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: 12 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. Eif3m Num ofGenesinQueryGeneset:12.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Eif3g Eif3d Eif3b Eif3h Eif3e Eif3a Eif3c Eif3k Eif3f Eif3i Eif3l

Eif3l Eif3d Eif3i Eif3g Eif3k Eif3h Eif3c Eif3f Eif3m Eif3b Eif3a Eif3e Singletons CEM 1(564datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 2700060E02Rik Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page1 Tomm20 Nudt21 Ruvbl1 Ruvbl2 Psmb4 Rpl13a Rpl18a Rpl10a C1qbp Wdr74 Aimp1 Ddx39 Apex1 Rps19 Naa10 Snrpb Prmt1 Rplp2 Rplp0 Emg1 Rpl7a Rpl27 Eif3m Nhp2 Phb2 Rps5 Eif3b Eif3h Eif3g Eif3d Naca Eif3c Eif3k Pes1 Tcp1 Rtcb Rpl7 Cct7 Rpl4 Cct4 Rpl6 Rpl8 Cct2 Cct5 Eif3f Eef2 Eif3i Eif3l Ncl 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE6998 [32] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE46443 [12] GSE7838 [9] GSE13693 [9] GSE28389 [20] GSE38031 [8] GSE6065 [100] GSE40230 [15] GSE13874 [14] GSE5425 [6] GSE35593 [6] GSE51628 [15] GSE2527 [6] GSE16454 [24] GSE27605 [8] GSE25257 [6] GSE12881 [6] GSE6689 [12] GSE6837 [8] GSE24121 [9] GSE52542 [9] GSE10989 [6] GSE15587 [6] GSE27379 [6] GSE11333 [6] GSE18586 [9] GSE49050 [72] GSE21900 [12] GSE36378 [20] GSE51608 [6] GSE55356 [6] GSE55607 [18] GSE48203 [9] GSE48935 [12] GSE14753 [6] GSE45744 [12] GSE18660 [10] GSE30192 [6] GSE36392 [9] GSE54653 [6] GSE13149 [25] GSE32903 [12] GSE58296 [9] GSE9013 [12] GSE53951 [10] GSE19338 [24] GSE47196 [6] GSE51365 [28] GSE34761 [8] GSE21278 [48] GSE27114 [6] GSE13225 [6] GSE48790 [8] GSE15458 [8] GSE23502 [8] GSE17462 [8] GSE29241 [6] GSE13805 [7] GSE33121 [10] GSE9400 [8] GSE28031 [6] GSE43381 [26] GSE13963 [15] GSE30293 [8] GSE26355 [6] GSE56345 [9] GSE18460 [16] GSE32386 [13] GSE11496 [16] GSE31013 [12] GSE23598 [8] GSE11859 [27] GSE6957 [12] GSE23600 [10] GSE19194 [14] GSE42135 [42] GSE16874 [12] GSE17709 [18] GSE17553 [16] GSE30485 [15] GSE15872 [18] GSE12001 [6] GSE28025 [18] GSE12454 [13] GSE21491 [9] GSE4786 [9] GSE24628 [16] GSE11120 [10] GSE21944 [6] GSE4098 [16] GSE18115 [8] GSE6030 [6] GSE7309 [12] GSE30865 [68] GSE5671 [18] GSE4411 [11] GSE55855 [6] GSE46500 [6] GSE11356 [9] GSE34961 [9] GSE38693 [8] GSE36415 [14] GSE1999 [15] GSE8156 [6] GSE27720 [6] GSE24512 [29] GSE6675 [8] GSE15772 [8] GSE39621 [51] GSE11044 [6] GSE11201 [18] GSE20954 [14] GSE41925 [8] GSE2019 [12] GSE9044 [6] GSE15303 [11] GSE40260 [6] GSE27786 [20] GSE1435 [27] GSE12518 [6] GSE24437 [6] GSE46094 [10] GSE7050 [18] GSE40856 [8] GSE9975 [36] GSE28417 [12] GSE31598 [12] GSE40087 [15] GSE17097 [20] GSE28895 [6] GSE56542 [8] GSE45044 [12] GSE4694 [6] GSE30488 [52] GSE46209 [21] GSE11186 [33] GSE12948 [9] GSE13707 [20] GSE11220 [44] GSE11194 [9] GSE27019 [6] GSE26096 [10] GSE20391 [11] GSE17617 [18] GSE3501 [6] GSE30056 [24] GSE20513 [12] GSE11420 [15] GSE19512 [6] GSE24928 [9] GSE16675 [72] GSE13692 [8] CEM+ CEM GSE9123 [8] GSE53299 [6] GSE38837 [6] GSE21380 [7] GSE26476 [6] GSE34959 [10] 0.0 GSE9803 [9] GSE12499 [10]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 301.64 306.02 310.69 311.95 315.50 316.29 318.33 328.09 329.44 329.98 330.97 334.21 338.45 346.49 346.56 369.53 372.00 374.88 377.82 381.22 388.79 392.93 406.12 406.45 410.99 411.75 413.65 419.69 420.42 441.62 446.74 456.07 469.05 477.62 488.20 503.25 505.64 556.60 559.86 603.40 1.0 Notes Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page2 Ebna1bp2 Hsp90ab1 Mybbp1a Mrps18b Ctnnbl1 Ranbp1 Rps3a1 Atp5g2 Stoml2 Psmb6 Psmg1 Trim28 Rpl37a Psmc3 Psma7 Psmc4 Polr1d Polr1c Nsun2 Aimp2 Ddx49 Uba52 Cdc37 Eif2b5 Rps11 Eif2s2 Snrpg Gmps Prmt5 Polr2f Polr2j Phf5a Cct6a Pold2 Sf3b5 Nme1 Rpl26 Sf3a3 Lsm4 Taf10 Gtf3a Rps7 Ddx1 Imp3 Gars Drg1 Ipo5 Gart Srm Fau 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 233.84 240.42 241.07 241.44 244.18 244.21 248.41 249.17 250.22 250.34 250.40 250.42 250.65 251.18 251.47 252.84 252.94 254.01 254.23 256.01 256.60 257.79 258.97 260.26 261.29 261.55 261.80 263.55 267.51 269.60 269.84 270.17 270.54 271.60 271.88 272.81 277.26 279.43 279.70 280.49 281.45 283.19 284.48 285.30 290.05 291.60 294.23 296.98 298.58 301.54 1.0 Notes Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page3 Rps19bp1 Rnaseh2a Hnrnpab Snrnp40 Timm13 Timm23 Ppp1ca Sssca1 Dctpp1 Rbm8a Psmb3 Eef1b2 Psmb5 Rsl1d1 Psma6 Psma2 Mrpl11 Mrpl23 Magoh Polr2h Prpf31 Polr2c Cops3 Nop16 Cops4 Ddx56 Rps4x Pa2g4 Snrpc Mcm7 Banf1 Park7 Bola2 Puf60 Noc4l Paics Gps1 Hint1 Nob1 Bop1 Rps2 Rae1 Imp4 Mars Rars Sars Adsl Nip7 Nifk Mif 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 179.60 180.29 180.37 180.72 182.80 183.44 183.69 183.87 184.54 184.83 185.59 185.69 187.20 189.12 192.95 193.16 193.81 194.97 196.27 196.44 197.61 198.38 199.04 200.07 200.53 200.72 201.02 202.01 202.32 203.66 204.77 206.45 207.74 207.98 208.75 209.00 209.90 210.93 212.25 215.44 216.43 217.73 219.23 223.62 224.36 227.54 227.65 230.90 233.70 233.74 1.0 Notes 2700094K13Rik Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page4 Tamm41 Psmd12 Rbmxl1 Mrps17 Mrps35 H2-Ke2 Arl6ip4 Ppm1g Psmd4 Psmd6 Psmd2 Psmg3 Psmg4 Psmc2 Mrpl12 Mrpl22 Nubp1 Rpp30 Cops6 Cpsf3l Haus1 Ddx27 Dpy30 Eif2b3 Ddx18 Eif4a1 Thoc5 Cpsf3 U2af1 Noc2l Nme2 Smu1 Nol12 Mrpl2 Strap Plrg1 Nelfe Eif4b Dcps Pcna Qtrt1 Drg2 Clpp Vars Lars Tars Lyar Tbl3 Aatf 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 140.13 141.16 142.49 142.52 143.97 144.44 145.52 145.57 145.58 145.89 148.24 148.30 150.02 150.12 150.31 151.41 153.02 153.50 154.77 154.98 155.11 155.22 155.42 156.45 158.41 159.59 161.18 161.20 161.90 162.30 163.16 164.18 164.45 165.65 166.39 166.44 166.55 169.13 170.00 170.13 170.66 171.21 172.06 172.12 172.37 173.79 174.20 174.55 175.99 178.51 1.0 Notes Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page5 Samm50 Tomm22 Psmd14 Csnk2b Exosc4 Exosc5 Mrps16 Mrps10 Mrps30 Metap2 Psmb2 Dcaf13 Hnrnpf Psma4 Mrpl28 Mrpl40 G3bp1 Grwd1 Polr1e Nop10 Cops5 Nup85 Nop56 Eif2b1 Usp39 Pcbp1 Ddx54 Mrps7 Gspt1 Snrpe Rrp15 Cpsf1 Trmt1 Rpl38 Rpl14 Siva1 Tsta3 Mbd3 Glrx3 Prpf8 Cnbp Nop9 Ppan Nans Kti12 Dap3 Bysl Faf1 Parl Atic 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 106.16 107.99 108.17 108.35 108.54 110.16 110.21 110.92 111.10 112.45 112.89 114.93 115.22 115.68 116.81 117.58 119.12 119.44 120.85 120.92 120.98 121.21 121.64 122.09 123.16 123.19 123.37 123.83 123.98 125.78 126.36 126.95 127.13 127.42 128.46 128.93 129.79 130.27 131.54 132.23 133.23 133.56 134.82 135.13 135.69 136.05 136.27 136.33 137.13 140.08 1.0 Notes Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page6 Cdk2ap1 Tomm40 Tmem11 Chchd1 Anp32b Rpl22l1 Exosc7 Mrps22 Mrps28 Snrpd3 Akr1b3 Rps27l Cmss1 Mrpl52 Mrpl13 Grpel1 Nup93 Hddc2 Wdr18 Cand1 Ncbp1 Dtymk Hspe1 Hspa4 Pdcd2 Pebp1 Cks1b Pbdc1 Mrp63 Gtf2f2 Mcm6 Mcm5 Polr2i Bccip Dus1l Sf3b3 Cse1l Lsm3 Snrpf Myg1 Ddb1 Nop2 Uba2 Hax1 Ybx1 Ece2 Ftsj3 Pgls Dis3 Fxn 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 74.78 75.32 75.48 75.94 76.62 76.65 77.59 78.63 78.87 79.22 80.34 80.73 80.88 81.94 82.62 84.71 86.07 86.54 87.17 87.50 87.72 88.14 90.07 90.18 90.97 91.16 91.31 91.80 91.83 92.11 93.16 93.95 94.70 94.78 95.73 96.93 97.97 98.01 98.46 98.79 99.01 100.14 100.82 102.82 103.11 103.82 104.59 104.90 105.33 105.90 1.0 Notes Gadd45gip1 Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page7 Hsd17b10 Trnau1ap Nsmce4a Ccdc101 Gemin5 Ncaph2 Nup133 Exosc2 Atp5a1 Psmd8 Mrpl43 Mrpl37 Cirh1a Nedd8 Wdr55 Nup62 Dhx15 Pdap1 Ahsa1 Ppp4c Ddx41 Eif2b4 Thoc6 Lrwd1 Msto1 Mcm2 Cfdp1 Ssrp1 Xrcc6 Nol11 Pwp1 Ttc27 Lsm2 Gpn1 Msh2 Ngdn Xpo5 Rpa2 Ppil1 Pus1 Eif5a Aaas Tipin Fen1 Mtx1 Cdt1 Rfc3 Nxt1 Mri1 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 51.54 51.94 51.98 52.25 52.49 52.86 52.95 53.21 53.38 53.45 53.46 55.43 55.91 56.12 56.70 57.13 58.11 58.11 58.88 58.96 59.11 59.22 60.52 60.63 61.20 61.58 62.97 63.63 63.66 65.02 65.09 65.13 65.19 65.70 66.64 66.68 67.43 67.65 67.92 67.96 68.38 69.43 69.59 70.49 70.78 71.55 72.08 72.39 73.46 74.70 1.0 Notes 0610009D07Rik 1810009A15Rik Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page8 Wbscr22 Mrps18a Snrnp25 Timm10 Krtcap2 Anapc7 Asnsd1 Exosc3 Mrps34 Mrps26 Zc3hc1 Atp5g1 Atp5c1 Atad3a Psmc5 Psmc1 Mrpl46 Mrpl16 Polr2b Nubp2 Lrrc47 Polr1a Mak16 Nop14 Nup88 Rpl7l1 Ube2k Actl6a Ssna1 Srp68 Pfdn4 Hmbs Pycr2 Emc6 Idh3g Txnl1 Elof1 Stip1 Pno1 Lsg1 Hdgf Rfc4 Elp3 Ppie Tsr1 Bax Iars Set 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 30.14 30.53 31.37 31.44 32.04 32.49 32.71 33.20 33.40 34.40 34.56 34.82 35.00 35.12 36.02 36.32 36.49 37.21 37.92 38.84 38.86 38.90 39.22 39.77 40.41 40.96 41.77 42.67 44.12 44.57 45.12 45.30 46.02 46.38 46.71 46.84 47.05 47.28 47.39 47.40 47.51 47.64 48.12 48.66 48.73 49.03 49.28 49.32 50.68 51.05 1.0 Notes Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page9 Thumpd3 Zmynd19 Commd2 Dnajc11 Prpf38a Anapc5 Pdcd11 Ccdc58 Ndufv2 Chaf1b Rbm19 Pgam5 Smyd2 Psmd3 Eef1e1 Psma1 Mrpl24 Rangrf Heatr1 Polr2d Polr2g Rbbp7 Lrrc59 Polr3c Nop58 Shmt2 Ddx46 Nsfl1c Cdc20 Tsen2 Gtf2f1 Prmt3 Gins4 Pprc1 Prim1 Parp1 Supt5 Galk1 Smn1 Nat10 Trap1 Mrpl3 Bzw2 Rcc2 Tdp1 Tbca Ppib Rfc2 Rfc5 Aprt 0.0 1.0

GSE23833 [12] GSE7275 [8]

GSE11222 [42] Scale ofaveragePearsoncorrelations GSE13408 [14] GSE5841 [6] GSE11679 [25] GSE4712 [21] GSE13690 [38] GSE33199 [64] 0.2 GSE30746 [16] GSE27816 [14] GSE10535 [6] GSE24793 [8] GSE41342 [26] GSE8307 [68] GSE7897 [60] GSE38277 [18] GSE11148 [6] 0.4 GSE15767 [6] GSE35366 [78] GSE4734 [61] GSE52075 [9] GSE22824 [24] GSE3203 [16] GSE10365 [9] GSE27563 [93] GSE24789 [9] 0.6 GSE22903 [24] GSE31776 [10] GSE10262 [18] GSE17112 [8] GSE31313 [22] GSE25252 [10] GSE17256 [8] GSE10182 [7] GSE13033 [6] 0.8 GSE53077 [8] GSE11684 [16] GSE51075 [12] GSE34064 [6] Score 11.61 11.71 11.91 11.91 12.04 12.17 12.50 12.54 12.96 13.98 14.09 14.68 15.19 16.56 16.98 17.04 17.55 17.55 17.91 18.39 18.47 18.79 19.60 19.66 19.81 21.24 21.97 22.56 23.33 23.68 23.70 24.24 25.07 25.33 25.78 25.97 26.07 26.32 26.33 27.19 27.54 27.67 28.05 28.41 28.73 29.43 29.57 29.66 29.86 30.01 1.0 Notes 1110004F10Rik Symbol Num ofCEMGenes:10.Predicted466.SelectedDatasets:564.Strength:15.1 CEM 1,Geneset"[C]eIF3complex",Page10 Smarca4 Malsu1 Ppp1r7 Dmap1 Psmb7 Mthfd1 Mrpl42 Adrm1 Rps29 Ddx47 Uqcc2 Thoc3 Tceb2 Tex10 Atp5d H2afx Sf3b2 Bms1 Asf1a Elac2 Rrm1 Rrp9 Elp5 Vcp Itpa 0.0 1.0

GSE23833 [12] GSE7275 [8]

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 (0.108875)2h_co._total1 (0.0652723)2h_co._total2 (0.0627445) (0.060203)2h_co._total3 (0.0464044)2h_TGFbeta_enriched1 (0.167553)2h_TGFbeta_enriched22h_TGFbeta_enriched32h_TGFbeta_total1 (0.0850564)2h_TGFbeta_total2 (0.10546)2h_TGFbeta_total3 (0.0818582) (0.0736408) (0.0580776) (0.0848554)[ min ] [ medium ] [ max ] CEM 1 Eif3l 1381.0 8150.4 9658.1 P ( S | Z, I ) = 1.00 Eif3d 2059.6 6479.7 8676.6 Mean Corr = 0.98633 Eif3i 1383.5 6877.5 9471.2 Eif3g 1898.7 5183.4 6648.3 Eif3k 470.0 2513.9 3985.3 Eif3h 1488.0 8175.1 9336.9 Eif3c 1609.8 6647.8 9410.0 Eif3f 2485.0 14027.9 16405.1 Eif3m 1128.0 3145.6 4111.3 Eif3b 1521.3 5679.8 6902.6 Cct5 4058.4 13271.9 15970.5 Cct2 4122.1 14445.3 19743.7 Rpl8 5692.7 22053.0 23516.7 Rpl6 7827.2 22981.4 27939.6 Rpl27 2724.9 7917.7 11097.1 CEM 1 + Tcp1 7106.5 15504.3 18642.6 Top 10 Genes Naca 2020.0 9681.3 15476.4 Cct4 5830.1 10631.3 13364.1 Rps5 7399.0 21272.7 30296.7 Rps19 2594.3 9651.5 14484.3

Null module Eif3a Eif3e GEO Series "GSE7275" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

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

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

ExosomalExosomal RNA,Exosomal biological RNA,Exosomal biological RNA, rep1Mast biological(0.172891) RNA, rep2 cellsMast biological(0.114689) RNA, rep3 cellsMast biological(0.0987287) RNA, rep4 cellsMast biological(0.129913) RNA, rep1 cells biological(0.0733861) RNA, rep2 biological(0.0727438) rep3 (0.177015) rep4[ (0.160634)min ] [ medium ] [ max ] CEM 1 Eif3l 42.3 4983.2 5248.6 P ( S | Z, I ) = 1.00 Eif3d 497.9 6368.3 7269.5 Mean Corr = 0.98452 Eif3i 1123.4 12009.5 17120.1 Eif3g 77.5 4825.9 7382.4 Eif3k 30.5 8109.6 10783.1 Eif3h 1011.0 13255.5 17374.3 Eif3c 50.5 7516.4 9612.4 Eif3f 344.7 16140.8 24353.2 Eif3m 49.6 3992.8 4505.9 Eif3b 78.3 2419.4 2879.7 Cct5 65.7 9421.0 16298.6 Cct2 49.3 14589.3 22204.2 Rpl8 480.0 25298.3 34071.1 Rpl6 1304.4 27376.4 36085.1 Rpl27 3020.2 30354.6 37224.7 CEM 1 + Tcp1 132.2 8708.5 16807.0 Top 10 Genes Naca 1376.4 23441.3 37661.1 Cct4 159.1 9219.5 11640.0 Rps5 926.6 27666.0 32967.0 Rps19 1233.1 30546.6 35677.0

Null module Eif3a Eif3e GEO Series "GSE6998" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 32 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

and repair after injury. Whether this response

represents simple hyperplasia of various liver elements

or requires recapitulation of the genetic program of

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

we examined transcriptional programs of

adult liver after partial hepatectomy and contrasted

these with developing embryonic liver. Principal component

analysis demonstrated that the time series of

gene expression during liver regeneration does not segregate

according to developmental transcription patterns.

