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

Dataset: Num of genes in input gene set: 7 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. Smarcb1 Smarcc2 Smarcc1 Smarca4 Crebbp Arid1a Ep300 Num ofGenesinQueryGeneset:7.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting

Arid1a Smarca4 Crebbp Smarcc1 Smarcc2 Ep300 Smarcb1 Singletons CEM 1(162datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page1 Zmynd11 Smarcc2 Smarcc1 Smarca4 Dync1h1 Ankrd11 Mcm3ap Pip5k1c Crebbp Ubqln4 Setd1b Tnrc6c Trim28 Huwe1 Prrc2b Prrc2a Neurl4 Arid1a Kmt2b Polr2a Kmt2a Eif4g3 Ncoa6 Ylpm1 Casc3 Ep400 Ep300 Zc3h4 Zmiz1 Ncor2 Zmiz2 Gon4l Ctbp1 Cnot3 Kat6a Asxl1 Arid2 Phrf1 Trrap Ago1 Chd8 Bag6 Spen Phc1 Brd4 Bcl9 Szt2 Bptf Srrt Cic 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 68.93 69.53 69.98 70.04 70.46 70.76 71.66 72.68 73.34 74.81 74.94 75.37 76.30 80.27 82.39 82.80 83.07 84.38 84.90 87.87 89.28 89.53 90.47 92.45 92.50 92.63 93.54 93.83 95.49 96.06 100.04 101.83 102.85 105.45 106.22 108.97 111.18 112.96 118.74 120.24 122.90 125.39 130.48 137.52 1.0 Notes Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page2 Gpatch8 R3hdm2 Zmynd8 Nup214 Morc2a Numa1 Phf21a Zfp740 Zfp362 Arid1b Gigyf1 Dnmt1 Ubap2 Wdr33 Bach2 C2cd3 Lphn1 Mark2 Khsrp Ncor1 Cpsf1 Rnf38 Cpsf7 Rnf44 Supt6 Dip2b Pum2 Smg1 Axin1 Smg7 Phf12 Sf3b2 Wipf2 Scaf8 Pcm1 Srsf4 Gga3 Scrib Pcif1 Epc1 Pogz Ints1 Gtf2i Ubr4 Msl1 Mkl1 Ciz1 Tcf3 Helz Ski 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 37.98 38.11 39.26 39.38 39.88 40.78 41.56 41.68 43.46 43.83 45.53 46.75 47.00 48.02 48.06 49.04 49.59 49.64 50.65 51.18 51.32 51.90 52.68 53.92 54.54 54.98 55.82 56.34 56.92 56.99 57.10 57.50 57.96 58.30 58.47 58.74 59.04 59.27 59.45 59.67 61.37 62.45 62.96 63.65 65.11 65.86 67.24 67.72 67.88 68.66 1.0 Notes 2210018M11Rik Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page3 Gm15800 Camsap1 Fam168b Fam193b Eif4enif1 S100pbp Tubgcp6 Specc1l Fam53c Gapvd1 Dnmt3a Cbfa2t2 Gltscr1 Kdm2b Irf2bp1 Cabin1 Rbm27 Kdm2a Zbtb34 Zfp704 Prdm4 Carm1 Kmt2c Rpap1 Trip12 Akap8 Pygo2 Ncoa5 Trim8 Pum1 Plcg1 Tcof1 Nfrkb Prr12 Prpf8 Sart3 Chd3 Xpo6 Terf2 Bap1 Xpo5 Ldb1 Mta1 Brd1 Atn1 Phip Ctcf Fryl Cbl 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 26.48 26.50 26.77 27.01 27.58 27.59 27.64 27.81 27.87 27.93 27.97 28.20 28.25 28.26 28.69 29.00 29.09 29.23 29.84 30.98 30.99 30.99 31.14 31.27 31.27 31.78 32.06 32.11 32.44 32.61 32.71 33.11 33.34 33.35 33.45 34.26 34.27 34.34 34.61 35.32 35.43 35.54 35.59 35.73 35.85 36.05 36.22 36.44 36.88 36.93 1.0 Notes 2700081O15Rik Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page4 BC018507 Hnrnpul1 Ctdnep1 Capn15 Zmym3 Zc3h18 Med13l Gmeb2 Gm608 Tnrc6a Samd1 Zbtb39 Pcnxl3 Zfp579 Zfp746 Fbxl14 Mex3d Med16 Mical3 Lrrc47 Ap3d1 Pacs1 Ccar2 Kat6b Dctn1 Sf3b3 Setd5 Setd2 Ttyh3 Pi4ka Ttc28 Brpf1 Mlxip Adnp Chd6 Dpp9 Dgkd Dot1l Sox4 Pbx2 Midn Sbf1 Mtor Nktr Fiz1 Unk Son Trio Mnt 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 15.81 16.01 16.05 16.12 16.91 17.08 17.22 17.30 17.48 17.58 17.68 18.15 18.42 18.53 19.72 20.04 20.10 20.31 20.31 20.36 20.40 20.68 20.71 21.08 21.12 21.61 21.76 22.02 22.22 22.51 22.64 22.78 22.93 22.97 23.21 23.27 23.31 23.37 23.64 23.71 23.88 23.97 23.98 24.13 24.35 25.54 25.56 25.73 26.19 26.24 1.0 Notes Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page5 Tbc1d10b Hmg20a Prdm15 Nup188 Atxn7l3 Csnk1e Kdm1a Setd1a Ino80d Zfp629 Zfp512 Hnrnpl Fem1c Med23 Gtf3c2 Gtf3c1 Bend3 Agap3 Usp21 Fnbp4 Pacs2 Foxk1 Strip1 Ctdp1 Srpk1 Dcaf7 Satb1 Bcl7a Scaf4 Ift140 Foxj3 Map4 Ubn1 Chd7 Wdr6 Rgp1 Traf3 Phc2 Edc4 Nav1 Pkd1 Grlf1 Tsc2 Grk6 Brd2 Abl1 Setx Ubtf Maz Irgq 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 5.19 5.43 5.76 5.84 5.88 6.46 6.74 6.74 7.47 7.57 7.76 7.88 8.29 8.42 8.68 9.01 9.02 9.03 9.09 9.26 9.29 9.29 9.42 10.08 10.09 10.21 10.35 10.39 10.49 11.01 11.29 11.31 11.35 11.98 12.00 12.19 12.43 12.54 12.65 12.68 13.19 13.90 13.94 14.42 14.67 14.75 14.91 15.25 15.29 15.36 1.0 Notes Symbol Num ofCEMGenes:6.Predicted272.SelectedDatasets:162.Strength:1.0 CEM 1,Geneset"[C]p300-CBP-p270-SWI/SNFcomplex",Page6 Atxn7l3b Ankrd17 Npepps Cd2bp2 Pabpn1 Nup210 Ccdc97 Sap130 Zmym4 Csrnp2 Kdm3b Tnrc6b Wdr90 Rc3h1 Usp34 Rcor1 Mast2 Auts2 Nlgn2 Safb2 Ptov1 Vezf1 Chtf8 Ncdn Sall2 Rfx7 Rsf1 Fbf1 0.0 1.0

GSE14395 [24] GSE11973 [6]

GSE27932 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE43042 [6] GSE41095 [6] GSE9441 [36] GSE49194 [14] GSE5891 [6] GSE30488 [52] GSE30012 [6] GSE39770 [10] GSE49237 [8] GSE21944 [6] GSE10344 [6] GSE4695 [6] GSE10516 [6] GSE24793 [8] GSE38304 [8] GSE23178 [6] GSE37676 [6] GSE19403 [12] GSE34324 [12] GSE18742 [13] GSE23398 [7] GSE17728 [12] GSE11149 [8] GSE23408 [39] GSE26668 [6] GSE8025 [21] GSE1074 [12] GSE9146 [27] GSE16675 [72] GSE21905 [6] GSE57797 [23] GSE41789 [45] GSE8322 [12] GSE54207 [9] GSE47065 [8] GSE45583 [8] GSE11684 [16] GSE21143 [6] GSE30767 [8] GSE19076 [12] GSE58296 [9] GSE58484 [15] GSE13553 [10] GSE21716 [28] GSE45222 [27] GSE39030 [6] GSE52474 [154] GSE8367 [12] GSE42264 [26] GSE33308 [10] GSE7685 [12] GSE19355 [6] GSE55002 [6] GSE9044 [6] GSE16679 [8] GSE20335 [8] GSE15871 [18] GSE10071 [10] GSE25767 [6] GSE6998 [32] GSE9545 [11] GSE24078 [6] GSE32287 [16] GSE16104 [24] GSE26771 [12] GSE33302 [17] GSE32386 [13] GSE8512 [207] GSE34126 [19] GSE18858 [242] GSE13149 [25] GSE4035 [24] GSE37431 [6] GSE31792 [18] GSE24614 [6] GSE11201 [18] GSE51285 [36] GSE27159 [8] GSE43419 [20] GSE21247 [60] GSE27901 [23] GSE12609 [8] GSE45430 [9] GSE27329 [24] GSE28261 [72] GSE18148 [6] GSE59437 [30] GSE24683 [8] GSE14406 [54] GSE46871 [6] GSE51628 [15] GSE46443 [12] GSE6689 [12] GSE56755 [13] GSE11766 [48] GSE22094 [12] GSE56345 [9] GSE20577 [12] GSE30192 [6] GSE38531 [35] GSE21041 [6] GSE14308 [12] GSE10113 [12] GSE13635 [6] GSE26616 [6] GSE48203 [9] GSE53951 [10] GSE28457 [24] GSE11165 [6] GSE51483 [45] GSE27564 [8] GSE15580 [14] GSE28417 [12] GSE20684 [12] GSE19657 [21] GSE39273 [6] GSE35366 [78] GSE45051 [18] GSE58483 [14] GSE9061 [6] GSE7676 [10] GSE10740 [6] GSE28559 [30] GSE43620 [8] GSE6933 [15] GSE9954 [70] GSE6210 [12] GSE20987 [12] GSE36665 [6] GSE38044 [6] GSE33942 [12] GSE42877 [14] GSE30855 [6] GSE5202 [12] GSE25926 [15] GSE39592 [8] GSE7050 [18] GSE28035 [9] GSE17796 [39] GSE17794 [44] GSE21263 [68] GSE21491 [9] GSE15767 [6] GSE13302 [30] GSE8690 [36] GSE50813 [24] GSE4481 [18] GSE24813 [10] GSE7333 [6] GSE27429 [8] GSE18907 [12] CEM+ CEM GSE18800 [25] GSE35763 [6] GSE35260 [21] GSE52358 [8] GSE31106 [18] GSE48811 [20] 0.0 GSE2433 [10] GSE27546 [51]

GSE41942 [6] Scale ofaveragePearsoncorrelations GSE21272 [44] GSE8488 [15] GSE32615 [10] GSE12134 [12] GSE22927 [38] GSE18765 [14] 0.2 GSE33156 [18] GSE31199 [12] GSE5041 [8] GSE15894 [8] GSE34618 [7] GSE2250 [18] GSE21224 [16] GSE36237 [64] GSE22180 [60] 0.4 GSE40296 [6] GSE9533 [35] GSE13259 [10] GSE35318 [12] GSE28830 [9] GSE42883 [12] GSE27811 [9] GSE31244 [6] GSE15872 [18] 0.6 GSE16002 [9] GSE20604 [6] GSE10273 [9] GSE44355 [10] GSE15808 [29] GSE11870 [6] GSE20325 [6] GSE3463 [12] GSE9804 [9] 0.8 GSE23002 [8] GSE48884 [12] GSE15325 [23] GSE35543 [6] Score 0.27 0.33 0.42 0.50 1.20 1.43 1.50 1.56 1.64 1.66 1.92 2.14 2.19 2.32 2.37 2.60 2.88 3.05 3.07 3.79 3.92 4.00 4.27 4.46 4.70 4.80 4.86 5.09 1.0 Notes GEO Series "GSE14395" 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=GSE14395 Status: Public on Sep 11 2009 Title: Gender-specific gene repression of PPAR-alpha KO mice in liver and heart Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19729835 Summary & Design: Summary: Most metabolic studies are conducted in male animals; thus, the molecular mechanism controlling gender-specific pathways has been neglected, including sex-dependent responses to peroxisome proliferator-activated receptors (PPARs). Here we show that PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and inflammation. In males, this effect is reproduced by the administration of synthetic PPARalpha ligand. Using the steroid hydroxylase gene Cyp7b1 as a model, we elucidated the molecular mechanism of this PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggers the interaction of PPARalpha with the GA-binding protein alpha bound to the target promoter. Histone deacetylase is then recruited, and histones and adjacent Sp1-binding site are methylated. These events result in the loss of Sp1-stimulated expression, and thus the down-regulation of Cyp7b1. Physiologically, this repression confers protection against estrogen-induced intrahepatic cholestasis, paving the way for a novel therapy against the most common hepatic disease during pregnancy.

Keywords: Genetic modification

Overall design: Expression profile difference between male and female PPARalpha wild-type and knock-out mice in liver and heart (3 pools of 4 animals in each group). Wild-type (12 males and 12 females) and knock-out PPARalpha SV129 mice (12 males and 12 females) approximately 10 to 12 weeks of age were killed at ZT14 and their livers and hearts quickly removed and frozen.

Background corr dist: KL-Divergence = 0.0171, L1-Distance = 0.0604, L2-Distance = 0.0059, Normal std = 0.8714

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

Liver_male_WT_pool1Liver_male_WT_pool2Liver_male_WT_pool3 Liver_male_KO_pool4(0.0260838) Liver_male_KO_pool5(0.0315131) Liver_male_KO_pool6(0.0399649) Liver_female_WT_pool7(0.0437085) Liver_female_WT_pool8(0.0559619) Liver_female_WT_pool9(0.0453472)Liver_female_KO_pool10 (0.0359389)Liver_female_KO_pool11 (0.0405807)Liver_female_KO_pool12 (0.034103)Heart_male_WT_pool1 (0.0303994)Heart_male_WT_pool2 (0.0378438)Heart_male_WT_pool3 (0.0770582)Heart_male_KO_pool4 (0.0527923)Heart_male_KO_pool5 (0.0256207)Heart_male_KO_pool6 (0.0352489)Heart_female_WT_pool7 (0.035263)Heart_female_WT_pool8 (0.0325579)Heart_female_WT_pool9 (0.0501635)Heart_female_KO_pool10 (0.0674169)Heart_female_KO_pool11 (0.0463235)Heart_female_KO_pool12 (0.0439268) (0.0335907) (0.0343978) (0.0441947)[ min ] [ medium ] [ max ] CEM 1 Arid1a 256.2 1987.0 2452.3 P ( S | Z, I ) = 1.00 Smarca4 671.6 1675.1 2090.5 Mean Corr = 0.92913 Crebbp 194.0 499.5 838.5 Smarcc1 247.5 349.3 475.4 Smarcc2 410.4 1486.0 1857.1 Ep300 211.4 1017.4 1293.3 Trrap 174.1 266.2 467.2 Polr2a 328.4 1214.1 1669.9 Ylpm1 201.2 328.3 450.9 Ep400 259.9 702.1 865.4 Kmt2b 220.8 672.2 838.0 CEM 1 + Kmt2a 249.7 1490.5 2240.6 Top 10 Genes Kat6a 418.4 809.1 1057.5 Asxl1 194.0 287.0 400.3 Casc3 209.4 711.1 1114.5 Zc3h4 232.0 434.9 652.0

Null module Smarcb1 GEO Series "GSE11973" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11973 Status: Public on Jul 31 2008 Title: Wild-type cultured neutrophils versus miR-223 null cultured neutrophils Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18668037 Summary & Design: Summary: This array analysis is to study the regulation of target messages expression in in vitro cultured murine neutrophils versus miR-223 null neutrophils. Culture media was SILAC-IMDM for MS analysis.

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

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

0.624 Kernel fit Pairwise Correlations Normal fit

Density 0.312

0.000 CEM 1

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

Pre-normalization Quantiles

NeutrophilsNeutrophils culturedNeutrophils cultured fromNeutrophils miR-223 cultured fromNeutrophils miR-223 cultured null fromNeutrophils mouse miR-223 cultured null from bonemouse wild-type cultured null from marrow bonemouse wild-type frommouse marrow - boneRep wild-type bonemouse 1 [marrow -(0.309777) Repmin marrow bonemouse 2 -(0.0285461) Rep marrow] - bone Rep3 (0.276982) 1 marrow -(0.19563) Rep[ 2 -(0.0283017)medium Rep 3 (0.160763) ] [ max ] CEM 1 Arid1a 1058.8 2099.3 2547.8 P ( S | Z, I ) = 1.00 Smarca4 1236.7 1758.9 2045.8 Mean Corr = 0.91786 Crebbp 219.9 399.3 546.3 Smarcc1 718.6 992.1 1236.1 Smarcc2 406.6 532.8 685.3 Ep300 1212.0 2456.8 2718.2 Trrap 813.7 1427.9 1916.4 Polr2a 484.8 700.5 906.4 Ylpm1 444.9 668.5 722.8 Ep400 570.8 966.9 1090.3 Kmt2b 420.3 613.6 804.8 CEM 1 + Kmt2a 294.7 564.0 746.1 Top 10 Genes Kat6a 954.5 1500.7 1779.4 Asxl1 874.4 1268.6 1634.4 Casc3 553.3 857.8 958.3 Zc3h4 781.6 1150.0 1372.6

Null module Smarcb1 GEO Series "GSE27932" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.712 Kernel fit Pairwise Correlations Normal fit

Density 0.356

0.000 CEM 1

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

Pre-normalization Quantiles

Lung EC,Lung control, EC,Lung control, rep1 EC,Lung (0.0167235) experimental, rep2 EC,Liver (0.0668648) experimental, sinusoidalLiver rep1 sinusoidal (0.0155535)Liver rep2EC, sinusoidalcontrol, (0.0186313)Liver EC, sinusoidalcontrol, rep1Liver EC, (0.0621884) sinusoidalcontrol, rep2Liver EC, (0.0711959) sinusoidalexperimental, rep3Thymus, EC, (0.0459287) experimental,Thymus, EC,control, rep1 experimental,Thymus, control, rep1(0.0309759) rep2 Thymus,(0.155392) experimental, rep2(0.0344276) rep3 (0.16276) experimental, (0.0450493) rep1 (0.168535) rep2 (0.105773)[ min ] [ medium ] [ max ] CEM 1 Arid1a 942.4 1263.1 4855.7 P ( S | Z, I ) = 1.00 Smarca4 1710.4 2180.9 4489.2 Mean Corr = 0.89861 Crebbp 210.4 311.8 678.4 Smarcc1 594.3 1015.4 1623.8 Smarcc2 541.3 970.4 1923.2 Ep300 1065.2 1283.2 2073.0 Trrap 816.1 1182.0 2000.2 Polr2a 1782.9 2435.4 3928.8 Ylpm1 401.3 771.2 1278.8 Ep400 866.1 1047.7 2166.7 Kmt2b 606.1 886.8 2437.6 CEM 1 + Kmt2a 554.6 783.0 2111.6 Top 10 Genes Kat6a 1126.1 1554.0 2883.0 Asxl1 622.0 825.2 1675.6 Casc3 974.4 1198.8 1946.5 Zc3h4 531.8 719.9 950.4

Null module Smarcb1 GEO Series "GSE43042" 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=GSE43042 Status: Public on Feb 09 2013 Title: The role of Ldb1 in hemangioblast development: genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis (Affymetrix) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23390196 Summary & Design: Summary: The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.

We used microarrays to detail the global programme of gene expression underlying the Ldb1+/+ and Ldb1-/- in Flk1+ cells.

Overall design: RNA was isolated from Ldb1+/+ and Ldb1-/- Flk1+ cells with the QIAGEN RNeasy Mini Kit and integrity was checked on the Agilent 2100 Bioanalyzer. RNA was converted to biotin-labelled cRNA, hybridised on the Mouse Genome 430 2.0 Array and analyzed with the Affymetrix GeneChip® Scanner 3000 according to the manufacturer protocol.

