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

Dataset: Num of in input set: 65 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. Num ofGenesinQueryGeneset:65.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Trp53bp1 Rangap1 Csnk1a1 Dync1li1 Champ1 Dync1i1 Nudcd2 Cenpc1 Nup133 Nup107 Itgb3bp Mad1l1 Cenpm Clasp2 Clasp1 Cenpw Smc1a Incenp Knstrn Ss18l1 Zwilch Ahctf1 Cenpo Apitd1 Cenpu Cenpn Cenph Bub1b Stra13 Cenpv Dynlt3 Nup43 Nup85 Cenpk Ercc6l Spag5 Ndc80 Spc25 Casc5 Spc24 Tex14 Cenpt Kntc1 Dctn3 Sept2 Ndel1 Sept6 Sgol2 Sgol1 Sept7 Pinx1 Seh1l Hjurp Zwint Zw10 Birc5 Bub3 Kif2b Bod1 Bub1 Kif2c Nde1 Nek2 Nuf2 Tpr

Bub1 Birc5 Sgol1 Nuf2 Zwilch Bub1b Kntc1 Ndc80 Cenpk Spc24 Cenph Sgol2 Ercc6l Spag5 Incenp Nek2 Cenpn Cenpu Cenpw Apitd1 Casc5 Cenpm Nup107 Nup85 Nup133 Nup43 Nde1 Smc1a Cenpc1 Nudcd2 Cenpt Cenpo Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 0.0 Singletons CEM 1(674datasets) Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page1 Mis18bp1 Nudcd2 Nusap1 Shcbp1 Cenpc1 Nup133 Nup107 Cenpm Cenpw Smc1a Incenp Zwilch Cenpo Apitd1 Cenpu Cenpn Cenph Bub1b Ccnb2 Ncaph Ncapg Nup43 Nup85 Cenpk Ercc6l Cdca5 Rad51 Kif20a Ccna2 Spag5 Ndc80 Casc5 Spc24 Aurkb Aurka Cenpt Cenpi Kntc1 Sgol2 Sgol1 Birc5 Bub1 Kif11 Cdk1 Nde1 Nek2 Tpx2 Melk Nuf2 Pbk 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 668.25 673.55 675.34 675.47 676.98 677.63 683.06 683.80 685.40 690.19 691.05 692.38 700.01 715.15 719.92 729.18 737.56 740.92 1.0 Notes Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page2 Arhgap11a Rad51ap1 Depdc1a Racgap1 Ncapg2 Ncapd2 Ckap2l Cenpp Kif18b Cenpe Cdca2 Cdc45 Ckap2 Cep55 Ube2c Cdc20 Cdca8 Esco2 Fbxo5 Fignl1 Gmnn Mcm5 Cenpf Gins1 Brca1 Mki67 Prim1 Asf1b Aspm Spdl1 Espl1 Uhrf1 Rrm1 Cdc6 Kif22 Exo1 Ska3 Dbf4 Anln Prc1 Rfc5 Rfc4 Ect2 Pole Plk1 Plk4 Lig1 Kif4 Tk1 Stil 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 565.24 572.27 574.37 575.55 578.98 581.01 581.42 582.22 583.41 584.63 585.34 585.47 585.58 585.70 588.96 589.13 591.57 593.67 595.04 596.25 598.99 600.68 603.27 605.21 606.70 608.07 608.96 609.18 609.58 613.84 617.87 619.52 623.25 625.01 626.25 631.09 633.36 633.58 634.66 641.06 641.69 646.33 647.81 651.13 651.77 656.24 660.82 661.19 662.93 663.59 1.0 Notes 4930579G24Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page3 BC055324 Depdc1b Mms22l Rad54b Topbp1 Cdc25c Parpbp Wdhd1 Iqgap3 Cenpq Chtf18 Cdkn3 Kpna2 Ccne2 Trip13 Cks1b Kif18a Hirip3 Mcm2 Mcm6 Mcm7 Mcm4 Gins2 Prim2 Cenpl Atad5 Ube2t Atad2 H2afx Pole2 Eme1 Pola1 Mastl Rrm2 Gen1 Gsg2 Dsn1 Rpa2 Hells Cks2 Tipin Ezh2 Fen1 Orc6 Oip5 Ccnf E2f8 E2f7 Blm 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 437.97 440.76 442.29 444.39 445.08 450.55 453.25 458.53 462.36 464.29 466.41 467.83 472.18 475.32 475.96 484.31 487.42 488.64 491.60 491.68 495.50 495.66 496.55 498.91 499.35 502.48 503.03 505.22 506.63 514.67 519.45 521.59 526.41 528.57 531.11 534.81 535.67 537.21 537.37 538.41 545.17 547.56 550.98 552.54 555.39 556.32 559.26 561.86 562.06 562.93 1.0 Notes 2700029M09Rik 2700094K13Rik 2810417H13Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page4 Rnaseh2b Arhgef39 Timeless Suv39h1 Fam64a Ccdc34 Chaf1b Mis18a Dlgap5 Rad54l Dnajc9 Trim59 Lmnb1 Whsc1 Dnmt1 Dtymk Haus5 Haus1 Rfwd3 Poc1a Fancb Mybl2 Mcm8 Gtse1 Brca2 Diap3 Tfdp1 Fanci Tcf19 Prr11 Brip1 Rpa3 Cdc7 Mtfr2 Skp2 Pcna Ppil1 Neil3 Ska2 Orc1 Cdt1 Rbl1 Rfc3 Hat1 Dhfr Pif1 Ttf2 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 341.47 344.04 344.22 346.04 347.01 348.36 350.30 351.84 353.98 354.06 354.17 355.19 355.51 356.22 359.21 366.73 367.31 368.66 368.95 369.72 375.35 375.53 375.83 376.76 378.67 380.36 382.94 385.61 386.36 389.72 390.09 390.18 390.35 391.95 397.94 399.20 406.47 411.17 415.08 416.03 416.19 418.15 418.70 419.72 420.49 424.66 432.57 432.91 433.78 436.84 1.0 Notes 4632434I11Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page5 BC030867 Psmc3ip Suv39h2 Snrnp40 Fam83d Anp32b Ranbp1 Nup160 Nup155 Sapcd2 Pkmyt1 Cep192 Nudt21 Hmgb3 Hmgb2 Dnaaf2 Ankle1 Lrrc40 Nup93 Stmn1 Haus4 Rad18 Chek2 Ccne1 Actl6a Ddx39 Cdca7 Syce2 Sass6 Alyref Gins4 Pold2 Larp7 Pold1 Clhc1 Palb2 Cse1l H2afz Lsm3 Lsm2 Msh6 G2e3 Rpa1 Rcc1 Mtbp Pask Nxt1 Rfc2 Cit 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 265.14 266.07 266.83 267.67 269.34 269.89 273.37 273.72 275.80 276.50 279.78 281.43 282.53 282.62 284.23 286.56 287.94 288.58 289.07 289.88 290.02 290.24 292.05 292.19 292.35 292.83 295.28 297.29 297.54 304.22 305.91 306.30 306.38 307.34 310.27 310.49 310.92 310.95 312.80 315.82 316.84 319.16 325.25 325.55 326.63 327.98 330.49 330.53 333.54 341.32 1.0 Notes Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page6 Hnrnpab Tamm41 Efcab11 Fam72a Rbmxl1 Anp32e Cep128 Nucks1 Snrpa1 Dctpp1 Rbmx2 Recql4 Lmnb2 Zfp367 Nup35 Wdr90 Nup62 Rpp30 Rqcd1 Pbdc1 Dpy30 Haus3 Cdca4 Tubg1 Fanca Tex30 Gins3 Ssrp1 Banf1 Rnf26 Pold3 Uchl5 Sf3a3 Smc4 Siva1 Lin54 Mns1 Usp1 Uba2 Aaas Bora Rfc1 Hn1l Lyar Dis3 Lin9 Ung Eri1 Eri2 Lbr 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 189.18 189.39 195.22 198.56 202.24 203.04 203.19 203.52 205.87 206.71 208.30 209.11 211.40 215.80 219.11 220.82 222.62 224.70 225.21 226.26 226.34 228.48 231.88 232.56 233.29 235.50 235.65 237.11 239.28 239.45 243.13 243.59 244.86 246.40 247.44 247.86 249.28 250.20 250.42 251.11 251.38 255.07 256.76 257.11 258.36 259.43 261.93 262.13 262.26 263.50 1.0 Notes 4930422G04Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page7 Rnaseh2a Tmem194 Fam111a Anapc15 Cdc25b Ncaph2 Sephs1 Ccp110 Mthfd1l Ruvbl1 Ruvbl2 Zbtbd6 Gas2l3 Cdca7l Mrpl18 Magoh Mcph1 Kpnb1 Rbbp8 Ccnb1 Cep57 Ddx11 Haus8 Lrwd1 Hmmr Tacc3 Gmps Snrpe Gstcd Xrcc6 Defa3 Phf5a Smc3 Etaa1 Psip1 Smc2 Tonsl Snrpf Msh2 Mxd3 Terf1 Xpo1 Tdp1 Ints7 Pfas E2f1 Taf5 Nrm Lrr1 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 145.40 146.34 146.76 147.74 149.52 149.88 150.04 150.35 152.31 155.68 156.94 158.87 159.29 159.36 161.54 161.73 163.57 164.35 164.57 167.19 169.34 169.78 170.97 171.43 173.58 174.19 175.32 175.65 176.47 176.58 176.64 177.06 178.23 178.98 179.06 179.75 181.34 182.61 182.91 183.62 184.93 185.28 185.88 186.31 187.44 188.52 188.60 188.71 189.09 189.11 1.0 Notes 4930427A07Rik 2610318N02Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page8 Nsmce4a Zmynd19 Ankrd32 Snrnp25 Hnrnpm Gemin2 Tubb4b Rad51c Ccdc77 Exosc2 Dazap1 Gpsm2 Rbm8a Rnf168 Cmss1 Trim37 Prpf31 Rbbp7 Dnph1 Ncbp1 Usp39 Ddx20 Cep76 Reep4 Rad21 Haus6 Enkd1 Snrpc Nudt1 Mis12 Dars2 Xrcc2 Psrc1 Recql Asf1a Pole3 Pms2 Lsm6 Lsm4 Wee1 Fancl Mnd1 Srsf1 Ndc1 Dkc1 Tcp1 Gart Fxn 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 96.99 97.05 98.49 98.85 100.43 100.93 102.24 104.33 104.85 105.20 105.60 107.94 108.84 111.88 112.21 113.54 114.05 114.08 115.65 115.98 116.64 117.30 118.74 119.31 121.76 121.81 122.75 123.25 123.34 123.61 127.51 129.61 130.29 131.76 132.19 132.88 132.89 134.69 135.76 136.18 136.33 137.29 137.65 137.66 137.85 138.29 139.33 141.55 142.02 145.01 1.0 Notes D030056L22Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page9 Ebna1bp2 Casp8ap2 Smarca5 Tubgcp2 Tbc1d31 Donson Cdc123 Cdc25a Hnrnpu Ppp1r8 Arl6ip6 Ppm1g Supt16 Tcerg1 Trim28 G3bp1 Nop58 Kifc5b Nup54 Nelfcd Nop56 Nedd1 Znhit3 Pa2g4 Snrpb Snrpg Prmt1 Bard1 Parp2 Hmbs U2af1 Tmpo Myg1 Mdc1 Nhp2 Hus1 Nelfe Pmf1 Ddx1 Hdgf Sfpq Utp6 Ipo9 Ipo5 Dck Dut Ncl Ttk Ilf2 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 63.68 65.97 66.54 66.90 67.96 69.75 69.94 71.17 71.62 72.45 73.12 73.72 74.16 74.90 74.91 75.28 75.89 76.34 76.76 76.90 77.03 77.38 77.69 78.23 78.50 78.91 79.87 79.88 80.12 80.24 81.07 81.08 81.08 81.29 82.86 82.94 84.57 85.64 88.26 88.64 89.77 90.21 90.42 92.52 93.55 93.89 94.63 95.47 95.84 96.74 1.0 Notes Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page10 Tmem209 Cdk2ap1 Nfatc2ip Magohb Prpf38a Anapc1 Cep152 Exosc3 Zmym1 Skiv2l2 Snrpd3 Metap2 Ppp1r7 Aarsd1 Hmgn5 Stoml2 Mthfd1 Polr2d Nup50 Cops3 Rad50 Apex1 Cep72 Naa50 Naa10 Gspt1 Myef2 Parp1 Clspn Emg1 Nol11 Pms1 Paics Prpf3 Nudc Nop9 Dcps Eif4e Orc2 Dbr1 Ctps Ppat Alg8 Cct5 Cct7 Fzr1 Taf9 Ctcf Srrt Set 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 30.60 31.35 32.21 33.62 33.65 34.04 35.08 35.23 35.33 36.40 37.03 37.55 39.01 39.05 39.77 40.58 40.70 41.61 41.72 42.21 42.48 43.97 44.82 45.02 46.35 46.55 46.61 47.01 47.22 47.35 47.60 47.62 48.24 48.36 49.41 51.65 53.43 53.72 54.73 54.87 56.30 57.13 57.50 57.50 57.54 58.11 59.43 60.21 60.59 62.27 1.0 Notes 1600002H07Rik Symbol Num ofCEMGenes:32.Predicted522.SelectedDatasets:674.Strength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page11 Tmem107 Psmd14 Prps1l3 Nup188 Mrps22 Mcmbp Zcchc8 Rbm12 Nt5dc2 Psmg1 Wbp11 Psma1 Ppwd1 Med14 Gtf2e2 Nubp1 Srsf10 Nup88 Cpsf3l Aimp2 Senp1 Usp14 Pdap1 Ssna1 Thoc6 Mbnl3 Rrp15 Cetn3 Rpl14 Noc4l Nme1 Cct6a Ipo11 Srsf4 Nanp Cstf2 Rad1 Dna2 Mlh1 Vars Iws1 Alg6 Ctc1 Adsl Eif3l Rif1 Atic Eed Dtl 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 2.40 3.65 3.91 3.96 5.23 5.83 5.95 6.43 6.59 6.63 6.76 7.15 7.73 8.13 8.71 8.79 8.89 9.62 10.57 10.61 11.17 12.41 13.84 14.60 15.20 15.84 16.95 18.71 18.76 19.62 19.74 19.98 20.75 21.83 22.51 22.90 23.64 23.67 23.94 24.41 25.39 26.11 26.20 27.95 28.09 28.66 28.80 29.01 29.03 29.24 1.0 Notes Symbol Num ofCEMGenes:32.Predicted522. NumofSelectedDatasets:674.CEMStrength:326.4 CEM 1,Geneset"[G]condensedchromosomekinetochore",Page12 Nudcd1 Tsen15 Cep78 Hdac1 0.0 1.0

