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

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

Dataset: Num of genes in input gene set: 58 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. Mphosph9 Num ofGenesinQueryGeneset:58.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Tubgcp3 Sdccag8 Cep192 Ccdc92 Cep135 Cep170 Cep104 Cep164 Cep250 Cep128 Ccp110 Topors Cntrob Pla2g3 Spice1 Stard9 Neurl4 Lrrcc1 Poc1b Ccsap Rock1 Cep41 Cep19 Alms1 Cep76 Cep55 Tubd1 Poc1a Dzip1l Top2a Sass6 Tssk2 Crocc Parp3 Herc2 Cetn1 Cetn2 Cetn3 Cenpj Dzip1 Cntln Birc5 Bbs4 Poc5 Tsks Odf2 Ofd1 Ccnf Ahi1 Fbf1 Ftcd Plk4 Plk2 Ift20 Ift88 Sfi1 Nin

Birc5 Plk4 Cep55 Ccnf Sass6 Cep192 Poc1a Ccp110 Cep128 Cep76 Cenpj Alms1 Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 Singletons CEM 1(421datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page1 Arhgap11a Mis18bp1 Nusap1 Shcbp1 Cep128 Ccp110 Cep192 Zwilch Ncaph Ccnb2 Cenpe Ncapg Spag5 Ube2c Cdca8 Ndc80 Kif20a Ccna2 Alms1 Cep76 Cep55 Esco2 Poc1a Sass6 Aurkb Aurka Cenpf Mki67 Kntc1 Cenpi Aspm Cenpj Spdl1 Sgol2 Sgol1 Birc5 Bub1 Kif22 Cdk1 Kif11 Tpx2 Melk Nuf2 Ccnf Prc1 Ect2 Plk4 Plk1 Kif4 Pbk 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE20954 [14] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE12454 [13] GSE57543 [6] GSE17266 [59] GSE15741 [6] GSE27605 [8] GSE54215 [13] GSE50813 [24] GSE33308 [10] GSE28621 [21] GSE44260 [10] GSE21224 [16] GSE23845 [15] GSE39082 [6] GSE23925 [6] GSE17794 [44] GSE28457 [24] GSE30160 [6] GSE51883 [30] GSE17796 [39] GSE39034 [9] GSE32386 [13] GSE31359 [8] GSE13611 [8] GSE20500 [6] GSE23502 [8] GSE13873 [27] GSE16110 [16] GSE38696 [8] GSE34839 [6] GSE9763 [20] GSE4260 [6] GSE45143 [6] GSE12993 [6] GSE31028 [6] GSE10525 [18] GSE19004 [9] GSE53916 [6] GSE29241 [6] GSE21309 [9] GSE21900 [12] GSE6998 [32] GSE17316 [12] GSE32277 [33] GSE24628 [16] GSE54207 [9] GSE15326 [10] GSE19176 [10] GSE33156 [18] GSE16874 [12] GSE28035 [9] GSE51075 [12] GSE9338 [42] GSE51385 [8] GSE4768 [18] GSE18993 [13] GSE40655 [6] GSE13693 [9] GSE8039 [32] GSE46209 [21] GSE46606 [30] GSE13692 [8] GSE27546 [51] GSE30485 [15] GSE14012 [24] GSE7875 [16] GSE39469 [6] GSE48204 [6] GSE58296 [9] GSE48004 [6] GSE48382 [10] GSE6957 [12] GSE27261 [8] GSE11818 [6] GSE31099 [24] GSE21716 [28] GSE20620 [22] GSE15872 [18] GSE56135 [8] GSE48397 [10] GSE29318 [9] GSE38831 [7] GSE22005 [23] GSE30745 [12] GSE21299 [12] GSE52474 [154] GSE16925 [15] GSE55855 [6] GSE38693 [8] GSE35366 [78] GSE15267 [8] GSE35785 [10] GSE18135 [18] GSE26616 [6] GSE43419 [20] GSE24512 [29] GSE39449 [6] GSE39984 [18] GSE18358 [10] GSE45222 [27] GSE21278 [48] GSE25637 [9] GSE6383 [6] GSE8034 [17] GSE14406 [54] GSE31638 [15] GSE44175 [18] GSE39621 [51] GSE21393 [6] GSE15303 [11] GSE30834 [9] GSE46797 [6] GSE6689 [12] GSE47421 [24] GSE9287 [8] GSE28417 [12] GSE19616 [16] GSE13149 [25] GSE46185 [6] GSE26461 [6] GSE38257 [14] GSE46970 [15] GSE3126 [6] GSE9247 [15] GSE4694 [6] GSE39557 [15] GSE27932 [14] GSE7657 [12] GSE35593 [6] GSE20987 [12] GSE8091 [16] GSE12498 [12] GSE8960 [18] GSE36814 [20] GSE16675 [72] GSE9297 [27] GSE12881 [6] GSE22824 [24] GSE11420 [15] GSE26355 [6] GSE46942 [7] GSE18534 [15] GSE5041 [8] GSE17097 [20] GSE30855 [6] GSE51608 [6] GSE31570 [6] GSE29632 [42] GSE21606 [6] GSE13635 [6] GSE8660 [6] GSE21379 [10] CEM+ CEM GSE13408 [14] GSE34217 [7] GSE45744 [12] GSE51804 [10] GSE48790 [8] GSE27114 [6] 0.0 GSE47694 [10] GSE42047 [24]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 143.59 144.00 144.17 144.24 144.27 144.46 144.65 145.27 145.63 145.76 146.30 146.67 147.93 148.68 148.73 148.73 149.36 149.50 149.90 149.96 150.33 150.66 150.79 151.54 152.59 152.63 152.95 153.84 154.11 154.38 155.70 155.78 157.14 158.85 159.22 159.30 165.58 166.65 1.0 Notes Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page2 Rad51ap1 Depdc1a Racgap1 Ncapg2 Ncapd2 Topbp1 Cdc25c Parpbp Ckap2l Incenp Cenpp Cenph Bub1b Kif18b Cenpk Ercc6l Cdc45 Cdca2 Ckap2 Kif18a Cdc20 Rad51 Cdca5 Spc24 Fbxo5 Fignl1 Brca1 Gins1 Prim1 Cenpl Ube2t Atad5 Atad2 Asf1b Pola1 Espl1 Uhrf1 Mastl Rrm2 Rrm1 Cdc6 Exo1 Nek2 Cks2 Ska3 Dbf4 Anln E2f7 Lig1 Stil 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 124.60 125.24 125.52 125.71 125.88 126.14 126.25 126.58 126.94 127.08 127.54 127.55 127.84 128.70 129.34 129.54 130.26 131.46 131.88 132.46 132.93 133.28 133.54 134.35 134.59 135.32 135.56 136.82 137.01 137.15 137.77 137.78 137.79 138.67 138.83 138.99 139.02 139.15 139.66 139.98 140.93 141.07 141.11 141.55 141.58 141.72 141.99 142.78 142.95 143.44 1.0 Notes 4930579G24Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page3 BC055324 Depdc1b Mms22l Rad54b Wdhd1 Cenpw Dnmt1 Cenpq Chtf18 Cenpu Cenpn Cdkn3 Kpna2 Trip13 Ccne2 Cks1b Rfwd3 Casc5 Gmnn Mcm2 Mcm6 Mcm7 Mcm4 Mcm5 Prim2 H2afx Pole2 Eme1 Prr11 Brip1 Gen1 Gsg2 Cdc7 Dsn1 Mtfr2 Hells Pcna Tipin Fen1 Ezh2 Orc6 Oip5 Rbl1 Rfc5 Rfc4 E2f8 Pole Blm Tk1 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 105.37 105.63 105.80 106.37 106.39 106.66 107.10 107.24 108.06 108.39 109.32 109.32 109.70 110.37 111.28 111.39 111.86 113.19 113.29 113.84 114.44 114.90 115.18 116.07 116.45 116.68 116.95 117.11 118.47 118.51 119.00 119.81 120.45 120.53 120.61 121.06 121.19 121.88 121.93 121.95 122.15 122.33 122.59 122.83 122.91 122.94 123.34 123.39 124.05 124.14 1.0 Notes 2810417H13Rik 4632434I11Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page4 BC030867 Arhgef39 Timeless Suv39h1 Fam83d Fam64a Nup107 Ccdc34 Hmgb2 Cenpm Chaf1b Mis18a Dlgap5 Dnajc9 Trim59 Rad54l Lmnb1 Whsc1 Iqgap3 Apitd1 Haus5 Fancb Mybl2 Mcm8 Hirip3 Gins2 Gtse1 Brca2 Diap3 Tfdp1 Palb2 Tcf19 Fanci G2e3 Rpa3 Rpa2 Neil3 Skp2 Pask Ska2 Orc1 Cdt1 Rfc3 Hat1 Lin9 Dhfr Pif1 Ttf2 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 82.24 83.17 84.03 84.81 86.13 86.65 86.72 86.76 87.01 87.79 87.82 87.86 88.26 89.81 89.98 90.30 90.49 90.52 90.79 91.14 91.48 91.99 92.36 93.83 94.14 94.20 94.23 95.34 95.80 96.14 96.34 96.49 96.89 96.96 97.52 97.65 97.88 98.45 98.58 98.72 98.73 98.73 99.60 100.10 100.60 101.29 103.10 103.75 103.86 103.87 1.0 Notes 2700029M09Rik 2700094K13Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page5 Rnaseh2b Suv39h2 Nup160 Anp32e Nup155 Nup133 Nucks1 Sapcd2 Hmgb3 Dnaaf2 Rbmx2 Ankle1 Smc1a Rbbp8 Lrrc40 Wdr90 Dtymk Stmn1 Nup85 Cep57 Cdca7 Ccne1 Haus4 Rad18 Haus1 Haus3 Tex30 Gins3 Larp7 Clhc1 Cse1l Psip1 Smc3 Smc4 Lsm2 Lin54 Msh6 Mns1 Nde1 Rpa1 Ppil1 Mtbp Nxt1 Rfc2 Eri1 Eri2 Lbr Cit 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 69.32 69.63 69.74 69.78 69.95 70.31 70.48 70.61 70.68 71.16 71.20 71.54 71.74 71.87 72.28 72.78 72.82 72.91 73.00 73.29 73.58 74.39 74.84 75.02 76.37 76.47 76.64 76.75 77.02 77.27 77.33 77.41 77.45 77.57 77.65 78.03 78.31 78.43 78.57 78.64 79.01 79.33 80.00 80.23 80.25 80.97 81.10 81.23 81.28 81.37 1.0 Notes 4930422G04Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page6 Tmem194 Fam111a Psmc3ip Snrnp40 Ankrd32 Efcab11 Fam72a Ranbp1 Anp32b Cenpc1 Pkmyt1 Rad51c Gpsm2 Nudt21 Zbtbd6 Gas2l3 Recql4 Zfp367 Nup93 Rqcd1 Haus6 Ddx39 Actl6a Cdca4 Chek2 Fanca Tacc3 Alyref Gins4 Ssrp1 Mis12 Rnf26 Defa3 Pold3 Pold1 Etaa1 Smc2 H2afz Lsm3 Mxd3 Usp1 Uba2 Xpo1 Terf1 Rcc1 Bora Rfc1 Taf5 Dck 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 54.58 54.70 55.10 55.50 55.90 56.50 56.59 56.59 57.36 57.89 58.71 58.71 58.71 59.16 59.38 59.79 60.03 60.54 60.56 61.56 61.65 61.91 61.97 61.98 62.01 62.12 62.48 62.56 62.84 63.42 63.59 64.02 64.22 64.22 64.33 64.45 64.64 64.75 65.54 65.62 66.04 67.84 67.91 68.07 68.28 68.55 68.63 68.65 68.94 69.00 1.0 Notes 4930427A07Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page7 Casp8ap2 Hnrnpab Tbc1d31 Donson Cdc25b Rbmxl1 Sephs1 Ccdc77 Cep152 Snrpa1 Rnf168 Trim37 Lmnb2 Mcph1 Kifc5b Ccnb1 Nedd1 Nup62 Nup43 Nup35 Rpp30 Pbdc1 Ddx20 Dpy30 Haus8 Reep4 Enkd1 Ddx11 Rad21 Tubg1 Lrwd1 Syce2 Hmmr Pold2 Uchl5 Tmpo Pms2 Sf3a3 Tonsl Wee1 Ndc1 Aaas Tdp1 Ints7 Hn1l Dis3 Nrm Lrr1 Ung 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 41.90 41.95 42.14 42.27 42.30 42.50 43.20 43.31 44.02 44.23 45.20 45.31 45.35 46.10 46.38 46.43 46.50 46.54 46.59 46.76 47.29 47.80 47.86 48.13 48.23 48.41 48.47 48.66 48.97 49.05 49.30 49.91 50.04 50.85 51.08 51.42 51.67 51.70 51.90 52.06 52.26 52.34 52.58 52.70 53.07 53.28 53.79 54.01 54.28 54.45 1.0 Notes D030056L22Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page8 Rnaseh2a Nsmce4a Smarca5 Anapc15 Tubgcp2 Tamm41 Nfatc2ip Hnrnpm Gemin2 Ncaph2 Tubb4b Hnrnpu Dazap1 Zmym1 Zcchc8 Arl6ip6 Supt16 Cdca7l Tcerg1 Mrpl18 Magoh Med14 Cenpo Kpnb1 Nelfcd Cep72 Myef2 Gstcd Bard1 Gmps Dars2 Banf1 Xrcc2 Phf5a Asf1a Siva1 Fancl Mnd1 Msh2 Mdc1 Srsf1 Pfas Lyar E2f1 Fzr1 Ctcf Dut Ttk Ilf2 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 29.97 30.00 30.06 31.21 31.23 32.06 32.12 32.38 32.39 32.43 33.35 33.42 33.50 33.58 33.98 34.35 34.67 34.79 35.07 35.42 35.57 35.93 36.17 36.25 36.34 36.39 36.54 36.80 36.81 36.88 36.97 37.05 37.21 37.24 37.65 37.69 37.79 37.82 37.94 38.05 38.22 38.77 38.99 39.06 39.36 40.09 40.11 40.27 40.55 41.29 1.0 Notes 1600002H07Rik 2610318N02Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page9 Tmem209 Zmynd19 Eif4enif1 Snrnp25 Smchd1 Prpf38a Anapc1 Cdc25a Mthfd1l Exosc2 Mcmbp Skiv2l2 Ppp1r8 Dctpp1 Hmgn5 Rbm8a Ruvbl2 Ruvbl1 Cmss1 Ppwd1 Gtf2e2 Rbbp7 Srsf10 Ncbp1 Nup50 Nup54 Usp39 Usp37 Snrpe Cenpt Parp2 Xrcc6 Recql Pole3 Snrpf Prpf3 Srsf4 Dna2 Fmr1 Hus1 Pmf1 Tcp1 Dbr1 Sfpq Iws1 Ipo9 Srrt Fxn 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 20.56 20.64 20.70 20.78 21.11 21.20 21.44 21.53 21.54 22.01 22.03 22.08 22.13 22.33 22.64 22.71 22.72 22.78 22.82 22.93 23.07 23.29 23.49 23.60 23.69 24.66 24.74 25.08 25.66 25.79 26.16 26.29 26.82 27.15 27.68 27.68 27.70 27.72 27.74 28.00 28.32 28.34 28.40 28.64 28.83 28.94 29.41 29.48 29.67 29.83 1.0 Notes 2700049A03Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page10 BC052040 Hmgxb4 Magohb Prpf40a Nudcd2 Wrap53 Cdc123 Ccdc14 Metap2 Rbm12 Ppm1g Trim28 Hnrnpf Knstrn Dnph1 Cenpa Nup88 Hdac1 Dhx15 Senp1 Cep78 Pds5b Rad50 Znhit3 Mbnl3 Snrpg Snrpc Nudt1 Troap Clspn Psrc1 U2af1 Pms1 Hyls1 Lsm6 Lsm4 Spidr Dcps Dkc1 Tdp2 Orc2 Hdgf Npat Piga Ipo5 Rif1 Eed Ncl Dtl 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 11.69 11.87 11.99 12.32 12.53 12.71 12.79 12.91 13.10 13.12 13.13 13.24 13.37 13.37 13.39 13.54 13.59 13.73 13.75 13.75 13.83 14.05 14.23 14.56 14.62 14.93 15.09 15.18 15.49 15.86 15.93 16.28 16.49 16.62 16.66 17.17 17.39 17.73 17.76 17.93 18.08 18.48 18.88 19.00 19.07 19.56 19.76 20.21 20.28 20.42 1.0 Notes 9430015G10Rik 4930503L19Rik 1200014J11Rik Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page11 Fam122b Cdk2ap1 Fam98b Ctdspl2 Nup188 Cdkn2c Exosc3 Rprd1b Nt5dc2 Wbp11 G3bp1 Polr2b Cpsf3l Kpna3 Nop58 Cops3 Ddx46 Cep44 Naa50 Ewsr1 Pspc1 Sap30 Mum1 Snrpb Parp1 Xrcc1 Nol11 Paics Mbd4 Med4 Myg1 Prpf4 Srsf3 Cstf2 Nudc Nop9 Dhx9 Ddx1 Vbp1 Nelfe Nfyb Utp6 Alg6 Ppat Api5 Ctc1 Me2 0.0 1.0

GSE38031 [8] GSE40513 [6]

GSE49194 [14] Scale ofaveragePearsoncorrelations GSE42049 [8] GSE19657 [21] GSE41342 [26] GSE16992 [48] GSE14004 [9] GSE12956 [10] 0.2 GSE17096 [20] GSE20513 [12] GSE31313 [22] GSE6933 [15] GSE13493 [6] GSE31598 [12] GSE13106 [10] GSE13563 [6] GSE15580 [14] 0.4 GSE15770 [8] GSE19925 [6] GSE19885 [9] GSE44355 [10] GSE51243 [7] GSE34618 [7] GSE11186 [33] GSE10871 [32] GSE22283 [8] 0.6 GSE16389 [18] GSE23496 [9] GSE11149 [8] GSE58307 [20] GSE7348 [6] GSE5332 [12] GSE34729 [6] GSE54653 [6] GSE51628 [15] 0.8 GSE15155 [12] GSE7302 [6] GSE55705 [10] GSE8357 [6] Score 5.60 5.70 5.92 5.93 5.97 6.02 6.05 6.16 6.18 6.19 6.21 6.74 6.75 7.21 7.39 7.42 7.58 7.69 7.74 7.75 7.76 8.08 8.14 8.16 8.27 8.32 8.45 8.73 8.76 8.84 8.89 9.57 9.73 9.76 9.81 9.84 9.90 10.00 10.04 10.16 10.34 10.64 10.83 10.93 11.24 11.29 11.30 11.50 11.64 11.66 1.0 Notes Symbol Num ofCEMGenes:12.Predicted583.SelectedDatasets:421.Strength:19.5 CEM 1,Geneset"[G]centriole",Page12 Ebna1bp2 Tmem107 Ankrd26 Nsmce2 Nudcd1 Prps1l3 Anapc5 Ppp1r7 Aarsd1 Pradc1 Nap1l1 Prpf31 Polr2d Cactin Cdan1 Nop56 Cep70 Casp2 Tubb5 Pa2g4 Naa15 Ssna1 Thoc6 Prmt1 Srbd1 Hmbs Nupl1 Phf10 Sart3 Bub3 Nanp Rad1 Xpo7 Slfn9 Eif4e Mlh1 Ubr7 Xkr5 Alg8 Polh E2f2 Taf9 Gart Set Atr 0.0 1.0

GSE38031 [8] GSE40513 [6]

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

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

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

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

0.456 Kernel fit Pairwise Correlations Normal fit

Density 0.228

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl_rep1ctrl_rep2 (0.127482)ctrl_rep3 (0.116827)ctrl_rep4 (0.114487)irr_rep1 (0.14065)irr_rep2 (0.101438)irr_rep3 (0.135747)irr_rep4 (0.123314) (0.140055) [ min ] [ medium ] [ max ] CEM 1 Birc5 830.7 4419.1 4636.2 P ( S | Z, I ) = 1.00 Plk4 220.0 741.6 911.5 Mean Corr = 0.95785 Cep55 362.0 2542.3 2800.6 Ccnf 172.8 631.7 755.3 Sass6 231.4 504.2 533.8 Cep192 414.5 731.0 818.3 Poc1a 137.1 375.1 388.4 Ccp110 347.8 475.5 556.8 Cep128 45.5 77.1 97.1 Cep76 361.1 489.8 545.5 Cenpj 199.0 330.1 399.6 Alms1 103.2 172.0 199.8 Bub1 289.5 1330.4 1476.3 Ncapg 150.5 678.5 800.4 Kif11 151.9 767.5 892.6 Ccna2 924.6 4522.5 4853.4 Tpx2 629.5 2939.5 3082.5 CEM 1 + Shcbp1 398.8 1375.5 1737.0 Top 10 Genes Cenpe 257.6 836.5 1126.9 Sgol1 296.6 1230.9 1354.2 Cdk1 1462.8 5168.1 5852.3 Kif20a 502.8 2079.7 2301.9

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE40513" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE40513 Status: Public on Oct 16 2012 Title: Gene expression profile of mouse breast cancer V720 cells treated with vehicle or PD 0332991 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23079655 Summary & Design: Summary: D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains which allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D associated kinase activity in mice bearing ErbB2-driven mammary carcinomas halted cancer progression and triggered tumor-specific senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing T-cell acute lymphoblastic leukemias (T-ALL) triggered tumorspecific apoptosis. Such selective killing of leukemic cells can be also achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Hence, contrary to what one might expect from ablation of a cell cycle protein, acute shutdown of a D-cyclin leads not only to cell cycle arrest, but it also triggers tumor cell senescence or apoptosis, and it affects different tumor types through distinct cellular mechanisms. Inhibiting cyclin D-activity represents a highly-selective anticancer strategy which specifically targets cancer cells without significantly affecting normal tissues.