Background corr dist: KL-Divergence = 0.0325, L1-Distance = 0.0414, L2-Distance = 0.0024, Normal std = 0.6850

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

Ldb1+/+,Ldb1+/+, biologicalLdb1+/+, biological rep1Ldb1-/-, biological(0.257203) rep2Ldb1-/-, biological (0.0228398) rep3Ldb1-/-, biological (0.248119) rep1 biological(0.251544) rep2 (0.0862339) rep3 (0.13406)[ min ] [ medium ] [ max ] CEM 1 Arid1a 690.8 779.8 1557.1 P ( S | Z, I ) = 1.00 Smarca4 1675.1 1932.4 3774.7 Mean Corr = 0.88746 Crebbp 459.2 822.4 1602.9 Smarcc1 4724.5 6281.3 9910.0 Smarcc2 111.3 237.2 299.1 Ep300 857.2 1320.5 2173.2 Trrap 314.7 465.5 981.1 Polr2a 540.6 2009.3 3427.5 Ylpm1 698.4 1465.0 2285.7 Ep400 1138.4 1870.9 3096.6 Kmt2b 643.9 1042.8 1747.3 CEM 1 + Kmt2a 370.6 446.7 875.2 Top 10 Genes Kat6a 1130.9 1920.6 3004.0 Asxl1 1166.5 2190.4 3247.1 Casc3 752.7 1497.2 1666.5 Zc3h4 515.5 649.4 1013.7

Null module Smarcb1 GEO Series "GSE41095" 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=GSE41095 Status: Public on Sep 25 2012 Title: Maternal diabetes alters transcriptional programs in the developing embryo. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19538749 Summary & Design: Summary: Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs.

We compared E10.5 cntrol embryos to E10.5 embryos from diabetic pregnancies in the FVB mouse strain.

Overall design: Diabetes was induced in 7-9 week old female FVB mice by streptozotocin. Dams whose blood glucose levels exceeded 250 mg/dl were set up for mating. Embryos were dissected at E10.5 and total RNA was isolated. Equal amounts of RNA prepared from 3 individual embryos were pooled into one sample; each embryo was from a different pregnancy. Three pools were constructed for a total of nine embryos from diabetic pregnancies, and independently three pools for control embryos.

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0326, L2-Distance = 0.0011, Normal std = 0.7805

0.538 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

EmbryoEmbryo at E10.5,Embryo at control, E10.5,Embryo at control, E10.5,biologicalEmbryo at control, E10.5,biological rep1Embryo at diabetic, E10.5, biological(0.155181) rep2 at diabetic, E10.5, (0.364192)biological rep3 diabetic, (0.0787177)biological rep1 biological(0.104914) rep2[ min (0.12977) rep3 ](0.167225) [ medium ] [ max ] CEM 1 Arid1a 1870.3 4248.4 5472.8 P ( S | Z, I ) = 1.00 Smarca4 4571.4 7390.1 7505.6 Mean Corr = 0.87615 Crebbp 545.3 858.3 895.0 Smarcc1 737.5 814.2 1331.3 Smarcc2 627.5 1025.7 1119.9 Ep300 1443.5 1968.6 2305.7 Trrap 1415.7 2240.4 2650.5 Polr2a 2770.8 3390.6 3690.5 Ylpm1 1650.6 2165.6 2314.7 Ep400 1600.0 2600.9 2737.1 Kmt2b 468.7 1601.5 1989.9 CEM 1 + Kmt2a 611.7 828.5 1140.5 Top 10 Genes Kat6a 2309.8 2573.6 3159.8 Asxl1 1677.6 2240.1 2402.6 Casc3 991.6 1616.6 2026.0 Zc3h4 640.4 1458.2 1683.8

Null module Smarcb1 GEO Series "GSE9441" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9441 Status: Public on Dec 07 2007 Title: The effect of sleep deprivation on gene expression in the brain and the liver of three inbred mouse strains Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18077435 Summary & Design: Summary: These studies adress differential changes in gene expression between 6h sleep deprived and control mice in the brain and the liver. We profiled gene expression in three different inbred strains to understand the influence of genetic background.

Keywords: brain, genetic background, sleep deprivation

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

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

0.436 Kernel fit Pairwise Correlations Normal fit

Density 0.218

0.000 CEM 1

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

Pre-normalization Quantiles

B_AK_Control_ZTB_AK_Control_ZTB_AK_Control_ZT 6_1 B_AK_SleepDep_ZT(0.0368575) 6_2 B_AK_SleepDep_ZT(0.0278513) 6_3 B_AK_SleepDep_ZT(0.0266972) 6_1B_B6_Control_ZT (0.0240233) 6_2B_B6_Control_ZT (0.032765) 6_3B_B6_Control_ZT (0.0362885) 6_1 B_B6_SleepDep_ZT(0.0209774) 6_2 B_B6_SleepDep_ZT(0.0396012) 6_3 B_B6_SleepDep_ZT(0.0302142) 6_1B_D2_Control_ZT (0.0306709) 6_2B_D2_Control_ZT (0.026308) 6_3B_D2_Control_ZT (0.0174728) 6_1 B_D2_SleepDep_ZT(0.0198584) 6_2 B_D2_SleepDep_ZT(0.0232656) 6_3 B_D2_SleepDep_ZT(0.0423428) 6_1L_AK_Control_ZT (0.0242407) 6_2L_AK_Control_ZT (0.0394424) 6_3L_AK_Control_ZT (0.0322729) 6_1 L_AK_SleepDep_ZT(0.0285777) 6_2 L_AK_SleepDep_ZT(0.0252894) 6_3 L_AK_SleepDep_ZT(0.0211625) 6_1L_B6_Control_ZT (0.0191785) 6_2L_B6_Control_ZT (0.0228322) 6_3L_B6_Control_ZT (0.0277841) 6_1 (0.0366235)L_B6_SleepDep_ZT 6_2 (0.0197343)L_B6_SleepDep_ZT 6_3 (0.0180636)L_B6_SleepDep_ZT 6_1L_D2_Control_ZT (0.032177) 6_2L_D2_Control_ZT (0.0146498) 6_3L_D2_Control_ZT (0.0253856) 6_1 (0.025816)L_D2_SleepDep_ZT 6_2 (0.0299132)L_D2_SleepDep_ZT 6_3 (0.0430383)L_D2_SleepDep_ZT 6_1 (0.0236846) 6_2 (0.0233835) 6_3 (0.0315558)[ min ] [ medium ] [ max ] CEM 1 Arid1a 599.1 1173.2 1616.5 P ( S | Z, I ) = 1.00 Smarca4 1149.6 2585.0 3089.4 Mean Corr = 0.87015 Crebbp 287.9 780.9 991.6 Smarcc1 501.4 798.5 1077.3 Smarcc2 706.6 2317.9 3046.9 Ep300 522.9 770.7 1072.4 Trrap 282.7 898.8 1305.5 Polr2a 330.8 510.3 910.4 Ylpm1 286.0 865.9 1128.2 Ep400 670.8 887.7 1084.1 Kmt2b 529.1 864.0 1086.8 CEM 1 + Kmt2a 397.5 1397.7 2053.7 Top 10 Genes Kat6a 825.3 943.2 1321.4 Asxl1 295.8 740.2 1058.6 Casc3 517.1 967.5 1262.3 Zc3h4 304.8 609.2 849.1

Null module Smarcb1 GEO Series "GSE49194" 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=GSE49194 Status: Public on Oct 01 2013 Title: Expression data from neurospheres derived from the neocortex, striatum and subventricular zones of the adult mouse brain Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23974433 Summary & Design: Summary: Differential gene expression profiles of neurospheres derived from different regions of the adult brain.

In this dataset, we include data on triplicated biological samples from each of the following brain regions: neocortex, striatum, and subventricular zone. We also include duplicated data on neurospheres derived from the dorsal and ventralforebrain neural tubes and one spinal cord of E14.5 mouse embryos for comparison.

Overall design: Fourteen samples were analyzed in total. To compare the expression profiles across the samples, Affymetrix GeneChip Mouse Genome 430 2.0 Array Platform (total 41,170 probes) was used, and the data were analyzed using Silicon Genetics GeneSpring Software GX7.3.1. The data was normalized to median settings across the entire probe set and samples, and transcripts that are expressed across triplicated samples at levels two-fold or higher than the rest of the samples were considered as significantly enriched in particular biological samples. Comparisons between adult and embryonic samples also identified genes enriched in adult brain-derived samples.

Background corr dist: KL-Divergence = 0.0913, L1-Distance = 0.0376, L2-Distance = 0.0026, Normal std = 0.4673

0.877 Kernel fit Pairwise Correlations Normal fit

Density 0.438

0.000 CEM 1

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

Pre-normalization Quantiles

Adult neocortexAdult neocortexAdult sample neocortexAdult sample1 (0.0213426) striatumAdult sample2 (0.024305) striatum sampleAdult 3 (0.0597718) striatum sampleAdult1 (0.0876382) subventricular sampleAdult2 (0.0202827) subventricular Adult3 (0.0480224) subventricularzoneEmbryonic sample zoneEmbryonic dorsalsample1 zone(0.0443361)Embryonic forebrain dorsalsample2 (0.0329626)Embryonic forebrain ventral3 sample(0.041137)Embryonic ventralforebrain sample1 (0.0197687) spinalforebrain 2sample (0.208048) cord sample1 sample(0.0230428) 2[ (0.306816)(0.0625257) min ] [ medium ] [ max ] CEM 1 Arid1a 658.0 839.7 1700.0 P ( S | Z, I ) = 1.00 Smarca4 2526.6 3205.8 5546.4 Mean Corr = 0.85530 Crebbp 239.4 367.3 993.1 Smarcc1 614.2 1216.5 2686.0 Smarcc2 918.9 1301.4 4005.2 Ep300 356.5 512.6 784.0 Trrap 535.0 676.9 932.4 Polr2a 2619.5 3201.7 3488.7 Ylpm1 1160.5 1907.0 2958.3 Ep400 364.6 581.8 1032.1 Kmt2b 221.6 338.9 449.9 CEM 1 + Kmt2a 317.1 518.8 984.2 Top 10 Genes Kat6a 1584.5 2055.1 3159.5 Asxl1 700.0 1110.0 1617.8 Casc3 565.5 880.7 1635.6 Zc3h4 764.6 1466.8 2867.4

Null module Smarcb1 GEO Series "GSE5891" 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=GSE5891 Status: Public on Sep 22 2006 Title: Nuclear organization of active and inactive chromatin domains revealed by 4C technology Organism: Mus musculus Experiment type: Other Platform: GPL1261 Pubmed ID: 17033623 Summary & Design: Summary: The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We have developed 4C technology, or 3C-on-chip, which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active b-globin locus in fetal liver contacts mostly transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, while the inactive locus in fetal brain contacts different, transcriptionally silent, loci. A housekeeping gene in a gene dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.

Keywords: 4C technology

Overall design: Gene expression arrays were performed in triplicate, according to standard procedures (Affymetrix). 4C experiments were performed in duplo (biologically independent samples), dye swap was included. Hybriisation was performed on dedicated micro-arrays. Probes (60-mers) were selected from the sequences 100 bp up and downstream of HindIII sites. To prevent cross-hybridization, probes that had any similarity with highly abundant repeats (RepBase 10.09) were removed from the probeset. In addition, probes that gave more than two BLAST hits in the genome were also removed from the probeset. Sequence alignments were performed using MegaBLAST using the standard settings. A hit was defined as an alignment of 30 nt or longer.

Background corr dist: KL-Divergence = 0.0158, L1-Distance = 0.0653, L2-Distance = 0.0070, Normal std = 0.9745

0.409 Kernel fit Pairwise Correlations Normal fit

Density 0.205

0.000 CEM 1

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

Pre-normalization Quantiles

E14.5_fetal_brain_1E14.5_fetal_brain_2E14.5_fetal_brain_3 (0.089453)E14.5_fetal_liver_1 (0.108928)E14.5_fetal_liver_2 (0.276331)E14.5_fetal_liver_3 (0.309482) (0.158047) (0.0577588)[ min ] [ medium ] [ max ] CEM 1 Arid1a 676.1 2632.9 3602.6 P ( S | Z, I ) = 1.00 Smarca4 1791.9 11020.1 11841.1 Mean Corr = 0.83133 Crebbp 420.2 1331.9 1763.7 Smarcc1 651.9 9647.9 10234.6 Smarcc2 425.9 3797.1 3928.5 Ep300 1472.7 1848.8 2594.4 Trrap 782.1 1933.5 2750.3 Polr2a 710.6 929.3 6767.1 Ylpm1 461.9 925.9 1123.7 Ep400 1108.2 1586.4 1714.5 Kmt2b 452.6 1099.7 1219.3 CEM 1 + Kmt2a 115.8 844.0 1304.9 Top 10 Genes Kat6a 1007.5 3399.9 3555.2 Asxl1 1319.7 2053.4 2704.7 Casc3 452.7 821.8 1422.3 Zc3h4 1451.6 1706.3 2992.3

Null module Smarcb1 GEO Series "GSE30488" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 52 -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=GSE30488 Status: Public on Aug 31 2012 Title: Expression data from E2f7/E2f8/E2f3a null placentas and embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22516201 Summary & Design: Summary: To understand the underlying cause and mechanisms of embryonic lethality observed in combined loss of E2f7 and E2f8, we compared global gene expression profiles of wild type, germline deleted and sox2-Cre/Cyp19-Cre deleted embryos and placentas.

Overall design: RNA was extracted from E10.5 embryos and placentas. Gene deletion in samples confirmed by PCR genotyping of DNA isolated from each sample.

Background corr dist: KL-Divergence = 0.0427, L1-Distance = 0.0236, L2-Distance = 0.0008, Normal std = 0.5868

0.680 Kernel fit Pairwise Correlations Normal fit

Density 0.340

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

E2f3a-/-;E2f7-/-;E2f8-/-E2f3a-/-;E2f7-/-;E2f8-/-E2f3a-/-;E2f7-/-;E2f8-/- E2f3a-/-;E2f7-/-;E2f8-/-embryo E2f3a-/-;E2f7-/-;E2f8-/-embryo 3a78KO E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 1 (0.0209129) E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 2 (0.0173551) E2f3a-/-;E2f7+/+;E2f8+/+embryo 3a78KO 3 (0.0295979)E2f3a-/-;E2f7+/+;E2f8+/+ 3a78KO 4embryo (0.029591)E2f3a+/+;E2f7-/-;E2f8-/- 5embryo 3KO (0.02712) E2f3a+/+;E2f7-/-;E2f8-/-1 (0.0159715)embryo 3KO E2f3a+/+;E2f7-/-;E2f8-/-2 (0.0180242)embryo 3KO E2f3a+/+;E2f7-/-;E2f8-/-3 embryo (0.0125645) 3KO Cyp19Cre+;E2f7F/F;E2f8F/F4 embryo 78KO(0.00893467) Cyp19Cre+;E2f7F/F;E2f8F/F1 embryo 78KO(0.0119305) Cyp19Cre+;E2f7F/F;E2f8F/F2 embryo 78KO(0.0114456) Sox2Cre+;E2f7F/-;E2f8F/-3 78KO(0.00422751) embryo Sox2Cre+;E2f7F/-;E2f8F/-4 (0.018059) embryo Cyp19Sox2Cre+;E2f7F/-;E2f8F/- embryo 1Cyp19 Sox2Cre+;E2f7F/-;E2f8F/-(0.0204628) embryo 2Cyp19 E2f3a+/+;E2f7+/+;E2f8+/+(0.0192298) embryo Sox2 3 E2f3a+/+;E2f7+/+;E2f8+/+(0.0112829) 1 embryo (0.0128986)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 2 embryo (0.0147158)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 3 embryo (0.0441437)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 4 embryo (0.0275951)WT E2f3a+/+;E2f7+/+;E2f8+/+1 (0.0279526) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-2 (0.0394754) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-3 (0.0262884) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-4 (0.0196912) embryo WT E2f3a-/-;E2f7-/-;E2f8-/-placenta5 (0.015312) WT E2f3a-/-;E2f7-/-;E2f8-/-placenta6 3a78KO(0.0180203) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 1 (0.0150103) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 2 (0.0153019) E2f3a-/-;E2f7+/+;E2f8+/+placenta 3a78KO 3 (0.00904092)E2f3a-/-;E2f7+/+;E2f8+/+ 3a78KO placenta4 (0.0125543)E2f3a+/+;E2f7-/-;E2f8-/- placenta5 3KO (0.0177882)E2f3a+/+;E2f7-/-;E2f8-/- 1 placenta (0.0223233) 3KOE2f3a+/+;E2f7-/-;E2f8-/- 2 placenta (0.0242791) 3KOE2f3a+/+;E2f7-/-;E2f8-/- placenta3 (0.0220494) 3KOCyp19Cre+;E2f7F/F;E2f8F/F placenta4 78KO(0.022366)Cyp19Cre+;E2f7F/F;E2f8F/F placenta1 78KO(0.0162617)Cyp19Cre+;E2f7F/F;E2f8F/F placenta2 78KO(0.019372)Sox2Cre+;E2f7F/-;E2f8F/- 3 78KO(0.0180633) placentaSox2Cre+;E2f7F/-;E2f8F/- 4 (0.0235336) placenta Sox2Cre+;E2f7F/-;E2f8F/-cyp 19 placenta 3Sox2Cre+;E2f7F/-;E2f8F/-Cyp19 (0.0157689) placenta 1E2f3a+/+;E2f7+/+;E2f8+/+Cyp19 (0.0208966) placenta sox2 2E2f3a+/+;E2f7+/+;E2f8+/+ (0.0151922) 1placenta (0.0188495)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 2placenta (0.0163798)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 3placenta (0.0197418)sox2E2f3a+/+;E2f7+/+;E2f8+/+ 4placenta (0.0159899)WTE2f3a+/+;E2f7+/+;E2f8+/+ 1 (0.0216076)placenta WT 2 (0.0195981)placenta WT 3 (0.0143712)placenta WT 4 (0.0200457)placenta WT[ 5 min(0.0226254) WT 6 (0.0181863) ] [ medium ] [ max ] CEM 1 Arid1a 1119.1 2019.8 3801.6 P ( S | Z, I ) = 1.00 Smarca4 1577.3 3903.6 7228.0 Mean Corr = 0.81683 Crebbp 205.6 590.6 855.0 Smarcc1 1268.0 2992.5 5045.3 Smarcc2 350.3 670.7 1270.6 Ep300 555.4 1068.4 1823.2 Trrap 1875.3 2735.4 3503.3 Polr2a 661.7 2490.8 4822.0 Ylpm1 551.2 1171.5 2239.5 Ep400 1012.5 2153.0 3249.1 Kmt2b 634.3 1201.9 1515.9 CEM 1 + Kmt2a 472.6 713.6 1099.8 Top 10 Genes Kat6a 957.3 1466.7 2089.9 Asxl1 489.9 1610.3 3822.5 Casc3 809.5 1530.5 2063.0 Zc3h4 593.9 1117.4 1761.9

Null module Smarcb1 GEO Series "GSE30012" 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=GSE30012 Status: Public on Jun 18 2011 Title: A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target.

Overall design: Three replicates of mouse embryonic stem cells with Dicer (CTRL) compared to three replicates of mouse embryonic stem cells lacking Dicer (CRE)

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0179, L2-Distance = 0.0003, Normal std = 0.6434

0.627 Kernel fit Pairwise Correlations Normal fit

Density 0.313

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse EmbryonicMouse EmbryonicMouse Stem EmbryonicMouse Cells Stem EmbryonicMouseControl Cells Stem EmbryonicMouseControl replicate Cells Stem EmbryonicControl replicate Cells 1 Stem (0.0806793) Dicer replicate Cells 2 Stem (0.348759) Null Dicer Cells 3- (0.369264)replicate Null [Dicer min- replicate Null1 (0.112506) - replicate] 2 (0.0244585) 3 (0.0643331)[ medium ] [ max ] CEM 1 Arid1a 4190.8 5454.4 6138.9 P ( S | Z, I ) = 1.00 Smarca4 4278.9 5089.1 5807.8 Mean Corr = 0.81217 Crebbp 229.6 329.2 482.3 Smarcc1 4915.2 5295.6 5610.0 Smarcc2 32.3 61.1 77.7 Ep300 1186.9 1502.6 1837.8 Trrap 1512.8 2095.7 2375.1 Polr2a 1431.2 1655.7 2617.1 Ylpm1 691.2 936.1 1123.5 Ep400 977.5 1218.2 1588.2 Kmt2b 1130.7 1344.8 1691.1 CEM 1 + Kmt2a 350.4 527.5 822.4 Top 10 Genes Kat6a 827.7 1100.4 1193.7 Asxl1 2080.9 2803.5 3090.8 Casc3 338.5 462.4 767.4 Zc3h4 1186.9 1431.2 1563.5

Null module Smarcb1 GEO Series "GSE39770" 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=GSE39770 Status: Public on Aug 01 2012 Title: Expression data from embryonic stem cells following siRNA transfection of UPS members [Differentiation_ES] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23103054 Summary & Design: Summary: While transcriptional regulation of stem cell self-renewal and differentiation has been extensively studied, only a small number of studies have addressed the roles for post-translational modifications in these processes. A key mechanism of post-translational modification is ubiquitination by the ubiquitin-proteasome system (UPS). Using UPS-targeted RNAi screens, we identify novel regulators of pluripotency and differentiation. We focus on two of these proteins, the deubiquitinating enzyme, Psmd14, and the E3 ligase, Fbxw7, and characterize their importance in ES cell pluripotency and cellular reprogramming.