GSE20954 [14] GSE57543 [6]

GSE40513 [6] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE38031 [8] GSE16874 [12] GSE17794 [44] GSE31028 [6] GSE12454 [13] GSE54215 [13] GSE6957 [12] GSE12498 [12] GSE17266 [59] GSE54490 [12] GSE27605 [8] GSE38257 [14] GSE17796 [39] GSE51075 [12] GSE29241 [6] GSE51385 [8] GSE15741 [6] GSE48397 [10] GSE13611 [8] GSE39449 [6] GSE27114 [6] GSE6875 [8] GSE23502 [8] GSE20100 [15] GSE32386 [13] GSE15326 [10] GSE12993 [6] GSE18135 [18] GSE44260 [10] GSE6837 [8] GSE6689 [12] GSE13873 [27] GSE17316 [12] GSE51628 [15] GSE33308 [10] GSE51883 [30] GSE13693 [9] GSE38538 [6] GSE9247 [15] GSE46797 [6] GSE48382 [10] GSE44175 [18] GSE51243 [7] GSE34324 [12] GSE23925 [6] GSE19004 [9] GSE20696 [8] GSE48204 [6] GSE46209 [21] GSE16675 [72] GSE9763 [20] GSE28093 [6] GSE4694 [6] GSE28457 [24] GSE9287 [8] GSE50813 [24] GSE21224 [16] GSE35366 [78] GSE15303 [11] GSE52474 [154] GSE39621 [51] GSE13692 [8] GSE23845 [15] GSE7875 [16] GSE7348 [6] GSE10525 [18] GSE21491 [9] GSE16110 [16] GSE15872 [18] GSE15580 [14] GSE18115 [8] GSE54653 [6] GSE7020 [8] GSE53916 [6] GSE44101 [6] GSE28621 [21] GSE8025 [21] GSE21299 [12] GSE24628 [16] GSE38831 [7] GSE19925 [6] GSE15267 [8] GSE13225 [6] GSE31313 [22] GSE21900 [12] GSE8488 [15] GSE39984 [18] GSE15121 [6] GSE39082 [6] GSE22824 [24] GSE4260 [6] GSE46185 [6] GSE14769 [24] GSE8678 [6] GSE20302 [12] GSE12881 [6] GSE19436 [8] GSE29318 [9] GSE46090 [12] GSE39034 [9] GSE21309 [9] GSE30160 [6] GSE46091 [8] GSE21716 [28] GSE30962 [16] GSE30485 [15] GSE39469 [6] GSE22180 [60] GSE21568 [12] GSE51483 [45] GSE33471 [12] GSE15610 [12] GSE7657 [12] GSE21278 [48] GSE17096 [20] GSE32598 [11] GSE26616 [6] GSE18660 [10] GSE7694 [12] GSE17097 [20] GSE8660 [6] GSE20500 [6] GSE26355 [6] GSE19885 [9] GSE30192 [6] GSE24512 [29] GSE14012 [24] GSE40856 [8] GSE51608 [6] GSE46242 [12] GSE8039 [32] GSE18460 [16] GSE17509 [57] GSE5041 [8] GSE35593 [6] GSE45051 [18] GSE30745 [12] GSE24210 [16] GSE58296 [9] GSE31359 [8] GSE31598 [12] GSE7705 [10] GSE11759 [6] GSE20426 [35] GSE22005 [23] GSE13874 [14] GSE13408 [14] GSE48203 [9] GSE27786 [20] GSE45895 [27] GSE15155 [12] CEM+ CEM GSE24121 [9] GSE47959 [8] GSE4535 [6] GSE29632 [42] GSE14753 [6] GSE53951 [10] 0.0 GSE13302 [30] GSE14024 [12]

GSE13493 [6] Scale ofaveragePearsoncorrelations GSE15324 [8] GSE18534 [15] GSE45222 [27] GSE36814 [20] GSE20620 [22] GSE8156 [6] 0.2 GSE10176 [6] GSE26290 [12] GSE7460 [52] GSE13149 [25] GSE45820 [6] GSE12465 [14] GSE21379 [10] GSE22124 [18] GSE21393 [6] 0.4 GSE11358 [8] GSE16992 [48] GSE45465 [39] GSE14406 [54] GSE13635 [6] GSE28417 [12] GSE32330 [12] GSE17745 [6] GSE15069 [15] 0.6 GSE5309 [7] GSE22935 [24] GSE4671 [28] GSE1435 [27] GSE32277 [33] GSE18993 [13] GSE4768 [18] GSE41342 [26] GSE16454 [24] 0.8 GSE6065 [100] GSE39897 [36] GSE48790 [8] GSE27848 [16] Score 0.16 0.32 0.36 2.26 1.0 Notes 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 (0.12228) day lung-embryoMouse 14-rep1 (0.107848) day lung-embryoMouse 14-rep2 (0.0986866) day lung-embryoMouse 16-rep1 (0.0899588) day lung-embryoMouse 16-rep2 (0.056196) day lung-postnatalMouse 18-rep1 (0.063724) day lung-postnatalMouse 18-rep2 (0.052689) lung-postnatalMouseday (0.0524329) 2-rep1 lung-postnatalMouseday (0.043178)2-rep2 lung-postnatalMouseday (0.0401607)10-rep1 lung-postnatalday 10-rep2 (0.0600047) day 30-rep1 (0.0573363) day 30-rep2 (0.0794284)[ min (0.0760766) ] [ medium ] [ max ] CEM 1 Bub1 95.3 623.0 4385.5 P ( S | Z, I ) = 1.00 Birc5 91.1 620.8 4548.7 Mean Corr = 0.96923 Sgol1 160.6 326.6 1445.7 Nuf2 85.3 297.0 1534.0 Zwilch 82.0 443.8 2326.0 Bub1b 193.7 453.5 3391.3 Kntc1 106.4 348.3 1720.1 Ndc80 72.8 186.1 839.0 Cenpk 56.9 269.4 1601.5 Spc24 124.0 296.2 1326.8 Cenph 53.5 118.4 1032.0 Sgol2 79.1 308.6 1526.6 Ercc6l 131.8 364.5 1840.0 Spag5 31.1 106.9 698.4 Incenp 190.1 362.5 1315.3 Nek2 117.6 167.9 321.9 Cenpn 466.3 975.7 3336.5 Cenpu 166.6 494.4 1107.4 Cenpw 35.2 152.3 902.1 Apitd1 107.2 223.0 791.6 Casc5 88.9 267.7 1231.8 Cenpm 180.2 303.7 1002.4 Nup107 878.9 1168.6 3013.5 Nup85 788.4 975.0 2455.4 Nup133 390.0 499.4 1387.4 Nup43 146.2 241.1 971.8 Nde1 531.0 679.7 1691.9 Smc1a 2942.0 3459.9 5048.9 Cenpc1 433.0 758.7 1678.7 Nudcd2 260.5 467.5 1483.5 Cenpt 414.1 749.4 1206.8 Cenpo 95.4 176.7 272.7 Ncapg 30.7 185.4 1324.1 Shcbp1 79.5 486.6 3056.0 Ccna2 154.9 954.3 3800.4 Cdk1 138.5 1288.7 5556.8 Aurkb 45.0 153.1 1123.8 CEM 1 + Kif11 69.9 248.7 1351.8 Top 10 Genes Melk 44.1 285.2 1913.5 Kif20a 49.9 395.3 3391.5 Pbk 154.5 1192.4 4360.7 Tpx2 90.4 384.0 2807.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 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 (0.165174) repKO 2biological (0.163623) repKO 3biological (0.160276) repKO 1 biological (0.115038) rep 2 (0.306441) rep 3 (0.0894488)[ min ] [ medium ] [ max ] CEM 1 Bub1 448.5 2500.6 3315.2 P ( S | Z, I ) = 1.00 Birc5 1079.4 4492.1 6356.8 Mean Corr = 0.96847 Sgol1 291.9 1357.0 1901.1 Nuf2 297.7 1606.5 2101.1 Zwilch 357.6 1237.1 1640.2 Bub1b 293.8 1347.5 1683.1 Kntc1 217.8 1045.7 1904.6 Ndc80 190.5 407.9 604.1 Cenpk 344.0 2040.2 3066.8 Spc24 535.9 2068.0 2832.2 Cenph 181.4 1067.0 1737.0 Sgol2 145.6 655.6 987.8 Ercc6l 338.9 1022.8 1157.1 Spag5 110.8 592.1 925.7 Incenp 467.7 1457.5 1720.9 Nek2 136.6 609.9 1016.8 Cenpn 509.6 1536.5 2693.0 Cenpu 184.2 739.6 858.8 Cenpw 416.8 1441.7 2178.4 Apitd1 139.4 449.7 612.5 Casc5 258.4 685.3 899.5 Cenpm 202.4 724.8 1050.4 Nup107 1747.9 2174.3 2530.3 Nup85 1375.1 2449.6 2970.5 Nup133 822.7 1765.1 2319.4 Nup43 335.0 504.2 727.3 Nde1 605.4 739.6 933.4 Smc1a 4025.0 4483.7 4936.9 Cenpc1 767.8 1141.3 1483.1 Nudcd2 1470.1 2726.1 3581.6 Cenpt 391.8 559.2 706.5 Cenpo 177.9 263.2 391.6 Ncapg 173.3 844.7 1201.4 Shcbp1 337.9 1423.8 1927.5 Ccna2 892.6 4896.2 6686.9 Cdk1 756.0 3521.6 4546.7 Aurkb 252.8 1811.2 2589.4 CEM 1 + Kif11 234.6 1063.3 1622.7 Top 10 Genes Melk 198.7 760.3 1120.0 Kif20a 254.9 1222.0 1950.1 Pbk 868.2 5101.9 7068.2 Tpx2 264.8 1491.2 2080.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 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 , 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 (0.175211)V720_PD0332991_rep1 (0.183588)V720_PD0332991_rep2 (0.163177)V720_PD0332991_rep3 (0.190919) (0.140472) (0.146633)[ min ] [ medium ] [ max ] CEM 1 Bub1 608.4 2150.6 2190.0 P ( S | Z, I ) = 1.00 Birc5 1585.2 4564.5 4643.2 Mean Corr = 0.96657 Sgol1 297.9 1092.2 1197.8 Nuf2 520.3 1928.4 1955.4 Zwilch 557.8 1188.5 1214.2 Bub1b 230.6 936.0 977.1 Kntc1 212.9 791.8 880.4 Ndc80 208.9 826.1 863.4 Cenpk 519.7 1439.5 1473.8 Spc24 184.7 727.6 797.0 Cenph 451.6 1079.0 1164.1 Sgol2 552.3 1806.7 1939.4 Ercc6l 296.9 769.1 818.5 Spag5 193.1 510.3 543.8 Incenp 321.7 932.0 992.1 Nek2 302.3 1046.6 1120.5 Cenpn 288.3 773.6 827.5 Cenpu 189.5 612.2 669.2 Cenpw 973.2 1999.3 2106.3 Apitd1 113.8 308.3 319.6 Casc5 232.9 848.8 949.3 Cenpm 51.0 254.9 299.0 Nup107 747.4 1079.5 1145.2 Nup85 803.0 1130.2 1167.4 Nup133 687.3 1046.2 1127.8 Nup43 308.6 465.5 506.9 Nde1 300.3 519.5 549.5 Smc1a 1938.5 2681.8 2848.8 Cenpc1 1201.5 1621.4 1757.8 Nudcd2 2024.1 2149.8 2299.5 Cenpt 793.9 953.4 1000.8 Cenpo 136.0 158.6 170.0 Ncapg 514.7 1834.8 1920.4 Shcbp1 799.9 2916.3 2967.0 Ccna2 1538.2 4738.1 5049.6 Cdk1 3175.7 6326.4 6472.5 Aurkb 265.9 1045.8 1093.2 CEM 1 + Kif11 231.2 856.2 872.6 Top 10 Genes Melk 291.3 1152.3 1323.1 Kif20a 459.2 1928.7 2075.8 Pbk 2009.9 5297.8 5566.2 Tpx2 536.7 1735.9 1836.1