Gene ontology analysis revealed that liver restoration

after hepatectomy and liver development differ

dramatically with regard to transcription factors

and chromatin structure modification. In contrast, the

tissues are similar with regard to proliferationassociated

genes. Consistent with these findings, realtime

polymerase chain reaction showed transcription

factors known to be important in liver development

are not induced during liver regeneration. These three

lines of evidence suggest that at a transcriptional level,

restoration of liver mass after injury is best described

as hepatocyte hyperplasia and not true regeneration.

We speculate this novel pattern of gene expression may

underlie the unique capacity of the liver to repair itself

after injury.

Keywords: time course

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

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

0.727 Kernel fit Pairwise Correlations Normal fit

Density 0.364

0.000 CEM 1

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

Pre-normalization Quantiles

baselinebaseline sampleregeneration sampleat T0,regeneration rep1 at T0, (0.0145119)sampleregeneration rep2 (0.0199064) sampleatregeneration T1, rep1 sampleatregeneration T1, (0.0256826) rep2 sampleatregeneration T2, (0.0223713) rep1 sampleatregeneration T2, (0.0298936) rep2 sampleatregeneration T6, (0.025197) rep1 sampleatregeneration T6, (0.020197) rep2 sampleatregeneration T12, (0.0214661) samplerep1atregeneration T12, (0.0115411) samplerep2atregeneration T18, (0.023718) samplerep1atregeneration T18, (0.00335272) samplerep2atregeneration T24, (0.00513255) samplerep1atregeneration T24, (0.0266909) samplerep2atregeneration T30, (0.0104738) samplerep1atregeneration T30, (0.0246636) samplerep2atregeneration T48, (0.0184198) samplerep1atdevelopmental T48, (0.021707) samplerep2atdevelopmental T72, (0.0455217) rep1at developmentalsample T72, (0.0265461) rep2 developmental sampleat T105,(0.0186772) developmental sampleat rep1 T105, (0.0353044) developmental sampleat rep2 T115, (0.0402994) developmental sampleat rep1 T115, (0.0607196) developmental sampleat rep2 T125, (0.0757398) developmental sampleat rep1 T125, (0.0499967) developmental sampleat rep2 T135, (0.0507938) developmental sampleat rep1 T135, (0.0547576) developmental sampleat rep2 T145, (0.0658498) sampleat rep1 T145, (0.0350369) sampleat rep2 T165, (0.0383562) at rep1 T165, (0.0451976)[ rep2min (0.0322776) ] [ medium ] [ max ] CEM 1 Eif3l 1496.0 2277.2 5654.4 P ( S | Z, I ) = 1.00 Eif3d 1059.9 2117.3 5682.2 Mean Corr = 0.96244 Eif3i 2760.4 4193.8 9051.9 Eif3g 1145.8 3191.1 6866.1 Eif3k 673.7 1195.5 4896.4 Eif3h 1496.5 2538.1 5672.4 Eif3c 810.9 2204.3 4974.7 Eif3f 1703.3 2428.3 7411.4 Eif3m 720.7 1096.5 3049.1 Eif3b 897.2 1430.2 2860.8 Cct5 1217.9 2622.9 8179.1 Cct2 1134.5 2029.2 8495.3 Rpl8 2084.4 7781.0 17204.5 Rpl6 4322.8 9691.4 17543.5 Rpl27 4781.8 11535.3 18286.4 CEM 1 + Tcp1 1288.5 1741.0 8283.1 Top 10 Genes Naca 2022.8 6010.2 15435.4 Cct4 1504.7 2102.6 7352.0 Rps5 2591.1 14736.3 23069.3 Rps19 1508.1 6740.6 16136.4

Null module Eif3a Eif3e GEO Series "GSE46443" 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=GSE46443 Status: Public on Oct 21 2013 Title: Expression data from mouse cerebral cortex Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23800850 Summary & Design: Summary: Differential gene expression of cerebral cortex might be responsible for distinct neurovascular developments between different mouse strains

We used Affymetrix microarray to explore the global gene expression patterns of mouse cerebral cortex of different mouse strains at two developmental stages

Overall design: Cerebral cortex from two mouse strains [C57BL/6J(B6) and C3H/J (C3H)] at post-natal day 1 (p1) and post-natal 11 weeks (11 wk) were harvested for microarray experiments

Background corr dist: KL-Divergence = 0.0145, L1-Distance = 0.0214, L2-Distance = 0.0004, Normal std = 0.8048

0.506 Kernel fit Pairwise Correlations Normal fit

Density 0.253

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

p1 B6 cerebralp1 B6 cerebral p1cortex, B6 cerebral p1cortex,rep1 C3H (0.0983047) p1cortex,rep2cerebral C3H (0.0619393) p1rep3cerebral cortex, C3H (0.0815661) 11cerebral cortex,rep1 wk B6(0.072328)11 cortex,rep2cerebral wk B6(0.0908496)11 rep3cerebral wkcortex, B6(0.0938468)11 cerebral wkcortex,rep1 C3H11 (0.0743787) wkcortex,rep2cerebral C3H11 (0.0640442) wk rep3cerebral cortex,rep1 C3H (0.0921704) cerebral cortex, (0.0702063) cortex,rep2 (0.125047) rep3[ (0.0753191)min ] [ medium ] [ max ] CEM 1 Eif3l 2085.4 3993.7 4633.0 P ( S | Z, I ) = 1.00 Eif3d 1875.3 2947.5 3369.2 Mean Corr = 0.94805 Eif3i 5288.8 6491.7 7262.3 Eif3g 3060.4 4061.3 4965.6 Eif3k 1970.1 2779.3 3046.7 Eif3h 3809.9 6151.3 7117.9 Eif3c 3538.4 4712.4 5232.5 Eif3f 6286.7 11037.1 11933.8 Eif3m 1213.9 1678.6 1806.9 Eif3b 1227.2 1848.6 2246.2 Cct5 3608.6 6953.1 7254.1 Cct2 3130.1 6508.3 6800.9 Rpl8 7281.2 11953.3 12922.2 Rpl6 8433.4 13371.4 14305.0 Rpl27 5671.0 10047.0 11686.2 CEM 1 + Tcp1 3974.5 5697.2 6081.5 Top 10 Genes Naca 7310.9 12637.7 13797.5 Cct4 2946.9 5837.8 6124.3 Rps5 7535.0 16343.3 17047.0 Rps19 5931.1 11940.9 13381.7

Null module Eif3a Eif3e GEO Series "GSE7838" 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=GSE7838 Status: Public on Jul 01 2007 Title: Comprehensive Gene ExpressionProfiling of Peyers Patch M Cells, Villous M-like Cells, and Intestinal Epithelial Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Separate populations of M cells have been detected in the follicle-associated epithelium of Peyers patches (PPs) and the villous epithelium of the small intestine, but the traits shared by or distinguishing the two populations have not been characterized. Our separate study has demonstrated that M cells are rare but M-like cells positive for lectin Ulex europaeus agglutinin-1 and our newly developed M cell-specific mAb NKM16-2-4 are induced by oral administration of cholera toxin in the duodenal villous epithelium. Here, we determined the gene expression of PP M cells, villous M-like cells, and intestinal epithelial cells (IECs) isolated by a novel approach using FACS. Specific expression of glycoprotein 2 (GP2) and MARCKS-like protein (MLP) by PP M cells and not villous M-like cells was confirmed by additional mRNA and protein analyses. Comprehensive gene profiling also suggested that villous M-like cells share traits of both PP M cells and IECs, a finding that is supported by their unique expression of specific chemokines. The genome-wide assessment of gene expression facilitates discovery of M cell-specific molecules and enhances the molecular understanding of M cell immunobiology.

Keywords: Cell type comparison

Overall design: Epithelial cells in duodenal Peyer's patches or villi of BALB/c mice treated with or without cholera toxin were dissociated and stained with NKM16-2-4 monoclonal antibody (mAb)-FITC, lectin UEA-1-PE, and anti-CD45 mAb-APC-Cy7. Naive PP M cells (NKM16-2-4+, UEA-1+, and CD45- cells), CT-induced villous M-like cells (NKM16-2-4+, UEA-1+, and CD45- cells), and naive intestinal epithelial cells (NKM16-2-4-, UEA-1-, and CD45- cells) were isolated by FACS. Affymetrix GeneChip Mouse Genome 430 2.0 Array was used in triplicate for each cell fraction.

Background corr dist: KL-Divergence = 0.0509, L1-Distance = 0.0296, L2-Distance = 0.0011, Normal std = 0.5720

0.707 Kernel fit Pairwise Correlations Normal fit

Density 0.354

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

PP M CELL1PP M (0.206249)CELL2PP M (0.409728)CELL3CT-v-M (0.0473985) CT-v-Mcell1 (0.05374) CT-v-Mcell2 (0.0470408) IEC1cell3 (0.0215277)(0.080342)IEC2 (0.0662005)IEC3 (0.0677742) [ min ] [ medium ] [ max ] CEM 1 Eif3l 1933.6 2189.7 5442.1 P ( S | Z, I ) = 1.00 Eif3d 1383.7 1887.7 4523.8 Mean Corr = 0.94523 Eif3i 1819.6 2549.5 6771.2 Eif3g 985.3 1417.1 4281.0 Eif3k 747.7 1072.6 2176.5 Eif3h 2098.2 2410.7 6615.6 Eif3c 2305.4 2514.4 4904.8 Eif3f 3928.3 4816.8 14191.2 Eif3m 541.7 672.7 3164.9 Eif3b 1012.5 1139.1 2083.4 Cct5 2172.9 2657.8 7981.7 Cct2 1609.3 1961.1 6955.1 Rpl8 3532.7 4846.9 17984.6 Rpl6 2543.2 3807.5 20839.8 Rpl27 2027.5 2553.6 9271.7 CEM 1 + Tcp1 2833.4 3546.0 9722.9 Top 10 Genes Naca 1169.1 1664.2 5077.5 Cct4 2002.1 2486.4 8777.8 Rps5 3008.1 4226.0 16897.6 Rps19 1195.5 2628.6 6346.1

Null module Eif3a Eif3e 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 (0.191781)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.216709)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.21008)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.0987332) (0.0822454)[ min(0.0622837) (0.0362401)] (0.022158)[ (0.0797692) medium ] [ max ] CEM 1 Eif3l 1955.3 6575.4 8128.9 P ( S | Z, I ) = 1.00 Eif3d 1640.6 4889.0 6252.6 Mean Corr = 0.93883 Eif3i 1447.9 8330.4 10485.0 Eif3g 1414.1 7950.5 9247.4 Eif3k 2913.1 4633.9 6347.1 Eif3h 3706.4 8734.6 9403.4 Eif3c 1833.0 6851.7 8793.7 Eif3f 7867.3 12597.0 13610.3 Eif3m 141.2 2593.8 3341.4 Eif3b 275.7 5494.7 6476.8 Cct5 2225.7 9662.1 12413.9 Cct2 1357.0 7430.9 9699.6 Rpl8 4765.0 12845.6 14702.8 Rpl6 6532.3 15272.4 16980.2 Rpl27 4303.0 12451.9 14119.6 CEM 1 + Tcp1 1307.1 10765.6 12697.6 Top 10 Genes Naca 1917.4 7995.6 10627.5 Cct4 1790.2 6126.3 7871.3 Rps5 4416.1 14522.5 16389.3 Rps19 1838.3 12308.0 14344.6

Null module Eif3a Eif3e 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 (0.0933867) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0358283) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.0525135) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0496226) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.077382) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0407298) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0320139) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.0265989) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0167845) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0181377) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0206039) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0298629) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0490176) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0434077) developmentalMousestage 1 E14.5 (0.0594876) developmentalMousestage 2 E16.5 (0.046549) developmentalstage 1 E16.5(0.0592106) stage[ min 2 E18.5(0.0611322) stage 1] E18.5(0.0952871) 2 (0.0924434)[ medium ] [ max ] CEM 1 Eif3l 5773.5 11384.8 14903.5 P ( S | Z, I ) = 1.00 Eif3d 3066.2 9742.6 13714.0 Mean Corr = 0.92846 Eif3i 8002.4 16195.7 18569.6 Eif3g 3827.5 10011.8 13804.7 Eif3k 4703.3 9453.4 11876.6 Eif3h 7081.9 11803.3 13287.2 Eif3c 3677.1 9590.8 11544.6 Eif3f 9770.6 15291.6 19436.8 Eif3m 2475.8 5898.0 7044.5 Eif3b 1511.8 3337.1 4673.3 Cct5 7448.6 18928.1 24054.1 Cct2 6090.3 20091.2 26832.6 Rpl8 15272.0 32215.7 38735.6 Rpl6 16498.5 33305.8 40496.7 Rpl27 14705.4 33554.2 41534.2 CEM 1 + Tcp1 7434.1 19466.6 23112.2 Top 10 Genes Naca 14564.1 29242.0 35553.0 Cct4 7055.7 15978.6 19963.1 Rps5 16081.5 30982.0 40526.9 Rps19 13848.8 26478.3 33643.5

Null module Eif3a Eif3e 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 (0.115723)ctrl_rep3 (0.0951962)ctrl_rep4 (0.132816)irr_rep1 (0.140718)irr_rep2 (0.150835)irr_rep3 (0.167422)irr_rep4 (0.126604) (0.0706866) [ min ] [ medium ] [ max ] CEM 1 Eif3l 5948.5 9257.3 9914.2 P ( S | Z, I ) = 1.00 Eif3d 4083.3 6573.5 6924.3 Mean Corr = 0.92674 Eif3i 8233.1 11889.9 13177.5 Eif3g 4035.1 9102.4 9685.4 Eif3k 4573.9 6587.0 7224.8 Eif3h 9250.3 10627.9 11364.7 Eif3c 7625.9 9697.3 9922.7 Eif3f 14950.2 16541.0 17773.5 Eif3m 3804.7 4689.9 5404.7 Eif3b 3333.0 5182.6 5964.8 Cct5 9404.8 13466.4 13971.1 Cct2 9201.2 13338.6 14259.8 Rpl8 19496.4 23132.3 24375.6 Rpl6 18742.8 22374.5 23132.8 Rpl27 17134.0 18705.2 20020.0 CEM 1 + Tcp1 7129.7 11731.5 12421.9 Top 10 Genes Naca 19440.2 23149.9 24141.2 Cct4 7116.0 9990.6 10475.2 Rps5 22441.9 26306.1 27087.5 Rps19 18966.8 21853.9 22945.7

Null module Eif3a Eif3e GEO Series "GSE6065" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 100 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6065 Status: Public on Oct 21 2006 Title: Murine host cell response to Aeromonas infection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17897183 Summary & Design: Summary: Aims: To assess the virulence of multiple Aeromonas spp. using two models, a neonatal mouse assay and a mouse intestinal cell culture.