Overall design: Embryonic stem cells were reverse transfected with siRNA, and differentiated for 48hrs in conditions with retinoic acid, 48 hrs post transfection cells were isloated for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0856, L1-Distance = 0.0226, L2-Distance = 0.0006, Normal std = 0.4634

0.861 Kernel fit Pairwise Correlations Normal fit

Density 0.430

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

siNonTargetsiNonTarget replicate1siSox17 replicate2siSox17 (0.25979)replicate1siFbxw7 (0.0783578)replicate2 (0.0229737)siFbxw7 replicate1 (0.0391742)siSocs3 replicate2 (0.149125)siSocs3 replicate1 (0.0861289)siRnf31 replicate2 (0.17841)siRnf31 replicate1 (0.10945) replicate2 (0.018588) (0.0580029)[ min ] [ medium ] [ max ] CEM 1 Arid1a 427.2 502.3 617.9 P ( S | Z, I ) = 1.00 Smarca4 3932.8 4368.8 5157.1 Mean Corr = 0.81024 Crebbp 491.1 579.1 814.9 Smarcc1 3345.3 4691.3 6280.1 Smarcc2 228.1 308.1 381.4 Ep300 1818.5 2211.3 2687.3 Trrap 638.0 929.8 1478.9 Polr2a 1992.4 2529.9 3019.0 Ylpm1 1674.6 1942.2 2016.3 Ep400 1212.6 1409.7 1781.0 Kmt2b 890.2 1031.2 1278.3 CEM 1 + Kmt2a 311.0 412.4 585.0 Top 10 Genes Kat6a 753.1 972.6 1106.1 Asxl1 1242.4 1473.8 2095.3 Casc3 1118.4 1208.2 1340.1 Zc3h4 1117.2 1236.1 1352.6

Null module Smarcb1 GEO Series "GSE49237" 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=GSE49237 Status: Public on Dec 31 2013 Title: Analysis of TBR1 downnstream target genes in embryonic forebrains Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24441682 Summary & Design: Summary: TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala.

To investigate how TBR1 regulates neural development, the gene expression profile of Tbr1-/- brains was compared with WT littermates.

Overall design: Total RNAs purified from forebrains at embryonic day 16.5 were hybridized on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0472, L1-Distance = 0.0231, L2-Distance = 0.0006, Normal std = 0.5812

0.697 Kernel fit Pairwise Correlations Normal fit

Density 0.349

0.000 CEM 1

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

Pre-normalization Quantiles

WT #1 (0.0429021)WT#2 (0.0405435)WT#3 (0.0526448)WT#4 (0.232946)Tbr1-/-#1Tbr1-/-#2 (0.149092)Tbr1-/-#3 (0.0406374)Tbr1-/-#4 (0.100228) (0.341006) [ min ] [ medium ] [ max ] CEM 1 Arid1a 1704.0 1992.0 2707.2 P ( S | Z, I ) = 1.00 Smarca4 4893.9 5826.5 7356.4 Mean Corr = 0.80358 Crebbp 821.6 1016.8 1380.2 Smarcc1 2060.6 2302.0 3100.7 Smarcc2 1814.1 2305.7 2886.0 Ep300 1036.9 1206.2 1873.4 Trrap 1382.8 1625.2 2753.4 Polr2a 297.7 600.7 842.3 Ylpm1 984.0 1120.6 1530.6 Ep400 979.3 1095.3 1577.6 Kmt2b 1040.3 1508.5 1813.1 CEM 1 + Kmt2a 485.8 531.7 1140.2 Top 10 Genes Kat6a 1323.8 1774.1 2850.4 Asxl1 1369.3 1579.3 1996.2 Casc3 832.6 993.4 1273.3 Zc3h4 1167.4 1436.4 1581.1

Null module Smarcb1 GEO Series "GSE21944" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.475 Kernel fit Pairwise Correlations Normal fit

Density 0.238

0.000 CEM 1

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

Pre-normalization Quantiles

C57Bl/6C57Bl/6 P21, wildtypeC57Bl/6 P21, wildtype retina,C57Bl/6 x Sv129 1retina,C57Bl/6 x(0.0654133) P21, Sv129 ERRβ2C57Bl/6 x(0.0512535) P21, Sv129 -/-ERRβ P21, knockoutP21, wildtype -/-ERRβ knockout retina, -/- retina, knockout 1retina, (0.148612) 3[ (0.215941) min 2retina, (0.146476) 3 ](0.372304) [ medium ] [ max ] CEM 1 Arid1a 1000.6 1493.9 1558.1 P ( S | Z, I ) = 1.00 Smarca4 3265.6 3413.8 3879.9 Mean Corr = 0.79193 Crebbp 417.1 569.3 1552.0 Smarcc1 690.9 797.9 1147.5 Smarcc2 1078.2 1540.9 2672.7 Ep300 998.8 1413.2 3097.0 Trrap 776.0 2028.9 2390.2 Polr2a 558.5 987.7 2119.1 Ylpm1 596.0 1042.0 2226.9 Ep400 533.1 1000.9 1818.9 Kmt2b 823.3 1169.0 2020.1 CEM 1 + Kmt2a 571.6 1214.6 2799.7 Top 10 Genes Kat6a 1457.8 1814.6 3746.4 Asxl1 596.7 865.4 1169.4 Casc3 753.9 988.8 1516.0 Zc3h4 1301.1 1562.9 2061.0

Null module Smarcb1 GEO Series "GSE10344" 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=GSE10344 Status: Public on Dec 31 2008 Title: Expression data from garlic-fed mouse Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Garlic is a popular flavor enhancer in modern cuisines. Although anti-atherosclerotic, anti-proliferative, hypolipidemic and chemopreventative effects of garlic are known for a long time, the mechanisms of garlic as a dietary supplement ramain largely unknown.

We used microarrays to analyze the global programme of gene expression in control (cellulose) and garlic-fed mice and identified erythropoietic and heme biosynthetic genes that could, in part, be responsible for the pleiotropic effects of garlic on health

Keywords: diet, garlic

Overall design: 8-week old male C57BL/6J mice were divided into two diet groups and maintained at an SPF facility. Mice were fed (ad libitum) a special diet (Yeh and Yeh, 1994) with 4% cellulose (Control group, 3 mice) or 4% lyophilized raw garlic powder (Treatment group, 3 mice). At the end of the 15-week treatment, spleen organs were used for RNA isolation and arraying.

Background corr dist: KL-Divergence = 0.0471, L1-Distance = 0.0191, L2-Distance = 0.0004, Normal std = 0.5847

0.689 Kernel fit Pairwise Correlations Normal fit

Density 0.345

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

Spleen Spleenof 15-week Spleenof 15-week cellulose-fed Spleenof 15-week cellulose-fed Spleenof mouse,15-week cellulose-fed Spleenof mouse,15-weekbiological garlic-fed of mouse,15-weekbiological garlic-fed rep1mouse, biological (0.0956113)garlic-fed rep2 mouse,biological (0.137152) rep3 mouse,biological[ rep1min (0.0492229) biological(0.205974) rep2 ] (0.337784) rep3 (0.174256)[ medium ] [ max ] CEM 1 Arid1a 2633.3 2904.3 3248.5 P ( S | Z, I ) = 1.00 Smarca4 2227.4 2543.1 2887.6 Mean Corr = 0.78465 Crebbp 620.2 860.0 1013.6 Smarcc1 1237.6 1553.7 1791.3 Smarcc2 685.3 745.9 873.6 Ep300 2280.9 2554.0 2934.9 Trrap 1279.3 1555.2 1897.7 Polr2a 1036.3 1545.5 1694.0 Ylpm1 1078.6 1190.6 1220.5 Ep400 1857.4 1966.7 2339.5 Kmt2b 1362.6 1449.5 1746.1 CEM 1 + Kmt2a 1308.7 1426.4 1762.0 Top 10 Genes Kat6a 2370.7 2515.3 2951.0 Asxl1 1041.4 1107.5 1155.5 Casc3 905.9 999.5 1133.6 Zc3h4 869.9 970.0 1139.2

Null module Smarcb1 GEO Series "GSE4695" 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=GSE4695 Status: Public on Apr 25 2006 Title: Changes in gene expression in dermal fibroblasts following exposure to Et1 peptide Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16870175 Summary & Design: Summary: To determine if aberrant activation of endothelin-1 (Et1) could lead to the dysregulation of many downstream genes, we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional changes by microarray. Mouse dermal fibroblasts were treated with exogenous Et1 peptide for 24 hours. ET1 treatment resulted in significant expression changes primarily downregulation of a number of genes. In particular, Tgfβ2 and Tgfβ3 were among the downregulated genes, which in turn alter the expression status of their many target genes. These data suggest that the stable silencing of Et1 is important for the phenotypic stability of dermal fibroblasts, and perhaps many other cell types as well.

Keywords: endothelin-1; Et1; dermal fibroblast

Overall design: Three separate biological replicates were derived for both control and treated samples. The primary dermal fibroblasts were derived by explant procedure from the skin of mouse pups aged 0-3 days. By passage 5, cells were split to two separate cultures-- one with 100nM synthetic Et1 peptide added to the medium (treated) and the other with nothing added (control). Cells were exposed to Et1 for 24 hrs, then treated and control populations were harvested for total RNA.

Background corr dist: KL-Divergence = 0.0374, L1-Distance = 0.0203, L2-Distance = 0.0004, Normal std = 0.6307

0.640 Kernel fit Pairwise Correlations Normal fit

Density 0.320

0.000 CEM 1

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

Pre-normalization Quantiles

fibroblast_et1control_rep1fibroblast_et1treated_rep1fibroblast_et1control_rep2fibroblast_et1treated_rep2 (0.177876)fibroblast_et1control_rep3 (0.123962)fibroblast_et1treated_rep3 (0.118656) (0.231886) (0.24002) (0.107599)[ min ] [ medium ] [ max ] CEM 1 Arid1a 964.1 1683.1 1925.4 P ( S | Z, I ) = 1.00 Smarca4 2318.4 2937.8 2987.2 Mean Corr = 0.78268 Crebbp 120.4 172.7 269.5 Smarcc1 1848.6 2754.2 3177.9 Smarcc2 395.5 741.4 822.8 Ep300 661.4 919.3 1059.4 Trrap 645.5 1038.6 1177.1 Polr2a 321.9 2455.5 2885.1 Ylpm1 553.1 772.7 850.8 Ep400 911.8 1116.8 1242.9 Kmt2b 460.8 1031.1 1060.8 CEM 1 + Kmt2a 549.4 625.3 708.8 Top 10 Genes Kat6a 809.5 1050.5 1171.1 Asxl1 418.0 556.1 721.1 Casc3 655.4 1039.6 1317.7 Zc3h4 516.1 649.7 728.6

Null module Smarcb1 GEO Series "GSE10516" 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=GSE10516 Status: Public on Feb 15 2008 Title: Identification of genes controlled by LMX1B in the developing mouse hindlimb bud Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18351676 Summary & Design: Summary: A control vs. genetic knockout experiment aimed at determining what RNAs are upregulated or downregulated in e11.5 mouse proximal limb tissue lacking the Lmx1b gene. Because Lmx1b is required for dorsal-ventral patterning of the limb, this screen gives insight into what putative downstream targets of Lmx1b contribute to dorsal-ventral patterning.

Keywords: Genetic allele comparison

Overall design: The proximal portion of e11.5 hindlimb buds (~500um) was used for RNA extraction. Each array was hybridized with pooled cRNAs from both hindlimb buds of three embryos (6 hindlimbs/sample).

Background corr dist: KL-Divergence = 0.0438, L1-Distance = 0.0172, L2-Distance = 0.0003, Normal std = 0.5963

0.676 Kernel fit Pairwise Correlations Normal fit

Density 0.338

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWild-type E11.5Wild-type proximal E11.5Lmx1b proximal E11.5hindlimb -/-Lmx1b proximal E11.5 hindlimb pool -/-Lmx1b proximal E11.5 1hindlimb (0.349548) pool -/- proximal E11.52hindlimb (0.126637) pool proximal 3hindlimb (0.139568)pool 1hindlimb (0.256918) pool[ 2min (0.048526) pool 3 (0.0788039)] [ medium ] [ max ] CEM 1 Arid1a 4964.1 5720.7 6122.5 P ( S | Z, I ) = 1.00 Smarca4 5996.1 6426.0 6918.9 Mean Corr = 0.78221 Crebbp 900.7 1047.7 1138.9 Smarcc1 4837.9 5205.3 5299.5 Smarcc2 1346.1 1605.8 1712.7 Ep300 1790.3 1960.8 2060.4 Trrap 1556.1 1882.5 1912.5 Polr2a 3992.6 5091.2 5413.6 Ylpm1 1361.5 1393.9 1508.1 Ep400 1665.0 1721.3 1818.3 Kmt2b 1802.0 2077.2 2152.7 CEM 1 + Kmt2a 976.8 1261.6 1276.7 Top 10 Genes Kat6a 2151.8 2179.8 2262.5 Asxl1 1793.7 1956.8 2000.2 Casc3 1849.8 2187.2 2275.2 Zc3h4 1837.1 2093.7 2146.9

Null module Smarcb1 GEO Series "GSE24793" 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=GSE24793 Status: Public on Mar 30 2012 Title: Target genes of thyroid hormone in cerebellum neurons Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22586439 Summary & Design: Summary: Cerebellar post-natal development is particularly sensitive to thyroid hormone and low levels of thyroid hormone (hypothyroidism) result in permanent defects in cerebellar architecture and function. All cell types of the cerebellum are affected, but the main sign of hypothyroidism in mice is the persistence of the external granular layer, composed of mitotic neuronal precursors at P21.

To make the genetic link between thyroid hormone and cerebellar development, we sought to identify new thyroid hormone target genes, in particular in granule cells which represent the vast majority of cerebellar cells.

Overall design: Primary cultures of cerebellar neurons were made by dissociation of cerebella from newborn wild-type mice. These cells were plated 48 hours in serum-free medium to avoid invasion of the culture by glial cells. In order to include a kinetic and a maximum number of target genes, several cultures were either treated or left untreated as controls for 6 hours (T1), 16 hours (T2), 24 hours (T3) or 48 hours (T4) and results were pairwise compared for each time point.

Background corr dist: KL-Divergence = 0.0499, L1-Distance = 0.0304, L2-Distance = 0.0014, Normal std = 0.5750

0.720 Kernel fit Pairwise Correlations Normal fit

Density 0.360

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

NeuronsNeurons at 6h_T3Neurons at treatment 6h_untreatedNeurons at 16h_T3 (0.0550814)Neurons at (0.0834883) 16h_untreatedtreatmentNeurons at 24h_T3 (0.0510138)Neurons at 24h_untreated(0.0486172)treatmentNeurons at 48h_T3 (0.122939) at 48h_untreated(0.38141)treatment (0.148687) (0.108764)[ min ] [ medium ] [ max ] CEM 1 Arid1a 553.8 1059.1 1266.9 P ( S | Z, I ) = 1.00 Smarca4 2455.8 3183.6 5306.0 Mean Corr = 0.78111 Crebbp 392.0 708.9 1359.2 Smarcc1 2636.7 3145.1 5011.5 Smarcc2 391.2 593.9 1333.7 Ep300 947.2 1397.9 1489.7 Trrap 874.9 1224.4 1513.3 Polr2a 352.2 565.5 739.6 Ylpm1 958.8 1373.3 1653.3 Ep400 1352.7 2328.8 3003.6 Kmt2b 608.6 811.8 1030.7 CEM 1 + Kmt2a 387.9 657.0 952.1 Top 10 Genes Kat6a 1134.7 1860.4 2399.8 Asxl1 874.4 1251.5 1768.7 Casc3 818.0 1113.8 1539.5 Zc3h4 677.4 767.8 1443.5

Null module Smarcb1 GEO Series "GSE38304" 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=GSE38304 Status: Public on Sep 24 2012 Title: Gene Expression Profiles of MYC+ and MYC- mouse Germinal Center B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23001145 Summary & Design: Summary: Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas.

We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts.

Overall design: GFPMYC+ and GFPMYC- GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools of GFPMYC knock-in mice (12 days after SRBC immunization). 5-20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays.

Background corr dist: KL-Divergence = 0.0656, L1-Distance = 0.0311, L2-Distance = 0.0016, Normal std = 0.5216

0.766 Kernel fit Pairwise Correlations Normal fit

Density 0.383

0.000 CEM 1

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

Pre-normalization Quantiles

GFPMYCGFPMYC negativeGFPMYC negative GC GFPMYCB negativecells, GC GFPMYC BBiological negativecells, GC GFPMYC BBiological positivecells, GCreplicate GFPMYC BBiological positivecells, GC replicate 1 B(0.177666)GFPMYC Biological cells,positive GC replicate 2 B(0.148966)Biological cells,positive GC replicate 3 B(0.0648162)Biological cells, GCreplicate 4 B(0.095756)Biological cells, replicate 4 (0.136668) Biological[ minreplicate 5 (0.0298094) replicate ]6 (0.0612464) 7 (0.285073)[ medium ] [ max ] CEM 1 Arid1a 224.0 761.4 1430.2 P ( S | Z, I ) = 1.00 Smarca4 776.5 1928.6 2936.0 Mean Corr = 0.77827 Crebbp 290.7 1711.7 2578.4 Smarcc1 1949.4 2737.3 2954.6 Smarcc2 905.6 1740.5 2749.6 Ep300 647.0 2602.1 3911.0 Trrap 111.4 639.4 1014.7 Polr2a 1592.1 3956.5 4725.2 Ylpm1 608.1 1204.8 1455.1 Ep400 674.3 1386.2 1866.0 Kmt2b 166.6 577.6 970.2 CEM 1 + Kmt2a 670.4 3707.6 7212.2 Top 10 Genes Kat6a 1766.3 3648.9 4475.4 Asxl1 1016.4 2702.7 3144.6 Casc3 2833.8 3505.0 3916.5 Zc3h4 1928.9 4761.4 5257.9

Null module Smarcb1 GEO Series "GSE23178" 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=GSE23178 Status: Public on Jul 29 2010 Title: Expression data analysis in lungs from mice induced for pulmonary arterial hypertension (PAH) by inhalation of Stachybotrys chartarum spores Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23157700 Summary & Design: Summary: It has been reported that repeated intra-tracheal instillation of S. chartarum spores induced significant pulmonary arterial remodeling in mice, which resulted in pathological changes like human pulmonary arterial hypertension (PAH) and elevation right ventricle systolic pressure.

Then, we used microarrays to know the complex molecular mechanisms that underlie pathogenesis of PAH.

Overall design: Isolates of Stachybotrys chartarum were used. Ddy mice were anesthetized and the spore suspension was intratracheally injected 12 times, i.e. 1ˆ104 spores into each mouse at 4-5 day intervals for 8 weeks. Mice were sacrificed one week after the final injection and then examined. Lung tissue specimens from mice model of PAH (n=3) and normal controls (n=3) were obtained. RNA targets preparation were performed according to the manufacturer's protocol using GeneChip(R) 3' IVT Express Kit (Affymetrix). One hundred nanograms of total RNA was converted into double-stranded cDNA template for transcription. In vitro transcription synthesized amplified RNA (aRNA) and incorporated a biotin-conjugated nucleotide. After purification and fragmentation of aRNA, 12.5 ug of them was hybridized to GeneChip(R) Mouse Genome 430 2.0 Array (Affymetrix).The Probe Array was scanned using a GeneChip(R) Scanner 3000 7G.