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE38031" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.456 Kernel fit Pairwise Correlations Normal fit

Density 0.228

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl_rep1ctrl_rep2 (0.130101)ctrl_rep3 (0.12371)ctrl_rep4 (0.139733)irr_rep1 (0.112127)irr_rep2 (0.122117)irr_rep3 (0.126451)irr_rep4 (0.119091) (0.126671) [ min ] [ medium ] [ max ] CEM 1 Bub1 289.5 1330.4 1476.3 P ( S | Z, I ) = 1.00 Birc5 830.7 4419.1 4636.2 Mean Corr = 0.96212 Sgol1 296.6 1230.9 1354.2 Nuf2 416.0 1039.7 1193.5 Zwilch 479.7 1428.8 1656.5 Bub1b 336.3 1940.9 2109.0 Kntc1 377.7 1314.6 1446.3 Ndc80 176.6 584.2 653.3 Cenpk 437.8 815.5 1143.4 Spc24 349.5 1829.3 2110.2 Cenph 242.5 867.6 879.7 Sgol2 345.0 1077.4 1287.3 Ercc6l 325.2 1184.8 1246.2 Spag5 121.7 624.2 693.7 Incenp 468.0 1699.4 1867.8 Nek2 161.9 643.0 700.3 Cenpn 650.3 2341.7 2435.5 Cenpu 132.9 444.9 554.6 Cenpw 475.0 1783.0 2004.4 Apitd1 262.7 743.3 916.8 Casc5 110.1 445.1 884.2 Cenpm 327.0 1519.7 1950.9 Nup107 816.9 2016.7 2141.1 Nup85 1024.4 2209.7 2452.9 Nup133 1135.7 1808.5 1929.0 Nup43 222.6 651.3 770.8 Nde1 897.8 1355.2 1475.7 Smc1a 2914.2 4179.1 4696.7 Cenpc1 618.0 962.4 1130.5 Nudcd2 1971.0 2721.3 3038.6 Cenpt 633.6 766.5 800.2 Cenpo 115.7 171.1 234.4 Ncapg 150.5 678.5 800.4 Shcbp1 398.8 1375.5 1737.0 Ccna2 924.6 4522.5 4853.4 Cdk1 1462.8 5168.1 5852.3 Aurkb 236.6 1509.6 1694.0 CEM 1 + Kif11 151.9 767.5 892.6 Top 10 Genes Melk 367.5 1978.5 2111.4 Kif20a 502.8 2079.7 2301.9 Pbk 1751.0 5622.9 6119.2 Tpx2 629.5 2939.5 3082.5

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE16874" 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=GSE16874 Status: Public on Dec 07 2010 Title: Expression in wild type and TgDREAM mouse B cells unstimulated or 2 days after LPS+IL4 stimulation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21059893 Summary & Design: Summary: DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.

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

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

0.423 Kernel fit Pairwise Correlations Normal fit

Density 0.212

0.000 CEM 1

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

Pre-normalization Quantiles

BCells_WildType_day0_REP1BCells_WildType_day0_REP2BCells_WildType_day0_REP3BCells_Transgenic_day0_REP1 BCells_Transgenic_day0_REP2(0.0947581) BCells_Transgenic_day0_REP3(0.0935993) BCells_WildType_day2_REP1(0.0940107)BCells_WildType_day2_REP2 (0.0876491)BCells_WildType_day2_REP3 (0.0733491)BCells_Transgenic_day2_REP1 (0.0881663) BCells_Transgenic_day2_REP2(0.0855955) BCells_Transgenic_day2_REP3(0.0693598) (0.0844643) (0.076616) (0.0726939)[ (0.0797379)min ] [ medium ] [ max ] CEM 1 Bub1 119.1 3295.7 4133.5 P ( S | Z, I ) = 1.00 Birc5 351.1 5246.1 6541.2 Mean Corr = 0.95180 Sgol1 194.8 1839.8 2166.3 Nuf2 128.3 1297.0 1789.5 Zwilch 132.1 1433.5 1804.0 Bub1b 291.2 2731.3 3227.9 Kntc1 166.9 1504.8 1682.5 Ndc80 255.2 637.1 714.6 Cenpk 204.5 1959.6 2249.4 Spc24 284.7 1258.1 1512.9 Cenph 108.1 704.8 817.7 Sgol2 128.5 859.3 917.1 Ercc6l 309.9 1203.6 1380.5 Spag5 74.3 574.2 644.0 Incenp 324.8 2454.1 3096.4 Nek2 107.9 688.4 779.9 Cenpn 535.8 1754.8 2298.3 Cenpu 260.6 462.4 586.7 Cenpw 322.5 1839.8 2015.7 Apitd1 373.6 1232.2 1737.9 Casc5 125.0 442.9 590.3 Cenpm 237.7 969.4 1188.8 Nup107 875.1 2027.3 2085.8 Nup85 1004.8 3181.2 4029.5 Nup133 606.9 2203.1 2970.3 Nup43 224.9 945.8 1315.1 Nde1 731.9 1283.0 1479.6 Smc1a 3531.0 5276.4 5685.8 Cenpc1 266.1 927.0 1178.8 Nudcd2 176.8 1625.9 1982.6 Cenpt 582.4 668.7 761.7 Cenpo 170.7 253.0 288.2 Ncapg 149.7 1829.2 2101.3 Shcbp1 314.3 3507.9 3745.6 Ccna2 488.9 4715.3 5698.6 Cdk1 389.6 5943.4 6640.3 Aurkb 186.9 2249.4 2562.2 CEM 1 + Kif11 196.2 1292.0 1451.3 Top 10 Genes Melk 99.4 2055.6 2454.1 Kif20a 103.4 827.8 1434.5 Pbk 239.4 2548.3 3375.7 Tpx2 172.0 2731.3 3127.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.025603)liver-2BE-4hours-rep 2 (0.0270424)liver-2BE-4hours-rep 3 (0.0267182) 1liver-2BE-4hours-rep (0.0259748) 2spleen-vehicle-4hours-rep (0.0249656) 3spleen-vehicle-4hours-rep (0.0253415) 4spleen-vehicle-4hours-rep (0.0241188)spleen-vehicle-4hours-rep 1 (0.011009)spleen-2BE-4hours-rep 2 (0.010507)spleen-2BE-4hours-rep 3 (0.0128361)spleen-2BE-4hours-rep 4 (0.0109659)spleen-2BE-4hours-rep 1 (0.0126211)liver-vehicle-7days-rep 2 (0.0123933)liver-vehicle-7days-rep 3 (0.0121865)liver-vehicle-7days-rep 4 (0.011786)liver-vehicle-7days-rep 1 (0.0253209)liver-2BE-7days-rep 2 (0.0264987)liver-2BE-7days-rep 3 (0.0272027)liver-2BE-7days-rep 4 (0.0262844) 1 (0.0258224)liver-2BE-7days-rep 2 (0.0243883)liver-2BE-7days-rep 3 (0.0258153)bone 4marrow-vehicle-7days-rep (0.0276625)bone 5marrow-vehicle-7days-rep (0.0249284)bone marrow-vehicle-7days-repbone marrow-vehicle-7days-repbone 1 (0.0144776) marrow-vehicle-7days-repbone 2 (0.0224244) marrow-2BE-7days-repbone 3 (0.0164351) marrow-2BE-7days-repbone 4 (0.0200565) marrow-2BE-7days-repbone 5 (0.0174832) marrow-2BE-7days-rep 1bone (0.0311287) marrow-2BE-7days-rep 2spleen-vehicle-7days-rep (0.0306711) 3spleen-vehicle-7days-rep (0.029878) 4spleen-vehicle-7days-rep (0.0288673) 5spleen-vehicle-7days-rep (0.0244839) 1 (0.0154898)spleen-vehicle-7days-rep 2 (0.00934484)spleen-2BE-7days-rep 3 (0.0159951)spleen-2BE-7days-rep 4 (0.0108496)spleen-2BE-7days-rep 5 (0.0150785) spleen-2BE-7days-rep1 (0.0436237) spleen-2BE-7days-rep2 (0.0606454) 3 (0.0257506) 4 (0.0391833) 5 (0.0201403)[ min ] [ medium ] [ max ] CEM 1 Bub1 25.3 718.0 2602.6 P ( S | Z, I ) = 1.00 Birc5 45.2 2845.4 11317.0 Mean Corr = 0.94910 Sgol1 80.3 733.4 3602.8 Nuf2 25.6 679.4 3606.5 Zwilch 30.5 398.4 1800.7 Bub1b 66.3 639.2 2364.2 Kntc1 26.2 413.9 2209.6 Ndc80 46.5 387.5 1007.0 Cenpk 36.1 736.7 4056.5 Spc24 175.8 520.0 2142.7 Cenph 27.2 216.7 926.0 Sgol2 40.0 332.7 1832.7 Ercc6l 61.5 380.4 1330.5 Spag5 23.4 277.1 1448.0 Incenp 71.3 1013.0 3889.8 Nek2 68.7 282.9 1249.6 Cenpn 194.6 836.6 2925.5 Cenpu 57.9 331.4 1294.1 Cenpw 85.8 315.9 1114.6 Apitd1 77.6 382.0 632.6 Casc5 34.1 427.5 2253.2 Cenpm 193.1 487.7 1395.3 Nup107 373.3 1389.2 1897.0 Nup85 459.9 1309.8 2292.6 Nup133 271.4 838.8 1785.9 Nup43 89.2 257.3 427.0 Nde1 235.1 703.4 1593.4 Smc1a 1582.0 2900.7 4558.0 Cenpc1 63.7 847.1 2021.1 Nudcd2 293.4 628.0 1203.1 Cenpt 135.7 552.3 1089.8 Cenpo 48.6 241.2 424.8 Ncapg 26.2 530.3 2086.2 Shcbp1 44.8 480.4 1987.5 Ccna2 100.9 2548.0 10211.9 Cdk1 208.2 1490.7 6496.1 Aurkb 21.9 416.7 2292.7 CEM 1 + Kif11 48.6 570.5 3367.1 Top 10 Genes Melk 43.5 356.9 1426.1 Kif20a 35.0 377.6 1763.0 Pbk 37.1 1177.1 5221.7 Tpx2 38.9 1126.5 4262.7