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

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

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

Keywords: Aeromonas; Virulence; Gene expression; Host response

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

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

0.881 Kernel fit Pairwise Correlations Normal fit

Density 0.441

0.000 CEM 1

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

Pre-normalization Quantiles

NRMRLNRMRL controlNRMRL replicatereplicate01,NRMRL control control02, batch032405NRMRL controlreplicate03, batch032405NRMRL controlreplicate04, (0.0120927) batch032405NRMRL testreplicate05, (0.00989273) replicate01, batch032405NRMRL test (0.00768258) replicate02, batch032405NRMRL test EPA1, (0.0133148) replicate03,NRMRL test batch032405 EPA1 (0.0154806) replicate04,NRMRL testbatch032405 EPA1 replicate05, (0.0157506)NRMRL testbatch032405 EPA1 replicate01, (0.0132771)NRMRL testbatch032405 EPA1 replicate02, (0.0130915)NRMRL testbatch032405 EPA5 replicate03, (0.0138714)NRMRL testbatch032405 EPA5 replicate04, (0.0176146)NRMRL testbatch032405 EPA5 replicate05, (0.00861474)NRMRL testbatch032405 EPA5 replicate01, (0.0115113)NRMRL testbatch032405 EPA5 replicate02, (0.0329822)NRMRL testbatch032405 EPA9 replicate03, (0.00977894)NRMRL testbatch032405 EPA9, replicate04, (0.0173193)NRMRL test batch032405 EPA9 replicate05, (0.00771739)NRMRL testbatch032405 EPA9 replicate01, (0.00499857)NRMRL testbatch032405 EPA9 replicate02, (0.025488)NRMRL testbatch032405 EPA61 replicate03, (0.0135171)NRMRL test batch032405EPA61 replcate04, (0.00769699)NRMRL test batch032405EPA61 replicate05, NRMRL(0.0149412)test EPA61batch replicate01, NRMRL (0.01891)test032405 batch032405 EPA61 replicate02,NRMRL test(0.0104748) batch032405EPA63 replicate03, (0.0131053)NRMRL test batch032405EPA63 replicate04, NRMRL(0.0130296)test batch032405EPA63 replicate05, NRMRL(0.0342405)test batch032405EPA63 replicate01, NRMRL(0.0159714)test batch032405EPA63 replicate02, NRMRL(0.0315625)test batch032405EPA71 replicate03, NRMRL(0.0172602)test batch032405EPA71 replicate04, NRMRL(0.0161766)test batch032405EPA71 replicate05, NRMRL(0.0315098)control batch032405EPA71 NRMRL (0.035708)controlreplicate01, batch032405EPA71 NRMRL (0.0390655)controlreplicate02, batch032405 uninfected, NRMRL (0.0174146)controlreplicate03, uninfected NRMRL (0.026298)controlreplicate04, batch051905 uninfectedNRMRL testreplicate05, batch051905 replicate01, uninfectedNRMRL test(0.00742085) batch051905 replicate02, uninfected NRMRL (0.00498509)test batch051905EPA2 replicate03, NRMRL (0.00241093)testbatch051905 batch051905EPA2 replicate04, NRMRL (0.00384103)testbatch051905 EPA2 replicate05, (0.00239359) NRMRL (0.00628584)testbatch051905 EPA2 replicate01, (0.00206585)NRMRL testbatch051905 EPA2 replicate02, (0.00343034)NRMRL testbatch051905 EPA5 replicate03, (0.00232417)NRMRL testbatch051905 EPA5 replicate04, (0.00261717)NRMRL testbatch051905 EPA5 replicate05, (0.00510149)NRMRL testbatch051905 EPA5 replicate01, (0.00470357)NRMRL testbatch051905 EPA5 replicate02, (0.00365604)NRMRL testbatch051905 EPA9 replicate03, (0.00212988)NRMRL testbatch051905 EPA9 replicate04, (0.00377684)NRMRL testbatch051905 EPA9 replicate05, (0.00608282)NRMRL testbatch051905 EPA9 replicate01, (0.00618611)NRMRL testbatch051905 EPA9 replicate02, (0.00522689)NRMRL testbatch051905 EPA10 replicate03, (0.00594021)NRMRL test batch051905EPA10 replicate04, (0.00572628)NRMRL test batch051905EPA10 replicate05, NRMRL(0.00499561)test batch051905EPA10 replicate01, NRMRL(0.00589436)test batch051905EPA10 replicate02, NRMRL(0.00399979)test batch051905EPA61 replicate03, NRMRL(0.00237641)test batch051905EPA61 replicate04, NRMRL(0.00308416)test batch051905EPA61 replicate05, NRMRL(0.00226874)test batch051905EPA61 replicate01, NRMRL(0.00192067)test batch051905EPA61 replicate02, NRMRL(0.00195719)test batch051905EPA72 replicate03, NRMRL(0.00219502)test batch051905EPA72 replicate04, NRMRL(0.00219654)test batch051905EPA replicate05, 72 NRMRL(0.0304104)test EPA72batch replicate01, NRMRL(0.00404822)test 051905 batch051905EPA replicate02, 72NRMRL test (0.00180973) EPA51batch051905 replicate03, NRMRL(0.00347024)test batch093005EPA51 replicate04,NRMRL test(0.00208621) batch093005EPA51 replicate05, NRMRL(0.00796124)test batch093005EPA51 replicate01, NRMRL(0.00504457)test batch093005EPA51 replicate02, NRMRL(0.00676481)test batch093005EPA52 replicate04, NRMRL(0.00675454)test batch093005EPA52 replicate03, NRMRL(0.00732753)test batch093005EPA52 replicate05, NRMRL(0.00778741)test batch093005EPA52 replicate01, NRMRL(0.00762119)test batch093005EPA52 replicate02, NRMRL(0.00827173)test batch093005EPA73 replicate03, NRMRL(0.00995976)test batch093005EPA73 replicate04, NRMRL(0.00909818)test batch093005EPA73 replicate05, NRMRL(0.00818835)test batch093005EPA73 replicate01, NRMRL(0.00643373)test batch093005EPA73 replicate02, NRMRL(0.00561777)test batch093005EPA80 replicate03, NRMRL(0.00786705)test batch093005EPA80 replicate04, NRMRL(0.00546018)test batch093005EPA80 replicate05, NRMRL(0.0096403)test batch093005EPA80 replicate01, NRMRL(0.00785163)test batch093005EPA80 replicate02, NRMRL(0.00926759)test batch093005EPA82 replicate03, NRMRL(0.0107138)test batch093005EPA82 replicate04, NRMRL(0.0110148)test batch093005EPA82 replicate05, NRMRL(0.00899668)control ba CEM 1 Eif3l 2665.0 4385.3 11534.8 P ( S | Z, I ) = 1.00 Eif3d 2262.8 3812.3 16619.1 Mean Corr = 0.91366 Eif3i 5083.6 7131.8 10901.1 Eif3g 2442.4 3571.6 8118.1 Eif3k 2321.8 4171.5 8947.3 Eif3h 4002.1 5222.8 11713.4 Eif3c 3040.3 4404.1 12510.8 Eif3f 5742.5 9925.6 18485.6 Eif3m 1049.1 1751.9 4897.5 Eif3b 2041.6 3306.5 6758.1 Cct5 2981.9 4229.8 13369.1 Cct2 2576.6 4464.8 17473.4 Rpl8 6519.5 11557.7 31864.4 Rpl6 10764.6 16597.4 35452.8 Rpl27 9603.7 12066.5 32714.1 CEM 1 + Tcp1 3997.7 5248.4 12264.9 Top 10 Genes Naca 9884.9 13640.9 31437.4 Cct4 3599.2 5069.8 12473.9 Rps5 12063.0 17192.1 35628.2 Rps19 6314.2 9937.3 20696.4

Null module Eif3a Eif3e GEO Series "GSE40230" 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=GSE40230 Status: Public on Aug 27 2012 Title: Expression data from primary and secondary CD4 T cell effectors responding towards influenza A virus infection Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22927425 Summary & Design: Summary: How secondary CD4 T cell effectors, derived from resting memory cells, differ from primary cells, derived from naÃ¯ve precursors, and how such differences impact recall responses to pathogens is unknown.

We used microarrays to detail the global programme of gene expression underlying differences between primary and secondary CD4 T cell effectors purified from the spleen, dLN, and lung on day 7 following A/PR8/34 influenza infection.

Overall design: Congenic naÃ¯ve or in vivo influenza primed memory HNT TCR trangenic CD4 T cells were sort purifed from the spleens, dLNs, and lungs of infected mice on day 7 post infection for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain only CD4 T cell populations that had entered into the immune response by also sorting and collecting only those cells that had divided at least 5 times by CFSE analysis.

Background corr dist: KL-Divergence = 0.0525, L1-Distance = 0.0533, L2-Distance = 0.0050, Normal std = 0.5678

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

PrimaryPrimary Spleen,Primary Spleen, biologicalPrimary Spleen, biological replicatePrimary dLN, biological replicate biological1Primary (0.0407398)dLN, replicate biological2Primary (0.0506275)dLN, replicate biological3Primary (0.140736)Lung, replicate 1 (0.0414861) biologicalPrimary Lung, replicate 2 (0.0372149) biologicalSecondary Lung, replicate 3 (0.101799) biologicalSecondary replicate Spleen, 1 (0.022995)Secondary replicate Spleen, biological2 (0.10915)Secondary dLN, biological3 (0.0115167) Secondaryreplicate biological dLN, Secondaryreplicate biological1 (0.0881493)Lung, replicate 2 biological (0.0780711)Lung, replicate 1 (0.0500753) biological replicate 2 (0.124715) replicate 1[ (0.0392693)min 2 (0.0634545) ] [ medium ] [ max ] CEM 1 Eif3l 269.2 1426.2 5290.3 P ( S | Z, I ) = 1.00 Eif3d 212.1 567.9 5648.1 Mean Corr = 0.91214 Eif3i 1278.8 3885.0 15023.8 Eif3g 253.9 1909.0 6669.3 Eif3k 1081.4 4578.1 16150.5 Eif3h 2387.9 7589.1 30753.8 Eif3c 181.0 1969.8 4765.5 Eif3f 1346.1 6074.1 22250.7 Eif3m 1035.8 2361.5 5917.3 Eif3b 91.8 684.5 1791.0 Cct5 32.4 2451.7 8898.8 Cct2 747.4 6728.5 12139.6 Rpl8 2020.1 8564.2 33676.0 Rpl6 7428.4 36192.7 58487.5 Rpl27 4110.6 13326.3 28240.8 CEM 1 + Tcp1 1333.0 5812.8 9811.5 Top 10 Genes Naca 5481.2 21757.0 57527.6 Cct4 1254.3 6352.0 12894.6 Rps5 4053.4 16360.3 36641.0 Rps19 2580.9 14852.2 34759.3

Null module Eif3a Eif3e GEO Series "GSE13874" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.482 Kernel fit Pairwise Correlations Normal fit

Density 0.241

0.000 CEM 1

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

Pre-normalization Quantiles

NTg, biologicalNTg, biologicalNTg, replicate biologicalNTg, replicate 1 (Affymetrix) biologicalCalcineurin replicate 2 (Affymetrix)Calcineurin replicate (0.055713) 3 (Affymetrix)Tg,Calcineurin biological (0.0611164) 4 (Affymetrix)Tg,Calcineurin biological (0.0632263) replicate Tg,Differentiating biological (0.0516044) replicate Tg, 1 (Affymetrix)Differentiating biological replicate 2 P19CL6(Affymetrix)Differentiating replicate (0.042138) 3 P19CL6(Affymetrix)Differentiating cells (0.0447124) 4at P19CL6(Affymetrix)Differentiating cellsday (0.0395028)6 at afterP19CL6Differentiating cellsday DMSO(0.045754)6 at afterP19CL6 cellsday treatment, DMSO6 at afterP19CL6 cellsday treatment, DMSO10 at replicate aftercellsday treatment, 10 DMSOat replicate[ afterday 1min (Affymetrix) 10 treatment,DMSO replicate after 2 (Affymetrix)] treatment,DMSO (0.0734577)replicate 3 (Affymetrix) treatment, (0.184472)replicate [1 (Affymetrix)medium (0.172038)replicate 2 (Affymetrix) (0.0527127) 3 (Affymetrix) ] (0.048065) (0.0654879)[ max ] CEM 1 Eif3l 2969.1 3495.7 12328.3 P ( S | Z, I ) = 1.00 Eif3d 1760.0 2521.9 9997.3 Mean Corr = 0.90300 Eif3i 5304.3 7256.0 13539.6 Eif3g 2898.8 3739.3 9758.0 Eif3k 2232.5 2891.2 9786.4 Eif3h 5449.8 6700.3 14549.1 Eif3c 2906.7 3515.3 14159.0 Eif3f 6084.2 7746.0 20091.6 Eif3m 2192.6 2883.6 5151.8 Eif3b 1784.2 2103.1 3524.6 Cct5 3192.1 3719.6 16262.0 Cct2 2687.9 3524.4 20345.2 Rpl8 7507.0 8701.3 25356.0 Rpl6 9950.0 11886.0 29546.6 Rpl27 8365.5 9990.0 23020.4 CEM 1 + Tcp1 5141.6 5943.0 20259.0 Top 10 Genes Naca 6846.6 9496.9 27620.2 Cct4 3825.5 4696.8 19695.5 Rps5 11185.1 12822.8 34392.7 Rps19 5991.8 7671.6 30775.8

Null module Eif3a Eif3e GEO Series "GSE5425" 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=GSE5425 Status: Public on Aug 02 2006 Title: Spinal cord and dorsal root ganglion gene expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16824496 Summary & Design: Summary: We used microarrays to test the fundamental quantitative differences between central and peripheral nervous system transcriptomes.

Keywords: repeat

Overall design: 3 independent SC and 3 independent DRG samples were analyzed. Each sample contained material from 4 age-matched male C57B/6 mice.

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0458, L2-Distance = 0.0024, Normal std = 0.8355

0.509 Kernel fit Pairwise Correlations Normal fit

Density 0.255

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

Dorsal RootDorsal Ganglion RootDorsal Ganglion RootDRG_REPSpinal Ganglion CordDRG_REPSpinal 1 SC_REP(0.181787) CordDRG_REPSpinal 2 SC_REP(0.0670305) 1Cord (0.125319) 3 SC_REP(0.31154) 2 (0.147494) 3 (0.166829)[ min ] [ medium ] [ max ] CEM 1 Eif3l 372.1 614.0 641.2 P ( S | Z, I ) = 1.00 Eif3d 420.6 519.9 738.4 Mean Corr = 0.89989 Eif3i 424.1 516.7 569.6 Eif3g 397.7 581.3 597.6 Eif3k 416.2 542.4 612.0 Eif3h 461.5 491.7 552.2 Eif3c 471.6 491.1 541.9 Eif3f 449.5 517.7 588.9 Eif3m 416.1 549.1 627.6 Eif3b 428.4 497.2 583.7 Cct5 409.8 574.2 642.3 Cct2 434.6 522.4 613.6 Rpl8 462.4 485.9 606.8 Rpl6 435.8 542.2 555.8 Rpl27 434.2 534.5 610.7 CEM 1 + Tcp1 404.2 538.6 581.0 Top 10 Genes Naca 452.7 510.8 529.4 Cct4 369.7 592.1 619.7 Rps5 408.9 541.3 569.6 Rps19 439.5 519.3 575.8

Null module Eif3a Eif3e GEO Series "GSE35593" 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=GSE35593 Status: Public on Feb 16 2013 Title: Foxo1/3 depletion in granulosa cells reveals novel mechanisms controlling follicle growth and death and endocrine regulation of pituitary FSH. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23322722 Summary & Design: Summary: The Foxo transcription factors regulate multiple cellular functions. Foxo1 and Foxo3 are highly expressed in granulosa cells of ovarian follicles. Selective depletion of the Foxo1 and Foxo3 genes in granulosa cells revealed a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb. Equally notable and independent of FSH, depletion of Foxo1/3 altered the expression of specific genes associated with follicle growth versus apoptosis by disrupting critical regulatory interactions of Foxo1/3 with the activin and BMP2 pathways, respectively. As a consequence, granulosa cell proliferation and apoptosis were decreased. These data provide the first evidence that Foxo1/3 divergently regulate follicle growth or death by interacting with the activin and BMP pathways in granulosa cells and by modulating pituitary FSH production.

Overall design: A direct comparison of ovarian granulosa cells from wild type d25, Foxo1/3 dKO d25 and Foxo1/3 dKO 2 month mice.

Background corr dist: KL-Divergence = 0.0309, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6734

0.601 Kernel fit Pairwise Correlations Normal fit

Density 0.301

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

S22860_wt_d25_Rep1S22861_wt_d25_Rep2S22864_F_d25_Rep1 S22865_F_d25_Rep2(0.152387) S22862_F_2m_Rep1(0.303628) (0.0677567)S22863_F_2m_Rep2 (0.011518) (0.436444) (0.028266)[ min ] [ medium ] [ max ] CEM 1 Eif3l 4896.9 7087.0 8215.2 P ( S | Z, I ) = 1.00 Eif3d 2892.2 3689.6 4647.7 Mean Corr = 0.89757 Eif3i 6001.3 7102.8 7978.8 Eif3g 4844.4 6668.7 7424.1 Eif3k 3721.6 5087.6 5737.7 Eif3h 5870.5 6490.4 7426.9 Eif3c 5257.0 6405.4 7304.0 Eif3f 11492.2 14184.4 15191.7 Eif3m 2201.7 2954.7 3571.6 Eif3b 1908.3 2601.7 3110.1 Cct5 6868.9 9573.3 10792.8 Cct2 5899.2 7731.6 10028.1 Rpl8 17021.3 20405.9 22019.3 Rpl6 17068.1 20670.9 21997.1 Rpl27 9887.3 12247.1 13002.0 CEM 1 + Tcp1 3971.1 5854.3 7058.5 Top 10 Genes Naca 13384.8 18086.4 20205.1 Cct4 5001.8 6185.3 7617.4 Rps5 22344.9 26414.3 26537.8 Rps19 17375.8 22490.0 24082.5

Null module Eif3a Eif3e GEO Series "GSE51628" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.843 Kernel fit Pairwise Correlations Normal fit

Density 0.422

0.000 CEM 1

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

Pre-normalization Quantiles

TICNX_48h_rep1TICNX_48h_rep2TICNX_48h_rep3 (0.0824232)TICNX_48h_rep4 (0.0556334)TICNX_96h_rep1 (0.0833405)TICNX_96h_rep2 (0.0521271)TICNX_96h_rep3 (0.0449982)MTB/TICNX_48h_rep1 (0.00982488)MTB/TICNX_48h_rep2 (0.0239742)MTB/TICNX_48h_rep3 MTB/TICNX_48h_rep4(0.00805634) MTB/TICNX_96h_rep1(0.0225392) MTB/TICNX_96h_rep2(0.0168409) MTB/TICNX_96h_rep3(0.0185792) MTB/TICNX_96h_rep4(0.0419253) (0.192622) (0.167518) (0.179597)[ min ] [ medium ] [ max ] CEM 1 Eif3l 3509.9 4287.0 5404.6 P ( S | Z, I ) = 1.00 Eif3d 2675.5 3160.1 4820.2 Mean Corr = 0.89157 Eif3i 6911.5 8229.6 9960.3 Eif3g 3789.7 4475.2 6546.4 Eif3k 3018.1 3798.4 5344.9 Eif3h 5198.3 6338.1 9339.3 Eif3c 4773.8 5130.8 6772.7 Eif3f 7736.9 10487.9 14681.5 Eif3m 1871.4 2313.4 3292.7 Eif3b 1962.7 2263.3 2840.8 Cct5 5563.5 7569.1 9635.9 Cct2 4387.7 5534.5 8956.4 Rpl8 13905.6 17108.7 21320.8 Rpl6 13374.9 16915.9 22252.9 Rpl27 10215.9 12181.0 15453.0 CEM 1 + Tcp1 4645.6 5793.1 7008.2 Top 10 Genes Naca 14054.1 17281.5 21269.7 Cct4 5028.5 5990.7 8801.7 Rps5 16680.3 20627.6 25063.9 Rps19 13916.0 17067.3 22535.3

Null module Eif3a Eif3e GEO Series "GSE2527" 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=GSE2527 Status: Public on May 06 2005 Title: Gata-1 Knock Down - Wild Type Megakaryocyte Gene Expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 15860665 Summary & Design: Summary: Hematopoietic progenitor cells were isolated from 13.5 day mouse fetal livers by lineage depletion and expanded for three days. Fetal livers were isolated from both wild type and Gata-1 knock embryos. Gata-1 knock embryos contain a deletion of the Gata-1 promoter sequence that results in undetectable levels of Gata-1 protein specifically in the megakaryocyte lineage. Following progenitor outgrowth megakaryocytes were enriched in a differentiation media for three days and isolated on a discontinuous BSA gradient. The resulting megakaryocytes were >90% pure as determined by acetylcholinesterase staining. These cells were lysed in Trizol and the resulting RNA was used for hybridization.

Keywords = Gata-1

Keywords = Megakaryocytes

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0240, L1-Distance = 0.0329, L2-Distance = 0.0011, Normal std = 0.7666

0.546 Kernel fit Pairwise Correlations Normal fit

Density 0.273

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

Gata-1 KnockGata-1 DownKnockGata-1 A Down KnockGata-1(0.100709) B Down WildGata-1(0.198103) Type C WildGata-1(0.234768) A Type(0.114611) Wild B Type(0.196353) C (0.155456)[ min ] [ medium ] [ max ] CEM 1 Eif3l 4908.9 5573.7 6266.7 P ( S | Z, I ) = 1.00 Eif3d 4580.4 6289.2 7136.9 Mean Corr = 0.88880 Eif3i 7989.2 10133.0 10804.8 Eif3g 3722.2 5101.3 5412.3 Eif3k 5792.2 7207.1 8305.4 Eif3h 7914.7 9426.5 10818.0 Eif3c 4884.1 5675.1 6847.6 Eif3f 10693.3 13361.8 15016.6 Eif3m 2132.4 2847.9 3078.1 Eif3b 4553.9 5350.2 5954.3 Cct5 6973.6 8530.0 9206.8 Cct2 6096.4 7592.4 8718.9 Rpl8 13517.5 16116.2 18609.3 Rpl6 18024.9 20323.1 25016.2 Rpl27 15443.7 18706.8 22472.7 CEM 1 + Tcp1 6724.5 8836.7 10560.8 Top 10 Genes Naca 12843.5 15248.0 19783.2 Cct4 6663.8 7098.8 8370.2 Rps5 13541.3 15629.0 23010.5 Rps19 12486.1 16330.8 17259.0

Null module Eif3a Eif3e GEO Series "GSE16454" 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=GSE16454 Status: Public on Dec 17 2009 Title: Gene expression data from small intestines Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20016602 Summary & Design: Summary: Rb and E2F are thought to play antagonistic roles in celll proliferation. However, this model is based mostly from in vitro cell culture systems. We used small intestines to test this model in vivo.