Overall design: Mouse breast cancer V720 cells were cultured in the presence of the CDK4/6 inhibitor PD 0332991 (PD; 1 microM) or vehicle (VO) for 24 hrs. Experiment was done in biological triplicate. A total of 6 RNA samples (3 vehicle treated and 3 PD 0332991 treated samples) were used for microarray expression analysis.

Background corr dist: KL-Divergence = 0.0313, L1-Distance = 0.0429, L2-Distance = 0.0022, Normal std = 0.7225

0.600 Kernel fit Pairwise Correlations Normal fit

Density 0.300

0.000 CEM 1

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

Pre-normalization Quantiles

V720_vehicle_rep1V720_vehicle_rep2V720_vehicle_rep3 (0.191253)V720_PD0332991_rep1 (0.159136)V720_PD0332991_rep2 (0.146003)V720_PD0332991_rep3 (0.182805) (0.14276) (0.178042)[ min ] [ medium ] [ max ] CEM 1 Birc5 1585.2 4564.5 4643.2 P ( S | Z, I ) = 1.00 Plk4 248.4 658.8 722.3 Mean Corr = 0.95265 Cep55 958.0 3250.0 3447.5 Ccnf 136.0 401.0 458.9 Sass6 161.0 328.0 382.4 Cep192 971.0 1619.9 1693.4 Poc1a 92.3 148.4 172.4 Ccp110 390.3 666.7 672.4 Cep128 63.4 144.3 158.2 Cep76 221.3 285.3 327.2 Cenpj 462.0 610.4 652.0 Alms1 129.8 196.4 252.6 Bub1 608.4 2150.6 2190.0 Ncapg 514.7 1834.8 1920.4 Kif11 231.2 856.2 872.6 Ccna2 1538.2 4738.1 5049.6 Tpx2 536.7 1735.9 1836.1 CEM 1 + Shcbp1 799.9 2916.3 2967.0 Top 10 Genes Cenpe 325.4 1303.3 1396.0 Sgol1 297.9 1092.2 1197.8 Cdk1 3175.7 6326.4 6472.5 Kif20a 459.2 1928.7 2075.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE20954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.551 Kernel fit Pairwise Correlations Normal fit

Density 0.275

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse lung-embryoMouse lung-embryoMouse day lung-embryoMouse 12-rep1 day lung-embryoMouse 12-rep2 (0.113545) day lung-embryoMouse 14-rep1 (0.0888058) day lung-embryoMouse 14-rep2 (0.0746369) day lung-embryoMouse 16-rep1 (0.0641544) day lung-embryoMouse 16-rep2 (0.0672545) day lung-postnatalMouse 18-rep1 (0.0689904) day lung-postnatalMouse 18-rep2 (0.0532741) lung-postnatalMouseday (0.0597058) 2-rep1 lung-postnatalMouseday (0.0317655)2-rep2 lung-postnatalMouseday (0.0403115)10-rep1 lung-postnatalday 10-rep2 (0.0598578) day 30-rep1 (0.0626539) day 30-rep2 (0.096871)[ min (0.118174) ] [ medium ] [ max ] CEM 1 Birc5 91.1 620.8 4548.7 P ( S | Z, I ) = 1.00 Plk4 115.0 359.3 1263.9 Mean Corr = 0.94789 Cep55 92.4 624.4 2593.9 Ccnf 96.8 258.0 1432.3 Sass6 173.3 270.7 768.6 Cep192 278.5 473.6 1462.8 Poc1a 172.9 262.6 562.5 Ccp110 706.8 1085.6 1584.6 Cep128 68.5 149.1 308.7 Cep76 224.6 286.8 428.4 Cenpj 202.0 275.6 531.4 Alms1 79.3 145.6 245.7 Bub1 95.3 623.0 4385.5 Ncapg 30.7 185.4 1324.1 Kif11 69.9 248.7 1351.8 Ccna2 154.9 954.3 3800.4 Tpx2 90.4 384.0 2807.2 CEM 1 + Shcbp1 79.5 486.6 3056.0 Top 10 Genes Cenpe 82.4 350.7 1970.3 Sgol1 160.6 326.6 1445.7 Cdk1 138.5 1288.7 5556.8 Kif20a 49.9 395.3 3391.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE12454" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 13 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12454 Status: Public on Aug 01 2009 Title: The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18842153 Summary & Design: Summary: Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.

Overall design: At P0.5, n = 4 biological replicates of littermate-matched wt/ko pairs (for pair #2 there is one wt and 2 Atrx-null samples (2A & 2B) and we count this as 2 pairs).

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0308, L2-Distance = 0.0011, Normal std = 0.6463

0.648 Kernel fit Pairwise Correlations Normal fit

Density 0.324

0.000 CEM 1

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

Pre-normalization Quantiles

E13.5 wildE13.5 type wildE13.5 #1 type(0.0899184) wildE13.5 #2 type(0.0612903) Atrx-nullE13.5 #3 (0.0719907) Atrx-null E13.5#1 (0.0956645) Atrx-null P0.5#2 (0.0929674) wild P0.5#3 type (0.0933412) wild #1P0.5 type(0.0624947) wild #2P0.5 type(0.0967553) Atrx-null #3P0.5 (0.0811939) Atrx-null #1P0.5 (0.060798) Atrx-null #2AP0.5 (0.0563799) Atrx-null #2B (0.064938) #3 (0.0722677) [ min ] [ medium ] [ max ] CEM 1 Birc5 249.3 380.4 3544.3 P ( S | Z, I ) = 1.00 Plk4 215.3 315.4 1744.2 Mean Corr = 0.93199 Cep55 146.9 274.5 2688.9 Ccnf 171.3 214.4 1558.6 Sass6 158.7 304.7 513.5 Cep192 216.6 258.4 1136.8 Poc1a 165.9 250.6 422.8 Ccp110 886.8 1465.6 2162.0 Cep128 60.5 95.1 323.2 Cep76 109.9 160.5 669.3 Cenpj 197.4 316.9 738.2 Alms1 137.6 185.9 521.1 Bub1 84.4 153.0 2195.3 Ncapg 34.0 100.8 1078.0 Kif11 192.2 247.7 2015.0 Ccna2 442.4 726.6 3350.3 Tpx2 172.5 287.8 2265.6 CEM 1 + Shcbp1 117.8 253.1 2589.3 Top 10 Genes Cenpe 119.9 178.7 1319.7 Sgol1 52.5 167.3 1463.9 Cdk1 407.4 731.4 4345.7 Kif20a 59.1 111.1 1178.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE57543" 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=GSE57543 Status: Public on May 13 2014 Title: Expression data from B6 mouse miR-142 KO and WT T cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: T cells are critical for modulating immune responses. miRNAs are small, noncoding RNAs and play a significant role in T cell responses. miR-142 is a hematopoietic specific miRNA. To explore the potential role of miR-142 in regulating T cell responses, we generated mutant mice bearing a targeted deletion of the miR-142 gene.

We used microarrays to detail the global programme of gene expression underlying the profile changes between miR-142 KO and WT T cell and identified distinct classes of up-regulated genes during this process.

Overall design: miR-142 KO mice and WT littermates (biological triplicates) matched with age and sex were selected. T cells were purified from spleens by negative selection and processed for RNA isolation and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0094, L1-Distance = 0.0206, L2-Distance = 0.0006, Normal std = 0.8842

0.451 Kernel fit Pairwise Correlations Normal fit

Density 0.226

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 biologicalWT biological repWT 1 biological (0.147063) repKO 2biological (0.176279) repKO 3biological (0.153359) repKO 1 biological (0.166729) rep 2 (0.237037) rep 3 (0.119534)[ min ] [ medium ] [ max ] CEM 1 Birc5 1079.4 4492.1 6356.8 P ( S | Z, I ) = 1.00 Plk4 256.0 758.6 1060.5 Mean Corr = 0.90941 Cep55 323.0 1106.0 1201.9 Ccnf 154.7 678.9 1106.3 Sass6 225.7 504.1 626.6 Cep192 822.5 1083.0 1132.2 Poc1a 207.9 615.7 659.3 Ccp110 348.2 813.8 1116.7 Cep128 136.5 313.1 530.8 Cep76 346.6 902.3 1410.1 Cenpj 519.2 624.0 712.0 Alms1 50.3 144.5 218.3 Bub1 448.5 2500.6 3315.2 Ncapg 173.3 844.7 1201.4 Kif11 234.6 1063.3 1622.7 Ccna2 892.6 4896.2 6686.9 Tpx2 264.8 1491.2 2080.2 CEM 1 + Shcbp1 337.9 1423.8 1927.5 Top 10 Genes Cenpe 225.9 935.1 1298.0 Sgol1 291.9 1357.0 1901.1 Cdk1 756.0 3521.6 4546.7 Kif20a 254.9 1222.0 1950.1

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE17266" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 59 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17266 Status: Public on Jan 12 2010 Title: Expression data from B6C3F1 mice treated with baclofen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.

Overall design: Mice were sacrificed by cervical dislocation after either a single dose (1day) or 5 daily doses (5 days) of either baclofen or 0.5% methylcellulose two hours after the last dose. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 59 arrays.

Background corr dist: KL-Divergence = 0.0198, L1-Distance = 0.0483, L2-Distance = 0.0033, Normal std = 0.7864

0.507 Kernel fit Pairwise Correlations Normal fit

Density 0.254

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-vehicle-1day-repliver-baclofen-1day-repliver-baclofen-1day-rep 1liver-vehicle-1day-rep (0.0213056)liver-baclofen-1day-rep 1 (0.0245378)liver-vehicle-1day-rep 2 (0.0215661) 2liver-baclofen-1day-rep (0.0211164)liver-vehicle-5day-rep 3 (0.0262571) 3liver-baclofen-5day-rep (0.0228332)liver-vehicle-5day-rep 4 (0.0292622) 1liver-baclofen-5day-rep (0.0222621)liver-vehicle-5day-rep 1 (0.0217767) 2liver-baclofen-5day-rep (0.0221673)liver-vehicle-5day-rep 2 (0.0217623) 3liver-baclofen-5day-rep (0.0228831)liver-baclofen-5day-rep 3 (0.0249814) 4liver-baclofen-5day-rep (0.0222334)liver-baclofen-5day-rep 4 (0.0222075)liver-baclofen-5day-rep 5 (0.0243952)bone 6 (0.0220022) marrow-vehicle-1day-repbone 7 (0.0231722) marrow-baclofen-1day-repbone 8 (0.0242231) marrow-vehicle-1day-repbone marrow-baclofen-1day-repbone 1 (0.021406) marrow-vehicle-1day-repbone 1 (0.0136181) marrow-baclofen-1day-repbone 2 (0.0139316) marrow-vehicle-1day-repbone 2 (0.0126055) marrow-baclofen-1day-repbone 3 (0.0138898) marrow-vehicle-5day-repbone 3 (0.0137373) marrow-baclofen-5day-repbone 4 (0.0144481) marrow-vehicle-5day-repbone 4 (0.0173839) marrow-baclofen-5day-repbone 1 (0.0265669) marrow-vehicle-5day-repbone 1 (0.0166678) marrow-baclofen-5day-repbone 2 (0.0136172) marrow-vehicle-5day-repbone 2 (0.0176148) marrow-baclofen-5day-repbone 3 (0.0128396) marrow-baclofen-5day-repbone 3 (0.0157514) marrow-baclofen-5day-repbone 4 (0.0137358) marrow-baclofen-5day-repbone 4 (0.0141428) marrow-baclofen-5day-repspleen-vehicle-1day-rep 5 (0.0156609)spleen-baclofen-1day-rep 6 (0.0157121)spleen-vehicle-1day-rep 7 (0.0145291)spleen-baclofen-1day-rep 1 8 (0.01604) (0.0147853)spleen-vehicle-1day-rep 1 (0.0123431)spleen-baclofen-1day-rep 2 (0.00836818)spleen-vehicle-1day-rep 2 (0.0139168)spleen-baclofen-1day-rep 3 (0.0106222)spleen-vehicle-5day-rep 3 (0.0136965)spleen-baclofen-5day-rep 4 (0.00923059)spleen-vehicle-5day-rep 4 (0.015481)spleen-baclofen-5day-rep 1 (0.013319)spleen-vehicle-5day-rep 1 (0.0124913)spleen-baclofen-5day-rep 2 (0.0112159)spleen-vehicle-5day-rep 2 (0.0125891)spleen-baclofen-5day-rep 3 (0.00998797)spleen-baclofen-5day-rep 3 (0.00938683)spleen-baclofen-5day-rep 4 (0.00966492)spleen-baclofen-5day-rep 4 (0.0101362)spleen-baclofen-5day-rep 5 (0.0112294) 6 (0.0163571) 7 (0.0126407) 8 (0.0176945)[ min ] [ medium ] [ max ] CEM 1 Birc5 36.3 2404.1 7837.6 P ( S | Z, I ) = 1.00 Plk4 60.4 464.1 1809.0 Mean Corr = 0.90823 Cep55 27.7 350.2 1963.5 Ccnf 244.8 690.4 1863.3 Sass6 50.4 354.3 919.0 Cep192 82.9 739.1 1199.3 Poc1a 90.5 255.9 733.9 Ccp110 150.7 513.1 1134.8 Cep128 26.4 204.7 759.8 Cep76 72.0 427.2 1618.5 Cenpj 80.6 354.9 624.4 Alms1 37.3 121.9 222.1 Bub1 23.5 731.5 2834.4 Ncapg 26.3 364.2 1256.6 Kif11 44.2 394.2 2194.2 Ccna2 64.5 2076.2 7532.7 Tpx2 40.9 780.0 3250.9 CEM 1 + Shcbp1 32.1 520.0 1970.9 Top 10 Genes Cenpe 37.7 577.3 1981.2 Sgol1 99.1 627.6 1804.1 Cdk1 173.3 1282.1 5654.6 Kif20a 31.6 349.9 1685.4

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE15741" 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=GSE15741 Status: Public on Nov 10 2009 Title: Gene expression profiles of forced miR-200 expression in 344SQ lung adenocarcinoma cells with high metastatic potential Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19759262 Summary & Design: Summary: Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here we addressed this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. A feature of metastasis-prone tumor cells that distinguished them from metastasis-incompetent tumor cells was plasticity in response to changes in their microenvironment. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in 3-dimensional culture that underwent epithelial-mesenchymal transition (EMT) following treatment with transforming growth factor-beta or injection into syngeneic mice. This plasticity was entirely dependent upon the microRNA-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that microenvironmental cues direct tumor metastasis by regulating miR-200 expression.

Overall design: Cell lines from p53R172Hg/+ K-rasLA1/+ mice were derived from tumor tissues removed at autopsy from two different mice (#344 and #393). The tissues were minced, placed in culture, and passed serially in RPMI 1640 supplemented with 10% fetal bovine serum (FBS), which yielded mass populations of tumor cells derived from primary lung tumors (344P and 393P), mediastinal lymph nodes (344LN and 393LN), and a subcutaneous site (344SQ). Stable 344SQ cell lines expressing the miR-200b-200a-429 cluster or control vector were generated by transduction with lentivirus vectors. GFP positive transfectant pools were selected by growth in RPMI 1640 with 10% FBS and puromycin. RNA samples of miR-200b-200a-429 knockup versus control (from triplicate cultures of each) were processed and analyzed on Affymetrix Mouse Expression Array 430A 2.0 chips.

Background corr dist: KL-Divergence = 0.0327, L1-Distance = 0.0246, L2-Distance = 0.0007, Normal std = 0.6647

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

ControlControl A (0.144831)Control B (0.236451)429 C (0.10506) B (0.0954597)429 A (0.26145)429 C (0.156748) [ min ] [ medium ] [ max ] CEM 1 Birc5 167.9 4736.0 4758.2 P ( S | Z, I ) = 1.00 Plk4 219.5 1296.1 1640.7 Mean Corr = 0.90153 Cep55 900.5 4925.2 7004.6 Ccnf 37.4 370.1 497.9 Sass6 86.1 507.6 545.6 Cep192 308.4 1181.5 1408.1 Poc1a 80.0 266.8 285.7 Ccp110 171.6 331.7 536.1 Cep128 33.2 222.6 259.7 Cep76 161.9 199.7 243.8 Cenpj 101.0 205.4 238.7 Alms1 74.3 142.3 193.0 Bub1 241.4 2063.7 2386.9 Ncapg 149.8 1697.7 2114.2 Kif11 58.5 484.3 746.7 Ccna2 595.2 6334.9 6724.1 Tpx2 197.9 1065.9 1097.9 CEM 1 + Shcbp1 287.1 4173.1 5932.9 Top 10 Genes Cenpe 82.3 1152.8 1461.5 Sgol1 192.9 1760.0 1871.3 Cdk1 1511.0 5817.1 8028.5 Kif20a 45.4 774.1 1108.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE27605" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.614 Kernel fit Pairwise Correlations Normal fit

Density 0.307

0.000 CEM 1

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

Pre-normalization Quantiles

intestine-Lgr5High-R1intestine-Lgr5Low-R1intestine-EphB2High-R1 intestine-EphB2Medium-R1(0.134533) (0.0861672)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.101616)intestine-EphB2Medium-R2 (0.0554885)intestine-EphB2Low-R2 (0.177497) (0.143818) (0.0491514) (0.25173)[ min ] [ medium ] [ max ] CEM 1 Birc5 2365.3 6663.7 7308.3 P ( S | Z, I ) = 1.00 Plk4 82.6 309.9 430.4 Mean Corr = 0.89984 Cep55 333.0 1550.5 1900.7 Ccnf 111.7 544.3 716.2 Sass6 210.3 668.4 1003.9 Cep192 295.9 1271.1 1647.9 Poc1a 216.2 581.3 747.3 Ccp110 39.3 167.0 240.8 Cep128 33.0 96.7 131.0 Cep76 291.7 1062.2 1214.1 Cenpj 280.4 370.1 456.7 Alms1 36.2 220.5 304.2 Bub1 242.2 1544.5 1903.8 Ncapg 787.1 3310.9 4525.3 Kif11 91.6 591.0 810.8 Ccna2 982.1 3875.7 4870.2 Tpx2 238.2 1610.6 2318.3 CEM 1 + Shcbp1 420.3 2367.0 2814.5 Top 10 Genes Cenpe 260.1 1395.2 1780.3 Sgol1 356.0 1586.2 2101.5 Cdk1 773.8 3314.4 4331.3 Kif20a 198.6 1236.4 2091.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE54215" 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=GSE54215 Status: Public on Mar 02 2014 Title: Comparison of gene expression profiles of naÃ¯ve and in vitro effector CD8+ T cells from wild-type and BATF-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24584090 Summary & Design: Summary: The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.

Overall design: P14 TCR transgenic CD8+ T cells from wild-type or BATF-/- mice were examined either as naÃ¯ve cells or after 3 days of in vitro stimulation with antibodies to CD3 and CD28 in the presence of IL-2

Background corr dist: KL-Divergence = 0.0486, L1-Distance = 0.0713, L2-Distance = 0.0070, Normal std = 0.6584

0.695 Kernel fit Pairwise Correlations Normal fit

Density 0.348

0.000 CEM 1

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

Pre-normalization Quantiles

WT_P14_Naive_rep1WT_P14_Naive_rep2BATF_KO_P14_Naive_rep1 (0.107083)BATF_KO_P14_Naive_rep2 (0.106131)BATF_KO_P14_Naive_rep3WT_P14_D3_Effector_rep1 (0.102642)WT_P14_D3_Effector_rep2 (0.100908)WT_P14_D3_Effector_rep3 (0.114492)WT_P14_D3_Effector_rep4 (0.0660173)BATF_KO_P14_D3_Effector_rep1 (0.0520799)BATF_KO_P14_D3_Effector_rep2 (0.0485139)BATF_KO_P14_D3_Effector_rep3 (0.0707267)BATF_KO_P14_D3_Effector_rep4 (0.0732222) (0.0528098) (0.0483668)[ min (0.0570069) ] [ medium ] [ max ] CEM 1 Birc5 643.0 7210.7 8109.1 P ( S | Z, I ) = 1.00 Plk4 277.8 1395.9 1480.3 Mean Corr = 0.89903 Cep55 260.2 4928.3 5643.7 Ccnf 90.6 848.5 917.7 Sass6 283.0 620.3 772.8 Cep192 1211.3 2007.5 2121.6 Poc1a 175.3 972.3 1128.7 Ccp110 384.1 912.3 1143.6 Cep128 84.7 304.7 345.7 Cep76 231.3 323.2 384.5 Cenpj 587.8 854.2 1025.7 Alms1 55.6 123.6 174.7 Bub1 307.3 6553.5 7345.5 Ncapg 135.0 2297.7 2482.4 Kif11 182.4 1549.1 1781.7 Ccna2 808.6 9437.7 10151.6 Tpx2 163.4 2573.6 2878.6 CEM 1 + Shcbp1 385.7 3268.1 3732.3 Top 10 Genes Cenpe 200.9 2505.9 2635.2 Sgol1 224.3 2103.7 2202.5 Cdk1 414.6 5158.3 5403.1 Kif20a 191.4 2168.8 2337.6

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE50813" 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=GSE50813 Status: Public on Dec 31 2013 Title: Prevention of mammary tumor progression by silencing HoxA1 via intraductal injection of nanoparticle-formulated siRNA Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24382894 Summary & Design: Summary: Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.