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 modifications unwind in vivo 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 (0.124279) rep2 cells, stem (0.156389) rep1 cells, matrix (0.10814) rep2 cells,matrix (0.110768) rep1 cells,[ (0.173002)min rep2 (0.327421) ] [ medium ] [ max ] CEM 1 Bub1 28.5 355.1 2010.4 P ( S | Z, I ) = 1.00 Birc5 83.1 1465.9 5926.8 Mean Corr = 0.94621 Sgol1 75.2 288.0 1204.2 Nuf2 77.4 213.5 653.2 Zwilch 47.6 221.6 1101.8 Bub1b 79.9 531.2 2244.7 Kntc1 87.8 299.0 893.6 Ndc80 36.9 95.9 348.2 Cenpk 99.1 371.4 1213.8 Spc24 77.5 383.2 1715.9 Cenph 52.7 122.4 723.9 Sgol2 46.8 176.9 335.7 Ercc6l 118.4 316.5 1493.6 Spag5 33.1 103.5 604.8 Incenp 140.8 315.0 1313.4 Nek2 97.7 150.1 474.6 Cenpn 287.8 554.5 1642.9 Cenpu 80.7 195.9 709.3 Cenpw 100.5 323.8 1304.5 Apitd1 212.7 328.4 932.8 Casc5 75.2 135.9 327.6 Cenpm 170.2 352.9 1470.5 Nup107 883.4 1013.8 1910.8 Nup85 1326.7 1656.8 2601.6 Nup133 653.8 791.5 2074.4 Nup43 385.6 440.9 977.9 Nde1 506.4 649.4 1222.8 Smc1a 1400.0 2048.5 2476.3 Cenpc1 438.1 576.6 730.8 Nudcd2 509.2 874.5 2683.7 Cenpt 350.6 427.6 711.0 Cenpo 40.3 79.1 168.2 Ncapg 27.7 166.4 827.5 Shcbp1 39.2 304.4 1761.8 Ccna2 109.7 1026.9 4703.3 Cdk1 155.1 1624.7 7249.5 Aurkb 23.4 166.0 1200.2 CEM 1 + Kif11 51.3 222.7 1119.7 Top 10 Genes Melk 57.7 703.5 2300.5 Kif20a 55.2 416.5 1804.6 Pbk 256.0 2010.0 9785.7 Tpx2 66.9 342.2 1956.7

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 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 that play a critical role in the obligatory X-Y crossover during male . 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 . 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(0.116585) wildE13.5 #2 type(0.0549452) Atrx-nullE13.5 #3 (0.102331) Atrx-null E13.5#1 (0.100231) Atrx-null P0.5#2 (0.0840171) wild P0.5#3 type (0.0823607) wild #1P0.5 type(0.0637366) wild #2P0.5 type(0.0649143) Atrx-null #3P0.5 (0.0755177) Atrx-null #1P0.5 (0.0522483) Atrx-null #2AP0.5 (0.070506) Atrx-null #2B (0.0774894) #3 (0.0551185) [ min ] [ medium ] [ max ] CEM 1 Bub1 84.4 153.0 2195.3 P ( S | Z, I ) = 1.00 Birc5 249.3 380.4 3544.3 Mean Corr = 0.94377 Sgol1 52.5 167.3 1463.9 Nuf2 158.4 295.1 1772.5 Zwilch 126.0 209.3 1300.9 Bub1b 46.7 171.5 2183.0 Kntc1 134.1 186.9 1481.8 Ndc80 60.9 124.3 675.8 Cenpk 129.0 161.9 1297.3 Spc24 55.2 153.2 1626.7 Cenph 65.8 93.8 584.4 Sgol2 175.2 275.2 1425.2 Ercc6l 14.3 112.8 1019.8 Spag5 10.0 84.6 616.0 Incenp 197.1 308.3 1952.0 Nek2 155.6 191.6 746.9 Cenpn 309.0 394.7 2102.0 Cenpu 234.2 297.9 810.4 Cenpw 280.8 446.6 1411.8 Apitd1 99.3 192.1 617.5 Casc5 142.0 205.1 1089.0 Cenpm 206.8 306.8 893.8 Nup107 543.5 1011.0 2338.8 Nup85 869.6 1120.4 1903.3 Nup133 886.7 1133.0 2139.7 Nup43 381.0 454.0 985.4 Nde1 142.4 219.5 1445.8 Smc1a 1430.4 1674.0 3644.4 Cenpc1 1206.0 1801.2 2853.2 Nudcd2 487.8 675.6 1664.8 Cenpt 683.0 1036.8 1183.7 Cenpo 68.4 109.2 182.6 Ncapg 34.0 100.8 1078.0 Shcbp1 117.8 253.1 2589.3 Ccna2 442.4 726.6 3350.3 Cdk1 407.4 731.4 4345.7 Aurkb 76.9 135.2 1218.7 CEM 1 + Kif11 192.2 247.7 2015.0 Top 10 Genes Melk 50.7 136.1 2079.9 Kif20a 59.1 111.1 1178.8 Pbk 533.2 862.3 3991.0 Tpx2 172.5 287.8 2265.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 naïve 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 naïve 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 (0.115956)BATF_KO_P14_Naive_rep2 (0.124893)BATF_KO_P14_Naive_rep3WT_P14_D3_Effector_rep1 (0.0945667)WT_P14_D3_Effector_rep2 (0.132816)WT_P14_D3_Effector_rep3 (0.120762)WT_P14_D3_Effector_rep4 (0.0579895)BATF_KO_P14_D3_Effector_rep1 (0.0648198)BATF_KO_P14_D3_Effector_rep2 (0.0703176)BATF_KO_P14_D3_Effector_rep3 (0.0342655)BATF_KO_P14_D3_Effector_rep4 (0.0466645) (0.0507684) (0.0429937)[ min (0.0431881) ] [ medium ] [ max ] CEM 1 Bub1 307.3 6553.5 7345.5 P ( S | Z, I ) = 1.00 Birc5 643.0 7210.7 8109.1 Mean Corr = 0.94324 Sgol1 224.3 2103.7 2202.5 Nuf2 198.4 1990.9 2264.4 Zwilch 256.8 1587.0 1785.2 Bub1b 249.2 2581.1 2850.0 Kntc1 208.8 2518.6 2795.3 Ndc80 150.3 1238.0 1396.4 Cenpk 218.8 1860.8 2139.0 Spc24 284.0 2114.2 2307.2 Cenph 118.4 989.1 1098.4 Sgol2 138.1 1988.7 2436.1 Ercc6l 214.3 821.4 900.0 Spag5 51.6 900.1 1044.1 Incenp 337.9 1784.5 1991.5 Nek2 95.8 835.3 1086.2 Cenpn 454.1 1853.8 2041.4 Cenpu 161.5 307.7 345.7 Cenpw 352.9 2217.3 2546.6 Apitd1 106.7 413.8 478.9 Casc5 157.5 1222.6 1404.5 Cenpm 178.6 867.0 969.2 Nup107 1464.5 2534.7 2812.4 Nup85 1451.0 2274.5 2596.7 Nup133 726.6 1451.8 1584.6 Nup43 266.1 526.3 636.7 Nde1 554.4 1054.3 1276.1 Smc1a 4753.9 5749.0 6257.0 Cenpc1 756.0 1677.8 1860.1 Nudcd2 1080.5 1446.5 1624.9 Cenpt 452.8 689.6 807.6 Cenpo 170.7 422.7 517.9 Ncapg 135.0 2297.7 2482.4 Shcbp1 385.7 3268.1 3732.3 Ccna2 808.6 9437.7 10151.6 Cdk1 414.6 5158.3 5403.1 Aurkb 177.9 3246.3 3687.4 CEM 1 + Kif11 182.4 1549.1 1781.7 Top 10 Genes Melk 144.2 1518.6 1731.8 Kif20a 191.4 2168.8 2337.6 Pbk 367.6 4667.9 4962.2 Tpx2 163.4 2573.6 2878.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE6957" 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=GSE6957 Status: Public on Jul 19 2007 Title: Transcriptional profiling of bipotential embryonic liver cells to identify liver progenitor cell surface markers (430) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17641245 Summary & Design: Summary: The ability to purify to homogeneity a population of hepatic progenitor cells from adult liver is critical for their characterization prior to any therapeutic application. As a step in this direction, we have utilized gene profiling of a bipotential liver cell line from dpc 14 mouse embryonic liver to catalog genes expressed by liver progenitor cells. These cells, known as Bipotential Mouse Embryonic Liver (BMEL) cells, proliferate in an undifferentiated state and are capable of differentiating into hepatocyte-like and cholangiocyte-like cells in vitro. Upon transplantation, BMEL cells are capable of differentiating into hepatocytes and cholangiocytes in vivo. Microarray analysis of gene expression in the 9A1 and 14B3 BMEL cell lines grown under proliferating and differentiating conditions was used to identify cell surface markers preferentially expressed in the bipotential undifferentiated state. This analysis revealed that proliferating BMEL cells express many genes involved in cell cycle regulation whereas differentiation of BMEL cells by cell aggregation causes a switch in gene expression to functions characteristic of mature hepatocytes. In addition, microarray data and protein analysis indicated that the Notch signaling pathway could be involved in maintaining BMEL cells in an undifferentiated stem cell state. Using GO annotation, a list of cell surface markers preferentially expressed on undifferentiated BMEL cells was generated. One marker, Cd24a, is specifically expressed on progenitor oval cells in livers of DDC treated animals. We therefore consider Cd24a expression a candidate molecule for purification of hepatic progenitor cells.