Background corr dist: KL-Divergence = 0.0451, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.5935

0.682 Kernel fit Pairwise Correlations Normal fit

Density 0.341

0.000 CEM 1

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

Pre-normalization Quantiles

Lung_control_1Lung_control_2Lung_control_3 (0.483694)Lung_PAHmodel_1 (0.101835)Lung_PAHmodel_2 (0.105977)Lung_PAHmodel_3 (0.0470186) (0.0893271) (0.172148)[ min ] [ medium ] [ max ] CEM 1 Arid1a 191.9 316.4 395.5 P ( S | Z, I ) = 1.00 Smarca4 767.6 1036.0 1040.4 Mean Corr = 0.77513 Crebbp 272.1 369.6 384.3 Smarcc1 480.5 605.7 625.4 Smarcc2 741.4 880.9 906.5 Ep300 1032.1 1304.6 1433.2 Trrap 615.6 677.9 729.4 Polr2a 672.5 727.6 936.0 Ylpm1 582.8 603.5 740.0 Ep400 587.5 683.5 737.9 Kmt2b 510.5 621.2 677.0 CEM 1 + Kmt2a 587.1 637.3 684.3 Top 10 Genes Kat6a 1044.6 1331.7 1430.9 Asxl1 459.1 523.6 597.6 Casc3 600.3 697.7 730.4 Zc3h4 364.8 415.7 444.8

Null module Smarcb1 GEO Series "GSE37676" 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=GSE37676 Status: Public on May 02 2012 Title: Expression data from control and Ascorbic Acid (AA) stimulated Mc-3T3-E1 osteoblasts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23740245 Summary & Design: Summary: Despite advances in investigating functional aspects of osteoblast (OB) differentiation, especially studies on how bone proteins are deposited and mineralized, there has been little research on the intracellular trafficking of bone proteins during OB differentiation. Collagen synthesis and secretion is markedly upregulated upon Ascorbic Acid (AA) stimulation. Understanding the mechanism by which collagen is mobilized in specialized OB cells is important for both basic cell biology and diseases involving defects in bone secretion and deposition. RabGTPases are major regulators on protein trafficking throughout the cell. In this study, we identified the Rab GTPases that are upregulated during 5-day AA differentiation of OBs using microarray analysis, namely Rab1, Rab3d and Rab27b.

We used microarrays to detail the global programme of gene expression underlying procollagen production and trafficking and identified up-regulated genes during this process.

Overall design: Control Mc3T3-E1 cells and 5 day Ascorbic Acid stimulated cells were processed for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0412, L1-Distance = 0.0308, L2-Distance = 0.0013, Normal std = 0.6247

0.679 Kernel fit Pairwise Correlations Normal fit

Density 0.339

0.000 CEM 1

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

Pre-normalization Quantiles

Mc3T3 control_Mc3T3 control_Mc3T3 5day_rep1 control_Mc3T3 5day_rep2 (0.172534) AA_Mc3T3 5day_rep3 5day_rep1(0.156876) AA_Mc3T3 5day_rep2(0.242937) AA_ (0.224736) 5day_rep3 (0.102669) (0.100248)[ min ] [ medium ] [ max ] CEM 1 Arid1a 239.1 304.5 353.3 P ( S | Z, I ) = 1.00 Smarca4 2167.1 2566.1 2845.2 Mean Corr = 0.76722 Crebbp 371.6 477.5 621.2 Smarcc1 2253.3 2955.7 3318.4 Smarcc2 679.2 864.4 1041.8 Ep300 1635.9 1811.2 2161.6 Trrap 1386.3 1546.5 1750.7 Polr2a 2583.8 4126.4 4472.9 Ylpm1 1065.9 1187.1 1319.8 Ep400 1095.3 1262.4 1327.5 Kmt2b 513.2 696.0 738.7 CEM 1 + Kmt2a 342.0 501.2 660.2 Top 10 Genes Kat6a 1186.0 1369.4 1660.5 Asxl1 766.0 999.4 1254.6 Casc3 897.6 992.1 1128.6 Zc3h4 732.6 874.5 883.7

Null module Smarcb1 GEO Series "GSE19403" 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=GSE19403 Status: Public on Dec 10 2009 Title: Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21706018 Summary & Design: Summary: The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that …50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that ˛†-catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt˛†-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of β-catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt˛†-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.

Overall design: 12 samples total. Two variables in the experiment: genotype (wild type or Olig2cre/DA-Cat) and Developmental stage (Day 4 or Day 15). 4 phenotypes in total with 3 biological replicates for each phenotype.

Background corr dist: KL-Divergence = 0.0423, L1-Distance = 0.0614, L2-Distance = 0.0055, Normal std = 0.6512

0.693 Kernel fit Pairwise Correlations Normal fit

Density 0.346

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

spinal cordspinal wild cordspinal type wild atcordspinal 15type wilddays, atcordspinal 15type biological Olig2cre/DA-Catdays, atcordspinal 15 biological Olig2cre/DA-Catdays, replicate cordspinal biological Olig2cre/DA-Cat replicate atcord spinal1 15 (0.0843134) days,wild replicate atcord spinal2 15 type(0.0727251) biological days,wild atatcord spinal3 15 4type(0.134415) biological days, days,wild replicate atcordspinal 4typebiological biological days, Olig2cre/DA-Cat replicate atcord spinal1 4(0.0711579)biological days, Olig2cre/DA-Catreplicate replicate cord 2 (0.098731)biological Olig2cre/DA-Catreplicate at1 3 (0.0443199) 4(0.0265244) days, replicate at2 (0.0432653) 4biological days, at3[ (0.0338311) 4biological mindays, replicate biological replicate] 1 (0.090528) replicate 2 (0.130842)[ medium3 (0.169346) ] [ max ] CEM 1 Arid1a 413.4 642.2 795.2 P ( S | Z, I ) = 1.00 Smarca4 1602.6 2607.5 3067.0 Mean Corr = 0.75919 Crebbp 451.6 585.6 719.5 Smarcc1 858.0 1170.8 1210.0 Smarcc2 1224.9 1490.8 1594.8 Ep300 623.8 797.0 927.1 Trrap 743.9 1018.4 1259.5 Polr2a 538.3 792.3 874.6 Ylpm1 777.6 1131.7 1308.6 Ep400 816.7 1022.5 1143.9 Kmt2b 480.5 634.4 763.1 CEM 1 + Kmt2a 651.4 902.8 1145.3 Top 10 Genes Kat6a 1138.1 1655.0 1845.5 Asxl1 709.9 913.9 1062.5 Casc3 809.7 889.3 967.1 Zc3h4 402.0 552.2 611.0

Null module Smarcb1 GEO Series "GSE34324" 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=GSE34324 Status: Public on Feb 26 2013 Title: Gene expression by Retinoic Acid in mouse Dendritic Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23322377 Summary & Design: Summary: The purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.

Overall design:

Background corr dist: KL-Divergence = 0.0982, L1-Distance = 0.0355, L2-Distance = 0.0026, Normal std = 0.4484

0.890 Kernel fit Pairwise Correlations Normal fit

Density 0.445

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

[mDCs]_[control]_[1][mDCs]_[RA]_[1][mDCs]_[Ro]_[1] (0.104487)[mDCs]_[control+LPS]_[1] (0.0375248)[mDCs]_[RA+LPS]_[1] (0.149111)[mDCs]_[Ro+LPS]_[1][mDCs]_[control]_[2] (0.123667) [mDCs]_[RA]_[2](0.240176) [mDCs]_[Ro]_[2](0.0254159) (0.0217695)[mDCs]_[control+LPS]_[2] (0.0151337)[mDCs]_[RA+LPS]_[2] (0.0541405)[mDCs]_[Ro+LPS]_[2] (0.159821) (0.0346656) (0.0340884)[ min ] [ medium ] [ max ] CEM 1 Arid1a 344.6 568.2 980.5 P ( S | Z, I ) = 1.00 Smarca4 1944.5 2924.4 3709.4 Mean Corr = 0.75858 Crebbp 61.4 328.7 449.6 Smarcc1 327.6 993.5 1709.1 Smarcc2 534.6 1008.8 1238.7 Ep300 431.4 1699.2 2084.6 Trrap 741.9 1296.0 2133.3 Polr2a 485.1 1363.1 2054.6 Ylpm1 263.2 799.4 1024.0 Ep400 861.0 1222.2 1822.1 Kmt2b 686.2 1169.3 1479.3 CEM 1 + Kmt2a 640.5 805.7 1173.8 Top 10 Genes Kat6a 520.4 1012.5 1143.6 Asxl1 175.6 651.7 931.4 Casc3 626.0 948.0 1118.3 Zc3h4 297.2 929.1 1216.0

Null module Smarcb1 GEO Series "GSE18742" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18742 Status: Public on Dec 17 2010 Title: Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-null Embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20392836 Summary & Design: Summary: MEG3 (Maternally Expressed Gene 3) is a non-coding RNA that is highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically non-functioning pituitary adenomas. Meg3 knock-out mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type litter-mate controls using microarray analysis. Microarray data were analyzed with GeneSifter which uses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) classifications to identify signaling cascades and functional categories of interest within the data set. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knock-out embryos. Quantitative RT-PCR and histological staining showed increased expression of some VEGF pathway genes and increased cortical microvessel density in the knock-out embryos. These results are consistent with reported increases in VEGF signaling observed in human clinically non-functioning pituitary adenomas. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor by preventing angiogenesis.

Overall design: biological replicate: 148_15 KO, 219_12 KO, 238_1 KO, 238_5 KO, 250_1 KO, 250_3 KO, 262_1 KO

Background corr dist: KL-Divergence = 0.1145, L1-Distance = 0.0270, L2-Distance = 0.0012, Normal std = 0.4164

0.958 Kernel fit Pairwise Correlations Normal fit

Density 0.479

0.000 CEM 1

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

Pre-normalization Quantiles

E18.5 brain,E18.5 wild-type, brain,E18.5 wild-type, brain, E18.5rep 1 wild-type, (0.185486)brain, E18.5rep 2 wild-type, (0.0703449)brain, E18.5rep 3 wild-type, (0.0236634)brain, E18.5rep 4 wild-type, (0.0256249)brain, E18.5rep 5 Meg3 (0.0441951)brain, E18.5rep knock-out, 6 Meg3 (0.196564)brain,E18.5 knock-out, Meg3 brain, repE18.5 knock-out,1 Meg3(0.152857) brain, repE18.5 knock-out,2 Meg3(0.0129745) brain, repE18.5 knock-out,3 Meg3(0.0716459) brain, rep knock-out,4 Meg3(0.0377915) rep knock-out,5 (0.0233909) rep 6 (0.0460496) rep[ min 7 (0.109412) ] [ medium ] [ max ] CEM 1 Arid1a 1835.3 3004.6 3763.9 P ( S | Z, I ) = 1.00 Smarca4 5218.7 6831.6 9193.2 Mean Corr = 0.75672 Crebbp 754.9 1118.9 1527.5 Smarcc1 1209.2 1899.5 2485.6 Smarcc2 2238.2 3480.7 4434.1 Ep300 783.9 1264.9 1765.4 Trrap 968.4 1635.9 1849.7 Polr2a 410.0 772.2 1484.0 Ylpm1 875.3 1145.6 1611.4 Ep400 982.5 1416.4 1628.6 Kmt2b 708.4 1172.5 1675.9 CEM 1 + Kmt2a 761.0 1040.9 1491.1 Top 10 Genes Kat6a 1698.1 2124.8 2336.0 Asxl1 1281.5 1736.6 1919.8 Casc3 1008.3 1247.7 1591.1 Zc3h4 1024.1 1300.9 1840.6

Null module Smarcb1 GEO Series "GSE23398" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23398 Status: Public on Sep 18 2012 Title: IL-2 regulated genes in scurfy CD4+ T-cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21169543 Summary & Design: Summary: The goal of the study was to identify the genes which are regulated by Interleukin-2 in the CD4+ T cells of the scurfy mice during regulatory T-cell deficiency. Scurfy (Sf) mice bear a mutation in the forkhead box P3 (Foxp3) transcription factor, lack regulatory T-cells (Treg), develop multi-organ inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. Sf mice lacking the Il2 gene (Sf.Il2-/-), despite devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver, pancreas, submandibular gland and colon remained. Genome-wide microarray analysis revealed hundreds of genes were differentially regulated among Sf, Sf.Il2-/-, and B6 CD4+ T-cells but the most changes were those encoding receptors for trafficking/chemotaxis/retention and lymphokines. Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice in an apparent ""organ-specific"" manner through two novel mechanisms: by regulating the expression of genes encoding receptors for T-cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and lymphokine production. Thus, IL-2 is a master regulator for multi-organ inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation.

Methods: CD4+ T cells were purified by Fluorescence Assisted Cell Sorting from the peripheral lymph nodes of (A) three individual Scurfy (Sf; B6.Cg-Foxp3sf/J) male mice, (B) three individual Sf.Il2-/- male mice (Scurfy mice carrying a null Interleukin (IL)-2 gene (B6.129P2-Il2tm1Hor/J)) and (C) a pooled sample of lymph nodes from two B6 (C57BL/6J) mice. All the mice were 3 weeks old. Total RNA was prepared using RNeasy mini kit (Qiagen). RNA samples were converted to cRNA, labeled and hybridized to Affymetrix Mouse 430_2 chips (Mouse Genome 430 2.0 Array, Affymetrix, Santa Clara, CA) at the University of Virginia DNA Sciences Core Facility.

Overall design: 3. RNA from CD4+ T cells purified from peripheral lymph nodes of Sf.Il2-/- mice - 3 biological replicates.

Background corr dist: KL-Divergence = 0.0394, L1-Distance = 0.0267, L2-Distance = 0.0011, Normal std = 0.6124

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.326

0.000 CEM 1

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

Pre-normalization Quantiles

B6-CD4-LN-BiologicalScurfy-CD4-LN-BiologicalScurfy-CD4-LN-Biological Scurfy-CD4-LN-BiologicalreplicateSf.Il2-/--CD4-LN-Biological 1 (0.447258)replicateSf.Il2-/--CD4-LN-Biological replicate 1 Sf.Il2-/--CD4-LN-Biological(0.052494) replicate 2 (0.12226) replicate 3 (0.0696801) replicate 1 (0.0740769) replicate 2 [(0.102034) min 3 (0.132197) ] [ medium ] [ max ] CEM 1 Arid1a 1737.9 2413.8 7241.2 P ( S | Z, I ) = 1.00 Smarca4 1729.3 2003.8 3122.6 Mean Corr = 0.75622 Crebbp 386.4 454.3 579.7 Smarcc1 1291.9 1568.1 1937.0 Smarcc2 600.9 694.5 1206.5 Ep300 1711.2 2293.9 3539.6 Trrap 891.0 1234.0 1805.2 Polr2a 1850.7 2150.0 3237.1 Ylpm1 1042.3 1249.5 1958.1 Ep400 1299.1 1542.1 2286.2 Kmt2b 1446.1 1857.1 4625.0 CEM 1 + Kmt2a 1382.0 1558.1 2521.7 Top 10 Genes Kat6a 1879.9 2132.2 3858.8 Asxl1 1285.5 1591.4 1629.8 Casc3 1261.8 1496.4 2713.9 Zc3h4 1569.2 1912.1 2643.9

Null module Smarcb1 GEO Series "GSE17728" 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=GSE17728 Status: Public on May 26 2012 Title: Blood gene expression profile from mouse C57Bl/10 exposed to chronic hypoxia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22629407 Summary & Design: Summary: In order to study the gene expression profile in C57Bl/10 mouse blood, we exposed three different groups of animals. First was exposed to PO2 21% or normoxia. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. The blood was extracted from inferior vena cava, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.

Overall design: Each group of C57Bl/10 mouse had 4 individuals and they were divided into three different groups of animals. First was exposed to PO2 21% or normoxia for 14 days. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. After the exposure period, the animals were anaesthetized with a mix of Ketamine (100 mg/mL) and xylasine (20 mg/mL) in a proportion of 1:1. A incison was made on abdominal area and from kidneis and liver area of inferior vena cava venus blood was collected The blood was extracted from inferior vena cava. Then, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.

Background corr dist: KL-Divergence = 0.0545, L1-Distance = 0.0470, L2-Distance = 0.0038, Normal std = 0.5640

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

Blood C57Bl/10Blood C57Bl/10Blood mouse C57Bl/10Blood normoxiamouse C57Bl/10Blood normoxiamouse sample C57Bl/10Blood normoxicmouse sample1 (0.1039) C57Bl/10Blood normoxicmouse sample2 (0.102658) C57Bl/10Blood normobaricmouse sample3 (0.163957) C57Bl/10Blood normobaricmouse 4 hypoxia(0.089259) C57Bl/10Blood normobaricmouse hypoxia C57Bl/10sampleBlood normobaricmouse hypoxia C57Bl/10 sample1Blood recoverymouse(0.167362) hypoxia C57Bl/10 sample2 recoverymouse(0.118851) sample sample3 recoverymouse(0.0296712) sample1 (0.0425488) 4 recovery(0.102789) sample2 (0.0425933)[ minsample3 (0.0229047) 4 ](0.0135055) [ medium ] [ max ] CEM 1 Arid1a 89.2 545.7 1027.9 P ( S | Z, I ) = 1.00 Smarca4 508.5 839.2 1106.0 Mean Corr = 0.74844 Crebbp 14.8 949.7 1797.7 Smarcc1 231.0 490.7 633.9 Smarcc2 215.1 686.2 1235.1 Ep300 985.1 1760.5 3609.8 Trrap 40.9 466.3 1106.5 Polr2a 631.7 2374.3 3024.1 Ylpm1 431.1 637.2 1015.7 Ep400 680.6 1219.0 1807.0 Kmt2b 113.7 499.2 860.7 CEM 1 + Kmt2a 891.9 1619.8 5613.0 Top 10 Genes Kat6a 333.8 1702.1 2930.1 Asxl1 284.2 638.5 1201.6 Casc3 396.3 1531.9 2109.0 Zc3h4 685.7 2678.6 3482.4

Null module Smarcb1 GEO Series "GSE11149" 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=GSE11149 Status: Public on May 06 2008 Title: Cranial neural crest cells of E11.5 wild type and FAK mutants (valle-affy-mouse-480721) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Cranial neural crest cells (NCC) give rise to the majority of the cartilage, bone, connective tissue, and sensory ganglia in the head, and also participate in the remodeling of the cardiac outflow tract and pharyngeal arch arteries during cardiovascular development. Our preliminary results show that targeted deletion of focal adhesion kinase (FAK) in murine NCC results in cardiovascular and craniofacial alterations, resembling human congenital heart diseases The objective of this project is to elucidate the underlying mechanisms by which FAK mediates NCC function during development.

Compare gene expression in cranial neural crest cells of E11.5 wild type and FAK mutants.

FAK is a tyrosine kinase that transduces integrin and growth factor signaling pathways. Abnormal growth factor signaling leads to cardiovascular malformations caused by deficient cardiac NCC function. However, a direct role for FAK in NCC morphogenesis has not been demonstrated. We will test the hypothesis that FAK is a downstream target of essential growth factor signaling in cranial neural crest cells during development.

1) Generate E11.5 mouse embryos that are either control (FAK+/flox) or NCC specific FAK knockout (Wnt1Cre;FAKflox/flox). 2) Determine genotype by PCR. 3) Dissect head and torax from the different genotypes. 4) Obtain NCC from dissected tissue by magnetic cell sorting using p75 antibody. 5) Prepare total RNA from speciments. We will pool the NCC from 3 different embryos of the same genotype, and send total RNA to TGEN for probe preparation, hybridization and array result analysis.