Overall design: 8 week wild type FVB mouse whole mammary gland and 8week to 20 week transgenic FVB C3(1)-SV40Tag mouse whole mammary gland

Background corr dist: KL-Divergence = 0.1026, L1-Distance = 0.0245, L2-Distance = 0.0008, Normal std = 0.4380

0.911 Kernel fit Pairwise Correlations Normal fit

Density 0.455

0.000 CEM 1

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

Pre-normalization Quantiles

8 weeks8 wildweeks type8 wildweeks Mammary33 type8 wildweeks Mammary34 type8 wild(0.0229985)weeks Mammary35 type8 wild(0.0186263)weeks Mammary36 type8 tumor(0.0739053)weeks Mammary37 8Mammary1 tumor(0.0409156)weeks 8Mammary2 tumor(0.0173763)weeks (0.0208339) 8Mammary3 tumorweeks (0.014212) 12Mammary4 tumor weeks (0.0240723) 12Mammary5 tumorweeks (0.0317298)12 Mammary6 tumorweeks (0.0285796)12 Mammary7 tumorweeks (0.0235542)12 Mammary8 tumorweeks (0.0150119)16 Mammary9 tumorweeks (0.0192174)16 Mammary10 tumorweeks (0.0119949)16 Mammary11 tumorweeks (0.0115532)16 Mammary13 tumorweeks (0.0136611)16 Mammary14 tumorweeks (0.023188)20 Mammary15 tumorweeks (0.0200688)20 Mammary32 tumorweeks (0.0377181)20 Mammary22 tumorweeks (0.0280433)20 Mammary23 tumorweeks (0.0737463) Mammary24 tumor (0.118887) Mammary31 (0.178602) (0.131505)[ min ] [ medium ] [ max ] CEM 1 Birc5 116.6 950.2 3338.8 P ( S | Z, I ) = 1.00 Plk4 119.8 476.4 2273.2 Mean Corr = 0.89814 Cep55 54.5 682.3 2753.6 Ccnf 58.5 152.0 709.3 Sass6 133.9 283.1 648.6 Cep192 296.3 508.2 1243.6 Poc1a 80.7 147.0 317.2 Ccp110 304.3 479.1 1323.1 Cep128 29.9 65.1 278.2 Cep76 230.7 287.5 503.8 Cenpj 213.8 328.5 618.3 Alms1 91.5 148.1 339.4 Bub1 46.8 564.4 3046.0 Ncapg 28.1 194.9 1161.0 Kif11 54.2 290.1 941.9 Ccna2 201.4 2187.2 8165.3 Tpx2 102.7 402.1 2867.4 CEM 1 + Shcbp1 59.9 547.1 2804.4 Top 10 Genes Cenpe 69.3 431.6 2064.6 Sgol1 120.4 464.6 2417.7 Cdk1 212.1 1318.2 6335.5 Kif20a 60.1 378.7 1897.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE33308" 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=GSE33308 Status: Public on Jan 01 2013 Title: Keratinocyte Growth Factor and Dexamethasone Plus Elevated cAMP Levels Synergistically Support Pluripotent Stem Cell Differentiation into Alveolar Epithelial Type II Cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23176317 Summary & Design: Summary: Alveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.

Overall design: mESCs at d24 of differentiation with KGF and DCI treatment

Background corr dist: KL-Divergence = 0.0344, L1-Distance = 0.0193, L2-Distance = 0.0005, Normal std = 0.6401

0.623 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

mESCs mESCsat d8 of mESCsat differentiation d8 of mESCsat differentiation d17 of mESCs at(Control) differentiation d17 of mESCs atwith differentiation (0.313499)d17 KGF of mESCsat (Control)differentiation d17treatment of mESCsat withdifferentiation d24 (0.0481464) (0.192265) KGFof mESCsat withdifferentiation d24 treatment DCIof mESCsat withdifferentiation d24 treatment KGF(0.0577009)of at (Control)differentiation d24 and (0.0380081) of DCI withdifferentiation (0.0692612) treatment KGF with treatment DCI[ (0.031681) withmin treatment KGF(0.0744821) and] (0.0937887) DCI treatment[ medium (0.0811679) ] [ max ] CEM 1 Birc5 456.6 1683.7 4107.4 P ( S | Z, I ) = 1.00 Plk4 169.5 458.9 1024.7 Mean Corr = 0.89619 Cep55 321.6 1148.9 2018.9 Ccnf 135.4 312.5 960.1 Sass6 128.6 427.9 967.5 Cep192 350.8 661.5 1342.9 Poc1a 110.3 207.8 394.8 Ccp110 283.9 702.3 1018.3 Cep128 27.1 72.8 99.3 Cep76 144.7 167.7 287.5 Cenpj 137.8 251.0 553.1 Alms1 42.8 128.3 275.9 Bub1 400.5 1626.6 4064.9 Ncapg 102.3 378.8 876.6 Kif11 101.4 412.6 713.8 Ccna2 491.9 1601.8 3245.9 Tpx2 339.6 892.8 2309.9 CEM 1 + Shcbp1 239.1 968.3 2126.3 Top 10 Genes Cenpe 166.0 539.2 1339.9 Sgol1 199.1 572.5 1312.9 Cdk1 1144.7 3137.0 5440.3 Kif20a 245.1 789.3 2017.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE28621" 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=GSE28621 Status: Public on May 09 2014 Title: Transcriptional profiles of macrophages in resolving inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24762537 Summary & Design: Summary: We have performed a comprehensive transcriptional analysis of specific monocyte and macrophage (Mˆ) subsets during an acute self-resolving inflammatory insult. Following initial induction of acute inflammation, tissue resident (Resident) Mˆ are rapidly cleared from the inflammatory foci, only becoming recoverable as inflammation resolves. Monocytes are recruited to the inflammatory lesion where they differentiate into Mˆ. We term these monocyte-derived Mˆ inflammation-associated to distinguish them from Resident Mˆ which are present throughout the inflammatory response and can renew during the resolution of inflammation by proliferation. Comparative analysis of the Mo and Mˆ populations (both inflammation-associated and Resident Mˆ) identifies select genes expressed in subsets of inflammation-associated and Resident Mˆ that play important roles in the resolution of inflammation and/or for immunity, including molecules involved in antigen presentation, cell cycle and others associated with immaturity and Mˆ activation.

Overall design: We purified monocyte and macrophage populations from the peritoneal cavity of C57BL/6 mice 4, 18, 72 and 168 hours after the induction of inflammation with intraperitoneal administration of zymosan (2x10^7 particles). We also purified tissue resident macrophages and Ly-6B+ bone marrow monocytes from naive mice as reference populations.

Background corr dist: KL-Divergence = 0.1827, L1-Distance = 0.0365, L2-Distance = 0.0024, Normal std = 0.3564

1.131 Kernel fit Pairwise Correlations Normal fit

Density 0.565

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

F4/80(med-high),F4/80(med-high),F4/80(med-high), Ly-6B+F4/80(high), Ly-6B+inflammation-associatedF4/80(high), Ly-6B+inflammation-associated Ly-6B-F4/80(high), inflammation-associated inflammation-associatedLy-6B-Ly-6B+, inflammation-associatedLy-6B- macrophages_168Ly-6B+, Ly-6G- inflammation-associated macrophages_168Ly-6B+, inflammation-associatedLy-6G- macrophages_168 F4/80+, macrophages_168inflammation-associatedLy-6G- hours_biological F4/80+, macrophages_168CD11b+inflammation-associated hours_biological F4/80+,macrophages_168CD11b+ inflammation-associated hours_biological monocyte_4 hours_biological rep Ly-6B+/low,CD11b+ 1inflammation-associated (0.0330417)monocyte_4 hours_biological repLy-6B+/low, 2inflammation-associatedhours_biological (0.0352513)monocyte_4 hours_biological repLy-6G- repLy-6B+/low, 3hours_biological (0.0312205)1 macrophages_72inflammation-associatedLy-6G-(0.0386198) repF4/80(high), hours_biological 2 rep macrophages_72inflammation-associatedLy-6G-(0.0320674) rep F4/80(high),1 (0.0594599) 3 rep macrophages_72inflammation-associated(0.0283166)CD11b(high) hours_biological F4/80(high),2 (0.0768142) rep CD11b(high) hours_biological Ly-6B+Ly-6G-monocyte/macrophage_183 (0.0722328) peritoneal CD11b(high) hours_biologicalLy-6B+Ly-6G-monocyte/macrophage_18 rep peritoneal 1 residentbone Ly-6B+Ly-6G-monocyte/macrophage_18(0.021313) rep peritoneal marrow 2 residentbone macrophages_naive_biological(0.0468061) rep hours_biologicalmarrow monocyte_biological3 residentbone macrophages_naive_biological(0.0300956) hours_biologicalmarrow monocyte_biological macrophages_naive_biological hours_biological monocyte_biological rep[ min 1 rep (0.0308518) rep 1 rep (0.11448) 2 ]rep (0.0426244)1 rep(0.0313467) 2 rep (0.0617756) 3 rep (0.0464738)2 (0.0299339) 3 rep [(0.112551) medium3 (0.0247232) ] [ max ] CEM 1 Birc5 7.9 533.1 4271.1 P ( S | Z, I ) = 1.00 Plk4 96.4 215.9 1199.1 Mean Corr = 0.89201 Cep55 47.7 522.8 4589.3 Ccnf 17.6 219.7 1435.3 Sass6 140.6 315.2 745.6 Cep192 126.0 386.4 1378.4 Poc1a 38.9 125.9 575.6 Ccp110 86.1 207.0 466.6 Cep128 19.8 89.7 343.6 Cep76 75.1 144.3 394.8 Cenpj 186.4 313.8 685.0 Alms1 5.1 67.2 139.2 Bub1 2.6 347.4 3384.5 Ncapg 1.8 172.2 1845.2 Kif11 33.3 287.0 3254.9 Ccna2 64.8 689.3 6366.1 Tpx2 42.5 385.0 4768.5 CEM 1 + Shcbp1 5.1 495.7 4475.7 Top 10 Genes Cenpe 2.2 188.2 2231.6 Sgol1 16.7 204.8 1469.8 Cdk1 33.6 720.9 6106.1 Kif20a 20.5 215.5 1975.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE44260" 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=GSE44260 Status: Public on Mar 06 2013 Title: Murine germinal center and naive B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23514741 Summary & Design: Summary: Gene expressions of murine germinal center and naive B cells on Affymetrix platform

Overall design: The experiment include 3 d14 GC B1-8, 3 d14 GC V23 and 4 NaÃ¯ve samples

Background corr dist: KL-Divergence = 0.0522, L1-Distance = 0.0558, L2-Distance = 0.0041, Normal std = 0.6145

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

Navie_rep1Navie_rep2 (0.109929)Navie_rep3 (0.10181)Navie_rep4 (0.116788)d14 GC(0.106553) d14B1-8_rep1 GC d14B1-8_rep2 (0.0740004)GC d14B1-8_rep3 (0.0860252)GC d14V23_rep1 (0.0689415)GC d14V23_rep2 (0.0994814) GC V23_rep3 (0.0987318) (0.137741) [ min ] [ medium ] [ max ] CEM 1 Birc5 310.1 4721.0 5699.5 P ( S | Z, I ) = 1.00 Plk4 243.8 1516.7 1891.4 Mean Corr = 0.89144 Cep55 372.0 5841.2 6310.7 Ccnf 130.4 1096.1 1531.1 Sass6 232.3 471.1 611.9 Cep192 953.9 1501.3 1717.5 Poc1a 161.0 683.7 833.9 Ccp110 467.8 931.8 1364.6 Cep128 205.6 419.1 629.0 Cep76 134.2 223.7 288.5 Cenpj 433.9 650.2 774.6 Alms1 38.9 201.5 256.7 Bub1 187.9 2176.6 2936.7 Ncapg 165.2 2923.5 3297.5 Kif11 166.8 1619.1 2254.5 Ccna2 430.7 4564.9 5583.5 Tpx2 187.2 2359.0 3519.5 CEM 1 + Shcbp1 303.5 3771.8 5300.2 Top 10 Genes Cenpe 179.9 2475.2 3170.6 Sgol1 145.5 1437.1 2147.8 Cdk1 319.5 3890.5 4792.0 Kif20a 108.7 1420.7 1826.4

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE21224" 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=GSE21224 Status: Public on Oct 01 2010 Title: Transcriptional ontogeny of the developing liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22260730 Summary & Design: Summary: We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.

Keywords: gene expression/microarray

Overall design: We characterized gene expression changes in the developing mouse liver at gestational days (GD) 19 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 16 samples, with four mice in each of the four age groups, were analyzed.

Background corr dist: KL-Divergence = 0.0715, L1-Distance = 0.0857, L2-Distance = 0.0154, Normal std = 0.5557

0.910 Kernel fit Pairwise Correlations Normal fit

Density 0.455

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_GD19_4Mouse liver_GD19_5Mouse (0.106293) liver_GD19_10Mouse (0.0862959) liver_GD19_18Mouse liver_PND7_26Mouse(0.104255) liver_PND7_29Mouse(0.111198) liver_PND7_30Mouse(0.0402912) liver_PND7_31Mouse(0.0259464) liver_PND32_33Mouse(0.0318992) liver_PND32_34Mouse(0.0312285) liver_PND32_37Mouse (0.0597194) liver_PND32_40Mouse (0.0437398) liver_PND67_45Mouse (0.0493318) liver_PND67_46Mouse (0.0397925) liver_PND67_47Mouse (0.058346) liver_PND67_49 (0.0558409) (0.0513077) (0.104515)[ min ] [ medium ] [ max ] CEM 1 Birc5 6.5 984.1 3969.3 P ( S | Z, I ) = 1.00 Plk4 14.7 232.3 666.8 Mean Corr = 0.88449 Cep55 6.5 381.1 697.2 Ccnf 299.3 553.8 1339.2 Sass6 28.8 164.8 437.4 Cep192 131.2 503.4 1204.0 Poc1a 52.5 135.2 305.0 Ccp110 94.2 196.1 671.9 Cep128 7.6 49.0 264.4 Cep76 141.5 252.6 1202.7 Cenpj 84.4 208.8 374.0 Alms1 6.4 45.2 114.2 Bub1 6.5 375.3 1408.1 Ncapg 6.5 385.5 1680.2 Kif11 11.1 294.9 1412.0 Ccna2 8.3 1517.1 5025.6 Tpx2 55.2 484.4 1929.7 CEM 1 + Shcbp1 7.6 656.7 1544.3 Top 10 Genes Cenpe 6.5 193.9 861.6 Sgol1 6.5 63.5 1166.1 Cdk1 104.0 2388.5 5927.0 Kif20a 7.6 412.0 994.3

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE23845" 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=GSE23845 Status: Public on Aug 28 2010 Title: Time course for bladder UCC development in UPII-SV40Tag mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20501863 Summary & Design: Summary: We have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive UCC, respectively

Analysis of the microarray data sets has revealed …1,900 unique genes differentially expressed (¥3-fold difference at one or more time points) between wild-type and UPII-SV40Tag urothelium during the time course of tumor development.

Overall design: RNA from the urothelium of duplicate UPII-SV40Tag hemizygous and age-matched wild type littermate mice was isolated at 3, 6, 20, and 30 weeks of age and gene expression profiles were obtained.

Background corr dist: KL-Divergence = 0.1356, L1-Distance = 0.0293, L2-Distance = 0.0013, Normal std = 0.3985

1.002 Kernel fit Pairwise Correlations Normal fit

Density 0.501

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

3wk Wild3wk type Wild biological3wk type UPII-SV40Tag biological3wk rep UPII-SV40Tag #16wk (0.0620159) rep biological Wild #26wk (0.0465113)type biological UPII-SV40Tag repbiological6wk #1 UPII-SV40Tag (0.0533182) rep20wk rep #2 biological Wild(0.0625464)#120wk (0.0633691) type biological Wild rep20wk biological type#1 UPII-SV40Tag(0.0524197) rep20wk biological #2rep UPII-SV40Tag(0.0661204) 30wk#1 (0.0466318) rep biological Wild 30wk#2 (0.0631804)type biological Wild30wk repbiological type #1 UPII-SV40Tag (0.06994)30wk repbiological rep #2 UPII-SV40Tag (0.0587007)#1 (0.0869504) rep biological #2 (0.0740381) biological rep #1 (0.129167) [rep min #2 (0.0650902) ] [ medium ] [ max ] CEM 1 Birc5 4.4 3844.9 5856.6 P ( S | Z, I ) = 1.00 Plk4 5.1 742.3 1395.2 Mean Corr = 0.87972 Cep55 52.7 3571.5 5789.7 Ccnf 3.6 695.7 1265.4 Sass6 27.2 590.9 925.5 Cep192 357.3 935.2 1165.7 Poc1a 50.3 330.1 472.4 Ccp110 93.9 443.2 786.8 Cep128 19.7 210.0 514.1 Cep76 152.6 434.0 701.2 Cenpj 78.1 375.4 944.3 Alms1 34.4 134.1 294.1 Bub1 3.5 1953.6 2795.0 Ncapg 2.0 1119.2 2199.4 Kif11 4.3 658.3 1036.3 Ccna2 6.9 4376.2 9257.7 Tpx2 137.2 2280.2 3021.6 CEM 1 + Shcbp1 2.7 2168.6 4586.5 Top 10 Genes Cenpe 2.5 941.5 1566.3 Sgol1 26.0 1207.2 2216.1 Cdk1 13.0 6716.5 8841.8 Kif20a 3.5 1020.8 1989.6

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE39082" 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=GSE39082 Status: Public on Jul 04 2012 Title: Expression data from cultured c-Kit+Sca-1+Lin- (KSL)cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The Notch signaling pathway plays a critical role in regulating the proliferation and differentiation of stem and progenitor cells including hematopoietic stem and progenitor cells (HSPCs). Notch receptors and ligands are expressed in BM stromal and hematopoietic cells. A large body of evidence has demonstrated that activating Notch signaling enhances HSCs self-renewal and facilitates its expansion ex vivo. We report that an endothelium-targeted soluble Notch ligand, the DSL domain of mouse Delta-like 1 fused with a RGD motif (mD1R), efficiently promotes the expansion ex vivo of mouse bone marrow HSPCs in a Notch signaling and endocytosis dependent manner. HSPCs expanded in the presence of mD1R kept long-term HSPC repopulation capacity.

We used microarrays to compare the gene expression profiles of HSPCs expanded in the presence of PBS and mD1R.

Overall design: KSL cells were plated on Human umbilical vein endothelial cells (HUVECs) and cultured in a serum-free medium supplemented with a cocktail containing 5 types of mouse cytokines (m5GF) in the presence of PBS or mD1R for 7 days. Then KSL cells were sorted from these cultured hematopoietic cells for RNA extraction and hybridization on Affymetrix microarrays. The experiments were repeated 3 times.

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0284, L2-Distance = 0.0010, Normal std = 0.6605

0.620 Kernel fit Pairwise Correlations Normal fit

Density 0.310

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

PBS-expandedPBS-expanded PBS-expandedKSL cells, mD1R-expandedKSL biological cells, mD1R-expandedKSL biological cells, rep1mD1R-expanded KSL biological(0.213321) rep2cells, KSL (0.120122) biological rep3cells, KSL (0.162105) biological cells, rep1 biological(0.180043)[ rep2 min (0.191549) rep3 ] (0.132861) [ medium ] [ max ] CEM 1 Birc5 845.5 4340.1 6289.3 P ( S | Z, I ) = 1.00 Plk4 245.6 656.7 1014.3 Mean Corr = 0.87641 Cep55 628.6 2308.8 2740.8 Ccnf 239.0 858.7 1102.3 Sass6 215.0 572.8 697.7 Cep192 856.8 1092.6 1356.9 Poc1a 182.5 573.4 713.6 Ccp110 408.5 834.3 1077.7 Cep128 87.0 405.1 526.3 Cep76 215.1 283.9 376.4 Cenpj 496.0 898.2 973.4 Alms1 71.9 125.8 231.1 Bub1 586.1 1962.4 2639.1 Ncapg 267.0 827.8 1439.1 Kif11 229.1 1293.1 1952.8 Ccna2 1066.9 4159.9 4947.6 Tpx2 498.6 1575.4 1808.2 CEM 1 + Shcbp1 326.3 2041.4 3043.0 Top 10 Genes Cenpe 255.7 1091.4 1387.1 Sgol1 213.1 834.9 1099.7 Cdk1 1353.8 4088.1 6023.7 Kif20a 126.0 966.0 1169.3

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE23925" 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=GSE23925 Status: Public on Sep 07 2010 Title: Gene expression in germinal center light zone, dark zone, and naÃ¯ve B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21074050 Summary & Design: Summary: Microarrays of gene expression in mouse germinal center B cells photoactivated in the light zone or dark zone, and of naÃ¯ve cells for comparison.

We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of the germinal center.