We found that deletion of E2f1-3 in the small intestine of mice suppressed the ectopic expression of E2F targets and cell proliferation caused by Rb-deficiency. Surprisingly, E2f1-3 deletion failed to arrest the proliferation of intestinal cells containing an intact Rb gene, and instead led to E2F target derepression and apoptosis.

Overall design: Total RNA of crypts and villi from wild-type, Rb-/-, E2f1-/-, E2f2-/-, E2f3-/-, E2f1-/-, E2f2-/-, and E2f3-/- small intestines. Small intestines were harvested 7 days after mice were injected intraperitoneally with beta-napthoflavone.

Background corr dist: KL-Divergence = 0.1386, L1-Distance = 0.0283, L2-Distance = 0.0011, Normal std = 0.3877

1.029 Kernel fit Pairwise Correlations Normal fit

Density 0.514

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-1-cryptsWT-2-crypts (0.0397887)Rb-1-crypts (0.0553843)Rb-2-crypts (0.0214339)WT-3-crypts (0.0589497)Rb-3-crypts (0.0135754)WT-1-villi (0.00972958)WT-2-villi (0.0471803)WT-3-villi (0.0721601)Rb-1-villi (0.055094)Rb-2-villi (0.0325242)Rb-3-villi (0.0327582)TKO-1-villi (0.0281399)TKO-2-villi (0.00549121)TKO-3-villi (0.037064)TKO-1-crypts (0.0435847)TKO-2-crypts (0.0706087)TKO-3-crypts (0.0660964)QKO-1-villi (0.0285585)QKO-2-villi (0.0131369)QKO-3-villi (0.0483496)QKO-1-crypts (0.0825174)QKO-2-crypts (0.0661473)QKO-3-crypts (0.0393733) (0.0323537) [ min ] [ medium ] [ max ] CEM 1 Eif3l 3180.3 5355.2 7802.6 P ( S | Z, I ) = 1.00 Eif3d 2022.8 3405.4 5317.2 Mean Corr = 0.88846 Eif3i 4419.3 7794.4 11913.5 Eif3g 2033.0 3592.6 5948.6 Eif3k 3410.9 5105.3 7479.6 Eif3h 4687.2 8206.2 11040.4 Eif3c 4169.6 6262.4 7725.2 Eif3f 6442.2 12802.1 19272.0 Eif3m 1428.1 2561.0 3616.8 Eif3b 1683.4 2940.4 4117.3 Cct5 3988.4 6742.0 10218.4 Cct2 3521.6 7140.8 10900.2 Rpl8 10080.5 21653.6 29706.4 Rpl6 12245.0 24601.8 29856.8 Rpl27 7044.1 13148.9 17540.8 CEM 1 + Tcp1 4352.7 8152.9 11609.4 Top 10 Genes Naca 8633.8 17578.6 21967.8 Cct4 4316.9 7264.1 10014.7 Rps5 13772.2 26943.5 33620.8 Rps19 7338.9 19062.1 26155.7

Null module Eif3a Eif3e GEO Series "GSE27605" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27605 Status: Public on Mar 14 2011 Title: The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21419747 Summary & Design: Summary: Using EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.

A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. The intestinal stem cell signature predicts disease relapse in CRC and identifies a stem cell-like population that displays robust tumor- initiating capacity in immunodeficient mice as well as long-term self-renewal potential.

Overall design: We FACS purified mouse intestinal crypt cells according to their EphB2 or Lgr5 contents. We used Affymetrix chips to hybridize 2 samples from EphB2 high, 2 samples from EphB2 medium and 2 samples from EphB2 low cells (one sample from each group in a first hybridization on February 2009 plus an additional sample from each group on March 2009). Additionally, we hybridized one sample from Lgr5-EGFP high and one sample from Lgr5-EGFP low cells, obtained from Lgr5-EGFP knock-in mice (Barker et al., 2007).

Background corr dist: KL-Divergence = 0.0298, L1-Distance = 0.0338, L2-Distance = 0.0014, Normal std = 0.6870

0.614 Kernel fit Pairwise Correlations Normal fit

Density 0.307

0.000 CEM 1

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

Pre-normalization Quantiles

intestine-Lgr5High-R1intestine-Lgr5Low-R1intestine-EphB2High-R1 intestine-EphB2Medium-R1(0.154365) (0.0210902)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.113348)intestine-EphB2Medium-R2 (0.0521182)intestine-EphB2Low-R2 (0.231051) (0.0995269) (0.0220495) (0.306451)[ min ] [ medium ] [ max ] CEM 1 Eif3l 4400.9 5745.6 6566.9 P ( S | Z, I ) = 1.00 Eif3d 3436.5 5505.9 6232.8 Mean Corr = 0.88593 Eif3i 7101.5 9409.3 10144.6 Eif3g 3674.4 5739.3 6457.3 Eif3k 7065.9 8978.9 9699.3 Eif3h 8595.6 10349.9 11133.0 Eif3c 3477.3 4072.6 4475.7 Eif3f 8218.3 9570.4 10651.0 Eif3m 2205.4 3422.4 3730.1 Eif3b 1469.4 2167.6 2494.6 Cct5 3399.4 5328.1 6016.0 Cct2 5690.8 8967.5 9677.6 Rpl8 8039.5 10000.4 11180.8 Rpl6 13715.5 15524.6 15781.1 Rpl27 8468.4 10628.9 11197.7 CEM 1 + Tcp1 5559.5 7728.3 8648.9 Top 10 Genes Naca 13360.8 14480.3 16387.5 Cct4 6078.3 7913.0 8569.7 Rps5 10286.2 11672.7 11972.7 Rps19 9728.1 12131.8 12766.9

Null module Eif3a Eif3e GEO Series "GSE25257" 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=GSE25257 Status: Public on Nov 11 2010 Title: Expression data from wild-type and Zmpste24-/- mouse embryonic fibroblasts (MEFs) at an early passage (passage 3, P3) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Zmpste24 is a metalloproteinase processing prelamin A into mature lamin A, a nuclear structure protein. Zmpste24-/- mice which accumulate prelamin A in cells recapitulate accelerated aging phenotypes observed in human premature aging disorder, Hutchinson Gilford progeria sydrome (HGPS). Zmpste24-/- mouse embryonic fibroblasts (MEFs) exhibited genomic instabiliy and accelerated aging at cellular level, which is premature senescence.

We performed microarray analysis on Zmpste24-/- MEFs, compared to wild-type littermates' MEFs, at an early passage (P3), which is a pre-symptom stage before cellular senescence occurs in the mutant MEFs, in order to examine gene expression profile and figure out the underneath mechanism triggering the premature aging process.

Overall design: Early passage wild-type and Zmpste24-/- MEFs were collected for RNA extraction, the quality of RNAs were determinded by Electrophoresis Assay (2100 Bioanalyzer, Agilent) and RNA extractions were used for hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0217, L1-Distance = 0.0450, L2-Distance = 0.0023, Normal std = 0.8008

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

WT1 (0.186761)WT2 (0.142372)WT3 (0.0868207)NT1 (0.353401)NT2 (0.184508)NT3 (0.0461366) [ min ] [ medium ] [ max ] CEM 1 Eif3l 5760.0 7826.4 8201.2 P ( S | Z, I ) = 1.00 Eif3d 3317.3 4963.0 5505.3 Mean Corr = 0.88092 Eif3i 7927.4 10418.6 11161.7 Eif3g 5356.0 7289.1 7714.0 Eif3k 6545.1 7550.1 8472.4 Eif3h 7997.0 9636.0 9963.6 Eif3c 6913.4 9134.1 9722.6 Eif3f 11495.1 13097.6 14218.3 Eif3m 2914.0 3851.1 3950.7 Eif3b 2280.0 3279.5 3446.8 Cct5 8280.9 11907.2 12462.1 Cct2 8808.8 10997.5 12249.3 Rpl8 13085.0 14959.2 15388.3 Rpl6 17113.2 20462.3 21533.4 Rpl27 17028.2 20928.5 21764.6 CEM 1 + Tcp1 7776.5 11623.7 11858.4 Top 10 Genes Naca 15054.9 19111.4 19295.2 Cct4 7218.1 9736.2 9862.3 Rps5 14285.3 15858.2 16623.9 Rps19 16183.4 19753.4 20605.0

Null module Eif3a Eif3e GEO Series "GSE12881" 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=GSE12881 Status: Public on Jan 26 2009 Title: Loss of Caveolin-3 Induces the Development of a Lactogenic Microenvironment Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19164602 Summary & Design: Summary: Here, we show that functional loss of a single gene is sufficient to confer constitutive milk protein production and protection against mammary tumor formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly expressed in striated and smooth muscle cells. We demonstrate that Cav-3 is also expressed in myoepithelial cells within the mammary gland. To determine if genetic ablation of Cav-3 expression affects adult mammary gland development, we next studied the phenotype(s) of Cav-3 (-/-) null mice. Interestingly, detailed analysis of Cav-3 (-/-) virgin mammary glands shows dramatic increases in ductal thickness, side-branching, and the development of extensive lobulo-alveolar hyperplasia, akin to the changes normally observed during pregnancy and lactation. Analysis by genome-wide expression profiling reveals the upregulation of gene transcripts associated with pregnancy/lactation, mammary stem cells, and human breast cancers, consistent with a constitutive lactogenic phenotype. The expression levels of three key transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc are also significantly elevated. Experiments with pregnant mice directly show that Cav-3 (-/-) mice undergo precocious lactation. Finally, using orthotopic implantation of a transformed mammary cell line (known as Met-1), we demonstrate that virgin Cav-3 (-/-) mice are dramatically protected against mammary tumor formation. Interestingly, Cav-3 (+/-) mice also show similar protection, indicating that even reductions in Cav-3 levels are sufficient to render these mice resistant to tumorigenesis. Thus, Cav-3 (-/-) mice are a novel preclinical model to study the protective effects of a constitutive lactogenic microenviroment on mammary tumor onset and progression. Our current studies have broad implications for using the lactogenic micro-environment as a paradigm to discover new therapies for the prevention and/or treatment of human breast cancers. Most importantly, a lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anti-cancer therapies.

Overall design: All WT and Cav-3 knockout (KO) mice used in this study were in the FVB/N genetic background. 4-month old virgin female mice were utilized in a micro array study between 3 wildtype and 3 Caveolin-3 knock-out mammary glands.

Background corr dist: KL-Divergence = 0.0260, L1-Distance = 0.0141, L2-Distance = 0.0002, Normal std = 0.6931

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

MammaryMammary Gland_WT_rep1Mammary Gland_WT_rep3Mammary Gland_WT_rep2 (0.0718904)Mammary Gland_Cav-3KO_rep1 (0.155612)Mammary Gland_Cav-3KO_rep2 (0.247886) Gland_Cav-3KO_rep3 (0.184167) (0.0814534)[ (0.258991)min ] [ medium ] [ max ] CEM 1 Eif3l 6394.9 8109.6 8894.0 P ( S | Z, I ) = 1.00 Eif3d 2919.7 3349.4 4258.9 Mean Corr = 0.87905 Eif3i 10508.7 12470.1 14719.1 Eif3g 7169.9 9876.4 11195.6 Eif3k 1981.1 2125.9 2730.8 Eif3h 3124.0 3668.0 4408.7 Eif3c 7694.7 9944.2 10470.3 Eif3f 12989.4 16286.3 17833.5 Eif3m 1775.3 1987.7 2651.8 Eif3b 4459.4 6280.5 7192.9 Cct5 6772.7 10235.0 11006.9 Cct2 5665.8 7480.4 10039.3 Rpl8 20730.8 22380.5 25844.0 Rpl6 20324.1 22268.8 25222.5 Rpl27 887.5 1114.3 1295.8 CEM 1 + Tcp1 8126.9 9871.9 11928.9 Top 10 Genes Naca 7585.2 9654.6 13756.0 Cct4 6578.5 8574.9 9043.2 Rps5 5033.4 6741.9 8323.1 Rps19 6181.7 7070.1 9312.1

Null module Eif3a Eif3e GEO Series "GSE6689" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6689 Status: Public on Jan 07 2008 Title: Expression data during stem cell differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18184438 Summary & Design: Summary: Stem cell development requires selection of specific genetic programs to direct cellular fate. Using microarray technology, we profile expression trends at selected timepoints during stem cell differentiation to characterize these changes.

Keyword(s): timecourse

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

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

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Control_ES-LIF(+)_rep1Timepoint1_ES-LIF(-)_rep1Timepoint2_CM_rep1Control_ES-LIF(+)_rep2 (0.0839074)Timepoint1_ES-LIF(-)_rep2 (0.0656739) (0.179661)Timepoint2_CM_rep2Timepoint1b_CP_rep1 (0.0572147)Control_ES-LIF(+)_rep3 (0.0777194) (0.135513)Timepoint1_ES-LIF(-)_rep3 Timepoint2_CM_rep3(0.0344732)Timepoint1b_CP_rep2 (0.0755691)Timepoint1b_CP_rep3 (0.0841418) (0.127013) (0.0207662) (0.0583477)[ min ] [ medium ] [ max ] CEM 1 Eif3l 6877.0 10476.3 11704.7 P ( S | Z, I ) = 1.00 Eif3d 6149.3 9181.0 10955.7 Mean Corr = 0.87391 Eif3i 8207.4 11489.7 12681.9 Eif3g 6465.8 10194.9 10854.9 Eif3k 5408.2 6535.5 7944.9 Eif3h 6587.8 8695.6 9522.1 Eif3c 7345.5 10033.8 11859.7 Eif3f 10593.9 12982.8 13887.7 Eif3m 3394.4 5579.5 6519.3 Eif3b 4887.1 7376.4 9184.4 Cct5 8153.8 15098.6 15703.5 Cct2 11106.4 14711.1 16648.7 Rpl8 16681.9 21777.0 26461.7 Rpl6 24297.1 26677.5 39815.6 Rpl27 28409.0 32860.6 42794.3 CEM 1 + Tcp1 11614.1 15656.8 17269.4 Top 10 Genes Naca 18187.6 22455.2 27151.9 Cct4 11258.6 17280.4 18162.4 Rps5 21513.0 24309.1 33961.5 Rps19 13494.1 22003.4 25358.9

Null module Eif3a Eif3e GEO Series "GSE6837" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6837 Status: Public on Jan 31 2007 Title: Expression data from wild type (wt) and Ikbke knockout (Ikke) embryonic fibroblasts (EF) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17332413 Summary & Design: Summary: WT and Ikbke-/- EF cells were stimulated with recombinant interferon beta for 6 hours. Cells lacking IKKe kinase show a defect in a subset of interferon stimulated gene transcription

Keywords: comparative study

Overall design: WT and Ikbke cells were either stimulated and left untreated to compare their response to interferon.

Background corr dist: KL-Divergence = 0.0231, L1-Distance = 0.0545, L2-Distance = 0.0038, Normal std = 0.8315

0.536 Kernel fit Pairwise Correlations Normal fit

Density 0.268

0.000 CEM 1

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

Pre-normalization Quantiles

unstimulatedunstimulated embryonicstimulated embryonicstimulated fibroblasts embryonicstimulated fibroblasts embryonic WT, stimulatedfibroblasts biologicalembryonic KO, stimulatedfibroblasts biologicalembryonicWT, rep1 stimulatedfibroblasts biological embryonicWT,(0.0934749) rep1 fibroblasts biological embryonicrep1WT,(0.0549988) fibroblasts biological(0.0785493) rep2KO, fibroblasts biological (0.0310817) rep3KO,[ biological (0.0667624) min rep1KO, biological(0.353386) rep2] (0.0470557) rep3 (0.274691)[ medium ] [ max ] CEM 1 Eif3l 2953.3 14392.5 16048.3 P ( S | Z, I ) = 1.00 Eif3d 3075.8 9501.1 11553.6 Mean Corr = 0.86845 Eif3i 7157.3 13103.9 15183.9 Eif3g 3055.0 6312.3 7832.5 Eif3k 4997.5 5801.3 6321.5 Eif3h 4832.9 15581.3 17218.9 Eif3c 4335.7 12396.8 13938.5 Eif3f 6732.6 14469.9 15339.9 Eif3m 1468.9 5540.8 5925.1 Eif3b 2195.1 6493.1 7052.1 Cct5 4900.7 19432.1 21766.2 Cct2 3923.3 26789.6 27834.7 Rpl8 18807.2 35688.9 42263.0 Rpl6 14741.8 34857.2 38228.4 Rpl27 19011.0 39467.8 41024.1 CEM 1 + Tcp1 4401.9 20188.1 21638.3 Top 10 Genes Naca 11234.3 33760.6 36120.8 Cct4 4224.8 14211.5 16172.5 Rps5 19806.1 31634.8 37403.6 Rps19 18385.9 28176.7 32502.3

Null module Eif3a Eif3e GEO Series "GSE24121" 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=GSE24121 Status: Public on Oct 20 2010 Title: Oligoarray analysis of mRNA species from DCs treated with C. parvum for 24 h. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To investigate whether C. parvum treatment of DCs regulates other inflammatory genes, mouse BMDCs (CD11c and CD11b positive) were treated with C. parvum for 24 hr. Control groups included untreated BMDCs and DCs treated with E. cuniculi. We noticed that a significant upregulation of the expression of interferon-related genes, which may correlation the critical role of interferon in host defense against C. parvum infection.

Overall design: DCs were treated with C. parvum for 24 hr. Control groups included untreated BMDCs and DCs treated with E. cuniculi. Group comparison was performed using the data of 3 replicate arrays from each time point.