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0369, L2-Distance = 0.0019, Normal std = 0.6042

0.691 Kernel fit Pairwise Correlations Normal fit

Density 0.345

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

head/neck:head/neck: E11.5FAKMut_le1head/neck: E11.5FAKCtls_le1head/neck: LM_Control_e1_le1 head/neck:(0.324439) LM_Mutant_e1_le1 head/neck:(0.105188) OFT_Control_e1_le1head/neck: (0.121684) OFThead/neck: (0.0786523)_Mutant_e1_le1 UM_Control_e1_le1 (0.112323) UM_Mutant_e1_le1 (0.0281324) (0.0843183)[ (0.145263) min ] [ medium ] [ max ] CEM 1 Arid1a 1188.2 1501.8 1854.5 P ( S | Z, I ) = 1.00 Smarca4 2861.5 3912.9 10781.1 Mean Corr = 0.73648 Crebbp 700.0 1004.8 2208.8 Smarcc1 3859.3 4957.3 8592.6 Smarcc2 597.3 867.3 1603.8 Ep300 1081.1 1623.8 1908.6 Trrap 1489.2 2193.3 3184.4 Polr2a 783.2 1070.8 2508.7 Ylpm1 1460.7 1505.7 2549.5 Ep400 1404.4 1829.8 5107.2 Kmt2b 580.7 879.1 1837.3 CEM 1 + Kmt2a 554.2 797.3 923.9 Top 10 Genes Kat6a 1474.2 2124.8 2850.1 Asxl1 1504.8 1998.3 3177.1 Casc3 737.7 1000.4 1885.5 Zc3h4 828.2 1353.1 2583.5

Null module Smarcb1 GEO Series "GSE23408" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 39 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23408 Status: Public on Aug 02 2011 Title: Global gene expression profiles and the progression of pro- and anti-inflammatory pathways in mouse models Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Gaucher Disease (GD) is caused by defective glucocerebrosidase (GCase) activity and the consequent accumulation of its substrate, glucosylceramide (GC). This excess of accumulation of GC leads to broad functional impairments in multiple organs, but the pathogenic pathways leading to lipid laden macrophages (Gaucher cells) in visceral organs and their abnormal function is obscure. To understand the molecular pathogenesis of GD, developmental global gene expression was conducted by microarray analyses of total mRNAs from lung and liver of two distinct GCase point-mutated mice (V394L/V394L and D409V/null) and genetic background matched wild-type controls. INFg regulated pro-inflammatory and IL-4 regulated anti-inflammatory cytokine/mediator network were constructed in the lung and liver of GCase mutant mice. Progressive alterations of the INFg and IL-4 pathways were similar, but to different degrees, in visceral tissues from the two different GCase mutated mice. These analyses implicate IFNg regulated pro-inflammatory and IL-4 regulated anti-inflammatory networks in the differential pathophysiological progression.

Overall design: In order to understand the molecular pathogenesis of GD, the disease progression in those models were inverstigated in two visceral tissues (lung and liver) at four time points according to the genotypes. 9V/null: 4 weeks (4w), 12 weeks (12w), 18 weeks (18w), 28 weeks (28w); 4L: weeks (4w), 12 weeks (12w), 18 weeks (18w), 28 weeks (28w). The data from those models were analyzed relative to the adult wild type at 28 weeks.

Background corr dist: KL-Divergence = 0.0891, L1-Distance = 0.0753, L2-Distance = 0.0105, Normal std = 0.4948

0.925 Kernel fit Pairwise Correlations Normal fit

Density 0.463

0.000 CEM 1

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

Pre-normalization Quantiles

lung_9V/null_lung_9V/null_ 4w_rep1lung_9V/null_ 4w_rep2lung_9V/null_ (0.0761611) 12w_rep1lung_9V/null_ (0.0794301) 12w_rep2lung_9V/null_ (0.0248412) 18w_rep1lung_9V/null_ (0.0574667) 18w_rep2lung_9V/null_ (0.00926617) 28w_rep1liver_9V/null_ (0.0124497) 28w_rep2liver_9V/null_ (0.00607414) 4w_rep1liver_9V/null_ (0.00566984) 4w_rep2liver_9V/null_ (0.00658679) 12w_rep1liver_9V/null_ (0.00761874) 12w_rep2liver_9V/null_ (0.00883541) 18w_rep1liver_9V/null_ (0.0240204) 18w_rep2liver_9V/null_ (0.0409769) 28w_rep1lung_4L_ (0.0212108) 28w_rep2lung_4L_ (0.0525936)4w_rep1lung_4L_ (0.0759681)4w_rep2 (0.00300948)lung_4L_ 12w_rep1 (0.00637645)lung_4L_ 12w_rep2 (0.00841026)lung_4L_ 18w_rep1 (0.00821087)lung_4L_ 18w_rep2 (0.005965)lung_4L_ 28w_rep1 (0.0501259)liver_4L_ 28w_rep2 (0.00618273)liver_4L_ 4w_rep1 (0.0245679)liver_4L_ 4w_rep2 (0.0248746)liver_4L_ 12w_rep1 (0.00523876)liver_4L_ 12w_rep2 (0.0143265)liver_4L_ 18w_rep1 (0.0127044)liver_4L_ 18w_rep2 (0.00889167)liver_4L_ 28w_rep1 (0.0181973)lung_WT_ 28w_rep2 (0.0209442)lung_WT_ 28w_rep1 (0.0188369)lung_WT_ 28w_rep2 (0.0347802)lung_WT_ 28w_rep3 (0.0316083)liver_WT_ 28w_rep4 (0.0575463)liver_WT_ 28w_rep1 (0.0531881)liver_WT_ 28w_rep2 (0.0158586) 28w_rep3 (0.0299018) (0.0310842)[ min ] [ medium ] [ max ] CEM 1 Arid1a 306.8 897.6 2812.6 P ( S | Z, I ) = 1.00 Smarca4 782.5 1934.0 3076.2 Mean Corr = 0.73526 Crebbp 38.9 395.8 1032.4 Smarcc1 395.0 805.0 1713.4 Smarcc2 544.0 1088.3 1986.3 Ep300 384.3 902.0 2974.0 Trrap 255.1 728.4 1387.1 Polr2a 184.7 824.1 3530.8 Ylpm1 254.8 483.8 1023.7 Ep400 298.4 713.8 1851.1 Kmt2b 319.7 776.2 1726.2 CEM 1 + Kmt2a 156.6 363.2 1280.6 Top 10 Genes Kat6a 340.1 717.0 3211.1 Asxl1 312.8 997.0 2082.3 Casc3 318.6 788.1 1365.5 Zc3h4 313.7 735.5 1368.5

Null module Smarcb1 GEO Series "GSE26668" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26668 Status: Public on Mar 23 2011 Title: Expression data from E13.5 Fz4-/-Fz8-/- and Fz4+/+Fz8-/- kidneys Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21343368 Summary & Design: Summary: Fz4 and Fz8 cooperate in regulating the branching morhpogenesis of the developing kidney during mouse embryonic development, hence determines the eventual kidney size.

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

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

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

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

Fz4Fz8 Fz4Fz8DKO C1 Fz4Fz8DKO (0.180542) C2 Fz4Fz8DKO (0.0571419) C3 Fz4Fz8DKO (0.115199) M1 Fz4Fz8DKO (0.220146) M2 DKO (0.342613) M3 (0.0843591) [ min ] [ medium ] [ max ] CEM 1 Arid1a 328.5 754.9 949.1 P ( S | Z, I ) = 1.00 Smarca4 1228.2 1890.6 2131.4 Mean Corr = 0.72709 Crebbp 1661.6 2290.8 2487.7 Smarcc1 1294.5 2215.6 2676.1 Smarcc2 1015.5 1507.0 1536.8 Ep300 1157.1 1394.3 1597.6 Trrap 914.8 1817.3 1958.1 Polr2a 1435.8 2157.7 2620.8 Ylpm1 845.2 1172.7 1314.6 Ep400 1151.8 1379.9 1575.0 Kmt2b 347.2 540.1 728.5 CEM 1 + Kmt2a 972.1 1571.3 1629.5 Top 10 Genes Kat6a 1860.5 2442.2 3174.2 Asxl1 924.9 1121.4 1178.3 Casc3 1584.5 2033.7 2490.0 Zc3h4 3053.6 3545.1 4099.9

Null module Smarcb1 GEO Series "GSE8025" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 21 -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=GSE8025 Status: Public on Dec 01 2007 Title: Diarrhea as a Cause of Mortality in a Mouse Model of Infectious Colitis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Examination of host genome-wide changes upon encounters with pathogens provides insight into the pathogenesis of infection and disease. When performed comparatively, it may shed light on the mechanisms underlying host susceptibility. In this study, gene expression in the mouse colon was investigated in two cognate lines of mice that differ in their response to Citrobacter rodentium infection; susceptible inbred FVB/N (FVB) and resistant outbred Swiss Webster (SW) mice. Gene expression in the distal colon was investigated prior to infection and at 4 and 9 days post-inoculation using a whole mouse genome Affymetrix array. Computational analysis identified 462 (1%) probe sets differentially expressed by more than 2-fold between uninoculated SW and FVB mice. In response to C. rodentium infection, 5,123 probe sets (11.4%) were significantly modulated in one or both lines of mice. Microarray data were validated by quantitative real time RT-PCR on 35 selected genes (r = 0.87, p < 0.001) and were found to have a 94% concordance. Transcripts represented by 1,547 probe sets (3.4%), were differentially expressed between FVB and SW mice regardless of infection status (host effect). Genes associated with transport were over-represented to a greater extent than immune response-related genes (25% vs. 11% of enrichment, respectively). Electrolyte analysis revealed hypochloremia and hyponatremia in susceptible animals. The results support the hypothesis that mortality in C. rodentium-infected FVB mice is associated with impaired ion transport and development of fatal hypovolemia. These studies contribute to our understanding of the pathogenesis of C. rodentium and suggest novel strategies for the prevention and treatment of diarrhea associated with bacterial infections of the intestinal tract.

Keywords: temporal change (post infection)

Overall design: Global gene expression analysis was performed on the distal colon with 2-3 mice per group. Because no difference for any parameters was observed in uninfected mice at 4 or 9 dpi, the animals were pooled into an uninoculated control groups for each line of mouse. The selection of representative samples for microarray analysis was based on known infection status and colonic lesions. The final number of biological replicates for each condition was n = 5 for uninoculated FVB mice (Fp group), n = 4 for uninoculated SW mice (Sp group), and n = 3 for infected animals from each line at each time point (Fi4, Si4, Fi9, and Si9 respectively).

Background corr dist: KL-Divergence = 0.1088, L1-Distance = 0.0280, L2-Distance = 0.0012, Normal std = 0.4228

0.944 Kernel fit Pairwise Correlations Normal fit

Density 0.472

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

F4_1, mouse,F4_2, mouse,FVB,F9_1, control mouse,FVB,F9_2, control(non-infected), mouse,FVB,F9_3, control(non-infected), mouse,FVB,Fi4_1, control (non-infected), 4 FVB,mouse, dayFi4_2, timecontrol (non-infected), 4 mouse, FVB,dayFi4_3, matched time (non-infected),infected, 9 mouse, FVB,dayFi9_1, matched control_rep time infected, 9 mouse, FVB,day4Fi9_2, matcheddays control_rep time infected, 9 mouse, FVB,postday4Fi9_3, 1 matcheddays (0.011579) control_rep time infection_repinfected, mouse, FVB,post4S4_1, 2 matcheddays (0.0107006) control_rep infection_repinfected, mouse, FVB,post9S4_2, 1 days (0.0164506) control_rep1 infection_rep infected,(0.0383349) mouse, SW, post9S9_1, 2 days (0.0658968) 2control infection_rep (0.0442317) mouse, SW, post9S9_2, 3 days (0.040286) 3control(non-infected), infection_rep (0.0992617) mouse, SW,postSi4_1, 1control(non-infected), infection_rep (0.0443183) SW,mouse,Si4_2, 2control (non-infected), 4(0.112409) daymouse,SW,Si4_3, time3 (non-infected),infected, 4(0.0257013) daymouse,SW,Si9_1, matched time infected, 9 daymouse,4SW,Si9_2, matcheddays control_rep time infected, 9 post daymouse,4SW,Si9_3, matcheddays control_rep time infection_repinfected, post mouse,4SW,1 matcheddays (0.0425899) control_rep infection_repinfected, post 9SW,2 days (0.057812) control_rep1 infection_rep infected,(0.0187361) post9 1 days (0.109039) 2 infection_rep (0.0510361) post9 2[ days (0.050038) min3 infection_rep (0.0861461) post 1 infection_rep ](0.0335271) 2 (0.0133016) 3[ (0.0286036)medium ] [ max ] CEM 1 Arid1a 681.0 1039.5 1612.4 P ( S | Z, I ) = 1.00 Smarca4 947.3 1494.8 2682.3 Mean Corr = 0.72638 Crebbp 308.8 496.8 666.9 Smarcc1 294.8 482.4 978.9 Smarcc2 375.0 545.8 941.7 Ep300 1114.0 1823.9 2648.4 Trrap 369.1 816.8 1391.9 Polr2a 564.9 1143.2 1556.0 Ylpm1 463.7 769.8 1302.8 Ep400 558.1 1070.3 1357.8 Kmt2b 532.9 807.2 1089.9 CEM 1 + Kmt2a 309.1 585.6 1039.2 Top 10 Genes Kat6a 878.7 1408.8 2132.0 Asxl1 656.8 1118.3 1500.6 Casc3 640.0 903.9 1275.8 Zc3h4 416.4 664.2 943.6

Null module Smarcb1 GEO Series "GSE1074" 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=GSE1074 Status: Public on Mar 11 2004 Title: Strain-dependent effects of alcohol on early mouse embryos Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17200951 Summary & Design: Summary: EXPERIMENT: Microarray expression profiles derived from the cranial neural folds (headfold) of neurulation-stage mouse embryos 3.0h after maternal alcohol exposure on 8 d.p.c.

ANIMAL MODEL: Pregnancies from 2 substrains of C57BL/6 mice that differ in relative risk of Fetal Alcohol Syndrome (FAS): C57BL/6J (B6J) high-risk condition, and C57BL/6NCrl (B6N) low-risk condition.

EXPOSURE: Dams dosed with ethanol (EtOH) by intraperitoneal injection at 2.9 g EtOH per kg body weight. Controls received vehicle (saline) alone. A third group of dams received EtOH + 4.0 mg/kg PK11195, a specific high-affinity ligand to the 18 KDa mitochondrial peripheral benzodiazepine receptor site.

INTERVAL: High blood alcohol content must be sustained in dams for several hours to invoke FAS and is traditionally accomplished by a double injection of EtOH 4.0h apart. Since these embryos were harvested for genetic analysis 1h before dams would have gotten the second alcohol injection, the interval represents a snapshot of the critical response, prior to the second maternal injection that invokes greater risk. Counter-exposure to PK11195 significantly lowers the adverse response of B6J embryos to EtOH.

PLATFORM: Two independent assays run. The first dataset (PE), run April 2002 January 2003, used samples pooled from 2 litters (PE) and the platform was a two-channel MPS621 array (http://www.lifesciences.perkinelmer.com/). This platform has 4800 sequence-verified gene elements derived from over 50 different human cDNA libraries reflecting a variety of well-annotated cellular processes and disease pathways. The second dataset (AF), run between May 2005 November 2005, used samples pooled from 1 litter and the platform was Affymetrix GeneChip® Mouse Genome 430A 2.0 Array (http://www.affymetrix.com/). The MG430A 2.0 platform has 45,102 oligonucleotide probe cells representing approximately 14,000 well-characterized genes in the draft mouse genome assembly. The corresponding GEO samples are GSM12218 - GSM12227 for the two-channel PE arrays, and GSM136067 - GSM136078 for the one-channel AF arrays.

Keywords = fetal alcohol syndrome

Keywords = alcohol-related birth defects

Keywords = EtOH

Keywords = PK11195

Keywords = embryo

Keywords = strain differences

Keywords: Ordered

Overall design: Assay of early mouse embryos during pathogenesis of Fetal Alcohol Syndrome (FAS). Replicate RNA samples were arrayed by one-channel oligonucleotide (Affymetrix) or two-channel cDNA (Perkin-Elmer) platforms.

Background corr dist: KL-Divergence = 0.0731, L1-Distance = 0.0209, L2-Distance = 0.0005, Normal std = 0.4915

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

B6J embryo,B6J embryo, salineB6J embryo,control-6J-SAL-1 salineB6J embryo,control-6J-SAL-2 alcoholB6J embryo, alcoholexposure-6J-EtOH-1 B6J(0.392959) embryo, alcoholexposure-6J-EtOH-2 B6N(0.0345686) embryo, alcohol&B6N PK11195-6J-CoT-1 (0.0365779)embryo, saline&B6N PK11195-6J-CoT-2 (0.11453)embryo,control-6N-SAL-1 salineB6N embryo,(0.116875)control-6N-SAL-2 alcoholB6N embryo,(0.0270146) alcoholexposure-6N-EtOH-1B6N (0.080138) embryo, alcohol-PK11195exposure-6N-EtOH-2 (0.0893049) alcohol-PK11195 (0.0498913) counterexposure-6N-CoT-1 (0.0200838)[ counterexposure-6N-CoT-2 min ] (0.0110817)[ medium (0.0269747) ] [ max ] CEM 1 Arid1a 584.3 694.4 766.3 P ( S | Z, I ) = 1.00 Smarca4 826.9 890.4 925.9 Mean Corr = 0.70840 Crebbp 602.0 683.7 713.3 Smarcc1 815.7 953.2 979.6 Smarcc2 508.2 556.3 587.9 Ep300 718.7 804.2 827.1 Trrap 722.3 778.8 827.6 Polr2a 714.9 767.2 818.6 Ylpm1 741.7 799.7 822.6 Ep400 769.4 825.2 841.0 Kmt2b 675.3 694.6 713.2 CEM 1 + Kmt2a 579.9 652.5 708.0 Top 10 Genes Kat6a 723.2 773.5 783.4 Asxl1 740.3 867.8 886.9 Casc3 703.2 740.7 758.8 Zc3h4 727.6 771.3 783.5

Null module Smarcb1 GEO Series "GSE9146" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 27 -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=GSE9146 Status: Public on Apr 04 2008 Title: Irradiation response in PKBalpha MEF Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18439899 Summary & Design: Summary: MEF proficient or deficient in PKBalpha, or PKBalpha knockout MEF where PKBalpha expression was reconstituted by stable transfection were subjected to 10Gy gamma-IR treatment. 4 or 24 hours after treatment, gene expression changes were analyzed.

Keywords: genotype0-specific stress response in PKBalpha MEF

Overall design: three biological replicates were included in the experiment for each condition analyzed. overall, 27 samples were included in the study. the reference samples were untreated MEF of each respective genotype.