Overall design: Light and dark zone cells were photoactivated in day 7 germinal centers and sorted by flow cytometry. NaÃ¯ve splenic B cells(IgD+CD19+) were sorted for comparison.

Background corr dist: KL-Divergence = 0.0123, L1-Distance = 0.0424, L2-Distance = 0.0027, Normal std = 0.8861

0.450 Kernel fit Pairwise Correlations Normal fit

Density 0.225

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

light zone,light biological zone,dark biological zone, replicatedark biological zone, replicatenaive, 1 (0.0795287) biological replicatebiologicalnaive, 2 (0.0842003) replicatebiological 1 replicate(0.137165) 2 replicate(0.118704) 1 (0.188215) 2 (0.392188)[ min ] [ medium ] [ max ] CEM 1 Birc5 49.8 3485.6 7102.1 P ( S | Z, I ) = 1.00 Plk4 140.8 1324.0 1551.7 Mean Corr = 0.87523 Cep55 56.9 3927.6 7615.9 Ccnf 181.6 845.9 1433.6 Sass6 219.6 679.3 806.5 Cep192 175.2 1668.0 2163.9 Poc1a 183.4 258.0 407.8 Ccp110 95.6 1263.1 1454.9 Cep128 144.2 238.2 336.0 Cep76 107.8 256.0 312.5 Cenpj 163.9 722.8 944.5 Alms1 66.2 263.9 298.3 Bub1 56.8 2543.0 3831.7 Ncapg 44.8 2403.0 3560.3 Kif11 81.1 1574.5 2395.7 Ccna2 216.1 6329.6 10083.2 Tpx2 99.4 1510.7 3574.8 CEM 1 + Shcbp1 75.1 2056.1 3643.8 Top 10 Genes Cenpe 83.5 1854.2 3778.7 Sgol1 113.1 1521.9 2369.4 Cdk1 97.1 3285.7 5939.8 Kif20a 44.9 1246.7 2971.9

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE17794" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 44 -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=GSE17794 Status: Public on Jan 11 2010 Title: Expression data from B6C3F1 mice treated with 2-butoxyethanol Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.

Overall design: Mice were euthanased by cervical dislocation under ketamine / acepromazine (100 mg/kg / 5 mg/kg, I.P) anesthesia. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 44 arrays.

Background corr dist: KL-Divergence = 0.0249, L1-Distance = 0.0283, L2-Distance = 0.0013, Normal std = 0.6953

0.574 Kernel fit Pairwise Correlations Normal fit

Density 0.287

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-vehicle-4hours-repliver-vehicle-4hours-repliver-vehicle-4hours-repliver-2BE-4hours-rep 1 (0.0277859)liver-2BE-4hours-rep 2 (0.0239444)liver-2BE-4hours-rep 3 (0.0316408) 1liver-2BE-4hours-rep (0.0273627) 2spleen-vehicle-4hours-rep (0.0292661) 3spleen-vehicle-4hours-rep (0.0284801) 4spleen-vehicle-4hours-rep (0.0317573)spleen-vehicle-4hours-rep 1 (0.0147419)spleen-2BE-4hours-rep 2 (0.0139449)spleen-2BE-4hours-rep 3 (0.0131658)spleen-2BE-4hours-rep 4 (0.0105391)spleen-2BE-4hours-rep 1 (0.0220999)liver-vehicle-7days-rep 2 (0.0160422)liver-vehicle-7days-rep 3 (0.0132713)liver-vehicle-7days-rep 4 (0.0158178)liver-vehicle-7days-rep 1 (0.0233177)liver-2BE-7days-rep 2 (0.0248294)liver-2BE-7days-rep 3 (0.0265061)liver-2BE-7days-rep 4 (0.0244403) 1 (0.0235049)liver-2BE-7days-rep 2 (0.0273576)liver-2BE-7days-rep 3 (0.0239671)bone 4marrow-vehicle-7days-rep (0.024754)bone 5marrow-vehicle-7days-rep (0.0321895)bone marrow-vehicle-7days-repbone marrow-vehicle-7days-repbone 1 (0.0187698) marrow-vehicle-7days-repbone 2 (0.0187984) marrow-2BE-7days-repbone 3 (0.0205829) marrow-2BE-7days-repbone 4 (0.015543) marrow-2BE-7days-repbone 5 (0.0197145) marrow-2BE-7days-rep 1bone (0.024179) marrow-2BE-7days-rep 2spleen-vehicle-7days-rep (0.0256261) 3spleen-vehicle-7days-rep (0.0239546) 4spleen-vehicle-7days-rep (0.0253523) 5spleen-vehicle-7days-rep (0.0194579) 1 (0.0187763)spleen-vehicle-7days-rep 2 (0.0105474)spleen-2BE-7days-rep 3 (0.0136731)spleen-2BE-7days-rep 4 (0.010853)spleen-2BE-7days-rep 5 (0.0160466) spleen-2BE-7days-rep1 (0.033182) spleen-2BE-7days-rep2 (0.0510161) 3 (0.0296192) 4 (0.0375807) 5 (0.0160003)[ min ] [ medium ] [ max ] CEM 1 Birc5 45.2 2845.4 11317.0 P ( S | Z, I ) = 1.00 Plk4 74.9 554.5 2228.2 Mean Corr = 0.87192 Cep55 25.0 262.9 1326.3 Ccnf 218.0 693.3 2494.0 Sass6 48.8 400.1 1021.2 Cep192 71.7 870.1 1410.6 Poc1a 108.2 300.8 829.6 Ccp110 159.5 516.2 1554.2 Cep128 29.3 239.1 718.6 Cep76 83.5 593.8 2843.7 Cenpj 46.1 339.5 482.4 Alms1 33.4 116.7 343.2 Bub1 25.3 718.0 2602.6 Ncapg 26.2 530.3 2086.2 Kif11 48.6 570.5 3367.1 Ccna2 100.9 2548.0 10211.9 Tpx2 38.9 1126.5 4262.7 CEM 1 + Shcbp1 44.8 480.4 1987.5 Top 10 Genes Cenpe 36.4 716.8 3327.8 Sgol1 80.3 733.4 3602.8 Cdk1 208.2 1490.7 6496.1 Kif20a 35.0 377.6 1763.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE28457" 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=GSE28457 Status: Public on May 31 2012 Title: Gene expression profile of E1A infected C2C12 myotubes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23027903 Summary & Design: Summary: Proliferating C2C12 myoblasts were induced to differentiate into myotubes and then infected with adenovirus expressing E1A (Ad-E1A), which induces cell cycle re-entry and dedifferentiation.

We analyzed the transcriptional profile of E1A infected C2C12-myotubes through the Affymetrix Mouse Genome 430 2.0 Array, searching for genes that were significantly regulated between two independent biological replicates at two different time points (24h and 36h after infection with Ad-E1A). In addition, we took advantage of the E1A mutant known as YH47/dl928 (hereafter referred as YH47), which bears two mutations in the pocket-binding region of E1A (Y48H, C124G) able to disrupt the interaction with Rb and its cognate proteins and to impair cell-cycle re-entry phenotype. YH47 mutant was used to identify the Rb independent transcriptional reprogramming of C2C12.

Overall design: C2C12 cells were differentiated in vitro to myotubes as previously described. Myotubes were, then, infected with an adenovirus carrying the 12S form of E1A (dl520), with the YH47 E1A mutant (dl928) or with a control adenovirus (CTR) expressing a deletion of essentially the entire E1A gene (dl312). Two different time points after infection were considered (24 hours and 36 hours) to evaluate changes in C2C12 cells expression profile. Technical (A or B) and biological replicates (EXP1 or EXP2) were done for each condition.

Background corr dist: KL-Divergence = 0.1997, L1-Distance = 0.0314, L2-Distance = 0.0016, Normal std = 0.3411

1.170 Kernel fit Pairwise Correlations Normal fit

Density 0.585

0.000 CEM 1

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

Pre-normalization Quantiles

C2C12, C2C12,dl312 infected, C2C12,dl312 infected, C2C12, dl31224h, biological infected, C2C12, dl31224h, biological infected, C2C12, dl520 36h,replicate biological infected, C2C12, dl520 36h,replicate 2, technicalbiological infected, C2C12, dl520 24h,replicate 1, technicalbiological infected, replicateC2C12, dl520 24h,replicate 2, technicalbiological infected, replicateC2C12, dl928 36h,replicate A 1, (0.0510962) technicalbiological infected, replicateC2C12, dl928 36h,replicate A 2, (0.0251635) technicalbiological infected, replicateC2C12, dl928 24h,replicate A 1, (0.0318473) technicalbiological infected, replicateC2C12, dl928 24h,replicate A 2, (0.0547156) technicalbiological infected, replicateC2C12, dl312 36h,replicate A 1, (0.0383651) technicalbiological infected, replicateC2C12, dl312 36h,replicate A 2, (0.0252594) technicalbiological infected, replicateC2C12, dl312 24h,replicate A 1, (0.0945556) technicalbiological infected, replicateC2C12, dl312 24h,replicate A 2, (0.0672395) technicalbiological infected, replicateC2C12, dl520 36h,replicate A 1, (0.027389) technicalbiological infected, replicateC2C12, dl520 36h,replicate A 2, (0.0239407) technicalbiological infected, replicateC2C12, dl520 24h,replicate A 1, (0.032553) technicalbiological infected, replicateC2C12, dl520 24h,replicate A 2, (0.0283988) technicalbiological infected, replicateC2C12, dl928 36h,replicate B 1, (0.0317511) technicalbiological infected, replicateC2C12, dl928 36h,replicate B 2, (0.0373693) technicalbiological infected, replicateC2C12, dl928 24h,replicate B 1, (0.0401345) technicalbiological infected, replicate dl928 24h,replicate B 2, (0.0516449) technicalbiological infected, replicate 36h,replicate B 1, (0.0349148) technicalbiological replicate 36h,replicate B 2, (0.0222913) technicalbiological replicate[ replicate B 1,min (0.0876563) technical replicate replicate B 2, (0.0794639) ]technical replicate B 1, (0.0262993) technical replicate B[ (0.028015) medium replicate B (0.0341919) B (0.0257439) ] [ max ] CEM 1 Birc5 152.9 827.5 7598.7 P ( S | Z, I ) = 1.00 Plk4 19.8 170.7 989.4 Mean Corr = 0.87045 Cep55 67.2 284.6 3005.3 Ccnf 155.6 491.8 1411.0 Sass6 21.4 111.2 390.5 Cep192 156.5 353.5 788.5 Poc1a 23.0 181.0 569.3 Ccp110 112.2 358.1 802.7 Cep128 21.5 56.1 282.5 Cep76 300.1 505.1 997.2 Cenpj 94.7 251.2 666.2 Alms1 89.5 153.2 291.5 Bub1 10.7 288.9 3127.9 Ncapg 5.2 146.0 1395.5 Kif11 88.0 205.4 1050.0 Ccna2 228.9 701.6 4690.7 Tpx2 121.0 353.6 2192.5 CEM 1 + Shcbp1 3.4 176.2 2298.1 Top 10 Genes Cenpe 82.0 158.3 1263.1 Sgol1 7.6 178.1 1518.2 Cdk1 309.9 1198.9 8789.1 Kif20a 97.1 280.6 2542.3

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE30160" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.522 Kernel fit Pairwise Correlations Normal fit

Density 0.261

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild replicate typewild replicate 1 type (0.341616)knockin replicate 2 (0.103038)knockin replicate 3 (0.107341)knock replicate 1 (0.234617) in replicate 2 (0.117562) 3 (0.0958254)[ min ] [ medium ] [ max ] CEM 1 Birc5 2674.5 4239.7 5305.6 P ( S | Z, I ) = 1.00 Plk4 322.8 594.0 860.9 Mean Corr = 0.87005 Cep55 1065.8 1826.2 2601.0 Ccnf 488.4 1039.0 1629.4 Sass6 604.6 714.7 944.5 Cep192 1013.0 1113.4 1193.9 Poc1a 439.0 549.1 664.5 Ccp110 292.8 396.9 502.2 Cep128 193.5 258.4 351.2 Cep76 277.0 432.7 467.9 Cenpj 339.5 364.4 403.0 Alms1 71.2 90.8 100.8 Bub1 1234.0 2924.4 3664.8 Ncapg 286.3 584.5 826.9 Kif11 454.0 820.9 1249.0 Ccna2 1868.3 3449.8 4514.9 Tpx2 766.4 1251.6 1605.2 CEM 1 + Shcbp1 791.9 1710.6 2272.5 Top 10 Genes Cenpe 754.9 1206.6 1541.5 Sgol1 449.7 813.9 1334.2 Cdk1 2128.5 4240.2 5976.7 Kif20a 674.7 1335.5 1915.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE51883" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 30 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51883 Status: Public on Jan 28 2014 Title: Effect of Mirn378 overexpression on gene expression during C2C12 myogenic and BMP2-induced osteogenic differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Background: MicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. As such, they are believed to play a role in regulating the step-wise changes in gene expression patterns that occur during cell fate specification of multipotent stem cells. Here, we have studied whether terminal differentiation of C2C12 myoblasts is indeed controlled by lineage-specific changes in miRNA expression.

Results: Using a previously generated RNA polymerase II (Pol-II) ChIP-on-chip dataset, we show differential Pol-II occupancy at the promoter regions of six miRNAs during C2C12 myogenic versus BMP2-induced osteogenic differentiation. Overexpression of one of these miRNAs, miR-378, enhances Alp activity, calcium deposition and mRNA expression of osteogenic marker genes in the presence of BMP2.

Conclusions: Our results demonstrate a previously unknown role for miR-378 in promoting BMP2-induced osteogenic differentiation. #!#

Overall design: Stable C2C12 cell lines C2C12-pMirn0 and C2C12-pMirn378 were generated by lentiviral transduction of C2C12 myoblasts with a Mirn378-overexpression construct and its parent vector, respectively. C2C12-pMirn0 and C2C12-pMirn378 cells were plated at 2.5 x 10^4 cells/cm2 (day -1), cultured for 1 day in DMEM 10%NCS, then (d0) treated with or without 300 ng/ml bone morphogenetic protein 2 (BMP2) for 6 days. RNA was extracted on d0, d3 and d6 and hybridized to GeneChip Mouse Genome 430 2.0 array (Affymetrix).

Background corr dist: KL-Divergence = 0.1521, L1-Distance = 0.0728, L2-Distance = 0.0106, Normal std = 0.4058

1.104 Kernel fit Pairwise Correlations Normal fit

Density 0.552

0.000 CEM 1

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

Pre-normalization Quantiles

C2C12-pMirn0_d0_rep1C2C12-pMirn0_d0_rep2C2C12-pMirn0_d0_rep3C2C12-pMirn0_day (0.0794504)C2C12-pMirn0_day (0.0761411)C2C12-pMirn0_day (0.0574214) 3_untreated_rep1C2C12-pMirn0_day 3_untreated_rep2C2C12-pMirn0_day 3_untreated_rep3 C2C12-pMirn0_day(0.0206786) 6_untreated_rep1 C2C12-pMirn0_day(0.0229841) 6_untreated_rep2 C2C12-pMirn0_day(0.0214533) 6_untreated_rep3 C2C12-pMirn0_day(0.0289088) 3_BMP2 C2C12-pMirn0_day(0.0292268) 3_BMP2 treated_rep1 C2C12-pMirn0_day(0.0214021) 3_BMP2 treated_rep2C2C12-pMirn0_day (0.015538)6_BMP2 treated_rep3C2C12-pMirn378_d0_rep1 (0.0257751)6_BMP2 treated_rep1C2C12-pMirn378_d0_rep2 (0.0186713)6_BMP2 treated_rep2C2C12-pMirn378_d0_rep3 (0.0261299) treated_rep3C2C12-pMirn378_day (0.0722184)(0.0244741)C2C12-pMirn378_day (0.0621007)(0.0214125)C2C12-pMirn378_day (0.0612004) 3_untreated_rep1C2C12-pMirn378_day 3_untreated_rep2C2C12-pMirn378_day 3_untreated_rep3C2C12-pMirn378_day (0.023897) 6_untreated_rep1C2C12-pMirn378_day (0.0282376) 6_untreated_rep2C2C12-pMirn378_day (0.0331168) 6_untreated_rep3C2C12-pMirn378_day (0.0199652) 3_BMP2C2C12-pMirn378_day (0.0201204) 3_BMP2C2C12-pMirn378_day treated_rep1 (0.0209495) 3_BMP2C2C12-pMirn378_day treated_rep2 (0.0303514)6_BMP2 treated_rep3 (0.0349447)6_BMP2 treated_rep1 (0.0300056)6_BMP2 treated_rep2 (0.0251716)[ treated_rep3 min (0.024463) ] (0.0235901)[ medium ] [ max ] CEM 1 Birc5 195.0 482.4 6672.6 P ( S | Z, I ) = 1.00 Plk4 185.1 287.7 1780.3 Mean Corr = 0.86955 Cep55 184.6 417.9 3917.5 Ccnf 39.8 141.6 830.1 Sass6 90.1 133.4 525.3 Cep192 165.8 277.9 759.5 Poc1a 38.8 86.7 365.3 Ccp110 313.5 509.4 904.9 Cep128 38.9 106.6 269.3 Cep76 221.3 295.9 471.4 Cenpj 119.1 232.0 664.5 Alms1 77.7 112.5 282.4 Bub1 95.3 345.6 3643.2 Ncapg 51.2 131.6 1339.5 Kif11 66.9 203.1 1070.4 Ccna2 239.5 556.8 5259.4 Tpx2 192.9 388.0 2316.9 CEM 1 + Shcbp1 93.4 290.9 2985.9 Top 10 Genes Cenpe 72.7 224.4 1896.3 Sgol1 51.7 162.4 1427.0 Cdk1 632.3 1170.1 8837.8 Kif20a 104.7 324.9 3579.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE17796" 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=GSE17796 Status: Public on Jan 11 2010 Title: Expression data from B6C3F1 mice treated with reduced oxygen Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19812364 Summary & Design: Summary: Mice received decreasing oxygen concentrations from 21% to 6% O2 for ~ 30 minutes. Then, the mice remained an additional 120 minutes at 6% O2, control mice were placed insimilarchambers but recieved normal (21%) oxygen.

Background corr dist: KL-Divergence = 0.0270, L1-Distance = 0.0739, L2-Distance = 0.0083, Normal std = 0.7950

0.502 Kernel fit Pairwise Correlations Normal fit

Density 0.251

0.000 CEM 1

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

Pre-normalization Quantiles

liver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-repliver-vehicle-2hours-rep 1 (0.0228564)liver-hypoxia-2hours-rep 2 (0.0243985)liver-hypoxia-2hours-rep 3 (0.0291743)liver-hypoxia-2hours-rep 4 (0.0300921)liver-hypoxia-2hours-rep 1 (0.0240272)liver-hypoxia-2hours-rep 2 (0.0248716)liver-hypoxia-2hours-rep 3 (0.0429392)liver-hypoxia-2hours-rep 4 (0.0301892)liver-hypoxia-2hours-rep 5 (0.0273667)liver-vehicle-2hours-rep 6 (0.0264053)liver-vehicle-2hours-rep 7 (0.0273161)liver-vehicle-2hours-rep 8 (0.0253699)liver-vehicle-2hours-rep 5 (0.0260139)bone 6 (0.0288088) marrow-vehicle-2hours-repbone 7 (0.0307536) marrow-vehicle-2hours-repbone 8 (0.0253424) marrow-vehicle-2hours-repbone marrow-hypoxia-2hours-repbone 1 (0.043741)marrow-hypoxia-2hours-repbone 2 (0.0422111)marrow-hypoxia-2hours-repbone 3 (0.0365378)marrow-hypoxia-2hours-repspleen-vehicle-2hours-rep 1 (0.0319701)spleen-vehicle-2hours-rep 2 (0.0276577)spleen-vehicle-2hours-rep 3 (0.0272391)spleen-vehicle-2hours-rep 41 (0.0261927)(0.0184345)spleen-hypoxia-2hours-rep 2 (0.0365235)spleen-hypoxia-2hours-rep 3 (0.0223504)spleen-hypoxia-2hours-rep 4 (0.0162062)spleen-hypoxia-2hours-rep 1 (0.0178617)spleen-vehicle-2hours-rep 2 (0.0191102)spleen-hypoxia-2hours-rep 3 (0.0164744)spleen-hypoxia-2hours-rep 4 (0.0387357)spleen-vehicle-2hours-rep 5 (0.0143514)spleen-vehicle-2hours-rep 7 (0.0112887)spleen-vehicle-2hours-rep 8 (0.0145696)spleen-hypoxia-2hours-rep 6 (0.0190988)spleen-hypoxia-2hours-rep 7 (0.0236684) 8 (0.0213019) 5 (0.0163959) 6 (0.0121539)[ min ] [ medium ] [ max ] CEM 1 Birc5 39.0 2418.7 7612.4 P ( S | Z, I ) = 1.00 Plk4 62.9 512.6 1741.1 Mean Corr = 0.86860 Cep55 27.4 303.1 1889.3 Ccnf 278.4 783.0 1861.6 Sass6 54.4 308.0 824.1 Cep192 75.0 715.7 1163.3 Poc1a 88.2 260.1 604.8 Ccp110 79.1 419.0 1166.5 Cep128 33.7 234.3 690.2 Cep76 72.3 441.8 1649.6 Cenpj 82.0 237.8 546.9 Alms1 41.9 100.0 246.4 Bub1 26.6 513.3 2856.7 Ncapg 27.8 389.3 1529.5 Kif11 60.3 495.3 2230.7 Ccna2 81.1 1929.2 6905.1 Tpx2 57.3 683.6 3825.0 CEM 1 + Shcbp1 42.1 469.1 1965.5 Top 10 Genes Cenpe 51.0 522.9 2244.5 Sgol1 81.5 546.8 1823.5 Cdk1 204.1 1135.4 5325.6 Kif20a 43.7 382.1 1720.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE39034" 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=GSE39034 Status: Public on Nov 29 2012 Title: Mammalian cells acquire epigenetic hallmarks of human cancer during immortalization Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23143272 Summary & Design: Summary: Progression to malignancy requires cells to overcome senescence and switch to an immortal phenotype. Thus, exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation. In the present study, we have globally profiled DNA methylation in relation to gene expression in primary, senescent and immortalized mouse embryonic fibroblasts.