Keywords: cell type comparison

Overall design: RNA was extracted from two independently isolated BMEL cell lines (9A1 and 14B3) after culture under three conditions (basal, aggregate 1 day, and aggregate 5 days). Duplicate biological replicates were collected for each cell line:culture condition combination for a total of 12 samples. Samples were biotin-labeled, hybridized to mouse 430 2.0 chips, and scanned according to established Affymetrix protocols.

Background corr dist: KL-Divergence = 0.0532, L1-Distance = 0.0670, L2-Distance = 0.0087, Normal std = 0.5905

0.722 Kernel fit Pairwise Correlations Normal fit

Density 0.361

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

basal culture,basal culture, 9A1,basal rep culture, 9A1,basal 1 (430) rep culture, 14B3, D1(0.0268613)2 (430) aggregate rep 14B3, D1(0.135395) 1 aggregate(430) rep culture,D1 (0.220136)2 aggregate(430) culture, 9A1,D1 (0.116354) aggregate rep culture, 9A1,D5 1 (430)aggregate rep culture, 14B3,D5 (0.0596575)2 (430)aggregate repculture, 14B3,D5 (0.120007) 1 aggregate (430) repculture, 9A1,D5 (0.0383424)2 aggregate (430) rep culture, 9A1, 1 (0.0485519) (430) rep culture, 14B3, (0.0579328)2 (430) rep 14B3, (0.079743) 1 (430) rep[ (0.0436095)2min (430) (0.0534093) ] [ medium ] [ max ] CEM 1 Bub1 35.3 473.0 3231.5 P ( S | Z, I ) = 1.00 Birc5 62.6 990.4 4027.1 Mean Corr = 0.93735 Sgol1 212.3 435.3 2687.0 Nuf2 38.5 166.8 1619.3 Zwilch 51.7 164.1 1532.8 Bub1b 136.5 542.8 2577.3 Kntc1 51.5 177.1 1579.3 Ndc80 96.8 178.3 651.4 Cenpk 162.0 253.2 1726.4 Spc24 122.8 463.2 1529.7 Cenph 61.8 143.3 1099.3 Sgol2 76.3 229.2 1779.7 Ercc6l 94.7 202.3 1210.0 Spag5 41.1 91.1 633.3 Incenp 114.8 427.5 1529.9 Nek2 65.1 159.8 668.8 Cenpn 207.9 344.2 1397.6 Cenpu 99.3 145.9 841.8 Cenpw 50.3 176.5 1271.7 Apitd1 67.2 91.3 278.7 Casc5 71.2 111.1 510.5 Cenpm 122.0 203.8 645.6 Nup107 685.5 762.1 3039.1 Nup85 306.3 693.0 2268.6 Nup133 110.9 495.8 1622.4 Nup43 150.4 322.3 1026.7 Nde1 123.9 398.3 1405.9 Smc1a 1487.4 2680.6 4293.3 Cenpc1 314.9 506.5 967.7 Nudcd2 495.5 956.7 1875.6 Cenpt 252.5 764.5 1575.5 Cenpo 70.8 103.7 177.4 Ncapg 35.7 145.7 1476.9 Shcbp1 89.6 500.6 3230.4 Ccna2 52.7 1100.4 4698.1 Cdk1 221.6 1571.6 6498.1 Aurkb 58.0 160.3 1189.2 CEM 1 + Kif11 79.0 266.0 1047.1 Top 10 Genes Melk 52.9 101.8 1206.9 Kif20a 74.7 657.4 3413.7 Pbk 98.2 630.9 6394.6 Tpx2 119.2 576.5 3470.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE12498" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

Keywords: Cell density, genetic modification

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

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

0.805 Kernel fit Pairwise Correlations Normal fit

Density 0.402

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl-low-1ctrl-low-2 (0.227472)tead2VP16-conf-1 (0.222521)tead2VP16-conf-2yap-conf-1 (0.0492184)yap-conf-2 (0.0518199)(0.0485142)tead2EnR-low-1 (0.0487825)tead2EnR-low-2ctrl-over-1 (0.0751281)ctrl-over-2 (0.0664164) (0.0579231)tead2VP16-over-1 (0.0534131)tead2VP16-over-2 (0.0488056) (0.0499853) [ min ] [ medium ] [ max ] CEM 1 Bub1 277.3 359.7 3430.2 P ( S | Z, I ) = 1.00 Birc5 404.9 721.0 5213.2 Mean Corr = 0.93649 Sgol1 210.8 327.6 1546.1 Nuf2 176.2 237.6 1669.1 Zwilch 131.0 212.9 704.6 Bub1b 296.4 418.1 2126.4 Kntc1 132.1 159.1 830.6 Ndc80 179.1 225.4 1353.1 Cenpk 175.5 275.9 1109.0 Spc24 122.2 161.7 476.5 Cenph 98.1 136.3 810.3 Sgol2 180.3 242.0 986.0 Ercc6l 324.3 445.3 2315.4 Spag5 111.6 136.6 971.4 Incenp 305.2 419.3 2053.4 Nek2 103.6 134.1 689.9 Cenpn 481.0 621.6 1930.3 Cenpu 170.0 219.4 928.9 Cenpw 264.1 297.7 1357.4 Apitd1 133.3 193.1 748.3 Casc5 104.7 147.9 790.7 Cenpm 281.5 428.1 1254.5 Nup107 1091.6 1225.6 2927.8 Nup85 1249.3 1459.4 3815.9 Nup133 809.4 928.6 1914.9 Nup43 273.9 354.3 1044.1 Nde1 809.8 878.3 1271.2 Smc1a 2411.2 2999.7 3973.9 Cenpc1 514.4 572.4 717.9 Nudcd2 1016.7 1289.5 1450.0 Cenpt 593.3 720.9 1029.3 Cenpo 83.6 109.8 202.2 Ncapg 120.9 147.5 1230.3 Shcbp1 249.1 374.1 2391.5 Ccna2 439.7 606.3 3852.8 Cdk1 1012.3 1230.8 6611.2 Aurkb 176.6 237.3 1928.2 CEM 1 + Kif11 166.4 251.6 1265.9 Top 10 Genes Melk 194.1 271.9 1544.1 Kif20a 250.3 339.7 2331.6 Pbk 398.0 549.0 4201.1 Tpx2 405.0 483.0 3263.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.021619)liver-baclofen-1day-rep 1 (0.0213667)liver-vehicle-1day-rep 2 (0.0200323) 2liver-baclofen-1day-rep (0.0226823)liver-vehicle-5day-rep 3 (0.0223154) 3liver-baclofen-5day-rep (0.022827)liver-vehicle-5day-rep 4 (0.0227705) 1liver-baclofen-5day-rep (0.0235121)liver-vehicle-5day-rep 1 (0.0228405) 2liver-baclofen-5day-rep (0.0222227)liver-vehicle-5day-rep 2 (0.0228738) 3liver-baclofen-5day-rep (0.0244176)liver-baclofen-5day-rep 3 (0.0231875) 4liver-baclofen-5day-rep (0.0229141)liver-baclofen-5day-rep 4 (0.0221535)liver-baclofen-5day-rep 5 (0.020855)bone 6 (0.0218058) marrow-vehicle-1day-repbone 7 (0.0217792) marrow-baclofen-1day-repbone 8 (0.0238122) marrow-vehicle-1day-repbone marrow-baclofen-1day-repbone 1 (0.0187141) marrow-vehicle-1day-repbone 1 (0.022598) marrow-baclofen-1day-repbone 2 (0.015858) marrow-vehicle-1day-repbone 2 (0.0152757) marrow-baclofen-1day-repbone 3 (0.0163477) marrow-vehicle-5day-repbone 3 (0.0138297) marrow-baclofen-5day-repbone 4 (0.0138374) marrow-vehicle-5day-repbone 4 (0.0217535) marrow-baclofen-5day-repbone 1 (0.0152319) marrow-vehicle-5day-repbone 1 (0.0227665) marrow-baclofen-5day-repbone 2 (0.0188751) marrow-vehicle-5day-repbone 2 (0.0233112) marrow-baclofen-5day-repbone 3 (0.0176793) marrow-baclofen-5day-repbone 3 (0.0186057) marrow-baclofen-5day-repbone 4 (0.0143551) marrow-baclofen-5day-repbone 4 (0.0158725) marrow-baclofen-5day-repspleen-vehicle-1day-rep 5 (0.0234632)spleen-baclofen-1day-rep 6 (0.0213572)spleen-vehicle-1day-rep 7 (0.0214199)spleen-baclofen-1day-rep 1 8 (0.0215929) (0.0173742)spleen-vehicle-1day-rep 1 (0.0108479)spleen-baclofen-1day-rep 2 (0.008849)spleen-vehicle-1day-rep 2 (0.00867311)spleen-baclofen-1day-rep 3 (0.0119579)spleen-vehicle-5day-rep 3 (0.010985)spleen-baclofen-5day-rep 4 (0.00908559)spleen-vehicle-5day-rep 4 (0.00868106)spleen-baclofen-5day-rep 1 (0.00821219)spleen-vehicle-5day-rep 1 (0.0101883)spleen-baclofen-5day-rep 2 (0.0125938)spleen-vehicle-5day-rep 2 (0.00887862)spleen-baclofen-5day-rep 3 (0.00946008)spleen-baclofen-5day-rep 3 (0.00836647)spleen-baclofen-5day-rep 4 (0.0070069)spleen-baclofen-5day-rep 4 (0.00818174)spleen-baclofen-5day-rep 5 (0.00857964) 6 (0.0151111) 7 (0.0090683) 8 (0.00916707)[ min ] [ medium ] [ max ] CEM 1 Bub1 23.5 731.5 2834.4 P ( S | Z, I ) = 1.00 Birc5 36.3 2404.1 7837.6 Mean Corr = 0.93504 Sgol1 99.1 627.6 1804.1 Nuf2 23.1 552.9 2842.3 Zwilch 24.8 481.0 1531.2 Bub1b 70.5 618.5 2364.7 Kntc1 27.5 438.7 1419.3 Ndc80 40.1 307.3 906.7 Cenpk 35.5 737.9 2463.2 Spc24 240.3 573.9 1644.2 Cenph 26.4 185.7 715.7 Sgol2 41.2 349.7 1489.2 Ercc6l 53.2 462.3 1215.5 Spag5 24.1 237.1 1026.7 Incenp 76.8 975.5 3027.8 Nek2 60.0 290.5 845.7 Cenpn 175.6 872.1 2227.5 Cenpu 63.1 318.8 787.8 Cenpw 62.2 293.6 776.0 Apitd1 69.8 363.4 615.4 Casc5 34.6 547.0 1592.0 Cenpm 198.9 411.5 1263.5 Nup107 432.7 1498.5 1950.6 Nup85 499.8 1520.6 2324.0 Nup133 349.3 936.9 1551.1 Nup43 85.9 294.3 431.2 Nde1 227.7 666.4 1126.2 Smc1a 1841.6 3578.6 4686.3 Cenpc1 94.9 755.5 1583.5 Nudcd2 239.1 470.1 702.9 Cenpt 145.9 619.3 1037.4 Cenpo 38.1 219.9 418.1 Ncapg 26.3 364.2 1256.6 Shcbp1 32.1 520.0 1970.9 Ccna2 64.5 2076.2 7532.7 Cdk1 173.3 1282.1 5654.6 Aurkb 20.1 343.1 1800.7 CEM 1 + Kif11 44.2 394.2 2194.2 Top 10 Genes Melk 43.0 348.7 1229.1 Kif20a 31.6 349.9 1685.4 Pbk 34.5 1215.7 4376.3 Tpx2 40.9 780.0 3250.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE54490" 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=GSE54490 Status: Public on Feb 16 2014 Title: FoxA1 directs the lineage and immunosuppressive properties of FoxA1+ regulatory T cells in EAE and MS Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24531377 Summary & Design: Summary: Affymetrix gene expression analysis was carried out to investigate the differences in gene profile of MBP89-101-reactive encephalitogenic T cells before and after co-culture with cerebellar granular neurons (CGNs). Co-culture of MBP89-101-reactive encephalitogenic T cells with CGNs leads to generation of T cells with regulatory T cells phenotype (CD4+CD25+membrane bound TGF-b+ T cells) or a new regulatory phenotype (CD4highPD-L1high T cells). CGN-induced CD4+CD25+membrane bound TGF-b+ T regulatory cells, CD4highPD-L1high T cells were purified by FACSAria. IFN-beta induced T lymphocytes (CD4highPD-L1high T cells) were also FACSAria purified. All these populations were compared to MBP89-101-reactive encephalitogenic T cells. Samples were prepared from biological triplicates for each FACSAria sorted population.