Background corr dist: KL-Divergence = 0.0664, L1-Distance = 0.0336, L2-Distance = 0.0016, Normal std = 0.5257

0.785 Kernel fit Pairwise Correlations Normal fit

Density 0.392

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

DCs-C1DCs-C2 (0.0908946)DCs-C3 (0.117688)DCs-EC1 (0.195658)DCs-EC2 (0.249832)DCs-EC3 (0.209921)DCs-CP1 (0.0579251)DCs-CP2 IOWADCs-CP3 (0.0402325) IOWA (0.0232638) IOWA (0.0145864) [ min ] [ medium ] [ max ] CEM 1 Eif3l 1841.3 3912.5 5704.5 P ( S | Z, I ) = 1.00 Eif3d 3096.2 4011.3 5374.3 Mean Corr = 0.86425 Eif3i 3766.1 8728.1 10512.6 Eif3g 1908.2 3559.5 4606.2 Eif3k 3712.3 5609.0 7728.4 Eif3h 5607.4 7342.8 9458.7 Eif3c 5600.4 8638.6 12879.5 Eif3f 8294.2 11249.7 14687.9 Eif3m 1486.8 2049.4 2852.3 Eif3b 1245.8 2096.0 2334.6 Cct5 2649.6 6100.3 8609.3 Cct2 3316.0 6782.5 9141.5 Rpl8 11626.3 22456.5 25246.1 Rpl6 10389.0 20431.7 25042.0 Rpl27 15541.3 22007.8 25107.4 CEM 1 + Tcp1 4410.9 6794.6 8195.2 Top 10 Genes Naca 7948.2 12666.1 15205.0 Cct4 4277.6 7563.3 10943.3 Rps5 20307.8 21982.1 24866.0 Rps19 11935.6 22233.6 25000.7

Null module Eif3a Eif3e 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 (0.134829)forebrain_Vegf188_4 (0.165117)forebrain_wildtype_5 (0.084497)forebrain_wildtype_6 (0.154118)forebrain_Vegf120188_1 (0.116392)forebrain_Vegf120188_2 (0.162063)forebrain_Vegf120188_3 (0.0647532) (0.0466835) (0.0715484)[ min ] [ medium ] [ max ] CEM 1 Eif3l 6272.5 6356.4 9058.1 P ( S | Z, I ) = 1.00 Eif3d 2544.0 3654.4 6683.2 Mean Corr = 0.85754 Eif3i 7735.6 8794.9 12272.5 Eif3g 4468.8 6888.5 8937.1 Eif3k 2842.9 4536.9 7554.0 Eif3h 4700.7 5460.8 6857.3 Eif3c 3459.8 4230.1 7135.4 Eif3f 7416.5 9983.7 13776.8 Eif3m 2813.7 3570.6 4873.7 Eif3b 2000.0 3070.3 6085.3 Cct5 10611.1 13574.8 14470.1 Cct2 6491.2 7803.2 11209.5 Rpl8 10995.7 15936.9 20496.4 Rpl6 11351.4 16181.4 22400.5 Rpl27 11563.8 13579.4 22522.8 CEM 1 + Tcp1 8559.6 9590.3 14239.9 Top 10 Genes Naca 13071.0 17658.7 23716.3 Cct4 8718.3 10046.9 13945.0 Rps5 14925.2 20423.9 26344.4 Rps19 12798.5 17355.0 22236.5

Null module Eif3a Eif3e 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 (0.128082)knockout -kidneymouse 2 (0.17381)knockout -kidneymouse 3 (0.15647) -kidneymouse 1 (0.117264) -kidney 2 (0.304516) - 3 (0.119859)[ min ] [ medium ] [ max ] CEM 1 Eif3l 4612.8 4959.0 5457.8 P ( S | Z, I ) = 1.00 Eif3d 2792.5 4209.3 4552.7 Mean Corr = 0.85671 Eif3i 7520.3 7916.3 8592.9 Eif3g 2655.7 3296.2 3686.5 Eif3k 4884.3 5607.8 5948.7 Eif3h 4861.3 6425.2 7298.0 Eif3c 5312.6 7512.3 8165.6 Eif3f 5031.1 8409.0 8888.1 Eif3m 2382.3 2995.6 3440.2 Eif3b 1769.8 2217.1 2513.4 Cct5 4550.4 6504.5 7191.1 Cct2 3116.8 4882.3 5480.2 Rpl8 9943.9 15104.9 16804.3 Rpl6 11907.4 15102.2 17276.2 Rpl27 9524.1 12351.2 12828.2 CEM 1 + Tcp1 5132.7 6368.8 6738.1 Top 10 Genes Naca 11022.6 16805.3 18654.5 Cct4 4856.8 7009.2 7869.5 Rps5 14849.1 20972.0 23377.6 Rps19 9729.9 19585.6 21243.7

Null module Eif3a Eif3e GEO Series "GSE15587" 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=GSE15587 Status: Public on Feb 24 2011 Title: Identification of Metastasis-prone Lung Adenocarcinoma Cell Population That Is Sensitive to Notch Inhibition Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21403400 Summary & Design: Summary: Tumor cells that give rise to metastatic disease are a primary cause of cancer-related death and have not been fully elucidated in patients with lung cancer. Here, we addressed this question by using tissues from a mouse that develops metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. We identified a metastasis-prone population of tumor cells that differed from those with low metastatic capacity on the basis of having sphere-forming capacity in Matrigel cultures, increased expression of CD133 and Notch ligands, and relatively low tumorigenicity in syngeneic mice. Knockdown of jagged1 or pharmacologic inhibition of its downstream mediator phosphatidylinositol 3-kinase abrogated the metastatic but not the tumorigenic activity of these cells. We conclude from these studies on a mouse model of lung adenocarcinoma that CD133 and Notch ligands mark a population of metastasis-prone tumor cells and that the efficacy of Notch inhibitors in metastasis prevention should be explored.

Keywords: two group comparison

Overall design: 344SQ subcutaneous tumors (from a lung adenocarcinoma cell line derived from a KrasLA1/+; p53R172HdelG/+ mouse that metastasizes widely following subcutaneous injection into syngeneic mice) were sorted by flow cytometry into CD133high and CD133low fractions. RNA samples from these fractions were processed and analyzed on Affymetrix Mouse Expression Array 430A 2.0 chips.

Background corr dist: KL-Divergence = 0.0175, L1-Distance = 0.0233, L2-Distance = 0.0007, Normal std = 0.7784

0.512 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

H0019466:H0019467: CD133H0019468: lowCD133 (0.133861)H0019469: lowCD133 (0.235644)H0019470: lowCD133 (0.0558685)H0019471: highCD133 (0.0333021) highCD133 (0.194825) high (0.346499)[ min ] [ medium ] [ max ] CEM 1 Eif3l 2291.0 4003.0 5390.4 P ( S | Z, I ) = 1.00 Eif3d 1213.5 2831.7 3336.1 Mean Corr = 0.85374 Eif3i 3107.4 5699.7 6788.4 Eif3g 1619.1 3802.7 4331.5 Eif3k 1078.1 3149.9 4605.8 Eif3h 1852.9 6257.6 7105.7 Eif3c 2444.8 3969.4 4184.7 Eif3f 7879.4 13523.4 14461.1 Eif3m 1196.1 2612.8 3536.7 Eif3b 1866.1 2129.0 2304.8 Cct5 2951.2 5203.1 6876.1 Cct2 1369.7 3783.1 4016.3 Rpl8 9952.6 11622.7 12995.9 Rpl6 9647.0 13013.4 14859.8 Rpl27 7658.7 15684.8 17446.5 CEM 1 + Tcp1 4160.7 4589.4 5073.2 Top 10 Genes Naca 3487.8 11088.2 13870.8 Cct4 2515.9 3194.7 3652.6 Rps5 8745.8 16689.0 17927.0 Rps19 9992.4 15285.5 17577.2

Null module Eif3a Eif3e GEO Series "GSE27379" 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=GSE27379 Status: Public on Dec 21 2011 Title: CD8+ T cell mediated lung inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21518973 Summary & Design: Summary: Role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung.

Overall design: CD8+ T cell type comparison; lung disease state analysis

Background corr dist: KL-Divergence = 0.0455, L1-Distance = 0.0339, L2-Distance = 0.0016, Normal std = 0.6061

0.671 Kernel fit Pairwise Correlations Normal fit

Density 0.335

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 lung CL42 BLN activated CL43 BLN activated (0.149214)CL44 lung (naive) (0.405599) CL45 BLN (0.078172)(naive) SPC-HAxCL46 lung (0.205657) SPC-HAxCL4 (0.0906206) (0.0707382)[ min ] [ medium ] [ max ] CEM 1 Eif3l 2789.7 5549.7 12387.7 P ( S | Z, I ) = 1.00 Eif3d 5222.9 6112.5 10028.0 Mean Corr = 0.84983 Eif3i 6473.8 9967.5 17070.8 Eif3g 6373.5 7596.5 10658.7 Eif3k 2505.3 4966.2 6674.7 Eif3h 12511.6 13963.6 15652.6 Eif3c 3282.3 7006.1 11707.6 Eif3f 15283.6 22852.2 25524.1 Eif3m 4510.4 7227.7 9663.8 Eif3b 1381.3 2740.6 5208.3 Cct5 7580.1 11443.1 18732.1 Cct2 7403.7 9915.3 18660.0 Rpl8 26807.2 29832.1 34170.2 Rpl6 33679.1 37781.7 40203.2 Rpl27 21287.2 28516.2 34823.3 CEM 1 + Tcp1 6860.4 10044.3 18655.3 Top 10 Genes Naca 12900.3 15080.1 20320.8 Cct4 8383.6 14593.9 20967.3 Rps5 29902.9 32103.6 35437.8 Rps19 16814.7 20421.1 22777.2

Null module Eif3a Eif3e 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(0.178506) 1_le1 (0.284835) hippocampus:HuDpulldown(0.114352) HuDpulldown #1_e1_le1 Control #2_e1_le1 IP (0.143802) #2_e1_le1[ (0.14289)min (0.135614) ] [ medium ] [ max ] CEM 1 Eif3l 353.5 1053.1 2265.5 P ( S | Z, I ) = 1.00 Eif3d 330.7 1035.6 2741.9 Mean Corr = 0.84459 Eif3i 1952.5 5117.9 7345.3 Eif3g 1520.5 3647.6 5420.6 Eif3k 467.4 1973.1 2440.8 Eif3h 1040.6 3159.2 4844.6 Eif3c 440.0 1683.1 2977.1 Eif3f 4172.1 10233.6 14173.9 Eif3m 109.8 497.6 1237.5 Eif3b 497.5 851.3 1321.4 Cct5 1761.3 6565.7 7082.7 Cct2 1775.5 3832.0 4363.5 Rpl8 3296.5 11244.3 13966.6 Rpl6 4546.4 9965.3 14987.2 Rpl27 3890.6 5387.8 9534.5 CEM 1 + Tcp1 2128.2 5540.9 8430.9 Top 10 Genes Naca 711.3 2871.8 4636.8 Cct4 733.5 3079.3 4555.7 Rps5 4039.0 9011.6 18913.3 Rps19 1744.2 3517.2 9032.8

Null module Eif3a Eif3e GEO Series "GSE18586" 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=GSE18586 Status: Public on Jun 18 2012 Title: Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22700822 Summary & Design: Summary: We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.

Keywords: Diet intervention study

Overall design: Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.

Background corr dist: KL-Divergence = 0.0644, L1-Distance = 0.0264, L2-Distance = 0.0008, Normal std = 0.5278

0.773 Kernel fit Pairwise Correlations Normal fit

Density 0.386

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

SI1, 2 wksSI1, on 2 wksaSI1, HF-PO on 2 wksa SI2, dietHF-OO on 2(0.0518479) wksaSI2, dietHF-SO on 2 (0.139617) wksa SI2, dietHF-PO on 2(0.139569) wksa SI3, dietHF-OO on 2(0.0487552) wksaSI3, dietHF-SO on 2 (0.0144515) wksa SI3, dietHF-PO on 2(0.0380182) wksa dietHF-OO on (0.111041) a dietHF-SO (0.21896) diet (0.23774)[ min ] [ medium ] [ max ] CEM 1 Eif3l 3158.0 3465.5 4044.1 P ( S | Z, I ) = 1.00 Eif3d 2077.1 2387.2 3572.8 Mean Corr = 0.84409 Eif3i 4937.2 5390.6 6965.4 Eif3g 1878.1 2420.4 2980.7 Eif3k 3580.4 3844.4 4257.9 Eif3h 4457.6 5080.1 6691.0 Eif3c 3423.1 4621.6 6109.2 Eif3f 7188.1 8580.6 10889.2 Eif3m 988.3 1373.2 1998.9 Eif3b 1496.0 1643.7 2022.7 Cct5 2981.4 3523.9 4453.4 Cct2 3506.7 3893.9 5043.9 Rpl8 11522.1 12935.7 15742.9 Rpl6 10799.1 12927.0 17586.1 Rpl27 10785.4 12761.7 17249.0 CEM 1 + Tcp1 3607.4 3870.8 4760.8 Top 10 Genes Naca 9225.8 9827.3 11451.3 Cct4 3644.7 4092.0 5122.3 Rps5 14110.9 16106.0 20613.7 Rps19 8572.1 9679.9 12962.1

Null module Eif3a Eif3e GEO Series "GSE49050" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 72 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49050 Status: Public on Jul 23 2014 Title: Expression data from postnatal mouse brain regions of Ts1Cje and disomic C57BL/6 mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 25052193 Summary & Design: Summary: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. The mouse model develops various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points; postnatal day (P)1, P15, P30 and P84.

Overall design: RNA was extracted from thre brain regions (Cerebral cortex, hippocampus and cerebellum) for hybridization to arrays from 3 pairs of Ts1Cje and disomic C57BL/6 littermate control for each timepoints at postnatal (P) day 1, P15, P30 and P84.

Background corr dist: KL-Divergence = 0.1628, L1-Distance = 0.0657, L2-Distance = 0.0118, Normal std = 0.3740

1.103 Kernel fit Pairwise Correlations Normal fit

Density 0.551

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

WildtypeTs1Cje P1 hippocampus Ts1CjeP84 cerebral Ts1CjeP30 cerebralbiological cortex Ts1CjeP1 cerebellum biologicalcortex replicateWildtypeP30 hippocampus biological Ts1Cjebiological replicate 1P15 (0.0278989) cerebral WildtypeP84 replicate 1replicate biological(0.00451667)cerebellum Wildtypecortex P11 (0.00880474)1cerebellum (0.0568596)replicatebiologicalTs1Cje biological P84 hippocampus Ts1CjeP15 1 biological replicate(0.00493659) replicatecerebral Ts1CjeP84 1hippocampusreplicate biologicalcortex1(0.00398446) WildtypeP1(0.00582144) hippocampus biological 1Wildtype (0.0423148)replicate P30 biological hippocampusWildtype replicate P84 biological1 (0.00649058) cerebellumreplicateWildtype P151 (0.00397482) replicatebiological hippocampusTs1Cje 1 P84 (0.00341716)biological cerebral 1Ts1CjeP15 replicate(0.0281884) hippocampus biologicalreplicate WildtypeP30cortex 1 cerebellum(0.00410843) biological Ts1Cje1 replicate P30(0.00516226) biological cerebellum Ts1CjeP1 biological replicate1cerebral (0.00521929) replicate WildtypeP15 biological replicate1cerebellumcortex (0.00476261)Wildtype 1 P30 (0.00299439) biological 1replicatecerebral Wildtype(0.00904963) biological P15 cerebellum replicate Ts1Cjecortex1 P1(0.00826939) replicate cerebral biologicalTs1CjeP84 1 biological(0.020596) hippocampus 1cortex WildtypeP1(0.00615611) replicate cerebellum biologicalreplicateWildtype P15 biological 1 (0.00748634)hippocampus Wildtypebiological1 replicateP30(0.00255484) cerebralreplicateTs1Cje P30 replicate1 (0.0264287) biological hippocampus WildtypeP1cortex 2 (0.00383097)hippocampus 2 (0.0179424)biologicalTs1Cje replicate P15 biological cerebellum WildtypeP30 replicatebiological2 cerebellum(0.00487885)Ts1Cje replicate P1 biological 2 cerebral replicate(0.00859302) WildtypeP1 biological 2cerebral (0.00548271) replicatecortex 2Ts1Cje (0.0253741)P1 replicate cortexcerebellum biological WildtypeP152 (0.00533455) biologicalcerebral 2 Ts1Cje(0.00817054) replicatebiologicalP1 hippocampus cortex replicateWildtypeP30 2 hippocampus replicate(0.0301228)biologicalWildtype 2 P84 (0.0360441) biological cerebellum2Wildtype replicate(0.0453981) P15 biological cerebral replicateTs1Cje P84 2biological (0.00236428) cerebralreplicate WildtypeP15cortex 2 (0.0586363) cerebellum replicate biologicalWildtypecortex 2 P30 (0.00413388) cerebellum biological Ts1Cje2 biological P84 (0.00275327)replicate hippocampus Ts1CjeP15 replicatebiological replicate2hippocampus (0.00528008) Ts1CjeP84 2cerebral biological2replicate(0.00254468) Ts1CjeP30(0.00117323) biological cerebral cortex Ts1CjeP842 replicate (0.0078595) cerebellum biologicalcortex replicate Ts1CjeP15 2 cerebellum (0.0120761)biological Ts1CjeP30 replicate2biological (0.00883175) hippocampus WildtypeP1 replicatebiological 2 cerebellum replicate(0.00450141)Ts1Cje P302 biologicalreplicate(0.00578788) 2cerebellum Ts1CjebiologicalP84(0.00445001) hippocampus 3 replicate Ts1CjeP15(0.00321097) replicatebiological hippocampus WildtypeP15 3 (0.00695277) biological cerebral3 replicate(0.0363456)Wildtype P1 biological hippocampus cortex replicate Ts1Cje3 P30(0.00798652) biological cerebralreplicate WildtypeP84 3 (0.00187445) cerebellumbiological Ts1Cje cortex replicate3 P84 (0.0064924) hippocampus biologicalreplicateWildtypeP84 biological 3 (0.0103962)cerebralTs1Cje 3P84 replicate (0.0298908) replicate biological cortexcerebellum Ts1CjeP1 cerebral 3 biological 3(0.00855878) WildtypeP30(0.00754083) replicate biological cerebralcortexTs1Cje replicate P1 3 biological (0.0135224)cerebral cortexreplicate WildtypeP30 3 (0.00841924)cerebellum biological cortexreplicate Wildtype3 P15(0.00274831) biologicalcerebralWildtype replicatebiological3 P15 (0.0420727) hippocampus Wildtypecortex replicate P13 replicate(0.00246376) cerebellum biologicalTs1Cje P15 3 (0.0237673) biological3cerebellum WildtypeP1(0.00741982) biological replicate hippocampusWildtype replicate P30 biological 3replicate (0.00342518)hippocampus P84 biological3 (0.00427861) replicate cerebral3 (0.117296) replicatebiological cortex3 (0.00178641) biological3[ replicate (0.0347295)min replicate3 ](0.00194744) 3 (0.00531337)[ medium ] [ max ] CEM 1 Eif3l 1796.0 3052.8 8894.4 P ( S | Z, I ) = 1.00 Eif3d 2162.0 2908.5 6031.4 Mean Corr = 0.84298 Eif3i 2026.9 2734.4 6677.8 Eif3g 2241.2 3042.9 6461.4 Eif3k 2515.3 3925.4 7427.3 Eif3h 3982.5 5688.8 13354.9 Eif3c 4990.7 6407.3 11059.9 Eif3f 6800.7 8630.5 21986.0 Eif3m 1151.3 2095.1 5358.1 Eif3b 384.7 718.6 1762.9 Cct5 5474.5 8268.0 19506.9 Cct2 7218.0 10335.8 25234.7 Rpl8 8122.3 10627.1 30256.6 Rpl6 6649.7 9681.1 20492.1 Rpl27 7057.7 9355.3 25792.4 CEM 1 + Tcp1 3425.2 5144.7 11522.8 Top 10 Genes Naca 9497.3 14352.9 30666.1 Cct4 2745.5 4047.2 12672.8 Rps5 11799.4 17609.9 46135.2 Rps19 7383.9 11222.3 35109.5

Null module Eif3a Eif3e GEO Series "GSE21900" 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=GSE21900 Status: Public on May 18 2011 Title: Expression profiling of the Otx2 CKO retina Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21602925 Summary & Design: Summary: In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome regulated by Otx2 in the developing retina, we performed microarray analysis on the Otx2 CKO retina.