Background corr dist: KL-Divergence = 0.2065, L1-Distance = 0.0377, L2-Distance = 0.0026, Normal std = 0.3367

1.192 Kernel fit Pairwise Correlations Normal fit

Density 0.596

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

bh20061215m430v2_U_02_PKBa-MEF-WT_-_1bh20061215m430v2_U_01_PKBa-MEF-WT_-_0bh20061215m430v2_U_03_PKBa-MEF-WT_-_2bh20061215m430v2_U_04_PKBa-MEF-WT_4h_0bh20061215m430v2_U_05_PKBa-MEF-WT_4h_1bh20061215m430v2_U_06_PKBa-MEF-WT_4h_2bh20061215m430v2_U_07_PKBa-MEF-WT_24h_0 (0.0157608)bh20061215m430v2_U_08_PKBa-MEF-WT_24h_1 (0.0121341)bh20061215m430v2_U_09_PKBa-MEF-WT_24h_2 (0.156259)bh20061215m430v2_U_10_PKBa_-_-_MEF_-_0 (0.0344499)bh20061215m430v2_U_11_PKBa_-_-_MEF_-_1 (0.00864261)bh20061215m430v2_U_12_PKBa_-_-_MEF_-_2 (0.0448141)bh20061215m430v2_U_13_PKBa_-_-_MEF_4h_0 (0.0248684)bh20061215m430v2_U_14_PKBa_-_-_MEF_4h_1 (0.0294089)bh20061215m430v2_U_15_PKBa_-_-_MEF_4h_2 (0.0240983)bh20061215m430v2_U_16_PKBa_-_-_MEF_24h_0 (0.00437189)bh20061215m430v2_U_17_PKBa_-_-_MEF_24h_1 (0.0124304)bh20061215m430v2_U_18_PKBa_-_-_MEF_24h_2 (0.153911)bh20061215m430v2_U_19_PKBa_-_-_R_MEF_-_0 (0.0074435)bh20061215m430v2_U_20_PKBa_-_-_R_MEF_-_1 (0.00424789)bh20061215m430v2_U_21_PKBa_-_-_R_MEF_-_2 (0.00751005)bh20061215m430v2_U_22_PKBa_-_-_R_MEF_4h_0 (0.0247293)bh20061215m430v2_U_23_PKBa_-_-_R_MEF_4h_1 (0.017936)bh20061215m430v2_U_24_PKBa_-_-_R_MEF_4h_2 (0.00468159)bh20061215m430v2_U_25_PKBa_-_-_R_MEF_24h_0 (0.0123226)bh20061215m430v2_U_26_PKBa_-_-_R_MEF_24h_1 (0.15475)bh20061215m430v2_U_27_PKBa_-_-_R_MEF_24h_2 (0.0146266) (0.0519192) (0.0168179) (0.0419221)[ min (0.0321432) ] (0.0292681) (0.0585332)[ medium ] [ max ] CEM 1 Arid1a 604.3 830.0 1885.5 P ( S | Z, I ) = 1.00 Smarca4 3144.2 3784.8 5962.3 Mean Corr = 0.70197 Crebbp 262.0 446.6 1130.1 Smarcc1 3149.7 4670.8 7729.9 Smarcc2 351.7 488.7 1541.1 Ep300 557.4 832.1 1363.1 Trrap 858.9 1214.3 3786.8 Polr2a 687.7 1069.6 3108.2 Ylpm1 561.1 769.5 1208.2 Ep400 974.9 1477.6 2306.2 Kmt2b 378.3 613.8 1354.3 CEM 1 + Kmt2a 522.7 816.0 2383.4 Top 10 Genes Kat6a 1088.2 1560.8 2382.6 Asxl1 997.1 1173.0 2376.8 Casc3 628.9 1048.0 2320.7 Zc3h4 727.9 1166.4 1617.8

Null module Smarcb1 GEO Series "GSE16675" 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=GSE16675 Status: Public on Nov 17 2010 Title: The influence of segmental copy number variation on tissue transcriptomes through development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21084671 Summary & Design: Summary: A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes mapping within. They were shown to also affect the expression of genes located on their flanks, sometimes at great distance. Here, we show by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained throughout life. However, we find that some brain-expressed genes appear to be under compensatory loops only at specific time-points, indicating that the influence of CNVs on these genes is modulated through development. We also observe that CNV genes are significantly enriched upon transcripts that show variable time-course of expression in different strains. Thus modifying the number of copy of a gene not only potentially alters its expression level, but possibly also its time of expression.

Keywords: comparative genomic

Overall design: Expression from brain and liver tissues from C57BL/6J, DBA2/J and 129S2 mouse strains at different developmental time points.

Background corr dist: KL-Divergence = 0.0580, L1-Distance = 0.0593, L2-Distance = 0.0060, Normal std = 0.5608

0.711 Kernel fit Pairwise Correlations Normal fit

Density 0.356

0.000 CEM 1

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

Pre-normalization Quantiles

129_E14.5_brain_rep1129_E14.5_brain_rep2129_E14.5_brain_rep3 B6_E14.5_brain_rep1(0.0695522) B6_E14.5_brain_rep2(0.0902328) B6_E14.5_brain_rep3(0.014475) (0.0114344)D2_E14.5_brain_rep1 (0.0397833)D2_E14.5_brain_rep2 (0.0438548)D2_E14.5_brain_rep3 (0.0386224)129_E14.5_liver_rep1 (0.0316926)129_E14.5_liver_rep2 (0.0655747)129_E14.5_liver_rep3 (0.00865111)B6_E14.5_liver_rep1 (0.0161716)B6_E14.5_liver_rep2 (0.00490385)B6_E14.5_liver_rep3 (0.00738352)D2_E14.5_liver_rep1 (0.00843238)D2_E14.5_liver_rep2 (0.00612291)D2_E14.5_liver_rep3 (0.00381947)129_P1_brain_rep1 (0.00990305)129_P1_brain_rep2 (0.00520798)129_P1_brain_rep3 (0.0139881)B6_P1_brain_rep1 (0.0102308)B6_P1_brain_rep2 (0.0172721)B6_P1_brain_rep3 (0.012295)D2_P1_brain_rep1 (0.0061625)D2_P1_brain_rep2 (0.00824724)D2_P1_brain_rep3 (0.0048782)129_P1_liver_rep1 (0.00923058)129_P1_liver_rep2 (0.0110728)129_P1_liver_rep3 (0.0113303)B6_P1_liver_rep1 (0.00925052)B6_P1_liver_rep2 (0.00770073)B6_P1_liver_rep3 (0.0101149)D2_P1_liver_rep1 (0.00837837)D2_P1_liver_rep2 (0.0095042)D2_P1_liver_rep3 (0.00687841)129_P7_brain_rep1 (0.00498858)129_P7_brain_rep2 (0.00398604)129_P7_brain_rep3 (0.00446148)B6_P7_brain_rep1 (0.00543958)B6_P7_brain_rep2 (0.00577319)B6_P7_brain_rep3 (0.0031434)D2_P7_brain_rep1 (0.00346061)D2_P7_brain_rep2 (0.0070941)D2_P7_brain_rep3 (0.00410236)129_P7_liver_rep1 (0.00419545)129_P7_liver_rep2 (0.00689094)129_P7_liver_rep3 (0.0172225)B6_P7_liver_rep1 (0.0137189)B6_P7_liver_rep2 (0.0156639)B6_P7_liver_rep3 (0.0206787)D2_P7_liver_rep1 (0.0108612)D2_P7_liver_rep2 (0.0192786)D2_P7_liver_rep3 (0.0171848)129_P90_brain_rep1 (0.0254612)129_P90_brain_rep2 (0.0186794)129_P90_brain_rep3 (0.00526462)B6_P90_brain_rep1 (0.00496478)B6_P90_brain_rep2 (0.00537512)B6_P90_brain_rep3 (0.00589712)D2_P90_brain_rep1 (0.00506095)D2_P90_brain_rep2 (0.00554673)D2_P90_brain_rep3 (0.00504919)129_P90_liver_rep1 (0.00435997)129_P90_liver_rep2 (0.00565175)129_P90_liver_rep3 (0.014145)B6_P90_liver_rep1 (0.011869)B6_P90_liver_rep2 (0.0123388)B6_P90_liver_rep3 (0.0118176)D2_P90_liver_rep1 (0.01061)D2_P90_liver_rep2 (0.010573)D2_P90_liver_rep3 (0.0122967) (0.0112096) (0.0133324)[ min ] [ medium ] [ max ] CEM 1 Arid1a 428.8 1154.2 4891.3 P ( S | Z, I ) = 1.00 Smarca4 776.9 2058.6 6566.1 Mean Corr = 0.70061 Crebbp 353.3 889.7 1399.2 Smarcc1 486.7 1162.9 4853.8 Smarcc2 612.6 1627.6 3519.2 Ep300 447.0 914.4 2249.9 Trrap 462.3 1050.9 2610.4 Polr2a 409.6 1274.5 4556.3 Ylpm1 315.5 1074.1 1567.8 Ep400 578.7 1123.5 1899.8 Kmt2b 661.8 1255.7 2777.0 CEM 1 + Kmt2a 416.3 848.6 1982.5 Top 10 Genes Kat6a 578.5 1321.5 2718.4 Asxl1 462.2 1034.2 1737.3 Casc3 417.5 1094.3 1849.2 Zc3h4 339.4 825.1 1895.9

Null module Smarcb1 GEO Series "GSE21905" 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=GSE21905 Status: Public on May 21 2010 Title: Gene expression in Lineage negative bone marrow cells of C57B/L6 and B.D(Chr5) mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: These mouse strains differ in absolute numbers of hematopoietic stem cells but differ genetically only at the Chr 5 congenic locus.

We used microarray analysis to identify candidate regulators of hematopoietic stem cells based on differential gene expression patterns.

Overall design: Triplicate RNA samples were isolated from 500,00-800,000 Lineage negative bone marrow cells from each strain. Each of the six samples were analyzed on 6 separate MG 430 2.0 Affymetrix Microarray Chips.

Background corr dist: KL-Divergence = 0.0472, L1-Distance = 0.0190, L2-Distance = 0.0004, Normal std = 0.5846

0.688 Kernel fit Pairwise Correlations Normal fit

Density 0.344

0.000 CEM 1

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

Pre-normalization Quantiles

C57B/L6C57B/L6 biologicalC57B/L6 biological repB.D(Chr5) 1 biological (0.0304799) repB.D(Chr5) 2 (0.278222)biological repB.D(Chr5) 3 (0.370887)biological rep 1 biological (0.115124) rep 2 (0.124923) rep 3 (0.0803638)[ min ] [ medium ] [ max ] CEM 1 Arid1a 1954.9 2479.7 3083.5 P ( S | Z, I ) = 1.00 Smarca4 2989.9 3709.5 4694.2 Mean Corr = 0.69266 Crebbp 423.8 539.4 656.5 Smarcc1 3182.0 3798.8 4200.9 Smarcc2 603.0 813.8 1044.2 Ep300 1358.6 1672.4 2083.3 Trrap 1236.2 1590.2 1803.1 Polr2a 833.4 1285.7 1425.6 Ylpm1 1008.1 1445.9 1568.0 Ep400 1964.4 2339.4 2512.3 Kmt2b 842.2 1061.6 1174.7 CEM 1 + Kmt2a 816.7 1187.2 1326.9 Top 10 Genes Kat6a 1639.4 2066.7 2149.6 Asxl1 1666.1 1858.9 1892.6 Casc3 774.0 919.0 978.8 Zc3h4 1134.7 1322.0 1344.8

Null module Smarcb1 GEO Series "GSE57797" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 23 -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=GSE57797 Status: Public on Jul 13 2014 Title: Expression data from the subclones of Lewis Lung Carcinoma (LLC) cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees.

Subclones 2, 3, 6 and 28 produce significantly larger amount of thermogenic activity than the subclones 18, 19, 23 and 24. We compared gene expression profiles of these subclones to identify secreted factors enriched in the more thermogenic clones.

Overall design: LLC subclones were cultured under conditioned medium preparation conditiones and total RNA was extracted from biological replicates.

Background corr dist: KL-Divergence = 0.2154, L1-Distance = 0.0344, L2-Distance = 0.0019, Normal std = 0.3269

1.220 Kernel fit Pairwise Correlations Normal fit

Density 0.610

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

LLC-subclone-2,LLC-subclone-2,LLC-subclone-2, biologicalLLC-subclone-3, biological rep1LLC-subclone-3, biological(0.0175082) rep2LLC-subclone-3, biological(0.0211583) rep3LLC-subclone-6, biological(0.0385119) rep1LLC-subclone-6, biological(0.0983013) rep2LLC-subclone-28, biological(0.0893117) rep3LLC-subclone-28, biological(0.088548) rep1LLC-subclone-28, (0.0361232) biological rep2LLC-subclone-18, (0.0421292) biological rep1LLC-subclone-18, biological(0.0090206) rep2LLC-subclone-18, biological(0.0206386) rep3LLC-subclone-19, biological(0.00314962) rep1LLC-subclone-19, biological(0.0538289) rep2LLC-subclone-19, biological(0.0903896) rep3LLC-subclone-23, biological(0.0695655) rep1LLC-subclone-23, biological(0.0168725) rep2LLC-subclone-23, biological(0.0241355) rep3LLC-subclone-24, biological(0.0215615) rep1LLC-subclone-24, biological(0.03796) rep2LLC-subclone-24, biological(0.0444874) rep3 biological(0.0692536) rep1 biological(0.045592) rep2 (0.0380299) rep3[ min (0.023923) ] [ medium ] [ max ] CEM 1 Arid1a 493.2 722.1 966.6 P ( S | Z, I ) = 1.00 Smarca4 1376.9 2172.4 2935.1 Mean Corr = 0.68381 Crebbp 211.0 360.8 649.6 Smarcc1 2986.3 3849.5 4873.6 Smarcc2 288.6 544.2 708.1 Ep300 1542.3 2184.0 2801.6 Trrap 1412.9 1906.7 2333.1 Polr2a 2003.0 2909.9 4368.2 Ylpm1 1233.5 1525.6 2124.4 Ep400 756.3 999.4 1248.9 Kmt2b 480.5 689.8 861.0 CEM 1 + Kmt2a 693.6 1085.8 1433.3 Top 10 Genes Kat6a 404.6 604.5 788.4 Asxl1 927.2 1121.1 1416.8 Casc3 636.1 883.2 1095.7 Zc3h4 595.0 1014.0 1189.7

Null module Smarcb1 GEO Series "GSE41789" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 45 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41789 Status: Public on Nov 01 2013 Title: Senescence gene signature of radiation fibrosis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24052614 Summary & Design: Summary: Radiation lung injury is characterized by early inflammation and late fibrosis. The causes underlying the chronic, progressive nature of radiation injury are poorly understood. Here, we report that the gene expression of irradiated lung tissue correlates with that observed in the lungs in aged animals. We demonstrate that NOX4 expression and superoxide elaboration is increased in irradiated lungs and pneumocytes in a dose dependent fashion.

We used microarrays to detail the global programme of gene expression and report that irradiated lung tissue correlates with that observed in the lungs in aged animals.

Overall design: Female C57Bl/Ncr mice, aged 10 weeks were treated with/ without radiation to the thorax with a X-RAD 320 x-ray irradiator at a dose rate of 2.61 Gy/minute. An age-matched cohort of mice received no IR while additional cohorts received 5 Gy in a single dose, 17.5 Gy in a single dose. RNA was extracted and hybridization done on Affymetrix Mouse430_2 microarrays.

Background corr dist: KL-Divergence = 0.2852, L1-Distance = 0.0589, L2-Distance = 0.0090, Normal std = 0.2862

1.394 Kernel fit Pairwise Correlations Normal fit

Density 0.697

0.000 CEM 1

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

Pre-normalization Quantiles

mouse lungmouse tissue lungmouse at tissue week lungmouse at 2,tissue week 0lungmouse Gy, at 2,tissue biological week 0lungmouse Gy, at 2,tissue biological week 0lungmouse rep1Gy, at 2,tissue biological (0.144398)week 5Gy,lungmouse rep2 at 2,tissuebiological (0.00488523)week 5Gy,lungmouse rep3 at 2,tissuebiological (0.00560385)week 5Gy, lungmouserep1 at 2, tissuebiological(0.00238828) week 17.5 lungmouserep2 at Gy,2, tissue(0.0265856) week 17.5 lungmouse rep3biological at Gy,2, tissue(0.00135953) week 17.5lungmouse biological rep1at Gy,4,tissue week 0lungmouse biologicalGy,(0.00242515) rep2at 4,tissue biological week 0lungmouse Gy,(0.00287853) rep3at 4,tissue biological week 0lungmouse rep1Gy,(0.00637548) at 4,tissue biological (0.193909)week 5Gy,lungmouse rep2 at 4,tissuebiological (0.00173268)week 5Gy,lungmouse rep3 at 4,tissuebiological (0.00113992)week 5Gy, lungmouserep1 at 4, tissuebiological(0.0166305) week 17.5 lungmouserep2 at Gy,4, tissue(0.00102768) week 17.5 lungmouse rep3biological at Gy,4, tissue(0.022056) week 17.5lungmouse biological rep1at Gy,8,tissue week 0lungmouse biologicalGy,(0.00286539) rep2at 8,tissue biological week 0lungmouse Gy,(0.00238105) rep3at 8,tissue biological week 0lungmouse rep1Gy,(0.0045125) at 8,tissue biological (0.0508221)week 5Gy,lungmouse rep2 at 8,tissuebiological (0.0110688)week 5Gy,lungmouse rep3 at 8,tissuebiological (0.00229878)week 5Gy, lungmouserep1 at 8, tissuebiological(0.0156716) week 17.5 lungmouserep2 at Gy,8, tissue(0.00556106) week 17.5 lungmouse rep3biological at Gy,8, tissue(0.0472718) week 17.5lungmouse biological rep1at Gy,16,tissue week lungmouse 0 biological(0.024711) Gy, rep2at 16,tissue weekbiological lungmouse 0 (0.0180196) Gy, rep3at 16,tissue weekbiological lungmouse 0 (0.00821187) rep1Gy, at 16,tissue week biological(0.108161)lungmouse 5Gy, rep2 at 16,tissue biologicalweek (0.0128398)lungmouse 5Gy, rep3 at 16,tissue biologicalweek (0.00446097)lungmouse 5Gy, rep1 at 16,tissue biologicalweek(0.004418) lungmouse 17.5 rep2 at 16,tissue Gy, week(0.0091814) lungmouse 17.5 rep3biological at 16,tissue Gy, week(0.00476533) lungmouse 17.5 biological at 30,tissue rep1Gy, week lungmouse 0 biologicalGy,(0.0112435) at 30,tissuerep2 weekbiological lungmouse 0 Gy,(0.00744678) at 30,tissuerep3 weekbiological lungmouse 0 rep1Gy,(0.00468536) at 30,tissue week biological(0.0161566)lungmouse 5Gy, rep2 at 30,tissue biologicalweek (0.0135587)lungmouse 5Gy, rep3 at 30,tissue biologicalweek (0.0110946)lung 5Gy, rep1 at 30,tissue biologicalweek(0.0105038) 17.5 rep2 at 30, Gy, week(0.0179469) 17.5 rep3biological 30, Gy, (0.00545874)[ 17.5 biologicalmin rep1Gy, biological(0.0177367) ]rep2 (0.0207921) rep3 (0.0927586)[ medium ] [ max ] CEM 1 Arid1a 570.1 1301.5 2760.4 P ( S | Z, I ) = 1.00 Smarca4 726.3 1088.2 1975.3 Mean Corr = 0.68276 Crebbp 379.7 541.4 1005.1 Smarcc1 687.9 1029.3 1783.5 Smarcc2 509.6 650.2 1346.1 Ep300 1103.0 1497.4 2360.1 Trrap 460.9 758.6 1494.7 Polr2a 387.7 683.6 2409.5 Ylpm1 552.3 695.6 926.7 Ep400 719.2 1092.1 1357.3 Kmt2b 484.5 740.3 1404.8 CEM 1 + Kmt2a 355.2 544.4 1205.2 Top 10 Genes Kat6a 1249.0 1947.1 3109.2 Asxl1 679.8 930.5 1550.7 Casc3 738.2 898.1 1432.1 Zc3h4 337.5 567.0 1153.3

Null module Smarcb1 GEO Series "GSE8322" 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=GSE8322 Status: Public on Mar 06 2008 Title: Identification of MCIP1 as an ATF6-inducible ER Stress Response Gene in the Heart by Gene Expression Profiling Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18319259 Summary & Design: Summary: We recently found that the endoplasmic reticulum (ER) stress response (ERSR) is activated in surviving cardiac myocytes in a mouse model of in vivo myocardial infarction. ATF6 is an ER stress-activated transcription factor that induces ERSR genes, some of which encode proteins that may protect against ischemic damage. However, few ERSR genes have been identified in the heart, and there have been no gene expression profiling studies of ATF6-inducible genes, in vivo. We previously generated transgenic (TG) mice that express tamoxifen-activated ATF6, ATF6-MER, in the heart; ATF6-MER conferred tamoxifen-dependent ATF6 activation and protection from ischemic damage. To understand of the mechanism of ATF6-mediated cardioprotection, gene expression profiling of ATF6-MER TG mouse hearts was performed. Activated ATF6 changed expression levels of 1,162 genes in the heart; of the 775 ATF6-inducible genes, only 23 are known ERSR genes. One of the genes not expected to be induced by ATF6 is modulatory calcinuerin-interacting protein-1 (MCIP1). MCIP1 is induced in a calcineurin/NFAT-dependent manner during myocardial hypertrophy and it can feedback inhibit cardiomyocyte growth. We found that MCIP1 expression in cultured cardiomyocytes was increased by the prototypical ER stresser, tunicamycin (TM), or by simulated ischemia. Moreover, infecting cardiomyocytes with adenovirus encoding activated ATF6 induced MCIP1 expression and inhibited myocyte growth in response to the alpha 1-adrenergic agonist, phenylephrine. These results suggest that MCIP1 can be induced in the heart by ER stresses, such as ischemia. Moreover, b integrating hypertrophy and ER stress, MCIP-modulated myocyte growth may help rejuvenate nascent ER protein folding, which could contribute to protection from ischemic damage.

Keywords: Gene expression analysis of the effect of activating ATF6 in the hearts of transgenic mice upon treatment with tamoxifen.