Overall design: Primary, senescent and immortalized mouse fibroblasts obtained from three independent embryos. Compare immortalized versus primary and senescent versus primary cells.

Background corr dist: KL-Divergence = 0.0790, L1-Distance = 0.0213, L2-Distance = 0.0007, Normal std = 0.4801

0.831 Kernel fit Pairwise Correlations Normal fit

Density 0.415

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse embryonicMouse embryonicMouse fibroblasts, embryonicMouse fibroblasts, embryonicMouse primary, fibroblasts, embryonicMouse senescent, passage fibroblasts, embryonicMouse immortalized, fibroblasts,# passage <6 embryonicMouse primary,Mo.21 fibroblasts, # embryonicpassage Mouse(expression)6-10senescent, passage fibroblasts, Mo.22 embryonic immortalized, # >10fibroblasts,# (expression)passage <6(0.054698) Mo.23 primary,Mo.24 fibroblasts, #(expression) passage (expression)6-10senescent, passage(0.0892669) Mo.25 [immortalized, # min >10# (expression)passage(0.118619) <6(0.128869) Mo.26 Mo.27 ] #(expression) passage (expression)6-10 (0.172384) Mo.28 # [>10 (expression) (0.246894) (0.0556215)medium Mo.29 (expression) (0.0674026) ] (0.0662443)[ max ] CEM 1 Birc5 576.4 1205.5 2555.1 P ( S | Z, I ) = 1.00 Plk4 203.3 341.2 727.1 Mean Corr = 0.86815 Cep55 353.5 671.1 1414.2 Ccnf 137.8 216.0 408.5 Sass6 172.5 253.5 426.0 Cep192 488.8 582.7 822.3 Poc1a 126.2 188.8 275.1 Ccp110 176.0 258.7 543.0 Cep128 56.6 108.9 176.1 Cep76 193.4 260.6 367.6 Cenpj 163.4 209.3 280.6 Alms1 72.4 95.5 153.5 Bub1 409.9 752.3 1652.9 Ncapg 134.4 260.6 545.9 Kif11 125.5 288.2 620.6 Ccna2 559.0 1209.7 2538.0 Tpx2 555.3 896.2 2107.9 CEM 1 + Shcbp1 514.2 990.8 2132.5 Top 10 Genes Cenpe 190.4 331.4 653.5 Sgol1 199.2 345.0 663.9 Cdk1 961.0 1800.5 6868.5 Kif20a 308.4 728.7 1701.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE32386" 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=GSE32386 Status: Public on Apr 01 2012 Title: Expression profiling of murine neuroblastoma in transgenic mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22764207 Summary & Design: Summary: Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK.

Overall design: Expression profiling of murine neuroblastoma driven by MYCN were compared to those driven by mutated ALK or both oncogenes. Mouse normal adrenal tissue served as a control.

Background corr dist: KL-Divergence = 0.0643, L1-Distance = 0.0382, L2-Distance = 0.0025, Normal std = 0.5410

0.775 Kernel fit Pairwise Correlations Normal fit

Density 0.387

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

66389_lo66977_ro (0.0637471)66977_ru (0.0810586)70660_lu (0.0355921)74128_wlr (0.081305)74128_wr (0.0829906)74129_wl (0.0875297)C57Bl6_1 (0.0490929)C57Bl6_2 (0.107883)C57Bl6_3 (0.149049)86823-2x (0.0940529)82743-lo (0.0455725)77204-10 (0.0632371) (0.0588898) [ min ] [ medium ] [ max ] CEM 1 Birc5 126.9 3429.0 5026.4 P ( S | Z, I ) = 1.00 Plk4 97.4 992.9 2317.4 Mean Corr = 0.85949 Cep55 96.5 1612.8 2283.6 Ccnf 65.3 382.5 740.5 Sass6 132.1 821.5 2041.1 Cep192 186.7 555.2 1121.4 Poc1a 100.6 273.0 371.7 Ccp110 236.2 2040.6 2962.9 Cep128 28.9 119.6 256.9 Cep76 173.3 321.1 503.4 Cenpj 265.0 376.2 661.9 Alms1 70.0 175.1 425.8 Bub1 50.5 2033.2 4475.7 Ncapg 20.2 436.1 1052.6 Kif11 49.3 942.5 1459.3 Ccna2 237.9 5467.1 7398.2 Tpx2 87.6 1136.3 2059.8 CEM 1 + Shcbp1 78.5 1434.5 3205.0 Top 10 Genes Cenpe 96.0 1123.7 3179.2 Sgol1 104.2 879.4 1698.2 Cdk1 188.5 3763.5 4698.6 Kif20a 75.6 1033.9 2179.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE31359" 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=GSE31359 Status: Public on Aug 13 2011 Title: Expression data from mouse EMT-induced and non-induced cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The conversion of an epithelial cell to a mesenchymal cell is critical to vertebrate embryogenesis and a defining structural feature of organ development, such as forming fibroblasts in injured tissues, or in initiating metastases in epithelial cancer. From a general perspective, EMT is about disaggregating epithelial units and reshaping epithelia for movement. This phenotypic conversion requires the molecular reprogramming of epithelia with new biochemical instructions. It is known that commonly used molecular markers for EMT include increased expression of N-cadherin and vimentin, nuclear localization of beta-catenin, and increased production of the transcription factors such as Snail, Twist, and SIP1/ZEB2. Much of this conversion, however, has been studied during experiments that expose new transduction and signaling pathways in epithelia, and more recently in fibrogenic tissues. It is not yet clear whether the fibroblast transition of EMT is an expected middle phase of transdifferentiating epithelia, or whether EMT producing fibroblasts is an arrested form of transdifferentiation. EMT is easily engaged by a combination of cytokines associated with proteolytic digestion of basement membranes upon which epithelia reside. We analyzed PCA and hierarchical clustering method of the gene expression pattern of the renal tubular cells and mammary gland cells. We then identified the genes which discriminate between the renal tubular and the mammary gland epithelial cells (PC1), or EMT-induced and non-induced cells (PC3). Undergoing EMT identifies the genes that discriminate between the renal tubular and the mammary gland epithelial cells(PC1), or EMT-induced and non-induced cells (PC3).

Overall design: Affymetrix GeneChip Mouse Genome 430 2.0 Array was used to transcriptionally profile to compare mouse EMT-induced cells and non-induced cells.

Background corr dist: KL-Divergence = 0.0562, L1-Distance = 0.0330, L2-Distance = 0.0017, Normal std = 0.5554

0.725 Kernel fit Pairwise Correlations Normal fit

Density 0.362

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

NC-EpH4EMT-EpH4 (0.0981281)NC-mProx (0.0951895)EMT-mProx (0.156298)NC-MCT (0.111419)EMT-MCT (0.106075)NC-NMuMG (0.0963027)EMT-NMuMG (0.189169) (0.147419) [ min ] [ medium ] [ max ] CEM 1 Birc5 336.9 3863.4 4390.3 P ( S | Z, I ) = 1.00 Plk4 131.4 1370.5 2029.9 Mean Corr = 0.85655 Cep55 421.3 2470.3 3330.0 Ccnf 186.2 1009.7 1276.9 Sass6 77.7 361.3 501.3 Cep192 343.4 995.5 1072.5 Poc1a 170.5 564.0 676.5 Ccp110 163.1 842.9 1544.0 Cep128 73.4 260.8 357.9 Cep76 138.1 504.9 601.2 Cenpj 191.8 321.2 366.8 Alms1 95.2 215.6 335.3 Bub1 143.0 2218.8 2690.1 Ncapg 90.7 973.5 1507.0 Kif11 143.4 874.0 2386.5 Ccna2 331.1 2101.6 4500.2 Tpx2 251.1 1699.0 2207.2 CEM 1 + Shcbp1 192.2 2869.8 4069.4 Top 10 Genes Cenpe 129.5 987.4 1175.0 Sgol1 142.3 1369.5 1805.8 Cdk1 585.8 6436.2 8556.7 Kif20a 175.5 1003.0 1771.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE13611" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13611 Status: Public on Aug 15 2009 Title: Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19732723 Summary & Design: Summary: Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative

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

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

0.415 Kernel fit Pairwise Correlations Normal fit

Density 0.208

0.000 CEM 1

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

Pre-normalization Quantiles

BCR-ABL1BCR-ABL1 Aid-GFP-negative(1)BCR-ABL1 Aid-GFP-negative(2)BCR-ABL1 Aid-GFP-positive(1)Aid-GFP (0.0690318) Aid-GFP-positive(2)Aid-GFP negative (0.0814156)Aid-GFP negative(0.0722391) LPS+IL4-stimulatedAid-GFP positive(0.0584627) LPS+IL4-stimulated positive LPS+IL4-stimulated splenic LPS+IL4-stimulated splenicB cells [splenic (1)B min cells (0.253598) splenic B(2) cells (0.280934)] (1)B cells (0.0846249) (2)[ (0.0996937) medium ] [ max ] CEM 1 Birc5 732.2 6412.1 6559.4 P ( S | Z, I ) = 1.00 Plk4 152.6 725.3 926.2 Mean Corr = 0.85326 Cep55 241.4 3977.3 4724.9 Ccnf 96.9 1742.5 1821.7 Sass6 234.4 1044.7 1165.0 Cep192 1597.9 1891.4 2236.4 Poc1a 88.6 690.3 1042.1 Ccp110 122.2 907.6 992.7 Cep128 51.7 447.9 480.5 Cep76 208.9 1298.4 1458.7 Cenpj 463.3 1274.8 1530.0 Alms1 76.1 197.8 282.6 Bub1 44.0 2215.7 2594.8 Ncapg 396.0 4831.6 5055.1 Kif11 33.2 1279.7 1393.1 Ccna2 180.8 4518.6 4907.7 Tpx2 106.9 2890.8 3342.1 CEM 1 + Shcbp1 71.8 2583.9 2985.3 Top 10 Genes Cenpe 127.0 1675.6 2023.8 Sgol1 85.4 1587.7 1758.9 Cdk1 379.8 5457.2 5981.2 Kif20a 216.0 2096.2 2952.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE20500" 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=GSE20500 Status: Public on Feb 14 2011 Title: T cell genes regulated by retinoic acid Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20664575 Summary & Design: Summary: This is to determine the T cell genes regulated by retinoic acid.

Overall design: 2 arrays were used for each group

Background corr dist: KL-Divergence = 0.0330, L1-Distance = 0.0460, L2-Distance = 0.0029, Normal std = 0.7128

0.605 Kernel fit Pairwise Correlations Normal fit

Density 0.303

0.000 CEM 1

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

Pre-normalization Quantiles

[CD4+ T-Cells]_[Control]_[1][CD4+ T-Cells]_[Control]_[2][CD4+ T-Cells]_[RA]_[1][CD4+ (0.0893891)T-Cells]_[RA]_[2][CD4+ (0.298058)T-Cells]_[Ro]_[1][CD4+ (0.163515) T-Cells]_[RO]_[2] (0.101352) (0.180008) (0.167678)[ min ] [ medium ] [ max ] CEM 1 Birc5 1041.5 8061.0 12905.5 P ( S | Z, I ) = 1.00 Plk4 273.1 1311.4 2103.9 Mean Corr = 0.85186 Cep55 293.5 2635.5 3971.6 Ccnf 192.4 1524.1 2476.4 Sass6 166.5 467.2 754.2 Cep192 515.5 1153.2 2092.4 Poc1a 172.4 1016.8 1511.2 Ccp110 270.1 446.7 942.9 Cep128 24.6 264.1 447.0 Cep76 168.3 274.2 419.4 Cenpj 225.1 574.3 699.8 Alms1 46.5 166.0 271.0 Bub1 148.5 2223.9 4230.6 Ncapg 408.9 1501.4 2511.9 Kif11 133.5 2381.6 3919.0 Ccna2 600.1 6507.7 9143.8 Tpx2 422.9 2531.1 3750.2 CEM 1 + Shcbp1 289.7 2122.6 3945.4 Top 10 Genes Cenpe 231.8 2286.8 3340.8 Sgol1 318.1 2044.8 2651.8 Cdk1 1127.4 5891.2 9601.7 Kif20a 141.3 2289.6 3395.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE23502" 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=GSE23502 Status: Public on Dec 15 2010 Title: Differentially expressed genes of CD11b+Gr-1+ myeloid cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21170045 Summary & Design: Summary: Differentially expressed genes of CD11b+Gr-1+ immature myeloid cells (IMCs) in the bone marrow and colonic tumor setting of histidine decarboxylase (HDC)-KO mice were examined by microarray (Affymetrix Mouse 430.2 array). Myeloid differentiation-related candidate genes were sought to be isolated and functionally studied.

Overall design: Four sets of comparisons were performed to screen for upregulated or downregulated genes in the HDC-KO CD11b+Gr-1+ IMCs or MDSCs (experiment group) compared to the WT group: (1) HDC-expressing CD11b+Gr-1+ IMCs of bone marrow of HDC KO mice compared to bone marrow IMCs of WT mice; (2) CD11b+Gr-1+ MDSCs in tumors of HDC-KO mice compared to WT mice; (3) CD11b+Gr-1+ MDSCs of WT colon tumors compared to IMCs in the WT bone marrow; and (4) CD11b+Gr-1+ MDSCs of colon tumors of HDC-KO mice compared to IMCs in the bone marrow of HDC-KO mice.

Background corr dist: KL-Divergence = 0.0311, L1-Distance = 0.0412, L2-Distance = 0.0020, Normal std = 0.7230

0.594 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeWild-type myeloid-derivedHistidine myeloid-derivedHistidine decarboxylase suppressorWild-type decarboxylase suppressorWild-type cell nullmyeloid-derived from myeloid-derivedHistidine cell nullmyeloid-derived bone from myeloid-derivedHistidine marrow,decarboxylase bone suppressor suppressor marrow,decarboxylase rep1 suppressor (0.119791) suppressorcell null rep2 cellfrom myeloid-derived (0.13322) cell fromnull colon cellfrom myeloid-derived [bone tumor,frommin colon marrow, bone suppressor rep1tumor, ] marrow, (0.061675)rep1 suppressor rep2 (0.0919694) cell (0.0767539)rep2 from[ (0.0703693) cellmedium colon from tumor, colon rep1tumor, ] (0.217454) rep2 (0.228768)[ max ] CEM 1 Birc5 600.0 4800.5 5538.5 P ( S | Z, I ) = 1.00 Plk4 87.2 846.9 956.3 Mean Corr = 0.84730 Cep55 301.9 3060.3 3284.7 Ccnf 34.3 559.0 604.5 Sass6 104.0 380.3 468.9 Cep192 250.9 746.1 990.6 Poc1a 18.5 33.4 56.8 Ccp110 157.4 580.8 865.6 Cep128 48.9 550.5 620.9 Cep76 50.6 120.3 138.8 Cenpj 264.9 1793.5 1988.5 Alms1 12.2 19.1 25.0 Bub1 109.8 2469.4 2663.3 Ncapg 66.3 1349.7 1577.5 Kif11 67.6 1254.7 1467.6 Ccna2 322.1 3797.9 4391.6 Tpx2 65.1 1127.4 1376.6 CEM 1 + Shcbp1 318.0 3698.7 3842.8 Top 10 Genes Cenpe 67.5 1538.3 1791.2 Sgol1 45.2 1227.5 1415.6 Cdk1 199.9 3340.2 3676.7 Kif20a 34.6 927.4 1235.9

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE13873" 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=GSE13873 Status: Public on Mar 05 2009 Title: Expression data from murine gastric epithelium Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19454706 Summary & Design: Summary: Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in a majority of individuals. We report here that the C57Bl6 mouse model of experimental infection with the closely related H. felis recapitulates this wide range in host susceptibility. A majority of infected mice develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia and intestinal metaplasia, whereas a minority is completely protected from preneoplasia. Protection is associated with the failure to mount an IFN-gamma response to the infection and an associated high Helicobacter burden. We demonstrate that IFN-gamma is essential for clearance of Helicobacter, but also mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a specific transcriptional program in murine gastric epithelial cells in vitro and in vivo, and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could provide an explanation for the differential susceptibility to H. pylori-induced gastric pathology in the human population.

Keywords: response to in vitro stimulus / comparison of histopathological states

Overall design: We chose mice for gene expression profiling that following Helicobacter infection had (a) symptoms of gastritis, but no epithelial changes, (b) atrophic gastritis accompanied by corpus gland hyperplasia or (c) atrophic gastritis accompanied by intestinal metaplasia. An uninfected control group was also included in the analysis, as were two groups of mice that lacked mature T- and B-cells due to a deletion mutation in the rag1 gene (Rag-1-/-) and that were either experimentally infected or served as Rag-1-/- uninfected controls. To see the effects of IFNg on murine gastric epithelial cells we analysed an immortalized murine primary gastric epithelial cell line treated with three different concentrations of IFNg in comparison to an untreated control.

Background corr dist: KL-Divergence = 0.0517, L1-Distance = 0.0400, L2-Distance = 0.0031, Normal std = 0.5764

0.692 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

IMPGE untreatedIMPGE IFNGIMPGE (0.139363) 1 (0.116683)IFNGIMPGE 2 (0.13416)IFNGstomach 3 (0.105739)stomach uninfectedstomach uninfected 1 (0.0261781)stomach infected 2 (0.0292807)stomach infected gastritisstomach infected gastritis 1 (0.0201563)stomach infected gastritis 2 (0.0119666)stomach infected gastritis 3 (0.0371103)stomach infected metaplasia 4 (0.0175034)stomach infected hyperplasia 1stomach (0.0177974)infected hyperplasia stomach1 infected(0.0112624) hyperplasia stomach2 infected(0.0165673) hyperplasia stomach3 infected(0.0196307) hyperplasia stomach4 infected(0.0111353) metaplasia stomach5 infected(0.0165266) metaplasia 2stomach (0.0509004)infected metaplasia 3stomach (0.0327901)uninfected metaplasia 4stomach (0.029692)uninfected Rg 5stomach (0.0197969) infected1 (0.0228194) Rgstomach infected2 Rg (0.0170403) 1stomach (0.0144801)infected Rg 2stomach (0.0178907)infected Rg 3 (0.0211554)infected Rg 4 (0.0121644) Rg 5 (0.0302109)[ min ] [ medium ] [ max ] CEM 1 Birc5 590.2 1700.6 4509.6 P ( S | Z, I ) = 1.00 Plk4 104.4 256.0 1516.3 Mean Corr = 0.84055 Cep55 392.7 853.4 2561.8 Ccnf 142.4 286.9 674.7 Sass6 112.8 199.3 545.6 Cep192 160.8 285.6 830.4 Poc1a 132.9 193.0 540.6 Ccp110 89.5 137.8 442.8 Cep128 20.5 27.2 218.1 Cep76 183.9 259.5 652.5 Cenpj 103.9 157.8 544.9 Alms1 34.5 46.9 57.6 Bub1 103.7 335.4 3844.4 Ncapg 52.7 138.5 785.1 Kif11 163.8 284.5 965.0 Ccna2 801.1 1897.1 5027.2 Tpx2 179.8 390.0 4564.3 CEM 1 + Shcbp1 328.2 661.1 2998.7 Top 10 Genes Cenpe 295.4 743.9 1646.2 Sgol1 285.5 404.7 1678.4 Cdk1 642.4 1471.8 8807.3 Kif20a 149.1 313.2 3726.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE16110" 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=GSE16110 Status: Public on Jul 01 2009 Title: Altered mouse mammary gland gene expression and tumor growth following chronic social isolation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Clinical studies have revealed that social support improves the outcome of cancer patients while epidemiological studies suggest that social isolation increases the risk of death associated with several chronic diseases. However, the precise biological consequences of an unfavorable social environment have not been defined. To do so, robust, reproducible pre-clinical models are needed to study the mechanisms whereby an adverse environment impacts on gene expression and cancer biology. Because random assignment of inbred laboratory mice to well-defined social environments allows accurate and repeated measurements of behavioral and endocrine parameters, transgenic mice provide a pre-clinical framework with which to begin to determine gene-environment mechanisms. In this study, we found that female C3(1)/SV40 T-antigen mice deprived of social interaction from weaning exhibited increased expression of genes encoding key metabolic pathway enzymes in the pre-malignant mammary gland. Chronic social isolation was associated with upregulated fatty acid synthesis and glycolytic pathway gene expression - both pathways known to contribute to increased breast cancer growth. Consistent with the expression of metabolic genes, isolated mice subsequently developed significantly larger mammary gland tumors compared to group-housed mice. Endocrine evaluation confirmed that isolated mice developed a heightened corticosterone stress response compared to group-housed mice. Together, these transdisciplinary studies show for the first time that an adverse social environment is associated with altered mammary gland gene expression and tumor growth. Moreover, the identification of specific alterations in metabolic pathways favoring tumor growth suggests potential molecular biomarkers and/or targets (e.g. fatty acid synthesis) for preventive intervention in breast cancer.