Overall design: In order to clarify the molecular role of Otx2 in transcriptional regulation during development, we investigated the expression profile of the Otx2 CKO retina compared with that of the control retina with the genotype Otx2flox/flox;Crx-cre- using microarrays at two time points, P1 and P12.

Background corr dist: KL-Divergence = 0.0680, L1-Distance = 0.0265, L2-Distance = 0.0012, Normal std = 0.5091

0.784 Kernel fit Pairwise Correlations Normal fit

Density 0.392

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

P1-control-ex1P1-control-ex2 P1-control-ex3(0.0313395) P1-Otx2-CKO-ex1(0.0566835) P1-Otx2-CKO-ex2(0.0416984)P1-Otx2-CKO-ex3 (0.0353843)P12-control-ex1 (0.187791)P12-control-ex2 (0.0896373)P12-control-ex3 (0.216985)P12-Otx2-CKO-ex1 (0.0618149)P12-Otx2-CKO-ex2 (0.0815342)P12-Otx2-CKO-ex3 (0.124589) (0.0220151) (0.0505281)[ min ] [ medium ] [ max ] CEM 1 Eif3l 2225.9 5877.1 8778.3 P ( S | Z, I ) = 1.00 Eif3d 3175.4 5848.1 7854.0 Mean Corr = 0.84225 Eif3i 5021.9 9234.0 12621.1 Eif3g 3580.3 6795.2 9825.5 Eif3k 2385.2 5700.2 8261.5 Eif3h 4344.0 10468.0 13915.3 Eif3c 3759.5 6548.8 8639.4 Eif3f 6353.2 17512.8 28363.2 Eif3m 1199.9 2146.8 2625.9 Eif3b 1234.9 1645.2 2149.0 Cct5 4920.2 10283.4 14237.4 Cct2 3485.2 10239.3 14239.7 Rpl8 6744.1 19899.9 26305.2 Rpl6 8263.3 23744.2 27277.3 Rpl27 10308.2 22520.5 30011.4 CEM 1 + Tcp1 4674.4 9139.1 10889.6 Top 10 Genes Naca 6816.8 22514.6 25103.7 Cct4 4277.6 5527.3 7469.6 Rps5 8580.2 26316.5 38914.9 Rps19 5250.6 26088.7 31370.5

Null module Eif3a Eif3e GEO Series "GSE36378" 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=GSE36378 Status: Public on Mar 10 2012 Title: Mapping the Transcriptional Landscape of Autoimmune Targeted Tissues: Transient Alterations in the Extracellular Milieu Precede Innate and Delayed Adaptive Immune Responses in Spontaneous Experimental Autoimmunity. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjˆ¶grens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjˆ¶grens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.

To define the chronological interrelationships of biological themes associated with progression from pre- to sub-clinical to overt spontaneous experimental SjS-like disease involving the extracellular milieu (EM) of the salivary glands, we carried out a study utilizing microarray technology in which the parental C57BL/6J mouse was used as the healthy control strain. A bioinformatics-based data analysis methodology designed for comprehensive visualization of global datasets between C57BL/6J and C57BL/6.NOD-Aec1Aec2 mice has permitted a definition of the molecular changes that correlate with onset of stomatitis sicca (xerostomia) in the SjS-susceptible mice. The transcriptome data set of C57BL/6J permitted identification of normal physiological activity.

Overall design: The study was designed to define the changing gene expression profiles within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice at multiple time points representing a pre-disease stage (4 weeks), the early pre-clinical stage (8 weeks), the initial influx of leukocytes into the salivary glands (12 weeks), and the early clinical phase of autoimmunity (16 weeks) to characterize the influence of the extracellular milieu on early development of disease. Because the C57BL/6.NOD-Aec1Aec2 mouse was derived from the C57BL/6J line, C57BL/6J mice were used as the comparative healthy controls. This comparison permitted the identification of disease-associated gene expressions by subtracting out normal physiological processes. This present study represents the C57BL/6J healthy control mice. Series GSE15640 includes the data for the C57BL/6.NOD-Aec1Aec2 mice.

Background corr dist: KL-Divergence = 0.0794, L1-Distance = 0.0693, L2-Distance = 0.0110, Normal std = 0.4914

0.812 Kernel fit Pairwise Correlations Normal fit

Density 0.406

0.000 CEM 1

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

Pre-normalization Quantiles

SalivarySalivary gland ofSalivary gland C57BL/6J ofSalivary gland C57BL/6J male ofSalivary gland C57BL/6J mouse male ofSalivary gland C57BL/6J atmouse male4 wks,ofSalivary gland C57BL/6J atmouse biologicalmale4 wks,ofSalivary gland C57BL/6J atmouse biologicalmale4 wks,ofSalivary replicate gland C57BL/6J atmouse biologicalmale4 wks,ofSalivary replicate gland 1C57BL/6J atmouse (0.00628138) biologicalmale4 wks,ofSalivary replicate gland 2C57BL/6J atmouse (0.00566564) biologicalmale8 wks,ofSalivary replicate gland 3C57BL/6J atmouse (0.032241) biologicalmale8 wks,ofSalivary replicate gland 4C57BL/6J atmouse (0.0613696) biologicalmale8 wks,ofSalivary replicate gland 5C57BL/6J atmouse (0.386746) biologicalmale8 wks,ofSalivary replicate gland 1C57BL/6J atmouse (0.0274392) biologicalmale8 wks,ofSalivary replicate gland 2C57BL/6J atmouse (0.0293161) biologicalmale12 ofSalivary replicatewks,gland 3C57BL/6J atmouse (0.0526654) male12 biological ofSalivary replicatewks,gland 4C57BL/6J atmouse (0.00706552) male12 biological ofSalivary wks, glandreplicate 5C57BL/6J atmouse (0.103436) male12 biological ofSalivary wks, glandreplicate C57BL/6J atmouse1 male(0.0195856)12 biological of wks, glandreplicate C57BL/6J atmouse2 male(0.007255)16 biological of wks, replicate C57BL/6J atmouse3 male(0.0126791)16 biological wks, replicate atmouse4 male(0.01642)16 biological[ wks, replicate min atmouse5 (0.00548023)16 biological wks, replicate at 1] (0.040958)16 biological wks, replicate 2 (0.0471659) biological replicate [3 (0.0185145)medium replicate 4 (0.0887678) 5 (0.0309481) ] [ max ] CEM 1 Eif3l 368.3 1320.8 2929.1 P ( S | Z, I ) = 1.00 Eif3d 231.9 979.1 2428.5 Mean Corr = 0.84044 Eif3i 1693.6 5157.4 9087.2 Eif3g 1305.3 3575.7 5927.2 Eif3k 659.2 2318.0 6008.6 Eif3h 813.7 3195.6 8162.4 Eif3c 406.9 1899.8 4983.6 Eif3f 1803.6 4948.6 9681.5 Eif3m 185.2 440.7 1717.7 Eif3b 748.5 1510.0 3630.6 Cct5 298.2 1322.9 3813.5 Cct2 211.6 913.7 2123.4 Rpl8 1960.0 9826.4 21080.2 Rpl6 2979.6 10266.4 17540.6 Rpl27 1930.6 5940.9 14415.5 CEM 1 + Tcp1 740.5 2018.4 3695.6 Top 10 Genes Naca 779.6 5192.8 24373.9 Cct4 795.5 1970.0 4996.0 Rps5 3304.0 12622.6 22865.9 Rps19 1669.3 5905.8 14473.0

Null module Eif3a Eif3e GEO Series "GSE51608" 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=GSE51608 Status: Public on Oct 24 2013 Title: Expression profiling of Ebf2- and Ebf2- stromal cells in mouse bone marrow Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23184664 Summary & Design: Summary: To identify the true molecular features of the Ebf2+ cells, we performed microarray analysis of freshly sorted CD45-TER119-Ebf2+ and Ebf2- cells. This allowed for the detection of 1968 genes that were 2-fold differentially expressed in Ebf2+ and Ebf2- cells. Among these, 1075 genes were upregulated and 893 genes including Ebf2, were downregulated in the Ebf2- as compared to the Ebf2+ cells. These include Nov, Fmod, Ndn, Dcn, Ctgf, Angiopoietin like-1(Angptl1), Fn1 and Jag1, some of which has been reported to be expressed in culture-selected MSCs. Furthermore, consistent with antigen expression analysis by FACS, the Ebf2+ cells highly expressed transcripts of Pdgfra, Pdgfrb, Sca1/Ly6a, Thy1 and Itga7 and Itgav, that have been suggested to be linked to MSCs. Nestin was mainly expressed in the Ebf2+ cells whereas it was hardly detectable in the Ebf2- cells. Altogether, molecularly, the Ebf2+ cells displayed features of a MSC.

Ebf2 expression is not restricted to committed osteoblast progenitor cells but rather marks a multipotent mesenchymal progenitor cell population in adult mouse BM. These cells do not appear to be completely overlapping with the previous reported MSC populations. The findings provide new insights into the in vivo cellular identity and molecular properties of BM mesenchymal stem and progenitor cells.

Overall design: RNA was extracted from 1,000 or 2000 purified adult bone marrow cells using the RNAeasy microkit. RNA was labeled and amplified by dual amplification and hybridized to Affymetrix microarray MOE430_2, according to AffymetrixTM GeneChip Expression Analysis Technical Manual. Probe level expression values were calculated using the RMA algorithm.

Background corr dist: KL-Divergence = 0.0181, L1-Distance = 0.0273, L2-Distance = 0.0011, Normal std = 0.7703

0.518 Kernel fit Pairwise Correlations Normal fit

Density 0.259

0.000 CEM 1

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

Pre-normalization Quantiles

Ebf2+ rep1Ebf2+ (0.162622) rep2Ebf2+ (0.118919) rep3Ebf2- (0.199861) rep1Ebf2- (0.0964713) rep2Ebf2- (0.237862) rep3 (0.184266) [ min ] [ medium ] [ max ] CEM 1 Eif3l 4455.1 12107.7 13656.0 P ( S | Z, I ) = 1.00 Eif3d 2516.7 6636.9 11021.2 Mean Corr = 0.83923 Eif3i 5994.5 15981.1 24672.1 Eif3g 6410.9 12170.5 15654.8 Eif3k 2622.8 3544.2 6876.7 Eif3h 4408.0 9931.6 12401.1 Eif3c 4659.5 12129.5 15737.0 Eif3f 9712.4 24244.2 28014.6 Eif3m 326.0 2958.7 3371.5 Eif3b 1593.4 4200.9 6223.9 Cct5 6877.8 22002.6 27855.8 Cct2 4795.9 20718.8 26071.8 Rpl8 21568.7 33180.0 50571.4 Rpl6 19788.7 42803.3 43845.2 Rpl27 2678.2 3291.5 10802.5 CEM 1 + Tcp1 5485.9 17650.2 23126.6 Top 10 Genes Naca 4564.2 11693.6 15891.3 Cct4 6509.3 19070.4 24101.5 Rps5 25221.0 34077.8 51643.3 Rps19 4983.8 8212.6 13580.2

Null module Eif3a Eif3e 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 (0.170156)KO-B (0.0877272)KO-C (0.0598968)WT-A (0.156964)WT-B (0.160773)WT-C (0.364482) [ min ] [ medium ] [ max ] CEM 1 Eif3l 2009.9 4136.9 4715.4 P ( S | Z, I ) = 1.00 Eif3d 2028.3 2679.3 2989.4 Mean Corr = 0.83810 Eif3i 7783.2 10603.1 11576.4 Eif3g 1901.8 3233.7 4170.4 Eif3k 2872.1 3752.8 4050.3 Eif3h 4929.6 6590.9 6931.0 Eif3c 3288.2 4948.9 5583.4 Eif3f 7995.8 10891.3 11951.9 Eif3m 1144.4 2206.6 2625.6 Eif3b 1268.7 1444.1 1535.9 Cct5 3583.4 6190.1 7805.1 Cct2 2676.0 4983.8 6409.9 Rpl8 12005.0 16561.5 18395.2 Rpl6 12740.9 17581.8 21099.9 Rpl27 14377.1 17949.6 19898.1 CEM 1 + Tcp1 3466.5 6156.4 7156.6 Top 10 Genes Naca 7965.5 12825.5 15123.4 Cct4 3536.0 7159.6 8005.0 Rps5 18348.3 20283.6 21737.3 Rps19 12567.9 16424.5 20680.2

Null module Eif3a Eif3e 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(0.0621494)04-25-2012_J_Oshea3_AK_Mouse430_2_3_WT+LPS+IL10 (0.0646169)04-25-2012_J_Oshea4_AK_Mouse430_2_4_HIES-LPS (0.101211)04-25-2012_J_Oshea5_AK_Mouse430_2_5_HIES+LPS (0.0223065)04-25-2012_J_Oshea6_AK_Mouse430_2_6_HIES+LPS+IL10 (0.0478334)06-05-2012_J_Oshea1_AK_Mouse430_2_1_WT-LPS (0.0467105)06-05-2012_J_Oshea2_AK_Mouse430_2_2_WT+LPS(0.0320677) 06-05-2012_J_Oshea3_AK_Mouse430_2_3_WT+LPS+IL10(0.0167139)06-05-2012_J_Oshea4_AK_Mouse430_2_4_HIES-LPS (0.0189874)06-05-2012_J_Oshea5_AK_Mouse430_2_5_HIES+LPS (0.0361275)06-05-2012_J_Oshea6_AK_Mouse430_2_6_HIES+LPS+IL10 (0.0187229) (0.0188912)(0.012183) (0.0185293)[ min (0.0194975) (0.214909) ] (0.101262)[ medium (0.14728) ] [ max ] CEM 1 Eif3l 2617.3 6159.6 8255.4 P ( S | Z, I ) = 1.00 Eif3d 3782.4 5754.9 7675.8 Mean Corr = 0.83683 Eif3i 5173.7 11534.6 16725.0 Eif3g 3011.6 6342.2 9161.4 Eif3k 2644.3 5526.5 7671.3 Eif3h 4057.5 6889.9 8286.1 Eif3c 3403.7 6732.4 9773.9 Eif3f 9076.8 12806.9 16945.9 Eif3m 1490.5 3698.8 4308.3 Eif3b 1509.6 3808.8 4506.4 Cct5 3794.3 9301.8 12243.2 Cct2 4094.9 9850.7 11394.8 Rpl8 14424.8 22662.6 34968.2 Rpl6 19326.2 25534.0 32149.0 Rpl27 14003.3 20401.4 31215.5 CEM 1 + Tcp1 4750.0 9813.5 13719.5 Top 10 Genes Naca 14278.1 20486.5 29398.0 Cct4 4787.0 7868.8 12650.7 Rps5 24217.3 29376.9 41153.6 Rps19 15753.3 21356.6 31392.7

Null module Eif3a Eif3e GEO Series "GSE48203" 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=GSE48203 Status: Public on Jun 21 2013 Title: Expression data from tumoral thymocytes and DP thymocytes expressing an activated form of b-catenin in mouse T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23801632 Summary & Design: Summary: To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-Î²cat) in which high levels of active Î²-catenin are maintained throughout T cell development. Young R26-Î²cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-Î²cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age.

To identify the molecular pathways involved in tumor development, we profiled the global gene expression of transformed and pre-transformed DP cells.

Overall design: Thymocytes from 6-week-old mice (with a normal sized thymus and a polyclonal thymocyte population) were used to define the pre-transformed transcriptome. RNA from control and pre-leukemic R26-Î²cat DP thymocytes as well as R26-Î²cat total tumor cells were extracted and used for transcriptome analysis.

Background corr dist: KL-Divergence = 0.0301, L1-Distance = 0.0269, L2-Distance = 0.0010, Normal std = 0.6711

0.600 Kernel fit Pairwise Correlations Normal fit

Density 0.300

0.000 CEM 1

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

Pre-normalization Quantiles

R26-Î²catR26-Î²cat transformedR26-Î²cat transformedR26-Î²cat thymocytes transformedControl thymocytes transformed mouseControl thymocytesDP thymocytes #94mousePre-transformed thymocytesDP (0.226668) thymocytes #96mousePre-transformed mouse(0.12384) #31mousePre-transformed #21mouse(0.218851)DP #11(0.0568)thymocytes #22(0.0429689)DP (0.0446055)thymocytes DP mouse thymocytes #20mouse (0.0957412)[ min#23mouse (0.0946814) #24 ] (0.0958445)[ medium ] [ max ] CEM 1 Eif3l 3319.7 4150.1 16066.2 P ( S | Z, I ) = 1.00 Eif3d 3506.9 4278.9 11480.9 Mean Corr = 0.83590 Eif3i 7789.9 9272.2 14511.5 Eif3g 4237.2 4932.2 10681.7 Eif3k 4333.5 6439.1 9161.3 Eif3h 9965.6 13646.3 23116.4 Eif3c 4835.5 5970.9 11695.3 Eif3f 12882.9 14904.7 19627.0 Eif3m 3791.0 4755.9 10924.7 Eif3b 1407.1 1983.6 5276.3 Cct5 5530.7 7364.8 21871.9 Cct2 8066.9 9972.2 21250.5 Rpl8 15588.1 19707.8 44340.5 Rpl6 19237.3 24494.7 38496.7 Rpl27 18702.8 23197.1 41524.5 CEM 1 + Tcp1 4438.2 5916.3 18298.7 Top 10 Genes Naca 15872.7 22645.9 32743.9 Cct4 4642.6 7054.6 17371.5 Rps5 13635.0 19259.4 37562.7 Rps19 10731.2 16523.7 39460.3

Null module Eif3a Eif3e GEO Series "GSE48935" 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=GSE48935 Status: Public on Sep 04 2013 Title: Analysis of gene expression changes induced in wild-type or Atf6a-/- mice by treatment with tunicamycin for 34h Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24069029 Summary & Design: Summary: Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.

We used a functional genomics to link gene expression patterns taken from microarray data to the severity and persistence of ER stress, using mice lacking the UPR signaling molecule ATF6Î±. This approach revealed that functionally related genes clustered into a small number of distinct expression profiles, and that lipid oxidation and efflux were targets for coordinated transcriptional suppression during ER stress.Our results establish a framework for hepatic gene regulation during ER stress.

Overall design: Atf6a-/- or +/+ mice of variable age and gender were injected intraperitoneally with 1 mg/kg tunicamycin or vehicle. 3 separate mice were used in each group. 34h after injection, mice were sacrificed and total RNA was prepared from resected livers.