Overall design: 12 mice were analyzed in this study. Four treatment groups were included in this study: transgenic ATF6-MER mice treated with tamoxifen, transgenic ATF6-MER mice treated with vehicle, nontransgenic littermates treated with tamoxifen, and nontransgenic littermates treated with vehicle. Each treatment group included 3 separate biological replicate samples. Each mouse sampled was male, C57/BL6, ~30 weeks old. Each mouse was treated, then the mouse was sacrificed, the heart was extracted, and left ventricle was isolated. Total RNA was isolated from the left ventricle, and used for hybridization onto an Affymetrix mus 430 2.0 full-genome chip. Each heart was hybridized onto its own chip.

Background corr dist: KL-Divergence = 0.1158, L1-Distance = 0.0244, L2-Distance = 0.0009, Normal std = 0.4173

0.956 Kernel fit Pairwise Correlations Normal fit

Density 0.478

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

ATF6-MERATF6-MER TG mouse_tamoxifen1ATF6-MER TG mouse_tamoxifen2ATF6-MER TG mouse_tamoxifen3ATF6-MER TG (0.105036) mouse_vehicle1ATF6-MER TG (0.131269) mouse_vehicle2NTG TG (0.0989777)mouse_tamoxifen1 mouse_vehicle3NTG (0.0557986) mouse_tamoxifen2NTG (0.0394549) mouse_tamoxifen3NTG (0.0891794)(0.0673231) mouse_vehicle1NTG (0.0963706) mouseNTG (0.147773) vehicle2mouse_vehicle3 (0.0402389) (0.0487564) (0.0798227)[ min ] [ medium ] [ max ] CEM 1 Arid1a 504.5 1308.0 1969.3 P ( S | Z, I ) = 1.00 Smarca4 964.8 2332.3 2582.7 Mean Corr = 0.68230 Crebbp 278.2 723.1 939.5 Smarcc1 521.1 871.8 1274.8 Smarcc2 328.2 986.7 2093.5 Ep300 738.1 950.4 1044.1 Trrap 339.6 775.7 1164.5 Polr2a 320.9 1322.3 1573.2 Ylpm1 174.7 422.4 568.8 Ep400 654.8 1080.9 1650.1 Kmt2b 443.4 765.6 1161.2 CEM 1 + Kmt2a 461.3 994.0 1542.1 Top 10 Genes Kat6a 748.7 1217.2 1948.5 Asxl1 481.8 862.9 1712.4 Casc3 380.9 707.7 1006.3 Zc3h4 481.1 680.8 1129.6

Null module Smarcb1 GEO Series "GSE54207" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54207 Status: Public on Jan 18 2014 Title: Expression data from mouse limb tendon cells during development. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We have undertaken a screen of mouse limb tendon cells in order to identify molecular pathways involved in tendon development. Mouse limb tendon cells were isolated based on Scleraxis (Scx) expression at different stages of development: E11.5, E12.5 and E14.5

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

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

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

0.781 Kernel fit Pairwise Correlations Normal fit

Density 0.391

0.000 CEM 1

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

Pre-normalization Quantiles

E11.5 AE12.5 (0.0531986) AE14.5 (0.0551086) AE11.5 (0.130017) BE12.5 (0.364451) BE14.5 (0.0198532) BE11.5 (0.10796) CE12.5 (0.0408578) CE14.5 (0.150831) C (0.0777231) [ min ] [ medium ] [ max ] CEM 1 Arid1a 280.0 415.9 812.0 P ( S | Z, I ) = 1.00 Smarca4 3583.3 6188.3 9486.8 Mean Corr = 0.67684 Crebbp 736.2 881.3 1173.1 Smarcc1 4039.9 6530.8 9108.2 Smarcc2 1219.1 1564.4 1906.9 Ep300 1465.1 1616.7 2392.6 Trrap 1559.7 2134.6 3459.1 Polr2a 1931.3 2573.4 3891.0 Ylpm1 1700.1 2205.7 3201.7 Ep400 1487.9 1800.6 2732.3 Kmt2b 1219.4 1320.9 1948.5 CEM 1 + Kmt2a 304.4 640.9 756.5 Top 10 Genes Kat6a 778.9 1100.0 1739.5 Asxl1 815.0 1673.3 2250.2 Casc3 1043.6 1375.1 1978.3 Zc3h4 965.8 1584.4 2232.7

Null module Smarcb1 GEO Series "GSE47065" 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=GSE47065 Status: Public on May 18 2013 Title: Gene expression profiling of IR-/-, IGF-1R-/- (dKO) newborn epidermis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23906066 Summary & Design: Summary: Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis.

Overall design: RNA was isolated from newborn mouse epidermis.Gene expression profiling was on on Affymetrix 430-2.0 platform.

Background corr dist: KL-Divergence = 0.0742, L1-Distance = 0.0224, L2-Distance = 0.0008, Normal std = 0.4920

0.811 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

NewbornNewborn epidermisNewborn epidermis of NewborndKO epidermis ofbiological NewborndKO epidermis ofbiological Newborn dKOreplicate epidermis ofbiological Newborn dKOreplicate epidermis1 (0.163854) ofbiological Newborn ctrlreplicate epidermis2 biological(0.150234) of ctrlreplicate epidermis3 biological(0.0709773) of replicate ctrl 4 biological(0.123364) of replicate ctrl 1 (0.033062) biological replicate[ 2 min(0.319544) replicate 3 (0.0497064) ] 4 (0.0892579)[ medium ] [ max ] CEM 1 Arid1a 1792.0 1937.0 2299.5 P ( S | Z, I ) = 1.00 Smarca4 2784.4 3219.4 4116.1 Mean Corr = 0.67514 Crebbp 416.0 697.4 808.3 Smarcc1 3342.9 4007.1 4670.0 Smarcc2 463.3 599.3 792.4 Ep300 1020.2 1206.0 1398.9 Trrap 878.3 1209.5 1893.3 Polr2a 684.4 813.7 1013.0 Ylpm1 597.1 777.9 950.0 Ep400 1066.9 1327.9 1571.5 Kmt2b 647.4 838.9 1143.5 CEM 1 + Kmt2a 363.8 671.5 863.4 Top 10 Genes Kat6a 1328.8 1587.2 1833.3 Asxl1 476.0 752.2 1287.8 Casc3 690.6 831.0 1024.4 Zc3h4 771.5 928.3 991.6

Null module Smarcb1 GEO Series "GSE45583" 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=GSE45583 Status: Public on Mar 29 2013 Title: A hypomorphic Lsd1 allele results in heart development defects in mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Microarray characterization of Lsd1 knock-outs compared to littermate controls

Microarrays were employed to identify transcripts that were differentially modulated in the hearts of wild-type and Lsd1-hypomorphic late-stage embryos.

Overall design: Late-stage embryonic hearts were isolated from wild-type and Lsd1-hypomorphic hearts, in order to isolate RNA for hybridization on Affymetrix microarrays. We sought to identify gene products that are differentially regulated between the two genotypes, in order to explain the observed ventricular septal defects in the hypomorphic animals.

Background corr dist: KL-Divergence = 0.0787, L1-Distance = 0.0212, L2-Distance = 0.0005, Normal std = 0.4781

0.834 Kernel fit Pairwise Correlations Normal fit

Density 0.417

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_1 (0.304981)KO_2 (0.248608)KO_3 (0.0452528)WT_1 (0.0524292)WT_2 (0.109481)WT_3 (0.0317238)WT_4 (0.0676244)WT_5 (0.1399) [ min ] [ medium ] [ max ] CEM 1 Arid1a 1326.6 1669.2 2377.9 P ( S | Z, I ) = 1.00 Smarca4 2633.9 3062.7 3779.9 Mean Corr = 0.65999 Crebbp 652.6 669.8 786.6 Smarcc1 2160.9 2362.5 3348.9 Smarcc2 689.4 785.0 991.4 Ep300 1045.6 1117.4 1375.1 Trrap 2024.2 2349.2 2971.9 Polr2a 533.4 698.1 1036.3 Ylpm1 964.6 1042.9 1222.8 Ep400 1008.4 1146.4 1499.8 Kmt2b 553.9 577.9 779.3 CEM 1 + Kmt2a 557.0 592.4 710.9 Top 10 Genes Kat6a 1501.9 1590.8 2045.0 Asxl1 1104.0 1211.1 1313.6 Casc3 604.9 706.1 902.6 Zc3h4 679.8 739.4 797.9

Null module Smarcb1 GEO Series "GSE11684" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11684 Status: Public on Nov 10 2009 Title: Expression data from Perk wild-type and knockout mouse liver perfused without or with 2,5-di-tert-butylhydroquinone Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19509078 Summary & Design: Summary: In eukaryotes, regulation of mRNA translation enables a fast, localized and finely tuned expression of gene products. Within the translation process, the first stage of translation initiation is most rigorously modulated by the actions of eukaryotic initiation factors (eIFs) and their associated proteins. These 11 eIFs catalyze the joining of the tRNA, mRNA and rRNA into a functional translation complex. Their activity is influenced by a wide variety of extra- and intracellular signals, ranging from global, such as hormone signaling and unfolded proteins, to specific, such as single amino acid imbalance and iron deficiency. Their action is correspondingly comprehensive, in increasing or decreasing recruitment and translation of most cellular mRNAs, and specialized, in targeting translation of mRNAs with regulatory features such as a 5 terminal oligopyrimidine tract (TOP), upstream open reading frames (uORFs), or an internal ribosomal entry site (IRES). In mammals, two major pathways are linked to targeted mRNA translation. The target of rapamycin (TOR) kinase induces translation of TOP and perhaps other subsets of mRNAs, whereas a family of eIF2 kinases does so with mRNAs containing uORFs or an IRES. TOR targets translation of mRNAs that code for proteins involved in translation, an action compatible with its widely accepted role in regulating cellular growth. The four members of the eIF2 kinase family increase translation of mRNAs coding for stress response proteins such as transcription factors and chaperones. Though all four kinases act on one main substrate, eIF2, published literature demonstrates both common and unique effects by each kinase in response to its specific activating stress. This suggests that the activated eIF2 kinases regulate the translation of both a global and a specific set of mRNAs. Up to now, few studies have attempted to test such a hypothesis; none has been done in mammals.

We use array analysis to determine the global mRNA shift into polysomes following a stress response, and to compare the translational response following activation of GCN2 versus PERK, two of the four eIF2alpha kinases.

Keywords: stress response, comparative genomic

Overall design: Perk wild-type or knockout mouse liver were perfused without or with 2,4-di-tert-butylhydroquinone (tBuHQ) for RNA extraction and hybridization of Affymetrix microarrays. RNA was extracted from unfractionated liver samples and polysome fraction of samples separated on sucrose density gradient. To minimize biological variations, we pooled RNA from two perfused liver samples to use in each array analysis. The conditions were total and polysome fraction of Perk+/+, -tBuHQ or +tBuHQ; total and polysome fraction of Perk-/-, -tBuHQ or +tBuHQ. Each array analysis was done in duplicate.

Background corr dist: KL-Divergence = 0.2098, L1-Distance = 0.0435, L2-Distance = 0.0042, Normal std = 0.3267

1.221 Kernel fit Pairwise Correlations Normal fit

Density 0.611

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

Unfractionated,Unfractionated,Unfractionated, Perk wild-typeUnfractionated, Perk wild-typeUnfractionated, liver,Perk wild-type-tBuHQ,Unfractionated, liver,Perk wild-type-tBuHQ, Unfractionated,biological liver,Perk knockout+tBuHQ, Unfractionated,biological liver,Perk rep1 knockout+tBuHQ,Polysome, biological(0.022711)Perkliver, rep2 knockout-tBuHQ,Polysome, biological(0.00446561)Perkliver, Perkrep1 knockout-tBuHQ, Polysome,biological liver,(0.0781258)wild-type Perkrep2 +tBuHQ, Polysome,biological liver,(0.0547985)wild-type rep1liver,Perk +tBuHQ,Polysome, biological(0.0699282) wild-type-tBuHQ, rep2liver,PerkPolysome, biological(0.0696901) wild-type-tBuHQ, biological liver,Perkrep1Polysome, knockout(0.0298145)+tBuHQ, biological liver,Perkrep2 rep1Polysome, knockout(0.0566085)+tBuHQ, biological(0.100924)Perkliver, rep2 knockout-tBuHQ, biological(0.0162954)Perkliver, rep1 knockout-tBuHQ, biological liver,(0.072818) rep2 +tBuHQ, biological liver,(0.278914) rep1[ +tBuHQ,min biological(0.0176205) rep2 biological(0.069946)] rep1 (0.0323231) rep2[ (0.0250163) medium ] [ max ] CEM 1 Arid1a 243.1 816.7 1632.8 P ( S | Z, I ) = 1.00 Smarca4 759.0 1091.5 2498.4 Mean Corr = 0.65871 Crebbp 59.5 370.8 715.8 Smarcc1 283.8 490.9 903.4 Smarcc2 395.8 553.4 858.5 Ep300 245.8 560.2 1001.0 Trrap 92.1 324.0 543.5 Polr2a 115.2 186.6 581.0 Ylpm1 178.3 321.5 729.9 Ep400 146.9 402.6 1010.6 Kmt2b 100.2 196.3 315.4 CEM 1 + Kmt2a 95.5 188.0 288.1 Top 10 Genes Kat6a 138.9 421.8 623.7 Asxl1 166.5 299.7 554.4 Casc3 171.1 263.1 490.2 Zc3h4 206.1 373.8 514.6

Null module Smarcb1 GEO Series "GSE21143" 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=GSE21143 Status: Public on Jun 14 2010 Title: PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and glioma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20478531 Summary & Design: Summary: A hallmark feature of glioblastoma (GBM) cells is its strong self-renewal potential and immature differentiation state -- stem cell-like properties which may contribute to the plasticity and intense therapeutic resistance of GBM. The molecular basis of the immature differentiation profile remains an area of active investigation. Here, integrated genomic and biological analyses identified PLAGL2 as a potent proto-oncogene targeted for amplification/gain in malignant gliomas as well as in colorectal cancers. High level of PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell (GIC) differentiation while promoting their proliferation and self-renewal capacity under differentiation induction conditions. On the mechanistic level, the PLAGL2 transcriptome analysis revealed that these differentiation suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling via up-regulation of Wnt6 ligand as well as Fzd9 and Fzd2 receptor expression. Correspondingly, inhibition of Wnt signaling in PLAGL2-expressing NSC partially restores their differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics on malignant cells.

Overall design: p53-null mouse NSCs are infected with retrovirus expressing either control vector or PlagL2. Total RNA were collected upon differentiation in 1% FBS for 24 hr. 3 replicates each.

Background corr dist: KL-Divergence = 0.0436, L1-Distance = 0.0242, L2-Distance = 0.0007, Normal std = 0.6035

0.674 Kernel fit Pairwise Correlations Normal fit

Density 0.337

0.000 CEM 1

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

Pre-normalization Quantiles

NSC_FBS_V1NSC_FBS_L1 (0.191051)NSC_FBS_V2 (0.126997)NSC_FBS_L2 (0.125429)NSC_FBS_V3 (0.0687777)NSC_FBS_L3 (0.404524) (0.0832215) [ min ] [ medium ] [ max ] CEM 1 Arid1a 787.6 1623.8 1841.2 P ( S | Z, I ) = 1.00 Smarca4 3814.0 5272.2 6472.2 Mean Corr = 0.70097 Crebbp 328.3 608.7 626.2 Smarcc1 1257.6 1706.6 2147.5 Smarcc2 2405.4 3618.5 3805.6 Ep300 1169.0 1882.4 2756.7 Trrap 1676.1 2768.7 3074.3 Polr2a 4035.6 4537.6 5239.7 Ylpm1 1091.5 1502.4 1608.1 Ep400 1235.4 1578.1 1914.1 Kmt2b 894.6 1546.5 1621.4 CEM 1 + Kmt2a 837.6 1291.2 1494.3 Top 10 Genes Kat6a 2152.1 2703.5 3195.0 Asxl1 1092.1 1231.9 1387.0 Casc3 1272.3 1466.2 1775.8 Zc3h4 793.3 1049.9 1150.8

Null module Smarcb1 GEO Series "GSE30767" 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=GSE30767 Status: Public on Dec 01 2011 Title: Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21803034 Summary & Design: Summary: This work was designed to determine the role of the vascular endothelial growth factor A (VEGF) isoforms during early neuroepithelial development in the mammalian central nervous system (CNS), specifically in the forebrain. An emerging model of interdependence between neural and vascular systems includes VEGF, with its dual roles as a potent angiogenesis factor and neural regulator. Although a number of studies have implicated VEGF in CNS development, little is known about the role that the different VEGF isoforms play in early neurogenesis. We used a mouse model of disrupted VEGF isoform expression that eliminates the predominant brain isoform, VEGF164, and expresses only the diffusible form, VEGF120. We tested the hypothesis that VEGF164 plays a key role in controlling neural precursor populations in developing cortex. We used microarray analysis to compare gene expression differences between wild type and VEGF120 mice at E9.5, the primitive stem cell stage of the neuroepithelium. We quantified changes in PHH3-positive nuclei, neural stem cell markers (Pax6 and nestin) and the Tbr2-positive intermediate progenitors at E11.5 when the neural precursor population is expanding rapidly. Absence of VEGF164 (and VEGF188) leads to reduced proliferation without an apparent effect on the number of Tbr2-positive cells. There is a corresponding reduction in the number of mitotic spindles that are oriented parallel to the ventricular surface relative to those with a vertical or oblique angle. These results support a role for the VEGF isoforms in supporting the neural precursor population of the early neuroepithelium.

Overall design: Four samples each of E9.5 wildtype or VEGF120 mouse forebrain were analyzed with the Mouse 430 2.0 Affymetrix GeneChip

Background corr dist: KL-Divergence = 0.0833, L1-Distance = 0.0216, L2-Distance = 0.0007, Normal std = 0.4690

0.851 Kernel fit Pairwise Correlations Normal fit

Density 0.425

0.000 CEM 1

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

Pre-normalization Quantiles

E9.5 wildtypeE9.5 wildtype ms.E9.5 Forebrain, wildtype ms.E9.5 Forebrain, wildtype ms.repE9.5 1Forebrain, (0.167132)VEGF120 ms.repE9.5 2Forebrain, (0.0312131)VEGF120 rep ms.E9.5 3 Forebrain, (0.239706)VEGF120 rep ms.E9.5 4 Forebrain, (0.0802208)VEGF120 ms.rep 1Forebrain, (0.039002) ms.rep 2Forebrain, (0.0869857) rep 3 (0.135076) rep[ min 4 (0.220665) ] [ medium ] [ max ] CEM 1 Arid1a 1092.9 1958.6 2521.7 P ( S | Z, I ) = 1.00 Smarca4 4979.8 6821.3 8062.2 Mean Corr = 0.65541 Crebbp 371.6 515.4 586.6 Smarcc1 5958.1 7581.3 10132.6 Smarcc2 486.9 584.7 887.7 Ep300 958.7 1082.1 1190.3 Trrap 1681.9 2202.4 3237.0 Polr2a 765.3 1444.8 2918.0 Ylpm1 1727.1 1935.2 2294.5 Ep400 1366.6 2017.7 2503.3 Kmt2b 643.4 1023.7 1417.6 CEM 1 + Kmt2a 630.2 951.2 1133.9 Top 10 Genes Kat6a 881.1 1102.8 1470.2 Asxl1 1580.6 2219.8 2631.0 Casc3 898.3 1236.2 1387.8 Zc3h4 835.7 1375.8 1922.5

Null module Smarcb1 GEO Series "GSE19076" 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=GSE19076 Status: Public on Dec 01 2009 Title: Expression data from wild type, Ring1B-/-, Eed-/-, and Ring1B/Eed double deficient mouse ES cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20123906 Summary & Design: Summary: Polycomb complexes establish chromatin modifications for maintaining gene repression and are essential for embryonic development in mice. Here we use pluripotent embryonic stem (ES) cells to demonstrate an unexpected redundancy between Polycomb repressive complex 1 (PRC1) and PRC2 during the formation of differentiated cells. ES cells lacking the function of either PRC1 or PRC2 can differentiate into cells of the three germ layers, whereas simultaneous loss of PRC1 and PRC2 abrogates differentiation. On the molecular level the differentiation defect is caused by the derepression of a set of genes that is redundantly repressed by PRC1 and PRC2 in ES cells. Furthermore, we find that genomic repeats are Polycomb targets and show that in the absence of Polycomb complexes endogenous MLV elements can mobilize. This indicates a contribution of the PcG system to the defense against parasitic DNA and a potential role of genomic repeats in Polycomb mediated gene regulation.