Overall design: There are four different cell types, as determined by cell surface markers, in triplicate in the experiment.

Background corr dist: KL-Divergence = 0.0239, L1-Distance = 0.0546, L2-Distance = 0.0040, Normal std = 0.7910

0.572 Kernel fit Pairwise Correlations Normal fit

Density 0.286

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

EncephalitogenicEncephalitogenicEncephalitogenic Tcellsneuron rep1 Tcells (0.056063)neuroninduced rep2 Tcells (0.0608835)neuroninduced FoxA1Treg rep3 (0.0218855)Treginduced FoxA1Treg rep1rep1Treg FoxA1Treg (0.031157)(0.0643724) rep2rep2Treg (0.0611066)(0.0467484) rep3rep3IFN-beta (0.047545)(0.0683338)IFN-beta inducedIFN-beta induced FoxA1Treg induced FoxA1Treg rep1 FoxA1Treg (0.166314) rep2 (0.174736) rep3[ min (0.200854) ] [ medium ] [ max ] CEM 1 Bub1 918.6 2726.7 3144.4 P ( S | Z, I ) = 1.00 Birc5 1489.5 9772.4 10897.0 Mean Corr = 0.93057 Sgol1 352.7 1595.7 1990.8 Nuf2 605.6 3050.0 3657.4 Zwilch 351.3 1578.2 1789.4 Bub1b 309.9 2101.1 2490.9 Kntc1 239.8 1443.4 1722.5 Ndc80 279.5 1491.2 1702.6 Cenpk 401.4 2350.3 2701.1 Spc24 421.1 1558.6 1835.5 Cenph 275.4 1177.1 1451.6 Sgol2 224.9 1041.5 1214.3 Ercc6l 366.0 799.0 966.2 Spag5 120.8 913.5 977.6 Incenp 556.7 3139.1 3581.3 Nek2 265.7 1052.7 1326.7 Cenpn 378.1 1358.5 1601.1 Cenpu 222.0 501.1 589.9 Cenpw 832.2 1456.7 1738.3 Apitd1 205.9 518.3 612.7 Casc5 192.7 499.7 600.5 Cenpm 215.1 901.7 1084.6 Nup107 931.8 1638.0 1853.0 Nup85 1102.8 1960.5 2244.5 Nup133 747.8 1188.7 1326.8 Nup43 251.8 393.4 436.7 Nde1 368.5 1771.5 2051.0 Smc1a 2202.6 5898.8 6718.8 Cenpc1 814.9 1714.8 1778.9 Nudcd2 696.3 900.0 1029.7 Cenpt 293.9 1873.1 2364.3 Cenpo 256.1 634.1 802.6 Ncapg 654.6 3672.3 3952.1 Shcbp1 998.8 3703.1 4264.8 Ccna2 1812.5 8025.1 9258.6 Cdk1 1993.8 8078.6 9259.9 Aurkb 675.3 2418.5 2894.1 CEM 1 + Kif11 330.0 1942.4 2448.7 Top 10 Genes Melk 241.3 1943.8 2512.5 Kif20a 320.1 2197.9 2991.6 Pbk 936.2 2349.4 2778.5 Tpx2 504.9 3320.4 3920.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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(0.101941) (0.0597124)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.104774)intestine-EphB2Medium-R2 (0.0338356)intestine-EphB2Low-R2 (0.202154) (0.146729) (0.041307) (0.309546)[ min ] [ medium ] [ max ] CEM 1 Bub1 242.2 1544.5 1903.8 P ( S | Z, I ) = 1.00 Birc5 2365.3 6663.7 7308.3 Mean Corr = 0.93054 Sgol1 356.0 1586.2 2101.5 Nuf2 256.4 1464.1 2094.8 Zwilch 249.6 1599.7 1917.0 Bub1b 273.0 1539.5 2427.4 Kntc1 194.2 1202.4 1670.3 Ndc80 124.9 567.9 866.6 Cenpk 253.4 955.8 1215.9 Spc24 318.4 1546.6 1693.5 Cenph 133.0 711.0 1228.6 Sgol2 104.1 689.0 885.6 Ercc6l 123.5 640.6 849.6 Spag5 153.7 638.7 914.3 Incenp 200.7 982.3 1347.3 Nek2 195.4 957.3 1337.0 Cenpn 70.4 519.3 766.6 Cenpu 140.2 639.8 815.1 Cenpw 181.1 670.0 822.0 Apitd1 120.5 708.7 998.3 Casc5 49.4 344.6 512.7 Cenpm 106.4 459.1 602.7 Nup107 481.7 1210.3 1738.4 Nup85 938.8 3846.1 4716.0 Nup133 705.7 2941.1 3956.9 Nup43 58.3 200.1 283.2 Nde1 260.6 1120.3 1631.6 Smc1a 1110.3 1945.0 2315.1 Cenpc1 186.9 537.8 758.7 Nudcd2 342.5 870.1 1078.9 Cenpt 237.1 645.1 936.5 Cenpo 191.3 564.8 731.2 Ncapg 787.1 3310.9 4525.3 Shcbp1 420.3 2367.0 2814.5 Ccna2 982.1 3875.7 4870.2 Cdk1 773.8 3314.4 4331.3 Aurkb 225.8 1228.4 1631.2 CEM 1 + Kif11 91.6 591.0 810.8 Top 10 Genes Melk 220.1 1396.3 1806.4 Kif20a 198.6 1236.4 2091.7 Pbk 716.6 3452.3 4260.4 Tpx2 238.2 1610.6 2318.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE38257" 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=GSE38257 Status: Public on Dec 21 2012 Title: A Novel Tumor suppressor network in squamous malignancies Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23145321 Summary & Design: Summary: The specific ablation of Rb1 gene in stratified epithelia (RbF/F;K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues, however RbF/F;K14cre;p107-/- mice die postnatally. Acute pRb loss in stratified epithelia, using an inducible mouse model (RbF/F;K14creERTM), shows that p107 exerts specific tumor suppressor functions in its absence. After simultaneous absence of pRb and p107, p53 transcriptional function is impaired and Pten expression is reduced. All mutant mice develop spontaneous squamous tumors carcinomas rapidly. Gene expression analysis of mouse tumors, besides supporting the impaired p53 function and the susceptibility to Akt/mTOR inhibitors, also revealed significant overlap with human squamous carcinomas. Thus, RbF/F;K14creERTM;p107-/- may constitute a new mouse model for these malignancies. Collectively, these data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.

Overall design: Gene expression was compared between normal mouse skin and carcinomas arising in the skin of RbF/F;K14creERTM;p107-/- mouse. All mice were treated with tamoxifen.

Background corr dist: KL-Divergence = 0.0326, L1-Distance = 0.0283, L2-Distance = 0.0009, Normal std = 0.6484

0.639 Kernel fit Pairwise Correlations Normal fit

Density 0.320

0.000 CEM 1

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

Pre-normalization Quantiles

Skin_Normal_1Skin_Normal_2Skin_Normal_3 (0.162047)Skin_Normal_4 (0.144515)Rb_p107_carcinoma_rep1 (0.156707)Rb_p107_carcinoma_rep2 (0.156028)Rb_p107_carcinoma_rep3Rb_p107_carcinoma_rep4 (0.0434255)Rb_p107_carcinoma_rep5 (0.0341186)Rb_p107_carcinoma_rep6 (0.0400222)Rb_p107_carcinoma_rep7 (0.0344762)Rb_p107_carcinoma_rep8 (0.0492851)Rb_p107_carcinoma_rep9 (0.0381995)Rb_p107_carcinoma_rep10 (0.0266581) (0.0329425) (0.0435889) (0.0379848)[ min ] [ medium ] [ max ] CEM 1 Bub1 46.0 565.3 693.8 P ( S | Z, I ) = 1.00 Birc5 120.5 1746.2 1967.8 Mean Corr = 0.92641 Sgol1 133.9 733.9 838.9 Nuf2 59.9 429.2 537.7 Zwilch 92.4 737.1 956.7 Bub1b 187.5 647.2 755.1 Kntc1 76.6 983.9 1080.7 Ndc80 69.7 286.1 348.7 Cenpk 106.4 1177.1 1376.1 Spc24 103.3 406.5 480.5 Cenph 65.7 455.8 512.7 Sgol2 110.1 444.7 588.7 Ercc6l 109.0 777.3 976.0 Spag5 35.4 230.1 251.6 Incenp 207.3 848.0 924.8 Nek2 51.4 233.4 278.6 Cenpn 386.6 779.4 980.4 Cenpu 71.9 333.4 451.9 Cenpw 49.5 465.3 601.6 Apitd1 80.3 840.8 912.8 Casc5 99.3 443.2 549.3 Cenpm 149.9 571.1 662.4 Nup107 482.5 1122.3 1219.4 Nup85 772.8 1556.1 1774.2 Nup133 499.7 833.8 1032.7 Nup43 115.3 545.4 663.9 Nde1 603.2 936.5 1248.3 Smc1a 2790.6 3717.9 4291.8 Cenpc1 286.3 601.9 654.6 Nudcd2 327.6 1111.8 1353.7 Cenpt 245.6 715.4 794.3 Cenpo 89.0 125.6 156.3 Ncapg 29.5 323.6 376.4 Shcbp1 89.1 837.6 1095.9 Ccna2 196.0 1275.8 1555.9 Cdk1 193.3 2772.1 3070.7 Aurkb 55.8 494.0 551.9 CEM 1 + Kif11 82.4 487.9 615.9 Top 10 Genes Melk 88.4 589.4 739.9 Kif20a 62.5 551.3 622.6 Pbk 183.7 2217.8 2806.9 Tpx2 136.6 1073.3 1157.0

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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.

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. 39 arrays.