Overall design: SV40 Tag mice we isolated or grouped at weaning. Mouse mammary glands were rapidly excised at necropsy and immediatley flash frozen to detect difference in gene expression between thoraci MG from isolated versus group-housed female mice.

Background corr dist: KL-Divergence = 0.0385, L1-Distance = 0.0261, L2-Distance = 0.0009, Normal std = 0.6020

0.663 Kernel fit Pairwise Correlations Normal fit

Density 0.331

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_Group_15w_Rep1Mouse_Group_15w_Rep2Mouse_Group_15w_Rep3Mouse_Group_15w_Rep4 (0.0444405)Mouse_Iso_15w_Rep1 (0.0478968)Mouse_Iso_15w_Rep2 (0.078605)Mouse_Iso_15w_Rep3 (0.0602431)Mouse_Iso_15w_Rep4 (0.0478653)Mouse_Group_20w_Rep1 (0.045732)Mouse_Group_20w_Rep2 (0.0508221)Mouse_Group_20w_Rep3 (0.0697714)Mouse_Group_20w_Rep4 (0.0707883)Mouse_Iso_20w_Rep1 (0.0606671)Mouse_Iso_20w_Rep2 (0.0251704)Mouse_Iso_20w_Rep3 (0.0645129)Mouse_Iso_20w_Rep4 (0.182648) (0.0597267) (0.0495085) (0.0416019)[ min ] [ medium ] [ max ] CEM 1 Birc5 709.5 1260.0 2107.6 P ( S | Z, I ) = 1.00 Plk4 720.5 1012.5 1393.4 Mean Corr = 0.83831 Cep55 730.7 1435.8 1987.1 Ccnf 381.5 629.4 843.4 Sass6 284.9 350.6 421.6 Cep192 443.1 603.9 1083.6 Poc1a 288.0 319.5 385.9 Ccp110 334.1 432.2 544.7 Cep128 76.7 124.3 185.7 Cep76 162.3 219.8 343.4 Cenpj 228.3 270.5 315.6 Alms1 223.8 273.7 361.5 Bub1 335.9 694.4 1048.8 Ncapg 238.3 446.0 703.5 Kif11 664.3 953.9 1403.9 Ccna2 1567.6 2479.6 3346.9 Tpx2 343.1 635.9 912.3 CEM 1 + Shcbp1 330.3 600.2 1098.4 Top 10 Genes Cenpe 664.9 943.5 1352.2 Sgol1 574.3 1113.7 1482.8 Cdk1 1446.9 2208.4 3179.8 Kif20a 303.4 515.0 951.1

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE38696" 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=GSE38696 Status: Public on Jun 14 2012 Title: Gene expression in mouse germinal center light zone and dark zone B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22740445 Summary & Design: Summary: Microarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4

We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of germinal centers from mouse skin-draining lymph nodes 12 days after subcutaneous immunization with NP-OVA in alum.

Overall design: Germinal center B cells (B220+CD38-CD95+) were sorted from immunized mouse lymph nodes into light zone (CXCR4hi/CD83lo) and dark zone (CXCR4lo/CD83hi) populations, from which RNA was extracted

Background corr dist: KL-Divergence = 0.0538, L1-Distance = 0.0239, L2-Distance = 0.0006, Normal std = 0.5628

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse lightMouse zone, lightMouse biological zone, lightMouse biological zone, replicate lightMouse biological zone, replicate darkMouse 1 (0.0964181) biological zone, replicate darkMouse 2 (0.186947) biological zone, replicate darkMouse 3 (0.0932204) biological zone, replicate dark 4 (0.100903) biological zone, replicate 1 (0.155172) biological replicate 2 (0.134934) replicate [3 (0.118711)min 4 (0.113694) ] [ medium ] [ max ] CEM 1 Birc5 5057.9 8842.3 10357.5 P ( S | Z, I ) = 1.00 Plk4 735.2 1125.4 1232.6 Mean Corr = 0.83466 Cep55 5031.4 8767.8 9695.1 Ccnf 422.0 635.2 765.7 Sass6 551.8 809.5 865.8 Cep192 1668.1 1918.1 2246.2 Poc1a 284.2 548.1 613.4 Ccp110 1433.4 1835.7 1990.3 Cep128 110.9 129.5 156.9 Cep76 118.3 186.5 235.4 Cenpj 796.0 930.4 969.2 Alms1 123.1 144.4 153.4 Bub1 2825.0 4417.8 4837.3 Ncapg 2175.8 3370.3 3733.6 Kif11 1489.5 2223.2 2698.7 Ccna2 4796.9 7493.9 8125.4 Tpx2 1861.0 3835.1 4257.6 CEM 1 + Shcbp1 3002.6 4441.0 5331.1 Top 10 Genes Cenpe 1536.8 4000.8 4619.5 Sgol1 1316.8 2314.5 2469.7 Cdk1 2759.4 5237.9 5683.6 Kif20a 487.9 2065.5 2269.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE34839" 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=GSE34839 Status: Public on Feb 28 2012 Title: Pten loss and RAS/MAPK activation cooperate to promote EMT and prostate cancer metastasis initiated from stem/progenitor cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22350410 Summary & Design: Summary: PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.

Overall design: Murine mutants with prostate specific loss of Pten and K-ras activation (K-rasG12D) under regulation of the probasin promoter developed high grade, invasive prostate cancer. RNA was extracted from dissected prostate lobes from individual mutants with pathology thought to closely mimic human disease. Prostate tissue was subject to RNA extraction and hybridization on Affymetrix cDNA microarrays.

Background corr dist: KL-Divergence = 0.0408, L1-Distance = 0.0392, L2-Distance = 0.0022, Normal std = 0.6408

0.647 Kernel fit Pairwise Correlations Normal fit

Density 0.323

0.000 CEM 1

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

Pre-normalization Quantiles

Pb-Cre+;PtenL/W;K-rasG12D/W,Pb-Cre+;PtenL/W;K-rasG12D/W,Pb-Cre+;PtenL/W;K-rasG12D/W,Pten null,Pten biological null,Pten biological null,rep1 biological(0.119936)(0.102926) rep2 (0.207479)(0.319001) rep3 (0.10504)(0.145618)[ min ] [ medium ] [ max ] CEM 1 Birc5 168.1 370.1 1603.7 P ( S | Z, I ) = 1.00 Plk4 142.3 197.7 778.9 Mean Corr = 0.83134 Cep55 129.1 360.9 1628.9 Ccnf 74.8 107.2 257.9 Sass6 214.2 292.4 386.6 Cep192 322.6 406.7 771.0 Poc1a 114.7 141.9 170.3 Ccp110 238.1 279.9 365.8 Cep128 56.8 71.1 155.9 Cep76 118.9 164.6 204.1 Cenpj 213.5 301.4 462.0 Alms1 51.5 72.3 129.7 Bub1 128.3 244.4 1342.3 Ncapg 31.6 50.4 232.5 Kif11 103.1 141.9 607.5 Ccna2 259.3 417.3 1532.5 Tpx2 95.6 129.1 575.0 CEM 1 + Shcbp1 171.3 230.4 1199.3 Top 10 Genes Cenpe 105.6 155.5 715.7 Sgol1 144.0 190.3 550.8 Cdk1 391.7 487.0 2271.0 Kif20a 74.3 110.9 614.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE9763" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9763 Status: Public on Dec 04 2007 Title: Transformed glial progenitor cells (prosc-affy-mouse-450860) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The goals of this research are three-fold: (i) One is to identify genetic changes associated with tumorgenesis that interfere with the ability of transformed glial cells to differentiate. This is connected with (ii) our analysis of the regulation of differentiation in normal glial progentor cells, as only by understanding this in normal cells can we understand what is occurring when differentiation fails in transformed versions of the same cells. (iii) The third is to identify the molecular basis for the greater resistance of transformed glial progenitor cells to chemotherapeutic agents as compared with normal glial progenitor cells. Thus, analysis of the populations provided will yield data crucial to two of our central areas of research, as awarded by NINDS in ""Oligodendrocytes & precursors: toxicity of chemotherapy"" (5R01NS044701), and ""Low-level toxicant perturbation of neural cell function"" (1R01ES012708).

Our ability to work with essentially unlimited numbers of primary progenitor cells and transformed derivatives of these cells offers one of the few systems in which side-by-side comparison of normal and transformed cells at both the biochemical and molecular levels is possible. Using defined cell populations, expression profiles will be compared to reveal changes in cell type specific markers and regulatory factors associated with transformation. In addition, retention of markers despite transformation may enable identification of new markers useful in the diagnosis of glial tumors.

Transformation of glial progenitor cells is associated both with loss of the proteins required for normal differentiation and with an inability to normally activate proteins that function in differentiation control. By side-by-side analysis of gene expression in normal and transformed glial progenitor cells, and analysis of the response to inducers of differentiation in each these populations, we will identify candidate regulators critical in the control of normal differentiation. Identification of these regulators will also provide clues as to overcome the blockade of differentiation that occurs in glial cancers (which represent the majority of adult brain tumors).

RNA will be isolated from two separate preparations of glial progenitors. Preparation of purified populations has been described in multiple of our previous publications (Mayer, M. et al. (1994) Development 120, 142-153; Mayer-PrÃ¶schel, M. et al. (1997) Neuron 19, 773-785; Rao, M. and Mayer-PrÃ¶schel, M. (1997) Dev. Biology 188, 48-63). Total RNA from purified cell cultures will be extracted in a two step process. RNA will first be extracted by dounce homogenization in phenol/guanidine isothiocyonate solution (Trizol, Invitrogen, California) followed by isopropanol precipitation. Contaminating traces of DNA and protein will then be removed by silica-based affinity chromatography and Dnase treatment (NucleoSpin RNA Purification system, Clontech, California). Depending on the cell type, 5x105 cells will typically yield 5-15´g of high quality RNA (OD260/280=2.1 at pH7.5). In order to determine purity and molecular weight distribution, samples will be routinely tested on a Agilent Bioanalyzer. cDNA will be generated from total RNA and then be submitted to one round of amplification and labeling using the messageAmp system (Ambion). Probes are then hybridized to the Affymerix Rat 230 (A/B or 2.0) GeneChip expression array. Array data will be processed using the Micro Array Suite 5.0 (MAS, Affymetrix). .Cel files containing normalized, relative expression data for all genes tested will be used for downstream statistical analysis.

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.1052, L1-Distance = 0.0572, L2-Distance = 0.0056, Normal std = 0.4613

0.943 Kernel fit Pairwise Correlations Normal fit

Density 0.471

0.000 CEM 1

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

Pre-normalization Quantiles

brain, Cellbrain, line: Cellbrain, G1Fm_e_le1 line: Cellbrain, G2Fm_e_le1 line: Cell(0.0440726)brain, G3Fm_e_le1 line: Cell(0.0416245)brain, G4Fm_e_le1 line: Cell(0.0282305)brain, G5Fm_e_le1 line: Cell(0.0350953)brain, G1Tm_e_le1 line: Cell(0.0351178)brain, G2Tm_e_le1 line: Cell(0.0462782)brain, G3Tm_e_le1 line: Cell(0.0485011)brain, G4Tm_e_le1 line: Cell(0.0547637)brain, G5Tm_e_le1 line: Cell(0.0546639)brain, O1m_e_le1 line: Cell(0.0818908)brain, O2m_e_le1 line: (0.0356008) Cellbrain, O3m_e_le1 line: (0.0287912) Cellbrain, O4m_e_le1 line: (0.0228648) Cellbrain, O5m_e_le1 line: (0.0658272) Cellbrain, O1Tm_e_le1 line: (0.0632148) Cellbrain, O2Tm_e_le1 line: Cell(0.0756238)brain, O3Tm_e_le1 line: Cell(0.0663803) O4Tm_e_le1 line: (0.0522173) O5Tm_e_le1 (0.0608404) (0.0584009)[ min ] [ medium ] [ max ] CEM 1 Birc5 476.1 3230.0 5745.3 P ( S | Z, I ) = 1.00 Plk4 148.6 1282.5 1872.0 Mean Corr = 0.82944 Cep55 242.4 1982.3 2930.5 Ccnf 141.5 762.9 1370.8 Sass6 130.3 423.8 579.5 Cep192 290.1 722.2 1122.7 Poc1a 110.0 317.0 450.6 Ccp110 434.0 967.1 1505.5 Cep128 32.4 243.4 315.6 Cep76 301.9 486.8 721.2 Cenpj 106.7 610.8 889.0 Alms1 39.9 195.1 253.5 Bub1 385.3 3596.4 4468.9 Ncapg 138.6 1305.6 1882.4 Kif11 225.6 1310.3 2049.6 Ccna2 756.2 5726.7 8475.7 Tpx2 308.0 2693.0 3451.8 CEM 1 + Shcbp1 353.6 2758.3 4288.8 Top 10 Genes Cenpe 136.6 1508.1 2167.7 Sgol1 113.5 1184.2 1871.9 Cdk1 560.5 6342.7 7352.1 Kif20a 176.6 1344.3 1885.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE4260" 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=GSE4260 Status: Public on Feb 17 2006 Title: Cumulus-oocyte complex temporal expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16455817 Summary & Design: Summary: Cumulus-oocyte complexes were isolated a seperate time-points to generate temporal complexes. Targets from two biological replicates at each time point (0h, 8h, 16h post-hCG treatment) were generated and the expression profiles were determined using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Comparisons between the sample groups allow the identification of genes with temporal expression patterns.

Keywords: time course

Overall design: 2 eCG-primed (48h) pooled cumulus-oocyte complexes, 2 eCG-primed (48h) hCG-treated (8h) pooled cumulus-oocyte complexes, and 2 eCG-primed (48h) hCG-treated (16h) pooled cumulus-oocyte complexes replicates were analyzed

Background corr dist: KL-Divergence = 0.0244, L1-Distance = 0.0244, L2-Distance = 0.0006, Normal std = 0.7316

0.563 Kernel fit Pairwise Correlations Normal fit

Density 0.282

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

CumulusCumulus OocyteCumulus OocyteComplexCumulus OocyteComplex eCG-treatedCumulus OocyteComplex eCG-treatedCumulus Oocyte48h,Complex eCG-treated no Oocyte48h,ComplexhCG eCG-treated no replicate 48h,ComplexhCG eCG-treated hCG replicate 148h, (0.282376) eCG-treated8h hCG [replicate 248h,min (0.23519) 8h hCG replicate 148h, (0.111122) 16h] hCG replicate 2 (0.101946) 16h replicate [1 (0.14868)medium 2 (0.120687) ] [ max ] CEM 1 Birc5 629.1 1870.5 4674.1 P ( S | Z, I ) = 1.00 Plk4 672.1 1083.8 1666.5 Mean Corr = 0.82777 Cep55 986.0 1501.4 2566.9 Ccnf 275.4 540.2 992.0 Sass6 278.3 486.1 684.7 Cep192 358.0 440.4 625.6 Poc1a 236.1 363.3 522.0 Ccp110 372.3 485.2 957.3 Cep128 30.9 35.8 63.3 Cep76 256.9 373.2 395.2 Cenpj 468.1 615.3 780.3 Alms1 116.2 268.9 832.9 Bub1 746.2 1506.8 3587.3 Ncapg 190.9 551.5 1642.0 Kif11 371.3 700.3 1331.6 Ccna2 1182.7 2698.1 5928.1 Tpx2 1334.0 2429.8 3143.1 CEM 1 + Shcbp1 510.9 1312.9 2418.9 Top 10 Genes Cenpe 1138.9 1323.5 2860.5 Sgol1 540.1 1028.8 1205.1 Cdk1 2187.3 4569.7 7004.9 Kif20a 785.4 1282.3 1757.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE45143" 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=GSE45143 Status: Public on Aug 01 2013 Title: Pax6 is required for normal cell cycle exit and the differentiation kinetics of retinal progenitor cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24073291 Summary & Design: Summary: The coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but the mechanisms that link these processes are mostly unknown. Although the transcription factor Pax6 was implicated in both proliferation and differentiation of multiple regions within the CNS, its contribution to the transition between these successive states remains elusive. To gain insight into the role of Pax6 during the transition from proliferating progenitors to differentiating precursors, we investigated cell-cycle and transcriptomic changes occurring in Pax6- retinal progenitor cells (RPCs). Our analyses revealed a unique cell-cycle phenotype of the Pax6-deficient RPCs, which included a reduced number of cells in the S phase, an increased number of cells exiting the cell cycle, and delayed differentiation kinetics of Pax6- precursors. These alterations were accompanied by co-expression of factors that promote (Ccnd1, Ccnd2, Ccnd3) and inhibit (P27kip1 and P27kip2) the cell cycle. Further characterization of the changes in transcription profile of the Pax6-deficient RPCs revealed abrogated expression of multiple factors which are known to be involved in regulating proliferation of RPCs, including the transcription factors Vsx2, Nr2e1, Plagl1 and Hedgehog signaling. These findings provide novel insight into the molecular mechanism mediating the pleiotropic activity of Pax6 in RPCs. The results further suggest that rather than conveying a linear effect on RPCs, such as promoting their proliferation and inhibiting their differentiation, Pax6 regulates multiple transcriptional networks which function simultaneously, thereby conferring the capacity to proliferate, assume multiple cell fates and execute the differentiation program into retinal lineages.

Overall design: The data contains 3 control and 3 Pax6 negative samples representing biological repeats. Each sample was prepared from ~1.8 million cells taken from the distal retina of either E12 alpha-Cre or Pax6 floxed alpha-Cre animals. Distally located retinal progenitors expressing Cre and eGFP were separated using FACS.

Background corr dist: KL-Divergence = 0.0342, L1-Distance = 0.0165, L2-Distance = 0.0003, Normal std = 0.6438

0.625 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

E12 distalE12 retina distalE12 progenitors_control_rep retina distalE12 progenitors_control_rep retina distalE12 progenitors_control_rep retina distalE12 progenitors_mutant_rep retina distal1 (0.172509) progenitors_mutant_rep retina 2 (0.175394) progenitors_mutant_rep 3 (0.15992) 1 (0.142595)[ min 2 (0.199876) 3] (0.149706) [ medium ] [ max ] CEM 1 Birc5 3454.3 4193.3 4516.6 P ( S | Z, I ) = 1.00 Plk4 1083.8 1399.8 1555.0 Mean Corr = 0.82681 Cep55 1062.3 1391.0 1550.4 Ccnf 469.9 622.8 643.1 Sass6 524.0 725.6 803.1 Cep192 899.2 1089.2 1175.0 Poc1a 270.0 376.7 403.5 Ccp110 1062.5 1283.8 1535.0 Cep128 178.9 201.9 252.3 Cep76 651.3 731.9 852.9 Cenpj 399.0 515.5 603.5 Alms1 205.5 243.3 329.6 Bub1 2131.5 2688.5 2908.8 Ncapg 916.9 1285.2 1340.7 Kif11 692.6 869.5 1050.7 Ccna2 2465.0 2891.2 3618.6 Tpx2 2077.1 2645.8 2788.2 CEM 1 + Shcbp1 1595.7 1863.4 2050.1 Top 10 Genes Cenpe 1826.7 2090.7 2461.5 Sgol1 840.9 1104.2 1294.3 Cdk1 5227.0 6194.2 6363.9 Kif20a 1113.1 1427.3 1626.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE12993" 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=GSE12993 Status: Public on Jul 31 2009 Title: C2C12 culture: myogenesis timecourse and shRp58 treatment Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To predict Rp58-regulated gene involved in myogenesis, RNA profiling experiments were performed, comparing RNA derived from C2C12 with or without expressing shRNA for Rp58. As a result, 271 genes were upregulated in C2C12 stably expressing shRNA-Rp58 cells compared with control C2C12 cells. As Rp58 is repressor in C2C12, we hypothesized that Rp58 regulates gene cluster which expression is downregulated in accordance with Rp58 expression and myogenesis progression. In this regard, we also characterized dynamic gene expression patterns during myogenesis by microarray at 4 different stage (GM, day 0, 2, 4) of C2C12 myogenesis assays and found that 399 genes expression is characterized as downregulation pattern during myogenesis. Importantly, this down regulation gene set and upregulated genes by shRNA for Rp58 were highly overlapped.

Keywords: time course, shRNA

Overall design: MAPPFinder (www.genmapp.org) was used to integrate expression data with known pathways.