Overall design: RNA from wt and PcG mutant ES cells was extracted using Trizol and hybridized to an Affymetrix Mouse 430_2.0 chip. Labeling, hybridization and primary data analysis were performed by a commercial provider (Atlas Biolabs, Berlin). Before RNA extraction, the undifferentiated ES cell state was confirmed by colony morphology. All genotypes were hybridized in biological triplicates.

Background corr dist: KL-Divergence = 0.1022, L1-Distance = 0.0263, L2-Distance = 0.0012, Normal std = 0.4327

0.922 Kernel fit Pairwise Correlations Normal fit

Density 0.461

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 ES type cells,wild ES biological type cells,Ring1B ES biological cells, replicate Ring1Bdeficient biological replicate Ring1Bdeficient 1 ES (0.360172) cells, replicate Eeddeficient 2 ES (0.0404689) biologicaldeficient cells,Eed 3 ES (0.0402261) biologicaldeficient cells,ES replicateEed cells, biologicaldeficient ES replicateRing1B/Eed biological 1 cells, (0.0886288) ES replicateRing1B/Eed biological 2 cells, (0.0616302)replicate doubleRing1B/Eed biological 3 (0.10588)replicate doubledeficient1 (0.0625659) replicate doubledeficient2 ES(0.0584278) cells, deficient3 ES(0.0221987) biological cells, ES[ biological cells,min replicate biological replicate] 1 (0.026916) replicate 2 (0.0614989)[ medium3 (0.0713865) ] [ max ] CEM 1 Arid1a 628.5 932.0 2391.2 P ( S | Z, I ) = 1.00 Smarca4 1734.4 2101.6 3541.9 Mean Corr = 0.64167 Crebbp 65.2 90.1 225.2 Smarcc1 1704.4 2554.5 4113.3 Smarcc2 155.9 223.7 247.8 Ep300 959.0 1193.7 1739.1 Trrap 390.3 533.7 715.3 Polr2a 576.6 928.0 1197.9 Ylpm1 680.2 889.0 1128.0 Ep400 587.8 825.0 1112.2 Kmt2b 740.0 889.7 1066.2 CEM 1 + Kmt2a 445.6 600.2 872.6 Top 10 Genes Kat6a 646.5 929.9 1220.3 Asxl1 658.4 1210.6 1982.0 Casc3 557.5 846.0 905.3 Zc3h4 355.3 499.2 899.8

Null module Smarcb1 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 (0.0560947)Tgfbeta (0.0455783)Tgfbeta inhibitor_rep1 (0.0387885)Tgfbeta inhibitor_rep2 Tgfbeta1 (0.168658)inhibitor_rep3 Tgfbeta1(0.115749) ligand_rep1 Tgfbeta1(0.124538) ligand_rep2 (0.163826) ligand_rep3 (0.0535691) (0.233198)[ min ] [ medium ] [ max ] CEM 1 Arid1a 456.1 704.3 858.7 P ( S | Z, I ) = 1.00 Smarca4 2459.9 2746.9 3588.7 Mean Corr = 0.65072 Crebbp 177.5 284.4 415.8 Smarcc1 1345.6 1979.4 3218.2 Smarcc2 709.3 800.6 972.7 Ep300 2319.9 2952.0 3430.9 Trrap 1022.4 1200.6 1406.4 Polr2a 2419.1 3069.2 3952.6 Ylpm1 582.9 668.2 997.5 Ep400 1249.8 1795.4 2309.0 Kmt2b 896.1 964.7 1291.9 CEM 1 + Kmt2a 299.2 422.9 559.2 Top 10 Genes Kat6a 1387.5 1495.9 1798.1 Asxl1 314.5 624.2 918.2 Casc3 1088.0 1232.7 1340.8 Zc3h4 625.0 757.1 898.9

Null module Smarcb1 GEO Series "GSE58484" 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=GSE58484 Status: Public on Jun 14 2014 Title: Expression data from mus musculus subjected to traumatic brain injury (TBI) for treatment with cyclophosphamide Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We inflicted TBI to wildetype (wt) mice in order to establish whether the anti-inflammatory agent cyclophosphamide can be used therapeutically.

Cyclophosphamide was found to regulate distinct inflammatory cells such as activated microglia separate from invading phagocytes and dendritic cells. Cyclophosphamide postinjury selectively reduces antigen-presenting dendritic cells. Findings show feasibility of drug development to interfere with brain inflammation.

Overall design: TBI was carried out in injured wt B6 mice for postinjury treatment with cyclophospamide i.p. using saline as a control substance for comparison with injured but untreated mice. Total RNA was prepared from injured cerebral neocortex after three days. RNA samples were also from uninjured wt mice as reference for hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1498, L1-Distance = 0.0359, L2-Distance = 0.0025, Normal std = 0.3731

1.069 Kernel fit Pairwise Correlations Normal fit

Density 0.535

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

TBI 3 daysTBI ipsilateral3 daysTBI ipsilateral3 days neocortexNeocortex ipsilateral neocortexNeocortex wildtype uninjured neocortexNeocortex wildtype uninjuredB6 wildtype mouse_1TBI wildtype uninjuredB63 dayswildtype mouse_2TBIB6 (0.0872629) mouse_1ipsilateralB63 dayswildtype mouse_3TBIB6 (0.205565) mouse_2ipsilateral3 days(0.0365848) neocortex TBIB6 (0.0771721) mouse_3ipsilateral3 days(0.0370077) neocortex,TBI cyclophosphamide ipsilateral3 days(0.0135915) neocortexTBI PBS ipsilateral3 days neocortex, TBIi.p. cyclophosphamide ipsilateral3wildtype days neocortexi.p.TBI PBS wildtype ipsilateral3 B6days neocortex TBIi.p. mouse_1 cyclophosphamide ipsilateral3wildtype B6 days neocortex,i.p. mouse_1 cyclophosphamide wildtypeipsilateral(0.0855221) B6 neocortex mouse_2 PBS(0.0220861) B6 neocortex,i.p. i.p.mouse_2 cyclophosphamide wildtype (0.0996746)wildtype i.p.[ minPBS(0.0930537)wildtype B6 B6 i.p.mouse_3 mouse_3 wildtype ]B6 i.p. mouse_4 (0.0482624) wildtype(0.0382633) B6 mouse_4 [(0.0401202) B6medium mouse_5 (0.015131) (0.100702) ] [ max ] CEM 1 Arid1a 79.5 152.4 290.1 P ( S | Z, I ) = 1.00 Smarca4 1246.6 1581.5 2146.8 Mean Corr = 0.63175 Crebbp 278.3 428.9 704.5 Smarcc1 679.3 876.6 1075.5 Smarcc2 987.0 1395.0 1876.6 Ep300 545.0 710.6 1002.7 Trrap 343.0 642.9 1105.5 Polr2a 362.1 449.3 693.9 Ylpm1 322.0 547.1 1026.5 Ep400 416.3 518.0 643.6 Kmt2b 240.5 380.3 622.7 CEM 1 + Kmt2a 185.0 237.6 557.0 Top 10 Genes Kat6a 179.4 369.1 475.9 Asxl1 358.7 522.2 691.4 Casc3 561.1 669.9 774.6 Zc3h4 372.9 496.6 779.9

Null module Smarcb1 GEO Series "GSE13553" 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=GSE13553 Status: Public on Nov 19 2008 Title: The effect of dietary CLA on mammary tumorigenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20624750 Summary & Design: Summary: Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.

Overall design: Virgin, four-week-old PyV-mT mice were administered a diet of a mixed-isomer CLA formulation (1% wt/wt) (N=6) or control AIN96G diet (N=5) for four weeks. Measurements of food disappearance, weights and palpations were recorded weekly. All animals were euthanized at eight weeks of age. Formalin-fixed, paraffin-embedded mammary gland tissue was used for H&E and trichrome staining and immunohistochemistry for Ki67. Tissue levels of CLA were measured by gas chromatography. Thoracic mammary glands were fixed in glacial acetic acid:ethanol and carmine stained. cDNA microarray was performed on RNA from 6 CLA-fed mice and 4 control mice using the Affymetrix 430 2.0 mouse genome chips.

Background corr dist: KL-Divergence = 0.1131, L1-Distance = 0.0294, L2-Distance = 0.0015, Normal std = 0.4170

0.957 Kernel fit Pairwise Correlations Normal fit

Density 0.478

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

Exp 2773_controlExp 2879_controlExp (0.0353253) 2880_controlExp (0.0531148) 2775_CLAExp (0.0850436) 2877_CLA Exp(0.0518039) 2878_CLA Exp(0.0450953) 2876_CLA Exp(0.103238) 2968_control Exp(0.150916) 2971_CLAExp (0.0940654) 2970_CLA (0.203266) (0.178132) [ min ] [ medium ] [ max ] CEM 1 Arid1a 1583.3 2891.4 3820.5 P ( S | Z, I ) = 1.00 Smarca4 2377.9 3813.9 4383.9 Mean Corr = 0.62935 Crebbp 319.0 547.9 729.9 Smarcc1 1304.4 2283.9 3100.6 Smarcc2 685.4 1321.5 1696.5 Ep300 849.8 1679.7 2083.6 Trrap 821.6 1611.5 2498.8 Polr2a 567.9 2235.1 3289.2 Ylpm1 531.5 894.7 1420.3 Ep400 826.0 1562.9 1839.6 Kmt2b 906.7 1529.3 1632.5 CEM 1 + Kmt2a 325.2 1007.7 1208.3 Top 10 Genes Kat6a 1199.1 1763.2 2180.8 Asxl1 852.0 1041.1 1248.5 Casc3 895.6 1267.2 1554.8 Zc3h4 716.7 1006.0 1118.5

Null module Smarcb1 GEO Series "GSE21716" 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=GSE21716 Status: Public on Oct 01 2010 Title: Hepatic xenobiotic metabolizing enzyme gene expression through the life stages of the mouse Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Using full-genome arrays, the expression of all XMEs was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver and compared to young adults. Fetal and neonatal life stages had a dramatic effect on XME expression compared to the relatively minor effects of old age. At all life stages except PND30 down-regulated genes outnumbered up-regulated genes. The altered XMEs included those in all of the major metabolic phases including phase I (alcohol and aldehyde dehydrogenase and Cyp genes), phase II (aldo-keto reductase, glutathione-S-transferases, sulfotransferases and UDP-glucuronosyl transferases) and phase III (transporters). We have generated a comprehensive catalog of XME hepatic gene changes through the life stages of the mouse that can be used to predict chemicals and chemical classes different life stages are more sensitive to. Some CEL files used in this study have been submitted through GSE21224.

Keywords: gene expression/microarray

Overall design: We characterized gene expression changes in the developing mouse liver at gestational days (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver using full-genome microarrays and compared these changes to that in the adult liver.. We also compared results to GD19, PND32, and PND67 C3H mice. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 28 samples, four mice in each of the age groups for C57BL/6 and C3H, were analyzed.

Background corr dist: KL-Divergence = 0.1189, L1-Distance = 0.0776, L2-Distance = 0.0143, Normal std = 0.4578

1.037 Kernel fit Pairwise Correlations Normal fit

Density 0.519

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse liver_6month_2Mouse liver_6month_11Mouse liver_6month_16Mouse (0.0112426) liver_6month_21Mouse (0.0313465) liver_12month_3Mouse (0.0266509) liver_12month_6Mouse (0.00803425) liver_12month_13Mouse (0.0104039) liver_12month_17Mouse (0.00632994) liver_18month_4Mouse (0.0163682) liver_18month_9Mouse (0.00885109) liver_18month_14Mouse (0.0158051) liver_18month_19Mouse (0.00891936) liver_24month_25Mouse (0.012098) liver_24month_29Mouse (0.0162449) liver_24month_33Mouse (0.00982797) liver_24month_34Mouse (0.0153755) liver_C3H_GD19_1Mouse (0.00793465) liver_C3H_GD19_2Mouse (0.00831417) liver_C3H_GD19_3Mouse (0.188142) liver_C3H_GD19_4Mouse (0.0902853) liver_C3H_PD32_1Mouse (0.0610795) liver_C3H_PD32_2Mouse (0.322487) liver_C3H_PD32_3Mouse (0.00730569) liver_C3H_PD32_4Mouse (0.00414824) liver_C3H_PD67_1Mouse (0.0072396) liver_C3H_PD67_2Mouse (0.0440327) liver_C3H_PD67_3Mouse (0.00634679) liver_C3H_PD67_4 (0.0259927) (0.0100727) (0.0191212)[ min ] [ medium ] [ max ] CEM 1 Arid1a 498.6 769.5 3271.0 P ( S | Z, I ) = 1.00 Smarca4 906.8 1224.3 2512.7 Mean Corr = 0.62824 Crebbp 135.2 275.4 765.4 Smarcc1 529.4 729.1 2375.2 Smarcc2 606.8 846.6 1543.2 Ep300 592.0 731.1 1852.9 Trrap 397.8 738.9 1857.2 Polr2a 310.3 420.9 3247.3 Ylpm1 252.2 307.0 732.0 Ep400 427.5 636.8 2052.7 Kmt2b 458.2 651.6 1666.3 CEM 1 + Kmt2a 220.5 363.8 804.2 Top 10 Genes Kat6a 682.9 873.2 1774.5 Asxl1 407.7 520.2 1862.1 Casc3 160.2 296.3 1366.7 Zc3h4 381.4 537.6 1259.5

Null module Smarcb1 GEO Series "GSE45222" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 27 -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=GSE45222 Status: Public on Nov 27 2013 Title: Reversible mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts Organism: Mus musculus Experiment type: Non-coding RNA profiling by array Platform: GPL1261 Pubmed ID: 24156637 Summary & Design: Summary: Analysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.

Using Affymetrix microarrays, we compared the transcriptional profiles of Rasless fibroblasts to those of K-Raslox (MEFs lacking only H-Ras and N-Ras). We also compared the transcriptional profile of Rasless cells with those of BRAF and MEK1-transfected Rasless cells which recovered proliferative ability. Re-entry of the Rasless cells into cell cycle progression through ectopic expression of activated BRAF or MEK1 resulted in full reversion of most transcriptional alterations identified in cells lacking the three canonical Ras proteins.

Overall design: Regarding the miRNA expression study, the experimental samples analyzed included (i) 4 samples samples K-Raslox (used as Control): 2 biological replicates, technical duplicates each; (ii) 8 samples Rasless: the same cells after treatment with 4-OHT for 6 days (2 biological replicates, technical duplicates each) and 12 days (2 biological replicates, technical duplicates each); (iii) 4 samples BRAF-rescued, including 2 biological replicates, technical duplicates each; (iv) 4 samples MEK1-rescued,including 2 biological replicates, technical duplicates each, and (v) 4 samples Puromycin-resistant empty vector, containing 2 biological replicates, technical duplicates each. The miRNA expression study contains a total of 24 samples.

Background corr dist: KL-Divergence = 0.1968, L1-Distance = 0.0489, L2-Distance = 0.0056, Normal std = 0.3334

1.196 Kernel fit Pairwise Correlations Normal fit

Density 0.598

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

DU315-6-MDU315-6-M.r. (K-Raslox),DU315-6-S (K-Raslox),DU315-6-S.r. biological (K-Raslox),DU315-6-N technical rep1 (K-Raslox), DU315-6-N2biological (0.036704) (K-Raslox), rep1DU244-1-N technical(0.0299324) rep2 (K-Raslox),DU244-1-N2 biological(0.0189904) (K-Raslox). rep2DU315-6-12d-4OHT-M technical(0.00995704) rep3 (K-Raslox).DU315-6-12d-4OHT-M.r. biological(0.00469437) rep3DU315-6-12d-4OHT-S (0.0180546)technical rep4 (Rasless),DU315-6-12d-4OHT-S.r. (0.00409397) rep4DU315-6-12d-4OHT-N (0.0258511)(Rasless), biological (Rasless),DU244-1-12d-4OHT-N technical rep1DU244-1-12d-4OHT-N.r. (Rasless), biological (0.0115645) (Rasless),rep1LG7-6-5 technical(0.0184188) rep2 (Rasless),LG7-6-9 (BRAF-transfected), biological(0.0309863) rep2LG7-6-13 (BRAF-transfected),(Rasless), biological (0.0335653) rep3MCL1-6-14 (BRAF-transfected), (0.0280336) technical rep4 biologicalMCL1-6-18 (0.0183352) (MEK1-transfected), biologicalrep4MCL1-6-25 rep1 (MEK1-transfected), (0.0553681) (0.062395) MCL23-1-5biological rep2 (MEK1-transfected), (0.0707497)MCL23-1-5.r. biological rep3(Puromycin-resistantMCL23-1-2 (0.0536626) biological rep1 (Puromycin-resistantMCL23-1-2.r. biological(0.0542019) (Puromycin-resistant rep2JU10-2-2 (0.132145) empty rep3 (Puromycin-resistantJU10-2-3 (Hygromycin-resistantvector),(0.154792) empty (Hygromycin-resistant emptybiological vector), vector), emptytechnical rep1 empty biological(0.0150482) vector), rep1[ vector), emptymin (0.0325036)technical rep2 vector), biological (0.0331936)] rep2 biological (0.0163234)rep1 [(0.0115445) rep2medium (0.0188899) ] [ max ] CEM 1 Arid1a 453.6 1114.8 2223.3 P ( S | Z, I ) = 1.00 Smarca4 1503.5 2765.0 6298.4 Mean Corr = 0.62521 Crebbp 253.8 350.5 594.8 Smarcc1 1133.3 2753.3 5245.3 Smarcc2 336.5 466.8 1439.4 Ep300 661.2 998.5 2090.6 Trrap 375.8 616.0 1954.0 Polr2a 47.6 66.3 115.3 Ylpm1 412.0 685.1 1463.3 Ep400 527.5 742.9 1479.5 Kmt2b 393.9 594.6 1374.7 CEM 1 + Kmt2a 289.0 489.1 1092.7 Top 10 Genes Kat6a 532.4 1037.4 2428.1 Asxl1 501.1 865.0 1862.8 Casc3 470.3 663.1 1333.6 Zc3h4 405.1 631.3 1391.9

Null module Smarcb1 GEO Series "GSE39030" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.626 Kernel fit Pairwise Correlations Normal fit

Density 0.313

0.000 CEM 1

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

Pre-normalization Quantiles

BRAF nonBRAF activated activatedBRAF in activatedBRAF thein the murine activated BRAF murine + ZEB2 melanocytic activatedBRAF melanocytic +in SNAIL2 the activated murine+ melan-aTWIST1 in melan-athe melanocytic+ murineZEB1 incell the cell line in melanocytic murinelinethe (0.162381) melan-a [ (0.0470821)murine minmelanocytic cell melan-amelanocytic line] (0.0383299)melan-a cell linemelan-a cell [(0.49255) medium line cell (0.108134) line (0.151523) ] [ max ] CEM 1 Arid1a 230.4 251.3 413.6 P ( S | Z, I ) = 1.00 Smarca4 3196.3 4205.3 6966.6 Mean Corr = 0.63514 Crebbp 583.0 632.1 903.0 Smarcc1 2178.2 2908.5 3709.9 Smarcc2 755.2 815.4 993.9 Ep300 1475.1 1702.4 1845.8 Trrap 1409.1 1615.3 1875.9 Polr2a 2541.2 3296.1 5131.3 Ylpm1 1058.5 1257.9 1482.4 Ep400 1631.3 1740.6 2051.8 Kmt2b 795.7 860.9 1185.5 CEM 1 + Kmt2a 405.6 494.8 586.5 Top 10 Genes Kat6a 728.9 812.2 1226.9 Asxl1 666.9 851.7 1187.0 Casc3 723.5 911.8 1512.9 Zc3h4 831.6 1013.4 1244.9

Null module Smarcb1 GEO Series "GSE52474" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 154 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

Details of this dataset are not shown due to large number of samples and the page size limit. Find details in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52474

Background corr dist: KL-Divergence = 0.1954, L1-Distance = 0.0793, L2-Distance = 0.0167, Normal std = 0.3721