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 (0.0247285)liver-hypoxia-2hours-rep 2 (0.0269595)liver-hypoxia-2hours-rep 3 (0.0317633)liver-hypoxia-2hours-rep 4 (0.0289673)liver-hypoxia-2hours-rep 1 (0.0229898)liver-hypoxia-2hours-rep 2 (0.0246154)liver-hypoxia-2hours-rep 3 (0.0253609)liver-hypoxia-2hours-rep 4 (0.0294964)liver-hypoxia-2hours-rep 5 (0.0253307)liver-vehicle-2hours-rep 6 (0.0292999)liver-vehicle-2hours-rep 7 (0.0245939)liver-vehicle-2hours-rep 8 (0.0237212)liver-vehicle-2hours-rep 5 (0.0247104)bone 6 (0.0283037) marrow-vehicle-2hours-repbone 7 (0.0240572) marrow-vehicle-2hours-repbone 8 (0.0268112) marrow-vehicle-2hours-repbone marrow-hypoxia-2hours-repbone 1 (0.0574172)marrow-hypoxia-2hours-repbone 2 (0.0613575)marrow-hypoxia-2hours-repbone 3 (0.0454727)marrow-hypoxia-2hours-repspleen-vehicle-2hours-rep 1 (0.04427)spleen-vehicle-2hours-rep 2 (0.0368165)spleen-vehicle-2hours-rep 3 (0.0412637)spleen-vehicle-2hours-rep 41 (0.0392856)(0.0129087)spleen-hypoxia-2hours-rep 2 (0.0297031)spleen-hypoxia-2hours-rep 3 (0.0168156)spleen-hypoxia-2hours-rep 4 (0.0109594)spleen-hypoxia-2hours-rep 1 (0.0126901)spleen-vehicle-2hours-rep 2 (0.0137322)spleen-hypoxia-2hours-rep 3 (0.0109648)spleen-hypoxia-2hours-rep 4 (0.0471555)spleen-vehicle-2hours-rep 5 (0.00782382)spleen-vehicle-2hours-rep 7 (0.012798)spleen-vehicle-2hours-rep 8 (0.0149993)spleen-hypoxia-2hours-rep 6 (0.0111168)spleen-hypoxia-2hours-rep 7 (0.0134074) 8 (0.0104064) 5 (0.0112531) 6 (0.0156732)[ min ] [ medium ] [ max ] CEM 1 Bub1 26.6 513.3 2856.7 P ( S | Z, I ) = 1.00 Birc5 39.0 2418.7 7612.4 Mean Corr = 0.92074 Sgol1 81.5 546.8 1823.5 Nuf2 24.0 498.6 2441.2 Zwilch 31.4 437.1 1548.3 Bub1b 38.2 600.1 2524.7 Kntc1 27.5 408.1 1545.1 Ndc80 66.8 276.5 1007.2 Cenpk 39.6 645.0 2233.9 Spc24 200.6 580.8 1380.0 Cenph 31.8 221.8 679.0 Sgol2 46.9 334.9 1373.0 Ercc6l 88.5 433.9 1108.7 Spag5 25.1 243.6 1028.0 Incenp 67.3 844.9 3029.6 Nek2 83.1 226.9 742.7 Cenpn 163.2 836.5 2084.7 Cenpu 52.3 334.4 831.2 Cenpw 116.0 329.0 775.3 Apitd1 78.0 350.5 498.2 Casc5 33.5 339.6 1114.1 Cenpm 154.5 406.9 1182.0 Nup107 419.5 1340.0 1868.4 Nup85 530.6 1402.1 2339.4 Nup133 371.9 878.0 1938.8 Nup43 92.0 220.5 339.1 Nde1 279.0 609.2 1273.4 Smc1a 1485.6 3089.0 4866.4 Cenpc1 41.4 594.3 1859.6 Nudcd2 292.8 427.8 986.0 Cenpt 162.4 553.6 967.9 Cenpo 55.1 188.7 335.1 Ncapg 27.8 389.3 1529.5 Shcbp1 42.1 469.1 1965.5 Ccna2 81.1 1929.2 6905.1 Cdk1 204.1 1135.4 5325.6 Aurkb 24.0 336.8 1680.5 CEM 1 + Kif11 60.3 495.3 2230.7 Top 10 Genes Melk 42.6 348.8 1141.2 Kif20a 43.7 382.1 1720.0 Pbk 38.5 947.9 4438.7 Tpx2 57.3 683.6 3825.0

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE51075" 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=GSE51075 Status: Public on Sep 22 2013 Title: Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17890046 Summary & Design: Summary: Three different recombinant forms of CyaA were used to investigate transcriptional responses of murine bone marrow-derived macrophages (BMDMs) using Affymetrix Mouse Genome Genechips. These forms were enzymically active, invasive CyaA, nonenzymically active, invasive CyaA (CyaA*) and non-enzymically active, non-invasive CyaA (proCyaA*). BMMs, treated with 20 ng/ml of CyaA for 24 h, showed over 1000 significant changes in gene transcription compared with control cells. CyaA caused an increase in transcription of many inflammatory genes and genes associated with various signalling cascades such as those involved in cyclic AMP-dependent protein kinase A signalling. Most strikingly, CyaA caused down-regulation of numerous genes involved in cell proliferation. CyaA* at 20 ng/ml significantly up-regulated the transcription of only twelve genes after 24 h whereas proCyaA* at this concentration significantly increased the transcription of only two genes.

Overall design: The effect of administration of three different recombinant forms of pertussis toxin to mouse bone marrow derived macrophages are compared with a vehicle only contol 24 hours after treatment in technical triplicate measurements

Background corr dist: KL-Divergence = 0.0967, L1-Distance = 0.0706, L2-Distance = 0.0078, Normal std = 0.5189

0.873 Kernel fit Pairwise Correlations Normal fit

Density 0.437

0.000 CEM 1

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

Pre-normalization Quantiles

BMDM_CyaA*_24h_rep1BMDM_CyaA*_24h_rep2BMDM_CyaA*_24h_rep3BMDM_CyaA_24h_rep1 (0.0386979)BMDM_CyaA_24h_rep2 (0.0578752)BMDM_CyaA_24h_rep3 (0.0464989)BMDM_ProCyaA*_24h_rep1 (0.17937)BMDM_ProCyaA*_24h_rep2 (0.185328)BMDM_ProCyaA*_24h_rep3 (0.182785)BMDM_Urea_24h_rep1 (0.0632634)BMDM_Urea_24h_rep2 (0.054826)BMDM_Urea_24h_rep3 (0.0342914) (0.04224) (0.0525681) (0.0622567)[ min ] [ medium ] [ max ] CEM 1 Bub1 167.1 2230.1 2308.8 P ( S | Z, I ) = 1.00 Birc5 342.7 6132.3 7035.0 Mean Corr = 0.91998 Sgol1 107.1 667.4 813.0 Nuf2 100.6 1262.9 1313.8 Zwilch 66.0 554.0 688.5 Bub1b 140.4 1577.8 1723.1 Kntc1 107.3 1024.1 1144.7 Ndc80 74.8 838.2 995.3 Cenpk 85.0 808.1 926.9 Spc24 138.6 809.9 978.6 Cenph 68.8 404.4 537.8 Sgol2 67.8 627.7 801.7 Ercc6l 155.2 1115.9 1304.2 Spag5 72.3 485.7 625.4 Incenp 1243.0 3149.7 3619.5 Nek2 107.9 214.5 310.2 Cenpn 324.5 1447.5 1612.3 Cenpu 79.6 371.1 440.2 Cenpw 129.5 894.5 1107.6 Apitd1 91.2 425.0 505.7 Casc5 89.1 449.2 645.4 Cenpm 130.8 474.5 576.7 Nup107 618.7 1424.8 1706.6 Nup85 526.9 1588.2 1878.6 Nup133 506.3 1110.5 1406.9 Nup43 74.2 207.6 237.2 Nde1 489.0 1595.8 1710.0 Smc1a 1770.7 2840.5 3004.6 Cenpc1 182.9 423.8 514.4 Nudcd2 218.1 447.4 528.1 Cenpt 431.5 824.6 989.2 Cenpo 64.2 111.5 120.2 Ncapg 65.9 912.5 1006.5 Shcbp1 112.2 2683.1 3022.7 Ccna2 275.9 7120.8 7791.8 Cdk1 965.7 5757.2 6245.3 Aurkb 124.0 919.8 1063.9 CEM 1 + Kif11 70.2 792.2 958.5 Top 10 Genes Melk 84.7 1165.9 1435.4 Kif20a 130.2 1079.7 1410.2 Pbk 115.5 3694.6 4000.2 Tpx2 296.0 2616.0 2997.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.398088)(GM-DC_2) cell TNFa (0.122309) plus (0.144305) sample TNFa (0.0661756) sample1 (GM-TNFa-DC_1)[ 2min (GM-TNFa-DC_2) ] (0.159845) (0.109277)[ medium ] [ max ] CEM 1 Bub1 215.4 1563.3 2449.8 P ( S | Z, I ) = 1.00 Birc5 297.3 1796.8 4348.5 Mean Corr = 0.91037 Sgol1 115.8 572.7 1476.7 Nuf2 138.0 704.2 2351.4 Zwilch 55.3 505.6 722.0 Bub1b 330.5 733.1 2004.7 Kntc1 140.6 872.6 1299.1 Ndc80 147.5 450.5 945.3 Cenpk 120.4 846.7 1971.0 Spc24 189.2 612.1 1447.4 Cenph 59.9 289.0 638.0 Sgol2 110.7 480.0 874.2 Ercc6l 238.6 495.3 1165.2 Spag5 65.5 240.0 775.4 Incenp 341.8 837.2 1951.3 Nek2 64.8 118.3 365.4 Cenpn 342.0 518.4 1151.8 Cenpu 149.7 461.3 1152.6 Cenpw 66.8 372.7 948.2 Apitd1 78.5 147.1 346.8 Casc5 50.6 173.9 383.0 Cenpm 118.2 266.4 715.7 Nup107 611.8 1064.2 2101.6 Nup85 597.3 768.5 1905.7 Nup133 375.4 512.6 1316.7 Nup43 110.1 219.4 519.1 Nde1 503.8 666.2 835.4 Smc1a 1612.0 2636.0 4443.9 Cenpc1 257.3 486.2 617.9 Nudcd2 523.7 759.4 1193.5 Cenpt 245.5 473.5 1240.2 Cenpo 146.5 186.3 296.9 Ncapg 59.1 617.6 1476.9 Shcbp1 217.3 1520.0 3042.5 Ccna2 550.7 2380.9 5390.4 Cdk1 516.3 2050.4 4048.8 Aurkb 97.5 436.6 2061.6 CEM 1 + Kif11 93.4 496.4 1537.7 Top 10 Genes Melk 175.0 623.1 933.5 Kif20a 203.4 801.8 2107.8 Pbk 140.5 1651.6 4934.8 Tpx2 277.7 1324.2 3041.0

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE51385" 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=GSE51385 Status: Public on Oct 18 2013 Title: Expression profiling of ProB and PreB cells in Ebf1 heterozygous mouse bone marrow Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24078629 Summary & Design: Summary: Loss of one allele of Ebf1 impairs pre-B cell (B220+CD19+CD43low/negIgM-) expansion. In order to better understand the underlying cause of the reduced pre-B cell compartment in Ebf1+/- mice, we sorted pro-B (B220+CD19+CD43highIgM- ) as well as pre-B cells from Wt and Ebf1 heterozygote mutant mice and performed Affymetrix based microarray gene expression analysis.

While the overall gene expression patterns as well as Pax5 expression in Wt and Ebf1 pro-B cells were similar, gene set enrichment (GSE) analysis of the microarray data suggested a reduced expression of cell division (p<0.001) and mitosis (p<0.001) genes in the Ebf1+/- pre-B cells as compared to their Wt counterparts. This in combination with rather normal expression of B-lineage genes in Ebf1+/- pre-B cells opens for the possibility that the phenotypic loss of pre-B cells in Ebf1+/- mice could be a result of reduced expansion of progenitors rather than by a differentiation block.

Overall design: RNA was extracted from 20,000 or 25000 purified adult bone marrow cells using the RNAeasy microkit. RNA was labeled and amplified by dual amplification and hybridized to Affymetrix microarray MOE430_2, according to AffymetrixTM GeneChip Expression Analysis Technical Manual. Probe level expression values were calculated using the RMA algorithm.