Background corr dist: KL-Divergence = 0.0165, L1-Distance = 0.0127, L2-Distance = 0.0002, Normal std = 0.7749

0.515 Kernel fit Pairwise Correlations Normal fit

Density 0.257

0.000 CEM 1

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

Pre-normalization Quantiles

C2C12-GMC2C12-day0 (0.279495)C2C12-day2 (0.163431)C2C12-day4 (0.127496)C2C12-control-day0 (0.199838)C2C12-shRp58-day0 (0.105038) (0.124701)[ min ] [ medium ] [ max ] CEM 1 Birc5 404.9 3816.3 5023.7 P ( S | Z, I ) = 1.00 Plk4 277.3 1144.4 1322.2 Mean Corr = 0.82679 Cep55 246.1 1987.9 2353.6 Ccnf 191.0 729.4 1275.5 Sass6 173.8 334.5 654.2 Cep192 269.3 677.8 887.4 Poc1a 149.2 348.4 448.0 Ccp110 241.3 359.4 509.5 Cep128 84.9 141.7 186.1 Cep76 154.0 264.6 420.7 Cenpj 107.4 198.1 338.1 Alms1 105.4 174.2 210.4 Bub1 111.1 1270.8 1427.8 Ncapg 57.8 512.1 653.0 Kif11 177.9 794.7 1119.9 Ccna2 409.6 2279.0 2697.6 Tpx2 185.7 1516.9 1827.6 CEM 1 + Shcbp1 255.6 1353.6 1997.4 Top 10 Genes Cenpe 247.6 1232.8 1690.9 Sgol1 261.3 858.4 1263.7 Cdk1 814.0 4849.0 6245.7 Kif20a 187.4 1435.3 1774.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE31028" 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=GSE31028 Status: Public on Sep 02 2011 Title: Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21885018 Summary & Design: Summary: Mouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.

Overall design: Quiescent hair follicle stem cells (qHF-SCs), activated hair follicle stem cells (aHF-SCs) and transient-amplifying matrix cells (HF-TACs) were FACS-purified for RNA extraction and hybridization on Affymetrix microarrays. To obtain homogeneous populations of expression profiles, we applied the FACS technique to purify SC and TACs according to their cell surface markers.

Background corr dist: KL-Divergence = 0.0298, L1-Distance = 0.0230, L2-Distance = 0.0006, Normal std = 0.6841

0.594 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

QuiescentQuiescent hair Activatedfollicle hair Activatedstemfollicle hair cells, follicleTransient-amplifyingstem hair rep1 cells, stemfollicleTransient-amplifying (0.145183) rep2 cells, stem (0.178661) rep1 cells, matrix (0.123751) rep2 cells,matrix (0.133199) rep1 cells,[ (0.122433)min rep2 (0.296773) ] [ medium ] [ max ] CEM 1 Birc5 83.1 1465.9 5926.8 P ( S | Z, I ) = 1.00 Plk4 92.5 213.9 759.4 Mean Corr = 0.82643 Cep55 35.8 545.2 2662.5 Ccnf 59.2 152.2 663.2 Sass6 130.9 209.3 350.8 Cep192 131.0 255.4 673.9 Poc1a 111.2 123.0 241.5 Ccp110 183.9 366.6 630.5 Cep128 45.6 84.0 121.0 Cep76 114.1 179.6 316.4 Cenpj 88.1 126.1 210.7 Alms1 66.2 131.8 146.3 Bub1 28.5 355.1 2010.4 Ncapg 27.7 166.4 827.5 Kif11 51.3 222.7 1119.7 Ccna2 109.7 1026.9 4703.3 Tpx2 66.9 342.2 1956.7 CEM 1 + Shcbp1 39.2 304.4 1761.8 Top 10 Genes Cenpe 46.4 185.8 546.5 Sgol1 75.2 288.0 1204.2 Cdk1 155.1 1624.7 7249.5 Kif20a 55.2 416.5 1804.6

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE10525" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10525 Status: Public on Dec 31 2008 Title: Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18668517 Summary & Design: Summary: Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy

In this study, we have generated an open source TRAMP microarray dataset to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 9 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes).

Keywords: prostate cancer, TRAMP

Overall design: normal prostate vs. TRAMP

Background corr dist: KL-Divergence = 0.1784, L1-Distance = 0.0411, L2-Distance = 0.0039, Normal std = 0.3571

1.117 Kernel fit Pairwise Correlations Normal fit

Density 0.559

0.000 CEM 1

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

Pre-normalization Quantiles

Normal TransgenicprostatesTransgenic (NORP-1) AdenocarcinomaTransgenic Adenocarcinoma (0.0383833)Transgenic Adenocarcinoma ofTransgenic the Adenocarcinoma Mouse ofNormal the Adenocarcinoma ProstateMouse of Normalprostates the ProstateMouse of (TRAMP)Normalprostates the (NORP-2) ProstateMouse of (TRAMP)Normalprostates tumorthe (NORP-3) (0.0324354)ProstateMouse (TRAMP)Normalprostates (TRAMP-1) tumor (NORP-4) (0.0393425)Prostate (TRAMP)Transgenicprostates (TRAMP-2) tumor (NORP-5) (0.126937)(0.0323616) (TRAMP)Normal (TRAMP-3) tumor (NORP-6) Adenocarcinoma (0.0797475)(0.0297497) Normalprostates (TRAMP-4) tumor (0.0409573)(0.0339922) Normalprostates (TRAMP-5) (NORP-7) (0.0346632) of Transgenicprostates the (NORP-8) (0.0373878) (0.0450552)MouseTransgenic (NORP-9) Adenocarcinoma (0.0312168)ProstateTransgenic Adenocarcinoma (0.0318539) (TRAMP) Adenocarcinoma of tumorthe Mouse of (TRAMP-6) the ProstateMouse of[ themin (0.051471) ProstateMouse (TRAMP) ] Prostate (TRAMP) tumor (TRAMP) (TRAMP-7) tumor[ medium (TRAMP-8) tumor (0.0451354) (TRAMP-9) (0.0553706) ] (0.213939)[ max ] CEM 1 Birc5 48.3 360.1 8381.3 P ( S | Z, I ) = 1.00 Plk4 78.3 208.2 1197.6 Mean Corr = 0.82151 Cep55 75.9 302.4 7018.0 Ccnf 15.2 149.0 701.4 Sass6 106.3 203.4 927.1 Cep192 245.5 503.8 1158.8 Poc1a 28.2 158.6 582.5 Ccp110 197.5 524.6 4205.7 Cep128 6.2 46.5 267.7 Cep76 163.6 328.1 747.5 Cenpj 165.1 329.7 1336.1 Alms1 81.0 205.6 569.1 Bub1 7.3 146.5 3226.4 Ncapg 5.8 59.8 1202.3 Kif11 24.0 159.7 1905.8 Ccna2 174.4 739.8 10272.3 Tpx2 62.8 192.2 2072.0 CEM 1 + Shcbp1 12.8 185.7 3688.9 Top 10 Genes Cenpe 20.8 193.1 1490.6 Sgol1 18.1 212.9 1903.8 Cdk1 21.5 673.5 6123.8 Kif20a 19.7 78.8 1211.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE19004" 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=GSE19004 Status: Public on Jul 01 2010 Title: Mouse HCC model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: A mouse model of HCC has been developed based on the reported inactivation of the RB pathway in the majority of human HCC. This mouse model harbors floxed alleles of Rb and p130 genes, as well as germline mutation of the p107 gene. Various strategies to activate the activity of a Cre recombinase leads to the efficient deletion of the three genes in the liver of adult mice (TKO mice). Disruption of the RB pathway induces the rapid development of HCC. These HCCs share many similar features of human HCC.

Overall design: The goal of this array is to assess genome wide expression of TKO HCCs. Gene expression of control livers (n=4) or TKO HCCs (n=5) was measured using the Affymetrix GeneChip Mouse Genome 430-2.0 arrays

Background corr dist: KL-Divergence = 0.0372, L1-Distance = 0.0331, L2-Distance = 0.0020, Normal std = 0.6133

0.650 Kernel fit Pairwise Correlations Normal fit

Density 0.325

0.000 CEM 1

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

Pre-normalization Quantiles

triple knockouttriple knockouttriple hepatocellular knockouttriple hepatocellular knockouttriple carcinomahepatocellular knockoutnormal carcinomahepatocellular - 1 normal(0.115883)liver carcinomahepatocellular - -1 2 normal(0.10684)(0.132772)liver carcinoma - - 3 2 normal(0.098635) liver(0.073193)carcinoma - - 4 3 (0.133412) liver(0.108524) - - 5 4 (0.0967525) (0.133987) [ min ] [ medium ] [ max ] CEM 1 Birc5 35.9 3983.9 5732.6 P ( S | Z, I ) = 1.00 Plk4 42.1 741.1 1157.5 Mean Corr = 0.82134 Cep55 39.3 944.3 2239.9 Ccnf 107.3 893.5 2601.1 Sass6 73.5 396.9 677.8 Cep192 73.6 628.2 931.9 Poc1a 164.3 691.0 1015.4 Ccp110 132.4 226.7 557.5 Cep128 33.6 92.9 189.9 Cep76 127.0 350.5 480.0 Cenpj 90.4 228.9 357.2 Alms1 41.5 97.8 102.8 Bub1 23.2 830.0 1668.6 Ncapg 22.4 623.8 929.7 Kif11 43.3 812.0 1222.8 Ccna2 92.2 3462.1 6910.0 Tpx2 85.7 874.3 1481.7 CEM 1 + Shcbp1 60.7 1028.6 1876.7 Top 10 Genes Cenpe 66.8 556.8 1068.7 Sgol1 71.1 1171.5 1739.9 Cdk1 108.8 6408.4 7383.6 Kif20a 32.2 1890.2 2215.6

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE53916" 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=GSE53916 Status: Public on Feb 17 2014 Title: Expression data from mouse bone marrow cells expressing renin driven expression of green fluorescent protein. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24549417 Summary & Design: Summary: Local renin antiotensin systems have been identified for many extra-renal sites. Bone marrow has been proposed as one such site, although the nature of the renin-expressing cell type(s) has not been established.

Affymetrix microarrays were used to characterize the expression profile of renin-expressing GFP positive cells.

Overall design: Green fluorescent protein positive cells were sorted from whole bone marrow collected from adult transgenic mice. Bone marrow from several mice was collected and pooled on the day of a FACS sort. A portion of this was reserved for RNA extraction while the remainder was sorted. RNA was prepared with Trizol. Bone marrow collection and sorting was performed 3 times so that microarrays could be run in triplicate.

Background corr dist: KL-Divergence = 0.0206, L1-Distance = 0.0262, L2-Distance = 0.0007, Normal std = 0.7706

0.537 Kernel fit Pairwise Correlations Normal fit

Density 0.268

0.000 CEM 1

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

Pre-normalization Quantiles

Bone marrowBone marrow presortBone marrow sortedcellsBone biological marrow cellspresortBone biological marrow sortedcells Bonerep1 biological (0.112892) marrow cells presortrep1 biological(0.276161) sortedcells rep2 biological(0.168432) cells rep2 biological(0.158606) [rep3 min (0.11569) rep3 (0.168219)] [ medium ] [ max ] CEM 1 Birc5 234.1 2783.2 3963.6 P ( S | Z, I ) = 1.00 Plk4 306.8 1692.9 2160.7 Mean Corr = 0.82071 Cep55 352.3 2255.8 2646.3 Ccnf 171.3 1309.9 1368.3 Sass6 483.9 899.2 1053.9 Cep192 672.4 1110.2 1155.7 Poc1a 110.9 291.7 390.7 Ccp110 326.7 866.9 1183.0 Cep128 78.9 245.1 322.6 Cep76 297.6 1005.3 1294.9 Cenpj 649.7 785.9 832.8 Alms1 47.9 89.7 135.8 Bub1 321.5 2799.6 3177.3 Ncapg 163.8 1343.3 1538.7 Kif11 339.2 3044.6 3559.5 Ccna2 441.2 5456.4 5737.2 Tpx2 368.3 3235.8 4173.9 CEM 1 + Shcbp1 427.5 3305.5 3845.8 Top 10 Genes Cenpe 353.9 2402.8 2931.7 Sgol1 439.1 2306.1 2732.6 Cdk1 448.7 4337.9 4482.7 Kif20a 166.7 1787.1 2385.7

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE29241" 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=GSE29241 Status: Public on Nov 13 2011 Title: Dendritic cell lineage commitment is instructed by distinct cytokine signals Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22078373 Summary & Design: Summary: Dendritic cells (DC) develop from hematopoietic stem cells, which is guided by instructive signals through cytokines. DC development progresses from multipotent progenitors (MPP) via common DC progenitors (CDP) into DC. Flt3 ligand (Flt3L) signaling via the Flt3/Stat3 pathway is of pivotal importance for DC development under steady state conditions. Additional factors produced during steady state or inflammation, such as TGF-beta1 or GM-CSF, also influence the differentiation potential of MPP and CDP. Here, we studied how gp130, GM-CSF and TGF-beta1 signaling influence DC lineage commitment from MPP to CDP and further into DC. We observed that activation of gp130 signaling promotes expansion of MPP. Additionally, gp130 signaling inhibited Flt3L-driven DC differentiation, but had little effect on GM-CSF-driven DC development. The inflammatory cytokine GM-CSF induces differentiation of MPP into inflammatory DC and blocks steady state DC development. Global transcriptome analysis revealed a GM-CSF-driven gene expression repertoire that primes MPP for differentiation into inflammatory DC. Finally, TGF-beta1 induces expression of DC-lineage affiliated genes in MPP, including Flt3, Irf-4 and Irf-8. Under inflammatory conditions, however, the effect of TGF- beta1 is altered: Flt3 is not upregulated, indicating that an inflammatory environment inhibits steady state DC development. Altogether, our data indicate that distinct cytokine signals produced during steady state or inflammation have a different outcome on DC lineage commitment and differentiation.

Overall design: - GM-TNFa-DC_2

Background corr dist: KL-Divergence = 0.0220, L1-Distance = 0.0160, L2-Distance = 0.0003, Normal std = 0.7247

0.550 Kernel fit Pairwise Correlations Normal fit

Density 0.275

0.000 CEM 1

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

Pre-normalization Quantiles

MultipotentMultipotent progenitorDendritic progenitorDendritic sample cell sampleDendritic sample1 cell (GM-MPP_1) sample1Dendritic (GM-DC_1)2 cell (GM-MPP_2) plus2 (0.312755)(GM-DC_2) cell TNFa (0.117694) plus (0.149076) sample TNFa (0.105548) sample1 (GM-TNFa-DC_1)[ 2min (GM-TNFa-DC_2) ] (0.162853) (0.152074)[ medium ] [ max ] CEM 1 Birc5 297.3 1796.8 4348.5 P ( S | Z, I ) = 1.00 Plk4 262.3 570.2 1480.9 Mean Corr = 0.81869 Cep55 253.6 1425.4 1979.5 Ccnf 121.6 445.4 1435.6 Sass6 162.4 404.0 851.3 Cep192 489.6 750.7 1062.4 Poc1a 226.3 316.3 892.5 Ccp110 70.8 183.5 377.8 Cep128 73.4 162.1 614.6 Cep76 140.4 219.3 344.2 Cenpj 171.7 327.3 736.4 Alms1 26.1 52.1 61.6 Bub1 215.4 1563.3 2449.8 Ncapg 59.1 617.6 1476.9 Kif11 93.4 496.4 1537.7 Ccna2 550.7 2380.9 5390.4 Tpx2 277.7 1324.2 3041.0 CEM 1 + Shcbp1 217.3 1520.0 3042.5 Top 10 Genes Cenpe 195.7 1019.1 1907.9 Sgol1 115.8 572.7 1476.7 Cdk1 516.3 2050.4 4048.8 Kif20a 203.4 801.8 2107.8

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE21309" 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=GSE21309 Status: Public on Apr 13 2010 Title: Differential gene expression patterns in lung carcinogenesis mediated by loss of mouse tumor supressor Gprc5a Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20686609 Summary & Design: Summary: Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Moreover, we analyzed differential gene expression patterns between Gprc5a knockout normal lung epithelial cells as well as lung adenocarcinoma cells isolated and cultured from tumors of NNK-exposed Gprc5a knockout mice.

Overall design: Gprc5a wild type cells (WT-NLE) and Gprc5a knockout cells (NULL-NLE) were isolated and cultured from trachea of three week old Gprc5a wild type and knockout mice, respectively. MDA-F471 mouse lung adenocarcinoma cells were derived de novo from an adenocarcinoma that was found in the lung of a female Gprc5a-knockout mouse sacrificed 16 months after NNK tobacco carcinogen i.p. injection based on a protocol approved by the M.D. Anderson Cancer Center Institutional Animal Care and Use Committee. Following RNA extraction and purification, the transcriptome of the Gprc5a wild type and knockout cells were analyzed by microarray analysis using the Affymetrix MG-430 2.0 murine array platform.

Background corr dist: KL-Divergence = 0.0371, L1-Distance = 0.0368, L2-Distance = 0.0016, Normal std = 0.6593

0.642 Kernel fit Pairwise Correlations Normal fit

Density 0.321

0.000 CEM 1

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

Pre-normalization Quantiles

C032 Gprc5aC033 Gprc5awildC034 type Gprc5awildC035 mouse type Gprc5awildC036 normalmouse type Gprc5aknockoutC037 normalmouselung Gprc5aepithelialknockoutC023 normallungmouse NNK-exposedepithelialknockoutC024 celllungnormalmouse replicate NNK-exposedepithelialC025 cellnormalmouselung replicate Gprc5a NNK-exposed epithelial1 cell(0.108033)normallung replicate Gprc5aknockout epithelial2 (0.0966527)celllung replicateGprc5aknockout epithelial3 mouse(0.0893807)cell replicateknockout 1 [ lungmousecell(0.0610105) min replicateadenocarcinoma 2 lungmouse (0.069478) ] adenocarcinoma 3 lung (0.0868168) adenocarcinoma cell[ replicatemedium cell replicate 1 cell(0.154141) replicate 2 (0.174472)] 3 (0.160017)[ max ] CEM 1 Birc5 587.0 618.9 3743.4 P ( S | Z, I ) = 1.00 Plk4 156.3 308.1 1348.0 Mean Corr = 0.81684 Cep55 586.1 949.2 3893.1 Ccnf 308.5 348.7 950.7 Sass6 118.5 151.1 509.5 Cep192 274.4 292.5 1033.0 Poc1a 217.0 242.3 552.0 Ccp110 154.2 174.1 344.7 Cep128 34.2 41.9 196.3 Cep76 85.3 114.0 221.1 Cenpj 128.4 158.9 206.0 Alms1 76.5 84.7 136.6 Bub1 234.0 390.0 2453.6 Ncapg 96.5 152.3 889.6 Kif11 291.5 314.9 1175.2 Ccna2 600.0 1019.4 3868.7 Tpx2 296.0 428.4 2465.1 CEM 1 + Shcbp1 328.6 525.9 1229.9 Top 10 Genes Cenpe 254.2 314.6 1656.8 Sgol1 294.1 369.9 1081.8 Cdk1 1078.8 1411.3 5702.4 Kif20a 194.2 218.8 1778.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE21900" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.784 Kernel fit Pairwise Correlations Normal fit

Density 0.392

0.000 CEM 1

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

Pre-normalization Quantiles

P1-control-ex1P1-control-ex2 P1-control-ex3(0.0686837) P1-Otx2-CKO-ex1(0.0758149) P1-Otx2-CKO-ex2(0.0625993)P1-Otx2-CKO-ex3 (0.090001)P12-control-ex1 (0.0729377)P12-control-ex2 (0.0591514)P12-control-ex3 (0.102458)P12-Otx2-CKO-ex1 (0.131199)P12-Otx2-CKO-ex2 (0.0822188)P12-Otx2-CKO-ex3 (0.0950097) (0.105411) (0.0545159)[ min ] [ medium ] [ max ] CEM 1 Birc5 15.0 2336.5 4949.2 P ( S | Z, I ) = 1.00 Plk4 72.9 421.2 1017.6 Mean Corr = 0.81661 Cep55 4.6 976.6 1504.5 Ccnf 39.4 648.4 1122.3 Sass6 77.0 361.1 605.7 Cep192 48.2 564.3 1040.3 Poc1a 64.3 259.0 482.6 Ccp110 155.7 1089.8 1743.8 Cep128 44.1 177.6 451.9 Cep76 77.0 309.1 590.0 Cenpj 50.9 197.3 412.6 Alms1 47.2 267.8 462.7 Bub1 4.5 535.0 1698.3 Ncapg 4.6 361.1 1172.9 Kif11 5.1 478.1 1043.2 Ccna2 74.7 3103.9 3791.0 Tpx2 28.8 1505.6 2511.0 CEM 1 + Shcbp1 24.6 660.2 1808.2 Top 10 Genes Cenpe 33.8 184.4 976.9 Sgol1 7.7 576.2 864.0 Cdk1 98.6 3699.5 5734.6 Kif20a 31.8 841.4 1239.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE6998" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 32 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

and repair after injury. Whether this response

represents simple hyperplasia of various liver elements

or requires recapitulation of the genetic program of

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

we examined transcriptional programs of

adult liver after partial hepatectomy and contrasted

these with developing embryonic liver. Principal component

analysis demonstrated that the time series of

gene expression during liver regeneration does not segregate

according to developmental transcription patterns.

Gene ontology analysis revealed that liver restoration

after hepatectomy and liver development differ

dramatically with regard to transcription factors

and chromatin structure modification. In contrast, the

tissues are similar with regard to proliferationassociated

genes. Consistent with these findings, realtime

polymerase chain reaction showed transcription

factors known to be important in liver development

are not induced during liver regeneration. These three

lines of evidence suggest that at a transcriptional level,

restoration of liver mass after injury is best described

as hepatocyte hyperplasia and not true regeneration.

We speculate this novel pattern of gene expression may

underlie the unique capacity of the liver to repair itself

after injury.