Background corr dist: KL-Divergence = 0.0722, L1-Distance = 0.0377, L2-Distance = 0.0019, Normal std = 0.5191

0.806 Kernel fit Pairwise Correlations Normal fit

Density 0.403

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 vehiclewild-type vehicleanimalAtf6a-/- vehicle1animal (34h) Atf6a-/-vehicle (0.0518355)2animal (34h) Atf6a-/-vehicleanimal (0.0540049)3 (34h) wild-typevehicle1animal (34h)(0.0623696) wild-type(0.0748647)2animal (34h)TM animal wild-type(0.0468383)3 (34h)TM 1animal Atf6a-/-(34h)(0.0724037) TM (0.058891)2animal Atf6a-/-(34h)TM animal (0.0450812)3 Atf6a-/-(34h)TM 1animal (34h)(0.0510505) TM (0.112065)2animal (34h) (0.223893)3 (34h) (0.146702)[ min ] [ medium ] [ max ] CEM 1 Eif3l 3414.5 3783.0 4376.6 P ( S | Z, I ) = 1.00 Eif3d 3178.4 4182.9 11893.7 Mean Corr = 0.83501 Eif3i 8925.7 12570.3 16947.3 Eif3g 3670.8 6257.6 16425.3 Eif3k 4066.8 6410.1 9779.2 Eif3h 4598.5 6384.9 8658.9 Eif3c 5080.2 6373.3 8409.1 Eif3f 4753.6 8826.3 12139.3 Eif3m 1622.8 2664.1 5048.2 Eif3b 2657.8 3826.6 6337.6 Cct5 5041.7 6563.5 12573.3 Cct2 3722.0 4729.2 8925.7 Rpl8 15737.8 23276.1 34382.8 Rpl6 13251.0 21200.8 30914.5 Rpl27 11807.3 16519.1 24597.9 CEM 1 + Tcp1 4587.9 6813.8 11878.3 Top 10 Genes Naca 10870.3 14988.5 22901.9 Cct4 5198.4 5905.9 9309.5 Rps5 15663.0 32937.8 48729.5 Rps19 9719.0 20604.3 26901.3

Null module Eif3a Eif3e GEO Series "GSE14753" 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=GSE14753 Status: Public on Feb 10 2009 Title: Mammary tumors from K14-cre; ApcCKO/+ mice vs control mammary glands Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19197353 Summary & Design: Summary: Many components of Wnt/Î²-catenin signaling pathway also play critical roles in mammary tumor development. To study the role of Apc in mammary tumorigensis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-Cre (progenitor) and WAP-cre (lactaing luminal) transgenic mice. Only the K14-cre mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological and molecular heterogeneity, suggesting the progenitor cell origin of these tumors. These tumors harbored truncation mutation in a very defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of Î²-catenin signaling. Our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of Î²-catenin signaling optimal for mammary tumor development.

Overall design: We have compared 3 mammary tumors from K14-cre; ApcCKO/+ mice with 3 control mammary glands.

Background corr dist: KL-Divergence = 0.0282, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6907

0.582 Kernel fit Pairwise Correlations Normal fit

Density 0.291

0.000 CEM 1

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

Pre-normalization Quantiles

control controlmammary controlmammary gland, mammary biological gland,mammary biological tumor,gland, replicatemammary biologicaltumor, replicate 1 (0.160786) biologicaltumor, replicate 2 (0.11958) biological replicate 31 (0.18085)(0.178679) replicate 2[ (0.228158)min 3 (0.131947) ] [ medium ] [ max ] CEM 1 Eif3l 3142.4 4714.6 5313.6 P ( S | Z, I ) = 1.00 Eif3d 2357.7 4326.3 4989.7 Mean Corr = 0.83302 Eif3i 5614.7 11491.3 21194.6 Eif3g 2674.3 6368.2 7178.4 Eif3k 2776.2 4765.5 6031.5 Eif3h 4789.4 9196.4 13674.7 Eif3c 3334.8 4168.9 6998.8 Eif3f 9106.7 15099.3 16624.8 Eif3m 1559.9 3832.2 4999.4 Eif3b 1437.4 2554.1 3150.9 Cct5 4436.1 9905.6 14025.9 Cct2 3949.3 7058.5 8590.6 Rpl8 8835.5 16749.0 22830.2 Rpl6 14603.0 22484.7 31122.9 Rpl27 9711.2 17373.5 24431.5 CEM 1 + Tcp1 4739.3 7833.2 8845.6 Top 10 Genes Naca 11744.8 18814.1 23284.8 Cct4 5533.4 9022.9 11656.0 Rps5 14212.2 23538.4 31198.1 Rps19 10734.1 21296.3 27021.7

Null module Eif3a Eif3e GEO Series "GSE45744" 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=GSE45744 Status: Public on Apr 04 2013 Title: Whole-genome expression data from normal FVB mouse lung tissue, transgenic cyclin E overexpressing (CEO) normal mouse lung tissue, and transgenic CEO lung adenocarcinomas Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23621985 Summary & Design: Summary: FVB mice were engineered to express wild-type human cyclin E under control of the human surfactant C promoter (CEO mice; Ma et al, PNAS 2007). These mice develop spontaneous lung tumors, which were shown to be adenocarcinoma by histological analysis. Here we compare whole-genome RNA expression levels between the tumors and normal lung of 4 CEO mice as well as 4 nontransgenic animals.

Overall design: RNA was isolated from the lungs of 4 FVB mice and adjacent normal and tumor tissue from 4 FVB transgenes harboring human surfactant protein C- driven wild-type human cyclin E, all 7-11 months in age. These samples were divided into 3 groups of four, and 12 independent hybridizations were performed for analysis with Affymetrix GeneChip Mouse 430 2.0 arrays.

Background corr dist: KL-Divergence = 0.0712, L1-Distance = 0.0260, L2-Distance = 0.0008, Normal std = 0.5016

0.810 Kernel fit Pairwise Correlations Normal fit

Density 0.405

0.000 CEM 1

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

Pre-normalization Quantiles

normal normallung - nontransgenic normallung - nontransgenic normallung - nontransgenic- normallung1 (0.0127123) - nontransgenic- normallung2 (0.0403582) - transgenic-- normallung3 (0.0221379) - transgenic-- normallung4 (0.0739065) 1 -(0.0281281) transgeniclung 2 tumor-(0.0236193) transgenic-lung 3 - tumor(0.113166)transgeniclung 4 - tumor(0.0622335)transgeniclung - 1 - (0.21687) tumortransgenic - 2 - (0.0434623) transgenic - 3 (0.202052) - 4 (0.161354)[ min ] [ medium ] [ max ] CEM 1 Eif3l 2747.2 3452.8 6167.9 P ( S | Z, I ) = 1.00 Eif3d 2818.1 3201.9 3956.3 Mean Corr = 0.82587 Eif3i 7601.3 8759.1 13777.7 Eif3g 2976.9 3613.8 4245.7 Eif3k 916.0 4765.0 8409.0 Eif3h 5393.9 6584.2 11386.4 Eif3c 5963.5 6972.1 9681.6 Eif3f 3941.9 10775.2 18519.4 Eif3m 1475.4 1898.1 3243.5 Eif3b 1891.5 2018.6 2492.5 Cct5 4623.7 5707.8 10016.7 Cct2 4567.5 5492.3 9707.1 Rpl8 20923.4 23125.2 31734.1 Rpl6 16400.3 18446.0 30247.5 Rpl27 10773.7 14149.5 19939.5 CEM 1 + Tcp1 4498.5 5170.1 7925.8 Top 10 Genes Naca 13269.8 14511.2 26782.9 Cct4 251.5 3720.6 5722.9 Rps5 22996.5 27367.3 40784.3 Rps19 21656.7 26048.7 41913.5

Null module Eif3a Eif3e GEO Series "GSE18660" 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=GSE18660 Status: Public on Jan 03 2011 Title: Modulation of calcium activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker- like cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20956206 Summary & Design: Summary: Background: Ion channels are key determinants for the function of excitable cells but little is known about their role and involvement during cardiac development. Earlier work identified Ca2+-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here, we have investigated their impact on the differentiation of pluripotent cells towards the cardiac lineage. Methods and Results: We have applied the SKCa-activator EBIO on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa-activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation and diminished teratoma formation. Time-restricted SKCa-activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the EBIO-induced effects.

Conclusions: SKCa-activation drives the fate of pluripotent cells towards the cardiac lineage and preferentially into pacemaker-like cardiomyocytes. This provides a novel strategy for the enrichment of cardiomyocytes and in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification.

Overall design: - EBIO-treated differentiated ES cells sample 2 (EBIO_day5+10_2)

Background corr dist: KL-Divergence = 0.0149, L1-Distance = 0.0633, L2-Distance = 0.0051, Normal std = 0.9657

0.413 Kernel fit Pairwise Correlations Normal fit

Density 0.207

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

UntreatedUntreated controlUntreated controlES cellsEBIO-treated controlES sample cellsEBIO-treated ES sample1 ES (0.201577)cellsEBIO-treated cells sample2 ES (0.148077) sampleUntreated cells 3 ES (0.100325) sampleUntreated1 (0.0400462)cells control sampleEBIO-treated2 (0.0495284) controldifferentiated EBIO-treated3 (0.0223065) differentiated differentiated ES cellsdifferentiatedES ES sample ES cells cells sample1 (0.0926654) sample [cells min 2 (0.0987343)sample 1 (0.115966) ] 2 (0.130775)[ medium ] [ max ] CEM 1 Eif3l 4758.1 8371.6 13158.9 P ( S | Z, I ) = 1.00 Eif3d 5304.8 10422.0 15517.1 Mean Corr = 0.82527 Eif3i 9104.5 12913.1 15500.2 Eif3g 6278.6 10245.6 13052.0 Eif3k 4723.5 7186.0 12194.0 Eif3h 7579.8 9427.8 11620.8 Eif3c 6454.5 13234.1 17435.2 Eif3f 11271.1 12543.1 21122.8 Eif3m 2805.1 4221.9 6917.1 Eif3b 3275.5 4513.7 4694.3 Cct5 9982.3 19116.5 23505.8 Cct2 8251.5 22835.1 25462.7 Rpl8 20683.3 32289.5 44507.6 Rpl6 18806.8 29063.2 37045.9 Rpl27 19606.5 23190.3 30761.1 CEM 1 + Tcp1 9061.0 16274.9 20041.6 Top 10 Genes Naca 15856.6 25934.8 35844.2 Cct4 10212.3 15792.7 19672.4 Rps5 20382.0 34575.1 39587.4 Rps19 19298.9 34081.3 41702.0

Null module Eif3a Eif3e GEO Series "GSE30192" 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=GSE30192 Status: Public on Jan 01 2012 Title: Effect of 5-azacytidine on gene expression in C2C12 myoblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21795504 Summary & Design: Summary: Mesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been shown to play a key role in regulating the progressional changes in transcription necessary for muscle differentiation. In this study, we demonstrate that treatment of murine C2C12 mesenchymal progenitor cells with 10 ´M of the DNA methylation inhibitor 5-azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myotubes. Specifically, 5AC treatment resulted in the upregulation of muscle genes at the myoblast stage while at later stages nearly 50 % of the 5AC-treated myotubes displayed a mature, well-defined sarcomere organization as well as spontaneous contractions that coincided with action potentials and intracellular calcium transients. Both the percentage of striated myotubes and their contractile activity could be inhibited by 20 nM TTX, 10 ´M ryanodine and 100 ´M nifedipine, suggesting that action potential-induced calcium transients are responsible for these characteristics. Our data suggest that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2C12 myotubes from reaching full maturity.

Overall design: C2C12 cells were plated at 1500 cells/cm2 (day -1), cultured for 1 day in DMEM 10%NCS, then treated (d0) with or without 10uM 5-azacytidine (5AC) for an additional 3 days. RNA was extracted on day 3 and hybridized to GeneChip Mouse Genome 430 2.0 array (Affymetrix).

Background corr dist: KL-Divergence = 0.0286, L1-Distance = 0.0590, L2-Distance = 0.0044, Normal std = 0.7900

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

C2C12 untreatedC2C12 untreatedC2C12 day3 untreated C2C12rep1 day3 (0.171015) 5AC C2C12rep2 day3 treated (0.141068) 5AC C2C12rep3 treatedday3 (0.137416) 5AC rep1 treatedday3 (0.197887) rep2 day3 (0.130081) rep3 [(0.222533) min ] [ medium ] [ max ] CEM 1 Eif3l 10436.5 11062.8 11493.5 P ( S | Z, I ) = 1.00 Eif3d 7877.7 13116.6 13962.9 Mean Corr = 0.81827 Eif3i 10927.1 11246.6 11699.2 Eif3g 5502.1 8654.7 9124.3 Eif3k 4533.9 5296.1 5520.1 Eif3h 11576.1 11827.6 12232.1 Eif3c 6418.0 7036.6 7301.0 Eif3f 9260.7 10500.2 10908.9 Eif3m 3295.5 3925.5 4163.3 Eif3b 3285.9 3838.1 4121.1 Cct5 17051.3 20625.9 20705.2 Cct2 11053.2 12801.4 13639.6 Rpl8 24508.1 24929.0 25041.3 Rpl6 26416.6 27481.1 27865.0 Rpl27 13609.2 13920.9 14379.0 CEM 1 + Tcp1 13089.8 14310.1 15353.1 Top 10 Genes Naca 26172.4 30316.8 30631.8 Cct4 12448.9 15429.5 15972.2 Rps5 26259.0 27356.2 27908.0 Rps19 17434.1 18183.3 18357.4

Null module Eif3a Eif3e GEO Series "GSE36392" 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=GSE36392 Status: Public on Mar 10 2012 Title: Expression data from pulmonary Type 2 Myeloid (T2M) cells, Eosinophils, Neutrophils, and Macrophages, from IL-25 treated 4get mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22543263 Summary & Design: Summary: Many symptoms associated with allergic asthma result from the sequelae of type 2 inflammation. Interleukin (IL)-25 promotes type 2 inflammatory responses, and T2M cells represent an IL-4 and IL-13 producing granulocytic IL-25 responsive population.

We used microarrays to characterize the gene expression profile of T2M cells, and compared T2M cells to other inflammatory subsets (eosinophils, neutrophils, and macrophages) in the lungs of mice with IL-25-induced pulmonary inflammation.

Overall design: We analyzed 3 T2M replicates and 2 replicates each of the other inflammatory subsets.

Background corr dist: KL-Divergence = 0.0426, L1-Distance = 0.0583, L2-Distance = 0.0056, Normal std = 0.6219

0.641 Kernel fit Pairwise Correlations Normal fit

Density 0.321

0.000 CEM 1

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

Pre-normalization Quantiles

T2M cells_replicateT2M cells_replicateT2M cells_replicate1 (0.08433)Eosinophils_replicate 2 (0.0579387)Eosinophils_replicate 3 (0.0659348)Macrophages_replicate Macrophages_replicate1 (0.126078) Neutrophils_replicate2 (0.181797)Neutrophils_replicate 1 (0.174914) 2 (0.144398) 1 (0.0330411) 2 (0.131568)[ min ] [ medium ] [ max ] CEM 1 Eif3l 817.2 2680.9 4457.3 P ( S | Z, I ) = 1.00 Eif3d 377.8 1024.7 3341.2 Mean Corr = 0.81789 Eif3i 1016.8 3911.6 5697.4 Eif3g 813.0 2439.7 3688.0 Eif3k 737.5 3387.8 10675.7 Eif3h 1997.4 6461.7 9811.6 Eif3c 1154.6 3235.8 3797.8 Eif3f 1662.9 7975.1 10498.8 Eif3m 260.9 1112.8 2052.2 Eif3b 112.7 315.7 1158.6 Cct5 647.6 2476.7 4239.4 Cct2 650.9 2440.9 4811.9 Rpl8 730.8 6223.3 12825.8 Rpl6 5712.5 18633.4 25615.0 Rpl27 2505.9 5132.7 11895.5 CEM 1 + Tcp1 1395.9 6932.6 8537.5 Top 10 Genes Naca 3144.1 8734.2 20147.4 Cct4 897.3 2087.6 5308.8 Rps5 1314.4 8130.3 18358.4 Rps19 437.2 1533.6 8742.5

Null module Eif3a Eif3e GEO Series "GSE54653" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54653 Status: Public on May 07 2014 Title: Expression data from quiescent and activated neural stem cells from the adult mouse V-SVZ niche Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: RNA was purified from GFAP::GFP+CD133+ and GFAP::GFP+CD133+EGFR+ cells isolated from the adult mouse V-SVZ niche (GFAP::GFP mice, Jackson Mice Stock number 003257)

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

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

0.560 Kernel fit Pairwise Correlations Normal fit

Density 0.280

0.000 CEM 1

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

Pre-normalization Quantiles

adult V-SVZadult qNSCs V-SVZadult qNSCs,biological V-SVZadult qNSCs, biologicalV-SVZ adultreplicate aNSCs, biologicalV-SVZadult replicate 1 (0.19482) aNSCs,biologicalV-SVZ replicate 2 (0.153433) aNSCs,biological replicate 3 (0.115521) biological replicate 1 (0.202225)[ replicate 2min (0.190653) 3 (0.143349)] [ medium ] [ max ] CEM 1 Eif3l 834.0 2311.5 3963.0 P ( S | Z, I ) = 1.00 Eif3d 770.0 2761.4 4313.0 Mean Corr = 0.81779 Eif3i 2718.5 5695.6 6597.6 Eif3g 1033.3 3773.4 5347.4 Eif3k 562.7 3064.6 5282.1 Eif3h 2361.7 6319.9 8682.4 Eif3c 1022.3 2647.8 3532.4 Eif3f 1810.9 7429.0 8864.2 Eif3m 1042.8 1493.0 2078.6 Eif3b 483.3 957.4 1253.8 Cct5 1675.8 3632.7 4840.7 Cct2 1190.1 3825.0 4708.4 Rpl8 1909.5 12494.3 12789.3 Rpl6 3177.5 15108.8 16524.3 Rpl27 4020.0 12055.2 15042.4 CEM 1 + Tcp1 5082.0 10752.3 15543.8 Top 10 Genes Naca 4925.4 12559.5 18086.3 Cct4 1888.9 4672.2 5892.8 Rps5 1454.7 9722.6 10985.2 Rps19 918.5 5235.7 9373.2

Null module Eif3a Eif3e GEO Series "GSE13149" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 25 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13149 Status: Public on Oct 30 2008 Title: Multi-stage analysis of gene expression in C57/B6 mouse liver development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19015022 Summary & Design: Summary: The liver performs a number of essential functions for life. The development of such a complex organ relies on finely regulated gene expression profiles which change over time in the development and determine the phenotype and function of the liver.

