.7 3159.0 4125.3 Mrpl39 1269.4 2682.2 3767.8 Mrpl43 1339.4 2860.8 3902.5 Mrpl37 694.8 1337.6 1637.0 Mrpl48 1037.8 1733.1 2349.7 Mrpl49 592.3 1351.3 1597.5 Mrpl32 1640.5 2245.0 2686.7 Dap3 1941.8 3430.8 4937.8 Mrpl9 1533.4 1870.7 2540.8 Mrpl12 2602.8 4857.0 8997.4 Mrpl46 908.7 1866.6 2950.2 Timm13 2432.8 5650.6 8101.7 Mrpl22 1706.7 3570.5 6121.0 Mrpl42 3104.0 6296.2 9936.4 CEM 1 + Mrps28 1087.2 2488.4 3939.7 Top 10 Genes Grpel1 1984.4 3217.6 4952.0 Chchd1 2728.9 5412.9 6723.4 Mrps7 1351.5 1844.9 2664.1 Mrps35 793.2 1747.6 2403.4

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE15155" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.672 Kernel fit Pairwise Correlations Normal fit

Density 0.336

0.000 CEM 1

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

Pre-normalization Quantiles

quiescentquiescent satellitequiescent satellite cell_adultactivated satellite cell_adult muscle_rep1activated satellite cell_adult muscle_rep2activated satellite cell_adult (0.135046) muscle_rep3activated satellite cell_adult (0.0989038) regeneratingactivated satellite cell_adult (0.0802863) regeneratingactivated satellite cell_1wk mdx regeneratingactivated muscle_rep1satellite cell_1wk mdxoldactivated growing muscle_rep2satellite cell_1wk mdxoldactivated (0.0446457) growing muscle_rep3 satellite muscle_rep1cell_cultured old (0.0264881) growing satellite muscle_rep2cell_cultured (0.056716) (0.0118984) 3days_rep1 muscle_rep3cell_cultured (0.0171466) 3days_rep2 (0.169063)[ (0.0107464) 3days_rep3min (0.213813) ] (0.135246) [ medium ] [ max ] CEM 1 Mrpl40 492.8 1386.9 4128.3 P ( S | Z, I ) = 1.00 Mrpl18 481.5 1859.8 3884.4 Mean Corr = 0.73938 Mrps22 456.7 1462.7 3420.1 Mrpl11 1456.4 3062.7 4978.1 Mrpl28 549.8 1265.7 1729.0 Mrpl13 1940.3 3728.7 6627.6 Mrpl34 288.6 574.0 1036.8 Mrps12 674.3 1659.3 2303.9 Mrpl47 403.4 1446.0 3831.0 Mrpl20 831.9 1489.1 3348.7 Mrpl39 1175.6 1832.7 3502.4 Mrpl43 336.9 897.7 1427.6 Mrpl37 378.5 761.8 1478.0 Mrpl48 1691.7 2392.0 3391.1 Mrpl49 440.6 733.4 1337.5 Mrpl32 635.3 1351.6 1664.0 Dap3 1690.1 2157.0 3687.9 Mrpl9 1553.1 2420.8 3025.5 Mrpl12 1102.2 2508.7 4870.9 Mrpl46 534.1 941.8 1922.4 Timm13 1175.0 3695.8 4658.3 Mrpl22 926.3 3031.8 4181.3 Mrpl42 3322.7 4865.9 8038.9 CEM 1 + Mrps28 1401.4 1896.2 2496.9 Top 10 Genes Grpel1 1749.2 2525.1 4363.9 Chchd1 1054.5 2532.5 5043.0 Mrps7 1171.3 1990.5 2713.2 Mrps35 385.3 982.6 1583.3

Null module Mrpl51 Mrpl35 Mrps14 GEO Series "GSE28417" 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=GSE28417 Status: Public on Apr 02 2012 Title: Expression data from mouse tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The role of p53 in assuring longevity through prevention of cancer is well established, but how it specifically regulates aging is still controversial. Our assumption is that distinct p53-pathways regulate tumor suppression and aging and that p66Shc is one of the master regulators of the p53 aging function. p66Shc longevity determinant protein acts as a downstream target of p53 and it is indispensable for the ability of activated p53 to induce elevation of intracellular oxidants and apoptosis.

We used microarray to gain insight into the mechanism of the physiological activation of p53-p66Shc pathway

Overall design: Total RNA was extracted from freshly isolated thymus, liver, heart and lung of two months old mice (pool of four mice for each genotype)

Background corr dist: KL-Divergence = 0.0576, L1-Distance = 0.0878, L2-Distance = 0.0145, Normal std = 0.6092

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

Heart_WTLiver_WT (0.18767)Lung_WT (0.0246984)Thymus_WT (0.114524)Heart_p66KO (0.0411164)Liver_p66KO (0.0972785)Lung_p66KO (0.0188498)Thymus_p66KO (0.119922)Heart_p53KOLiver_p53KO (0.070745) (0.13392)Lung_p53KO (0.0244605)Thymus_p53KO (0.133868) (0.0329477) [ min ] [ medium ] [ max ] CEM 1 Mrpl40 824.4 1369.8 1598.3 P ( S | Z, I ) = 1.00 Mrpl18 352.9 1096.0 2048.9 Mean Corr = 0.73662 Mrps22 599.8 1478.5 1824.7 Mrpl11 977.9 1632.7 2537.6 Mrpl28 1217.4 2648.1 4233.2 Mrpl13 2205.0 3028.6 4516.3 Mrpl34 844.5 2035.6 3210.8 Mrps12 1064.7 1921.2 2049.7 Mrpl47 465.8 779.9 1520.1 Mrpl20 1386.2 2183.8 2731.5 Mrpl39 758.8 1363.4 2272.1 Mrpl43 1082.9 1961.8 2606.3 Mrpl37 388.7 910.0 1403.3 Mrpl48 1107.0 1561.3 2570.6 Mrpl49 344.1 661.7 1093.2 Mrpl32 1203.9 1982.2 2897.0 Dap3 1422.0 2288.6 3951.3 Mrpl9 687.0 1052.9 1673.4 Mrpl12 751.0 2313.9 2922.4 Mrpl46 809.1 1694.6 2196.2 Timm13 1863.5 2680.4 5310.4 Mrpl22 982.2 1890.1 2249.1 Mrpl42 1676.8 3578.8 17751.1 CEM 1 + Mrps28 1181.0 1847.0 4257.9 Top 10 Genes Grpel1 1439.6 3397.2 5095.2 Chchd1 2511.4 3986.7 7189.3 Mrps7 587.3 1400.2 2138.2 Mrps35 468.0 1078.9 2137.4

Null module Mrpl51 Mrpl35 Mrps14