Keywords: time course

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

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

0.727 Kernel fit Pairwise Correlations Normal fit

Density 0.364

0.000 CEM 1

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

Pre-normalization Quantiles

baselinebaseline sampleregeneration sampleat T0,regeneration rep1 at T0, (0.0252014)sampleregeneration rep2 (0.0174004) sampleatregeneration T1, rep1 sampleatregeneration T1, (0.0193522) rep2 sampleatregeneration T2, (0.0300255) rep1 sampleatregeneration T2, (0.0189601) rep2 sampleatregeneration T6, (0.0166521) rep1 sampleatregeneration T6, (0.0303061) rep2 sampleatregeneration T12, (0.0226237) samplerep1atregeneration T12, (0.0265289) samplerep2atregeneration T18, (0.0411997) samplerep1atregeneration T18, (0.0281464) samplerep2atregeneration T24, (0.0254213) samplerep1atregeneration T24, (0.0232283) samplerep2atregeneration T30, (0.0268248) samplerep1atregeneration T30, (0.0152291) samplerep2atregeneration T48, (0.0213143) samplerep1atdevelopmental T48, (0.0161847) samplerep2atdevelopmental T72, (0.0826172) rep1at developmentalsample T72, (0.0136521) rep2 developmental sampleat T105,(0.0201122) developmental sampleat rep1 T105, (0.053893) developmental sampleat rep2 T115, (0.0636883) developmental sampleat rep1 T115, (0.0319871) developmental sampleat rep2 T125, (0.0388437) developmental sampleat rep1 T125, (0.036663) developmental sampleat rep2 T135, (0.0375854) developmental sampleat rep1 T135, (0.0385818) developmental sampleat rep2 T145, (0.0408916) sampleat rep1 T145, (0.0378875) sampleat rep2 T165, (0.0380469) at rep1 T165, (0.0344788)[ rep2min (0.0264727) ] [ medium ] [ max ] CEM 1 Birc5 3.3 105.8 5878.8 P ( S | Z, I ) = 1.00 Plk4 10.3 89.0 990.1 Mean Corr = 0.81523 Cep55 18.9 110.8 1053.9 Ccnf 3.4 43.6 2757.6 Sass6 53.6 167.1 515.8 Cep192 60.7 225.6 1173.7 Poc1a 82.4 159.8 475.1 Ccp110 335.7 548.4 968.4 Cep128 3.4 26.8 339.8 Cep76 229.6 346.4 1658.2 Cenpj 58.6 134.6 351.9 Alms1 27.8 66.3 174.7 Bub1 3.3 21.6 2069.3 Ncapg 3.5 109.6 2208.5 Kif11 3.3 82.4 1616.4 Ccna2 9.1 245.6 7042.4 Tpx2 32.8 137.0 2233.0 CEM 1 + Shcbp1 3.3 122.4 1684.7 Top 10 Genes Cenpe 3.3 36.5 1238.3 Sgol1 3.3 31.7 1404.0 Cdk1 3.3 251.9 6343.5 Kif20a 49.8 112.4 1235.3

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE17316" 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=GSE17316 Status: Public on Nov 23 2009 Title: Reprogramming of a B cell line into macrophages Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19896445 Summary & Design: Summary: Transcription factor induced reprogramming of one specialized cell type into another is a promising approach for regenerative medicine. However, the process still remains poorly understood, in large part because of the lack of adequate experimental models. Here we describe a robust cell reprogramming system consisting of a B cell line with an inducible form of C/EBPa that can be converted into macrophages with essentially 100% efficiency in only 2 to 3 days. The conversion involves reciprocal changes in cell surface antigen expression, increase in cell granularity and size, alterations in cellular structures, formation of membrane extensions, acquisition of phagocytic capacity and an increased inflammatory responsiveness as well as migratory activity. Analysis of the transcriptome shows complex reciprocal regulation of B cell and macrophage genes, including transcription factors required for the formation of the two lineages. The fact that the cells become irreversibly committed to a macrophage fate within 1 to 2 days after activation of C/EBPa show that they are truly reprogrammed. The system should be useful to study epigenetic and cell biological mechanisms of transcription factor induced cell reprogramming.

Overall design: time points: vehicle control, 3h, 12h, 24h, 48h.

Background corr dist: KL-Divergence = 0.0922, L1-Distance = 0.0474, L2-Distance = 0.0035, Normal std = 0.4812

0.883 Kernel fit Pairwise Correlations Normal fit

Density 0.441

0.000 CEM 1

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

Pre-normalization Quantiles

HAFTL HAFTLcell line C10cell treated linecellC10 treatedwithline cell withbetaC10 withline an estradiol cell withinduciblebetaC10 line an estradiol cell samplewithinducibleC10 formline an cell samplewith1inducibleof (0.0510897)C10 formC/EBPa,line an cell with2inducibleof (0.0760331)C10 formC/EBPa,line treatedan cell withinducibleofC10 formC/EBPa,line treatedwithan cell withinducibleof ethanolC10 formC/EBPa,line treatedwithan cell withinducibleof ethanol C10 sampleformC/EBPa,line treatedwithan cell withinducibleof beta sampleform1C/EBPa,line treatedwith(0.0727798)an estradiol withinducibleof beta form2C/EBPa, treatedwith(0.0611853)an estradiol inducibleof for beta formC/EBPa, treatedwith3 hoursestradiol of for beta [ formC/EBPa, treatedwith3 minsample hoursestradiol of for beta C/EBPa, treatedwith12 sample1 ]estradiol (0.111074)hours for beta treatedwith12 2 sampleestradiol (0.11832)hours for beta with24[ sampleestradiol1 hoursmedium for(0.0514305) beta 24 sampleestradiol2 hours for(0.0750027) 48 sample1 hours for(0.0800235) ] 48 sample2 hours (0.0612763) sample1 (0.126522)[ max 2 (0.115264) ] CEM 1 Birc5 51.2 2596.6 6815.6 P ( S | Z, I ) = 1.00 Plk4 46.3 599.7 2632.8 Mean Corr = 0.81153 Cep55 23.0 2322.8 5086.4 Ccnf 25.1 540.5 2290.1 Sass6 160.3 292.1 535.5 Cep192 564.5 1433.1 1717.2 Poc1a 82.2 236.0 616.4 Ccp110 166.9 577.2 2314.9 Cep128 75.2 376.1 518.5 Cep76 267.1 444.7 1076.0 Cenpj 485.2 746.0 918.7 Alms1 6.6 114.4 196.2 Bub1 27.1 1647.8 4482.9 Ncapg 30.4 806.2 2185.9 Kif11 2.1 460.3 2035.6 Ccna2 59.4 2370.2 8322.5 Tpx2 141.9 1184.9 3696.3 CEM 1 + Shcbp1 5.7 1017.8 4113.0 Top 10 Genes Cenpe 29.7 802.1 2274.8 Sgol1 3.2 754.6 1606.8 Cdk1 120.1 2010.1 10509.1 Kif20a 14.2 514.4 1454.9

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE32277" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 33 -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=GSE32277 Status: Public on Apr 30 2012 Title: Kras is required for pancreatic tumor maintenance through regulation of hexosamine biosynthesis and the non-oxidative pentose phosphate pathway Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22541435 Summary & Design: Summary: The maintenance of advanced malignancies relies on continued activity of driver oncogenes, although their rate-limiting role is highly context-dependent with respect to tumor types and associated genetic alterations. Oncogenic Kras mutation is the signature event in human pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible KrasG12D-driven p53 mutant PDAC mouse model establishes that advanced PDAC remains strictly dependent on continued KrasG12D expression and that KrasG12D serves a vital role in the control of tumor metabolism, through stimulation of glucose uptake and channeling of glucose intermediates through the hexosamine biosynthesis pathway (HBP) and the pentose phosphate pathway (PPP). Notably, these studies reveal that oncogenic Kras regulates ribose biogenesis. Unlike canonical models of PPP-mediated ribose biogenesis, we demonstrate that oncogenic Kras drives intermediates from enhanced glycolytic flux into the non-oxidative arm of the PPP, thereby decoupling ribose biogenesis from NADPNADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in Kras-driven PDAC.

Overall design: Primary pancreatic tumor lines were established from p48Cre tetO_LKrasG12D ROSA_rtTAL+ p53L+ mice. Five independent tumor lines (iKras1-5) were used for pancreatic injection into nude mice to generate orthotopic tumors. The mice were kept on doxycycline for 2 weeks until obvious tumor formation. Half of the animals were pulled off doxycycline for 24 hours. Tumors with over 75% cellularity were collected for total RNA prepartion. For in vitro expression profiles, the same five tumor lines were cultured in the presence or absence of doxycycline for 24 hours and total cellular RNA was prepared. For control samples, two independent tumor lines from LSL-KrasG12D p53L+ tumors were cultured in the presence or absence of doxycycline for 24 hours and total cellular RNA was prepared.

Background corr dist: KL-Divergence = 0.1319, L1-Distance = 0.0356, L2-Distance = 0.0021, Normal std = 0.4008

1.012 Kernel fit Pairwise Correlations Normal fit

Density 0.506

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

iKras5-T-on-1iKras5-T-on-2 (0.0179889)iKras5-T-off-1 (0.011453)iKras5-T-off-2 (0.0159311)iKras1-T-on-1 (0.0361674)iKras1-T-on-2 (0.018944)iKras1-T-off-1 (0.0167567)iKras2-T-on-1 (0.0192606)iKras2-T-on-2 (0.0764587)iKras2-T-off-1 (0.0212533)iKras2-T-off-2 (0.0160871)iKras3-T-on-1 (0.0225265)iKras3-T-on-2 (0.020202)iKras3-T-off-1 (0.0185782)iKras3-T-off-2 (0.0175261)iKras4-T-on-1 (0.017195)iKras4-T-on-2 (0.012969)iKras4-T-off-1 (0.0219224)iKras4-T-off-2 (0.0189703)iKras5-C-on (0.016819)iKras1-C-on (0.027478)iKras2-C-on (0.0260109)iKras3-C-on (0.0301895)iKras4-C-on (0.0147556)iKras5-C-off (0.0187728)iKras1-C-off (0.0340542)iKras2-C-off (0.0242467)iKras3-C-off (0.0343178)iKras4-C-off (0.0189016)LSL-Kras2-on (0.0171937)LSL-Kras2-off (0.0753856)LSL-Kras1-on (0.100245)LSL-Kras1-off (0.0694671) (0.091972) [ min ] [ medium ] [ max ] CEM 1 Birc5 710.0 1357.2 7403.5 P ( S | Z, I ) = 1.00 Plk4 226.4 562.3 2450.8 Mean Corr = 0.81004 Cep55 416.9 885.1 4890.7 Ccnf 139.8 343.7 1530.9 Sass6 78.3 171.1 611.0 Cep192 366.7 614.9 1261.5 Poc1a 138.0 282.1 695.1 Ccp110 116.6 194.2 445.7 Cep128 30.6 80.0 290.5 Cep76 86.0 184.8 708.2 Cenpj 88.0 184.4 459.7 Alms1 14.5 149.9 356.6 Bub1 157.9 506.7 3586.5 Ncapg 42.8 215.3 1580.1 Kif11 148.0 332.4 1745.1 Ccna2 646.6 1454.7 6383.9 Tpx2 263.6 517.2 2062.1 CEM 1 + Shcbp1 189.2 411.3 3083.2 Top 10 Genes Cenpe 187.9 386.6 2080.8 Sgol1 81.4 328.7 1856.8 Cdk1 1109.2 2915.1 9642.2 Kif20a 126.0 339.3 2266.4

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE24628" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.963 Kernel fit Pairwise Correlations Normal fit

Density 0.482

0.000 CEM 1

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

Pre-normalization Quantiles

pgr003 pgr006(0.0730024) pgr010(0.0485381) pgr011(0.0505233) pgr012(0.0609526) pgr013(0.0750467) pgr014(0.0465612) pgr016(0.0972716) pgr029(0.0829112) pgr033(0.0395472) pgr035(0.0201458) pgr049(0.0318111) pgr051(0.0664991) pgr053(0.0692249) pgr055(0.0762471) pgr066(0.080865) (0.0808527) [ min ] [ medium ] [ max ] CEM 1 Birc5 86.1 1381.1 3413.1 P ( S | Z, I ) = 1.00 Plk4 135.4 448.6 1741.5 Mean Corr = 0.79918 Cep55 125.1 1479.9 4206.2 Ccnf 99.4 477.3 866.2 Sass6 228.2 346.9 801.5 Cep192 202.7 342.4 864.0 Poc1a 14.7 122.9 203.0 Ccp110 1054.1 2979.9 4285.7 Cep128 20.6 70.1 161.3 Cep76 81.3 365.3 688.5 Cenpj 133.3 487.5 1327.6 Alms1 55.5 158.5 280.4 Bub1 92.2 1271.3 3290.2 Ncapg 53.8 927.5 1968.5 Kif11 69.0 745.0 2171.0 Ccna2 383.5 2840.2 6382.1 Tpx2 158.7 2124.5 3614.8 CEM 1 + Shcbp1 166.0 1790.1 5593.4 Top 10 Genes Cenpe 122.6 1212.8 2440.2 Sgol1 100.4 702.7 2003.2 Cdk1 242.7 2613.9 6093.2 Kif20a 46.0 672.4 1725.0

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 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 (0.105559) AE14.5 (0.105372) AE11.5 (0.158869) BE12.5 (0.145124) BE14.5 (0.0489239) BE11.5 (0.106528) CE12.5 (0.102837) CE14.5 (0.109364) C (0.117423) [ min ] [ medium ] [ max ] CEM 1 Birc5 1925.4 4373.1 5804.3 P ( S | Z, I ) = 1.00 Plk4 649.5 1092.7 1499.9 Mean Corr = 0.79903 Cep55 623.3 1375.8 2028.1 Ccnf 290.6 499.9 1046.7 Sass6 312.6 713.5 862.5 Cep192 758.6 1054.9 1773.8 Poc1a 260.0 465.3 553.8 Ccp110 1708.1 2570.7 3705.5 Cep128 93.9 162.8 229.6 Cep76 294.3 463.3 640.3 Cenpj 316.2 682.9 1263.9 Alms1 225.9 341.2 501.8 Bub1 1271.1 3356.2 5153.0 Ncapg 418.6 1108.9 1413.2 Kif11 510.4 976.3 1383.5 Ccna2 2527.8 4676.7 5877.1 Tpx2 866.3 1843.5 2336.9 CEM 1 + Shcbp1 1320.3 2643.4 3750.6 Top 10 Genes Cenpe 573.3 1386.1 2207.3 Sgol1 365.0 928.9 1143.9 Cdk1 2361.2 4150.5 5092.5 Kif20a 609.9 1721.4 2643.5

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE15326" 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=GSE15326 Status: Public on Mar 01 2010 Title: LKR13-Kras-WT1-KO Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: K-ras is one of the most frequently mutated human oncogenes. However, activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we describe a novel loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor and at physiological levels, but had no effect on cells expressing wild-type K-ras. Furthermore, loss of Wt1 in lung cancer cell lines that harbor mutant K-ras leads to apoptosis. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras.

We compare the expression profiles of K-ras mutant mouse cell line (LKR13) upon shRNA knockdown of K-ras itself or Wt1. The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras.

Overall design: LKR13 cells were infected with plko.1s vectors carrying one of two shRNAs against K-ras or Wt1. Control cells were infected with an shRNA against GFP. 48 hours after infection, cells were selected with puromycin for 3 days. RNA was isolated using Trizol 7 days after infection. RNA was further prepared by passage over an RNeasy column. cDNA synthesis, biotinylation of cRNA and hybridization to mouse Genechip 430A v2 containing 39,000 probes was performed according to the manufacturers instructions (Affymetrix, Santa Clara). Microarray data was normalized with Expression Console software (Affymetrix, Santa Clara), using RMA algorithms.

Background corr dist: KL-Divergence = 0.0699, L1-Distance = 0.0280, L2-Distance = 0.0013, Normal std = 0.4948

0.806 Kernel fit Pairwise Correlations Normal fit

Density 0.403

0.000 CEM 1

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

Pre-normalization Quantiles

LKR13_KrasLKR13_Kras sh-1LKR13_Wt1 (0.123102) sh-2LKR13_Wt1 (0.0641181) sh-1LKR13_Control-1 (0.0966323) sh-2LKR13_Control-2 (0.0782818)LKR13_Control-3 (0.0617899)LKR13_Control-4 (0.0838823)LKR13_Kras (0.225765)LKR13_Kras (0.142477) sh-3 (0.0716025) sh-4 (0.0523483) [ min ] [ medium ] [ max ] CEM 1 Birc5 852.4 2733.0 5781.3 P ( S | Z, I ) = 1.00 Plk4 324.7 582.1 1521.4 Mean Corr = 0.79744 Cep55 1194.7 3366.3 7008.0 Ccnf 284.3 789.4 2141.0 Sass6 175.7 304.0 423.6 Cep192 409.2 682.7 1355.6 Poc1a 199.7 299.7 410.9 Ccp110 309.4 586.9 662.6 Cep128 44.6 146.8 306.7 Cep76 158.9 210.4 363.5 Cenpj 72.6 167.3 235.9 Alms1 78.7 92.8 149.1 Bub1 329.4 1319.2 3869.9 Ncapg 169.0 659.8 1759.9 Kif11 306.5 856.0 2011.1 Ccna2 635.0 2152.7 4654.8 Tpx2 520.5 1977.5 3911.7 CEM 1 + Shcbp1 478.7 998.1 3120.3 Top 10 Genes Cenpe 323.9 680.4 1804.0 Sgol1 334.2 848.3 1773.1 Cdk1 1940.0 4011.0 7538.6 Kif20a 503.4 1571.3 3436.2

Null module Cetn3 Topors Cep19 Cetn2 Nin Poc5 Tsks Ftcd Cep41 Mphosph9 Bbs4 Cep250 Dzip1 Tubd1 Cetn1 Rock1 Ccsap Cep164 Fbf1 Herc2 Tubgcp3 Sfi1 Plk2 Spice1 Ofd1 Crocc Top2a Lrrcc1 Poc1b Neurl4 Sdccag8 Cntrob Cep104 Stard9 Dzip1l Cep170 Ahi1 Odf2 Cep135 Ift88 Tssk2 Ccdc92 Ift20 Cntln Parp3 Pla2g3 GEO Series "GSE19176" 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=GSE19176 Status: Public on Jan 20 2010 Title: Role of Bmi1 in Shh-mediated shift in gene expression levels Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We investigated the role of Bmi1 in Shh-mediated shift in gene expression levels

Overall design: Total RNA was isolated using RNeasy Mini Kit (Qiagen) and reverse-transcribed into double-stranded cDNA with One-Cycle cDNA Synthesis Kit (Affymetrix Inc., P/N 900431, Santa Clara, CA) and labelled biotin. Biotin-labeled cRNA samples were fragmented randomly to 35200 bp and hybridized to GeneChip´ﬁ Mouse Genome 430 2.0. An Affymetrix GeneChip Scanner 3000 (Affymetrix Inc., Santa Clara, CA) was used to measure the fluorescent intensity emitted by the labeled target.

Background corr dist: KL-Divergence = 0.0722, L1-Distance = 0.0262, L2-Distance = 0.0009, Normal std = 0.5022

0.807 Kernel fit Pairwise Correlations Normal fit

Density 0.403

0.000 CEM 1

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

Pre-normalization Quantiles

Wild typeWild primary typeBmi1 primary cerebellar knockoutBmi1 cerebellar knockout granuleWild primary type granule progenitorBmi-1 primary cerebellar primary knockout progenitorWild cerebellar cerebellarcells granuletypeBmi-1- 1primary primary (0.0957279)cells granule progenitor granule knockoutWild 3 cerebellar (0.0623743)cerebellar typeprogenitor progenitorBmi-1-knockout cells primaryprimary granule granule2 (0.123614)cells cerebellarcerebellarcells progenitor 4progenitor treated(0.0707035)primary granulegranule with cellscerebellar cells Shh progenitor progenitor[treated 5 min(0.0748434)7 (0.107622)granule with cells cells ]Shh progenitor 6treated 8(0.133147) (0.094426) with cells[ mediumShh treated 9 (0.135799) with Shh ] 10 (0.101744)[ max ] CEM 1 Birc5 2491.7 2769.1 4204.2 P ( S | Z, I ) = 1.00 Plk4 413.2 726.4 1478.5 Mean Corr = 0.79445 Cep55 820.2 1066.0 2260.1 Ccnf 321.5 455.0 1264.9 Sass6 340.4 388.7 539.6 Cep192 387.3 591.8 868.0 Poc1a 172.1 213.7 287.2 Ccp110 2069.2 2544.6 2900.2 Cep128 185.5 313.9 455.5 Cep76 342.8 525.2 698.9 Cenpj 462.3 527.0 966.4 Alms1 102.0 165.8 187.3 Bub1 1842.0 2343.3 3512.2 Ncapg 525.5 768.1 2142.8 Kif11 468.4 739.3 1198.8 Ccna2 5777.3 7127.4 8985.2 Tpx2 2086.8 2435.6 3322.5 CEM 1 + Shcbp1 2235.9 2488.0 4390.6 Top 10 Genes Cenpe 691.3 1076.1 1922.3 Sgol1 1148.6 1482.9 2709.6 Cdk1 2783.5 3271.6 7007.6 Kif20a 529.9 659.7 1685.7