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

Keywords: time course

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

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

0.718 Kernel fit Pairwise Correlations Normal fit

Density 0.359

0.000 CEM 1

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

Pre-normalization Quantiles

Liver_development_E11.5_rep1Liver_development_E11.5_rep2Liver_development_E12.5_rep1Liver_development_E12.5_rep2Liver_development_E13.5_rep1 (0.230961)Liver_development_E13.5_rep2 (0.167763)Liver_development_E14.5_rep1 (0.0589872)Liver_development_E14.5_rep2 (0.0215919)Liver_development_E15.5_rep1 (0.0092625)Liver_development_E15.5_rep2 (0.00768891)Liver_development_E16.5_rep1 (0.0324849)Liver_development_E16.5_rep2 (0.00828014)Liver_development_E17.5_rep1 (0.00924577)Liver_development_E17.5_rep2 (0.00249534)Liver_development_E18.5_rep1 (0.00738664)Liver_development_Day0_rep1 (0.0110573)Liver_development_Day0_rep2 (0.0125747)Liver_development_Day3_rep1 (0.0229798)Liver_development_Day3_rep2 (0.0249408)Liver_development_Day7_rep1 (0.0208213)Liver_development_Day14_rep1 (0.00567734)Liver_development_Day21_rep1 (0.00982448)Liver_development_Day21_rep2 (0.0239237)Liver_development_NL_rep1 (0.0260175)Liver_development_NL_rep2 (0.0646728) (0.0476541) (0.0536588) (0.0748668) (0.045183)[ min ] [ medium ] [ max ] CEM 1 Eif3l 2188.5 4228.8 9361.9 P ( S | Z, I ) = 1.00 Eif3d 1659.8 3669.3 9666.6 Mean Corr = 0.81569 Eif3i 5168.9 8880.6 15240.9 Eif3g 2217.2 4020.3 10126.9 Eif3k 2170.7 6624.4 11882.2 Eif3h 2460.6 5117.4 8741.3 Eif3c 2346.9 4125.7 7766.9 Eif3f 4118.7 6062.8 13265.7 Eif3m 986.4 1635.1 2167.7 Eif3b 1050.5 2479.6 6862.6 Cct5 4132.5 8132.4 16609.7 Cct2 2951.5 6198.4 17334.9 Rpl8 9927.2 21255.6 30581.3 Rpl6 6953.8 20271.8 28049.8 Rpl27 8152.5 14398.0 19524.3 CEM 1 + Tcp1 2665.7 7962.2 13795.2 Top 10 Genes Naca 8183.9 15350.2 22506.0 Cct4 3836.4 6754.4 11219.9 Rps5 10212.2 23958.8 33486.9 Rps19 5597.4 16686.7 26711.6

Null module Eif3a Eif3e GEO Series "GSE32903" 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=GSE32903 Status: Public on Jan 09 2012 Title: Smad4 and Trim33 dependend nodal/activin responsive genes in differentiated mouse ESCs Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22196728 Summary & Design: Summary: In differentiated mouse ESCs, most of the nodal/activin responsive genes are dependent on both Smad4 and Trim33, some are solely dependent on Smad4, and some are dependent on Trim33.

Overall design: Ebs at Day2.5 from WT, Smad4 null, and Trim33 knock-down ESCs, were treated with activin or SB 431542 for 2 h.

Background corr dist: KL-Divergence = 0.0926, L1-Distance = 0.0220, L2-Distance = 0.0007, Normal std = 0.4528

0.881 Kernel fit Pairwise Correlations Normal fit

Density 0.440

0.000 CEM 1

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

Pre-normalization Quantiles

WT-ac-1WT-SB-1 (0.121674)Trim33-KD-ac-1 (0.168871)Trim33-KD-SB-1Smad4-null-ac-1 (0.0280869)Smad4-null-SB-1 (0.0229853)WT-ac-2 (0.225424)WT-SB-2 (0.037882) (0.0434305)Trim33-KD-ac-2 (0.202252)Trim33-KD-SB-2Smad4-null-ac-2 (0.0438685)Smad4-null-SB-2 (0.0234195) (0.0254077) (0.0566992) [ min ] [ medium ] [ max ] CEM 1 Eif3l 9806.3 11310.3 13205.9 P ( S | Z, I ) = 1.00 Eif3d 7659.2 9413.1 11607.5 Mean Corr = 0.81549 Eif3i 9554.6 10926.9 12472.6 Eif3g 7066.5 8567.2 10801.8 Eif3k 6986.8 7859.1 8627.2 Eif3h 7844.9 8747.7 10716.7 Eif3c 9048.1 10023.9 10918.9 Eif3f 10917.5 13051.2 15471.1 Eif3m 5610.0 6119.9 6672.6 Eif3b 7307.9 8650.2 9603.7 Cct5 11065.4 13422.5 14456.9 Cct2 11345.4 12460.5 15493.4 Rpl8 10918.4 12630.1 21258.1 Rpl6 16391.8 19602.6 25218.0 Rpl27 15260.8 18167.6 24787.3 CEM 1 + Tcp1 11458.1 13580.6 18750.4 Top 10 Genes Naca 13638.9 15448.1 22170.3 Cct4 10477.7 11846.5 14527.8 Rps5 12414.9 15632.7 24150.3 Rps19 14557.5 16153.2 21988.9

Null module Eif3a Eif3e GEO Series "GSE58296" 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=GSE58296 Status: Public on Jun 09 2014 Title: Expression data from intestinal organoids altered for Tgfbeta signaling Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We treated intestinal organoids continuously for 5 days with or without TgfbR1/2 inhibitor (LY2109761) or Tgfb1 ligand

Overall design: Organoids were continuously treated for 5 days, then RNA was extracted and hybridized to Affymetrix Mouse Genome 430 2.0

Background corr dist: KL-Divergence = 0.0550, L1-Distance = 0.0401, L2-Distance = 0.0021, Normal std = 0.5732

0.738 Kernel fit Pairwise Correlations Normal fit

Density 0.369

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

no treatment_rep1no treatment_rep2no treatment_rep3 (0.0163846)Tgfbeta (0.0847675)Tgfbeta inhibitor_rep1 (0.0371394)Tgfbeta inhibitor_rep2 Tgfbeta1 (0.214926)inhibitor_rep3 Tgfbeta1(0.109807) ligand_rep1 Tgfbeta1(0.194354) ligand_rep2 (0.0184557) ligand_rep3 (0.060457) (0.263709)[ min ] [ medium ] [ max ] CEM 1 Eif3l 3538.0 5222.0 6081.2 P ( S | Z, I ) = 1.00 Eif3d 4228.6 4767.9 5361.5 Mean Corr = 0.81136 Eif3i 7947.3 9994.2 12170.5 Eif3g 3726.2 4794.9 5381.0 Eif3k 4268.3 5354.4 5886.3 Eif3h 6481.6 8905.6 10001.9 Eif3c 6614.4 8287.0 8826.6 Eif3f 9757.3 15084.9 15873.7 Eif3m 2522.2 3303.5 3977.6 Eif3b 2370.8 3304.9 4329.0 Cct5 6857.8 9980.5 10825.1 Cct2 5168.7 6818.2 8620.1 Rpl8 11704.8 14354.6 18523.3 Rpl6 15622.6 20120.4 24623.0 Rpl27 14003.2 16165.4 20418.2 CEM 1 + Tcp1 6513.1 8425.0 9859.9 Top 10 Genes Naca 11242.1 14528.5 17366.2 Cct4 7738.9 9094.0 10293.5 Rps5 12301.0 15387.0 20853.1 Rps19 10903.8 15246.7 19050.4

Null module Eif3a Eif3e GEO Series "GSE9013" 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=GSE9013 Status: Public on Nov 12 2007 Title: Expression data from side-population sorted putative intestinal stem cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18006601 Summary & Design: Summary: While the existence of intestinal epithelial stem cells (IESCs) has been well established, their study has been limited due to the inability to isolate them. Previous work has utilized side population (SP) sorting of the murine small intestinal mucosa to isolate a viable fraction of cells enriched for putative IESCs. We have used microarray analyses to characterize the molecular features of this potential stem cell population.

Keywords: Comparitive gene expression analysis

Overall design: Fluorescence activated cell sorting of cells stained with Hoechst 33342 and FITC labeled anti-CD45 antibody was used to isolate CD45-/SP and CD45-/nSP cell fractions from mucosal specimens pooled from 3 mice. Intact jejunum specimens were collected prior to sorting. 4 sorts were completed. Therefore, 3 experimental groups were defined: CD45-/SP, CD45-/nSP and intact jejunum, each with 4 biological replicates. Total RNA was extracted from each experiment group for each sort, resulting in 12 specimens submitted for analysis using Affymetrix 430 2.0 Gene Chips.

Background corr dist: KL-Divergence = 0.0860, L1-Distance = 0.0298, L2-Distance = 0.0017, Normal std = 0.4720

0.845 Kernel fit Pairwise Correlations Normal fit

Density 0.423

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

CD45-negativeCD45-negative IntactSP cell jejunum, CD45-negativenSPfraction, cell CD45-negativebiological fraction,biological IntactSP biologicalrep1cell rep1 jejunum, CD45-negativenSPfraction, (0.133239) (0.0393144) cell rep1 CD45-negativebiological fraction,biological (0.122011) IntactSP biologicalrep2cell rep2 jejunum, CD45-negativenSPfraction, (0.10503) (0.104626) cell rep2 CD45-negativebiological fraction,biological (0.0953611) IntactSP biologicalrep3cell rep3 jejunum, nSPfraction, (0.101615) (0.0257033) cell rep3 biological fraction,biological (0.11608) biologicalrep4 rep4[ (0.0856984) (0.0133062)min rep4 (0.0580154)] [ medium ] [ max ] CEM 1 Eif3l 2971.3 4869.2 7019.8 P ( S | Z, I ) = 1.00 Eif3d 1518.2 2548.0 4361.9 Mean Corr = 0.80999 Eif3i 6108.4 8589.7 11061.8 Eif3g 4963.2 7426.0 10758.8 Eif3k 2708.6 4883.2 6508.1 Eif3h 4973.8 8593.4 10263.4 Eif3c 3034.0 4489.3 5817.0 Eif3f 9318.9 14904.8 16483.9 Eif3m 1079.2 1888.7 3138.9 Eif3b 1757.5 2732.5 4407.9 Cct5 7389.5 11009.5 14333.3 Cct2 2262.7 5228.6 7297.7 Rpl8 10960.9 15745.2 18483.0 Rpl6 12822.7 17151.7 19916.2 Rpl27 8227.9 13912.8 20068.6 CEM 1 + Tcp1 7299.7 8745.9 10786.4 Top 10 Genes Naca 4395.0 6392.2 9235.0 Cct4 4012.0 5092.0 8863.6 Rps5 14873.4 17721.3 20653.1 Rps19 9924.8 15812.9 21462.5

Null module Eif3a Eif3e GEO Series "GSE53951" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.611 Kernel fit Pairwise Correlations Normal fit

Density 0.305

0.000 CEM 1

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

Pre-normalization Quantiles

neurons_mock_sample1neurons_IFNb_sample1neurons_mock_sample2neurons_IFNb_sample2 (0.171254)MEFs_mock_sample1 (0.14078)MEFs_IFNb_sample1 (0.0984666)MEFs_mock_sample2 (0.0976061) MEFs_IFNb_sample2(0.0780993) (0.0663389)L929_mock L929_IFNb(0.0717171) (0.107102) (0.0552889) (0.113347) [ min ] [ medium ] [ max ] CEM 1 Eif3l 3252.4 6473.4 6915.0 P ( S | Z, I ) = 1.00 Eif3d 3316.7 5285.0 6902.0 Mean Corr = 0.80759 Eif3i 6481.7 9835.9 13649.6 Eif3g 3528.5 6571.4 7276.4 Eif3k 3253.4 3941.9 5631.0 Eif3h 6396.8 7966.3 8986.2 Eif3c 5294.3 9841.5 13516.1 Eif3f 9362.0 12153.5 15784.9 Eif3m 1879.7 3043.4 3718.3 Eif3b 1932.5 3620.3 4223.7 Cct5 7307.1 11463.2 17222.1 Cct2 7006.3 10600.3 12641.7 Rpl8 9603.5 20033.2 25584.8 Rpl6 12278.2 22103.8 26255.7 Rpl27 12120.4 21337.3 25894.3 CEM 1 + Tcp1 6374.7 12294.9 12941.1 Top 10 Genes Naca 10850.8 19241.2 22162.4 Cct4 6852.0 9959.1 13061.1 Rps5 11421.0 21143.2 23125.5 Rps19 9012.1 19325.7 21191.7

Null module Eif3a Eif3e GEO Series "GSE19338" 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=GSE19338 Status: Public on Oct 06 2010 Title: Expression profiles of villus and crypt layers of large intestine from C57Bl/6, Apc1638N+/-, and p21-/- mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20824133 Summary & Design: Summary: Expression profiles obtained from the villus and crypt layers of murine large intestine can elucidate the process of differentiation undergone by epithelial cells as they migrate from the undifferentiated bottom of the crypt to the villus tip before being shed into the intestinal lumen. This series includes profiles from wild type mice, as well as mice harboring mutations in genes (APC and p21) which play key roles in the differentiation process.

We used microarrays to characterize gene expression profiles at the base of the crypt and at the villus tip of the lumenal layer of the large intestine in order to better understand the process of differentiation and eventual shedding undergone by cells of the large intestinal epithelium.

Overall design: Four wild type, four APC1638+/- and four p21-/- mice were sacrified and the large intestines dissected out. Cells from the villus tip and from the bottom of the crypt were isolated from the lumenal face of the each large intestine using the Weiser method of sequential elution. RNA was extracted from each eluted sample and used to hybridize to Affymetrix 3' expression arrays.

Background corr dist: KL-Divergence = 0.0880, L1-Distance = 0.0747, L2-Distance = 0.0136, Normal std = 0.4767

0.837 Kernel fit Pairwise Correlations Normal fit

Density 0.418

0.000 CEM 1

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

Pre-normalization Quantiles

villus layer,villus APC layer,villus mutant, APC layer,villus mutant, mouse APC layer,villus mutant, m79mouse APC layer, villus(0.0142551) mutant, n80mouse wild layer, (0.0235765)villus type, m05mouse wild layer, mousevillus(0.019794) type, m64 wild layer, m81mousevillus(0.0484049) type, wild(0.041139) layer, n10mousevillus type, (0.0495057)p21 layer, i28mousevillus mutant, (0.0636114) p21 layer, h85villus mutant, mouse (0.020482)p21 layer,crypt mutant, i74mouse p21 (0.0338367)layer,crypt mutant, j29mouse APC (0.0213593)layer,crypt mutant,j04mouse APC (0.00779067)layer,crypt mutant,i49 mouse APC (0.0363147)layer,crypt mutant, m79mouse APC layer, (0.0590581)crypt mutant, n80mouse wild layer, (0.0358044)crypt type, m05mouse wild layer, mouse(0.125274)crypt type, m64 wild layer, m81mouse(0.0201641)crypt type, wild(0.125358) layer, n10mousecrypt type, (0.0171038)p21 layer, i28mousecrypt mutant, (0.0572046) p21 layer, h85crypt mutant, mouse (0.0294036)p21 layer, mutant, i74mouse p21 (0.0237425) mutant, j29mouse (0.072396) j04mouse (0.037075)[ i49min (0.0173458) ] [ medium ] [ max ] CEM 1 Eif3l 1110.2 2167.1 4962.3 P ( S | Z, I ) = 1.00 Eif3d 1149.5 2315.2 5108.0 Mean Corr = 0.80637 Eif3i 2897.1 8943.7 15249.1 Eif3g 956.1 2119.6 3860.7 Eif3k 2232.7 4428.1 9520.0 Eif3h 2440.3 4245.1 9462.5 Eif3c 1766.7 3187.2 5528.7 Eif3f 2829.3 6095.9 12927.7 Eif3m 768.4 1634.9 2866.6 Eif3b 626.1 1455.1 3366.7 Cct5 1631.2 3882.1 8474.7 Cct2 1637.5 3170.3 8666.2 Rpl8 6412.0 21318.5 43321.7 Rpl6 5047.2 13617.8 30191.9 Rpl27 5921.7 10517.0 19898.3 CEM 1 + Tcp1 1391.0 4410.3 7388.9 Top 10 Genes Naca 5472.1 11530.8 26543.2 Cct4 2253.7 4815.1 8298.7 Rps5 9332.6 27916.7 47490.7 Rps19 3834.4 10508.4 33510.5

Null module Eif3a Eif3e GEO Series "GSE47196" 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=GSE47196 Status: Public on May 23 2013 Title: Immunoglobulin-like domain receptor 1 mediates fat-stimulated cholecystokinin secretion. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23863714 Summary & Design: Summary: Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild type but not ILDR1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation is associated with increased [Ca2+]i consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.

Overall design: GFP positive cells from CCK-EGFP transgenic mice were isolated by FACS and the expression profile was compared with an equal number of non-fluorescent intestinal cells.

Background corr dist: KL-Divergence = 0.0167, L1-Distance = 0.0318, L2-Distance = 0.0015, Normal std = 0.7899

0.505 Kernel fit Pairwise Correlations Normal fit

Density 0.253

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

IntestinalIntestinal CCK-EGFPIntestinal non-EGFP cellsIntestinal CCK-EGFP rep1 cellsIntestinal (0.0540999)non-EGFP rep1 cellsIntestinal (0.326429) non-EGFP rep2 cells (0.26984)CCK-EGFP rep2 cells (0.158161) rep3 cells (0.0477097) rep3[ (0.14376)min ] [ medium ] [ max ] CEM 1 Eif3l 1664.2 3231.8 3828.1 P ( S | Z, I ) = 1.00 Eif3d 1064.2 1883.0 2099.7 Mean Corr = 0.80586 Eif3i 2143.1 4932.5 6468.0 Eif3g 1855.3 2825.4 3507.9 Eif3k 4535.3 7376.9 8431.7 Eif3h 2489.6 5504.5 6995.6 Eif3c 1947.3 2352.8 3309.5 Eif3f 3139.4 5399.2 6877.4 Eif3m 297.9 916.5 1235.9 Eif3b 396.4 796.1 941.4 Cct5 930.3 2860.3 3586.6 Cct2 2145.5 5372.4 6814.1 Rpl8 3728.5 8680.1 9757.8 Rpl6 4745.3 13428.3 15132.3 Rpl27 1589.2 3938.7 5055.9 CEM 1 + Tcp1 1402.6 3875.4 4552.7 Top 10 Genes Naca 5597.9 12103.3 12879.1 Cct4 2942.6 5257.3 5830.6 Rps5 5515.1 9243.3 10386.6 Rps19 2758.7 5881.3 7711.7

Null module Eif3a Eif3e GEO Series "GSE51365" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 28 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51365 Status: Public on Oct 18 2013 Title: Latent gammaherpesvirus 68 infection induces distinct transcriptional changes in different organs Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24155394 Summary & Design: Summary: Previous studies identified a role for latent herpesvirus infection in cross-protection to infection and exacerbation of chronic inflammatory diseases. Here, we compared the gene expression signature from livers, spleens and brains of mice infected with wild-type gammaherpesvirus 68 (MHV68), a mutant virus defective in the establishment of latency (ORF73.stop) or mockulum. We identified over 600 genes differentially expressed in organs of mice latently infected with MHV68 and found distinct sets of genes linked to different pathways were altered in spleen compared to liver. Several of the most differentially expressed latency-specific genes (e.g. IFNÎ³, Cxcl9, Ccl5) are associated with known latency-specific phenotypes.

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

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

0.657 Kernel fit Pairwise Correlations Normal fit

Density 0.328

0.000 CEM 1

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

Pre-normalization Quantiles

Null module Eif3a Eif3e