Background corr dist: KL-Divergence = 0.0357, L1-Distance = 0.0280, L2-Distance = 0.0014, Normal std = 0.6198

0.644 Kernel fit Pairwise Correlations Normal fit

Density 0.322

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

Ebf1 heteroEbf1 PreB_1heteroEbf1 PreB_2(0.17249)heteroEbf1 ProB_2(0.147321)heteroWT PreB_2 ProB_1(0.0739037)WT PreB_1(0.115242) (0.102966)WT ProB_1(0.0897664)WT ProB_2(0.120218) (0.178093) [ min ] [ medium ] [ max ] CEM 1 Bub1 108.9 1974.9 3300.2 P ( S | Z, I ) = 1.00 Birc5 570.1 5764.0 7911.6 Mean Corr = 0.90953 Sgol1 234.6 1715.1 1964.3 Nuf2 219.6 1956.7 2769.5 Zwilch 120.6 1325.7 2011.1 Bub1b 291.7 3318.7 4754.2 Kntc1 186.2 1496.9 2090.2 Ndc80 171.7 1692.7 1944.1 Cenpk 334.4 2590.7 3078.5 Spc24 349.3 1630.5 1926.8 Cenph 48.9 701.2 936.8 Sgol2 212.9 1231.1 1865.1 Ercc6l 298.1 1701.8 2399.2 Spag5 148.9 1027.4 1339.3 Incenp 242.3 1888.7 2640.6 Nek2 61.4 1072.2 1733.8 Cenpn 515.3 2631.4 3687.7 Cenpu 263.6 558.1 800.9 Cenpw 160.4 870.2 1382.9 Apitd1 257.7 1137.2 2150.7 Casc5 152.8 672.2 1366.7 Cenpm 205.6 1554.0 2120.0 Nup107 1061.8 2128.7 2649.1 Nup85 1106.7 3039.5 3687.7 Nup133 764.9 1738.9 2101.9 Nup43 123.8 552.0 858.9 Nde1 779.3 1585.0 2160.3 Smc1a 3341.1 6667.6 7845.5 Cenpc1 415.9 1119.6 1783.5 Nudcd2 44.2 254.5 503.3 Cenpt 495.9 965.6 1213.2 Cenpo 153.5 324.7 539.4 Ncapg 109.1 1979.1 2450.3 Shcbp1 351.0 3553.1 4016.5 Ccna2 907.3 5812.9 9488.6 Cdk1 730.5 6867.9 8942.1 Aurkb 123.0 2373.0 3142.3 CEM 1 + Kif11 114.6 1057.9 1558.9 Top 10 Genes Melk 102.7 748.9 1036.2 Kif20a 103.4 1577.6 2371.4 Pbk 888.6 8555.1 10683.3 Tpx2 266.6 4852.8 5864.0

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.127335)Control B (0.239557)429 C (0.103836) B (0.121694)429 A (0.252478)429 C (0.1551) [ min ] [ medium ] [ max ] CEM 1 Bub1 241.4 2063.7 2386.9 P ( S | Z, I ) = 1.00 Birc5 167.9 4736.0 4758.2 Mean Corr = 0.90889 Sgol1 192.9 1760.0 1871.3 Nuf2 115.1 1588.2 1727.2 Zwilch 284.0 1330.2 1456.0 Bub1b 56.4 682.9 871.1 Kntc1 121.8 480.8 518.8 Ndc80 32.5 481.4 562.4 Cenpk 113.8 939.5 1107.7 Spc24 72.9 1138.3 1625.7 Cenph 179.7 1118.8 1248.3 Sgol2 158.5 1989.7 2242.3 Ercc6l 165.9 1258.4 1498.8 Spag5 37.7 141.0 162.4 Incenp 218.1 783.5 1300.1 Nek2 166.5 869.4 1040.6 Cenpn 392.5 1018.8 1260.1 Cenpu 230.0 815.0 1115.2 Cenpw 290.6 1553.8 1864.9 Apitd1 75.6 316.4 376.1 Casc5 96.4 592.0 673.3 Cenpm 354.5 696.4 781.4 Nup107 565.3 912.0 1773.0 Nup85 574.7 1185.1 1426.9 Nup133 425.3 1096.0 1196.6 Nup43 209.3 742.0 864.0 Nde1 102.0 357.2 430.4 Smc1a 1433.2 1993.9 2585.6 Cenpc1 305.2 763.7 917.8 Nudcd2 1644.2 2320.9 2609.2 Cenpt 483.0 1279.8 1366.6 Cenpo 181.1 330.7 373.0 Ncapg 149.8 1697.7 2114.2 Shcbp1 287.1 4173.1 5932.9 Ccna2 595.2 6334.9 6724.1 Cdk1 1511.0 5817.1 8028.5 Aurkb 96.5 967.4 1026.1 CEM 1 + Kif11 58.5 484.3 746.7 Top 10 Genes Melk 151.9 1518.2 1955.9 Kif20a 45.4 774.1 1108.8 Pbk 350.9 4361.2 4716.7 Tpx2 197.9 1065.9 1097.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE48397" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 10 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.754 Kernel fit Pairwise Correlations Normal fit

Density 0.377

0.000 CEM 1

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

Pre-normalization Quantiles

lung fibroblasts,lung fibroblasts,lung biological fibroblasts,lung biological fibroblasts,replicatelung biological fibroblasts,replicate 1carcinoma-asssociated (0.105117) biological replicate 2carcinoma-asssociated (0.100865) biological replicate 3carcinoma-asssociated (0.24883) replicate 4carcinoma-asssociated (0.155261)fibroblasts, 5carcinoma-asssociated (0.0694418)fibroblasts, biological fibroblasts, biological fibroblasts,replicate biological fibroblasts,replicate 1 (0.0474303) biological[ replicate min2 (0.0482412) biological replicate 3 ](0.0993379) replicate 4 (0.052916) [5 (0.0725598)medium ] [ max ] CEM 1 Bub1 37.1 392.2 1507.3 P ( S | Z, I ) = 1.00 Birc5 89.0 988.7 5666.2 Mean Corr = 0.90738 Sgol1 115.0 309.1 1325.7 Nuf2 71.3 250.1 795.1 Zwilch 135.3 460.9 1279.5 Bub1b 115.5 340.3 1908.7 Kntc1 71.5 218.9 631.5 Ndc80 69.2 216.0 707.2 Cenpk 76.9 219.3 605.4 Spc24 55.4 218.0 2158.1 Cenph 41.3 149.8 537.4 Sgol2 73.9 228.0 833.4 Ercc6l 103.8 326.7 1067.7 Spag5 39.5 120.0 511.4 Incenp 201.5 523.8 1318.2 Nek2 89.1 158.5 417.8 Cenpn 478.0 827.8 1718.8 Cenpu 72.3 162.0 571.3 Cenpw 93.7 266.6 1448.9 Apitd1 90.3 199.0 917.8 Casc5 66.8 137.0 382.1 Cenpm 125.1 175.4 541.6 Nup107 577.4 832.7 1845.6 Nup85 417.0 710.2 1828.8 Nup133 472.8 677.2 1044.1 Nup43 149.6 254.4 663.4 Nde1 495.5 879.2 1075.5 Smc1a 1138.1 1584.8 1821.7 Cenpc1 413.0 567.5 674.7 Nudcd2 815.5 1138.8 2367.8 Cenpt 398.4 708.7 1053.3 Cenpo 68.3 94.3 159.9 Ncapg 31.8 197.1 551.4 Shcbp1 41.4 425.1 1559.1 Ccna2 84.4 670.3 2769.1 Cdk1 249.9 1693.8 7687.8 Aurkb 57.7 230.2 1153.1 CEM 1 + Kif11 60.9 150.5 619.8 Top 10 Genes Melk 60.8 348.2 1832.1 Kif20a 92.8 545.9 1834.0 Pbk 89.8 1248.1 4025.9 Tpx2 303.3 1124.5 3207.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.0525642) Aid-GFP-positive(2)Aid-GFP negative (0.0471171)Aid-GFP negative(0.0606606) LPS+IL4-stimulatedAid-GFP positive(0.0637282) LPS+IL4-stimulated positive LPS+IL4-stimulated splenic LPS+IL4-stimulated splenicB cells [splenic (1)B min cells (0.257085) splenic B(2) cells (0.321633)] (1)B cells (0.0939986) (2)[ (0.103212) medium ] [ max ] CEM 1 Bub1 44.0 2215.7 2594.8 P ( S | Z, I ) = 1.00 Birc5 732.2 6412.1 6559.4 Mean Corr = 0.90674 Sgol1 85.4 1587.7 1758.9 Nuf2 48.8 2493.6 2527.9 Zwilch 103.7 1424.7 2047.7 Bub1b 284.2 2446.8 2560.2 Kntc1 158.5 1349.1 1869.5 Ndc80 267.1 1433.5 1583.2 Cenpk 91.6 1347.7 1369.5 Spc24 146.2 1435.3 2187.0 Cenph 144.0 1538.7 1669.6 Sgol2 80.3 1543.2 1656.4 Ercc6l 77.7 1051.8 1217.1 Spag5 22.2 634.4 855.2 Incenp 95.6 1606.9 1656.3 Nek2 31.2 891.1 1058.7 Cenpn 45.6 1284.6 1407.2 Cenpu 105.1 533.2 760.4 Cenpw 55.4 1033.6 1110.8 Apitd1 541.6 2795.0 3302.0 Casc5 80.6 592.3 705.5 Cenpm 152.9 1320.9 1771.7 Nup107 1066.7 2054.7 2162.5 Nup85 2949.7 4274.7 5449.3 Nup133 1837.7 2850.1 3773.2 Nup43 57.5 310.8 476.1 Nde1 1187.9 2243.1 2460.0 Smc1a 1648.1 3248.2 3462.6 Cenpc1 577.6 959.1 1132.5 Nudcd2 122.7 1198.9 1627.7 Cenpt 583.6 930.9 974.5 Cenpo 204.1 1107.7 1266.1 Ncapg 396.0 4831.6 5055.1 Shcbp1 71.8 2583.9 2985.3 Ccna2 180.8 4518.6 4907.7 Cdk1 379.8 5457.2 5981.2 Aurkb 137.2 2517.8 2736.8 CEM 1 + Kif11 33.2 1279.7 1393.1 Top 10 Genes Melk 74.2 993.6 1713.4 Kif20a 216.0 2096.2 2952.5 Pbk 76.2 3879.0 4011.8 Tpx2 106.9 2890.8 3342.1

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE39449" 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=GSE39449 Status: Public on Feb 25 2014 Title: Differentially activated CD8 T cells in liver and gut Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19265543 Summary & Design: Summary: Naïve, liver- and gut-activated CD8 OT-I T cells show differential migration behaviour. To analyze which genes could be responsible for different migration patterns, naïve, liver-activated and gut-activated CD8 T cells were isolated and compared for their gene expression profile.

Overall design: After total RNA extraction, reverse transcription, cDNA extraction, the biotinylated cRNA was transcribed, fragmented, and 15 ´g cRNA hybridized in duplicates for each of the three groups to the GeneChip arrays. Group1: naïve, Group2: liver-activated Group3: gut-activated. Lists of differentially regulated genes were created using High Performance Chip Data Analysis (HPCDA) with Bioretis database (http://www.bioretis-analysis.de). Worldwide data sharing is possible via Bioretis, please ask the authors.

Background corr dist: KL-Divergence = 0.0358, L1-Distance = 0.0497, L2-Distance = 0.0032, Normal std = 0.6979

0.630 Kernel fit Pairwise Correlations Normal fit

Density 0.315

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

DifferentiallyDifferentially activatedDifferentially activatedDifferentially CD8 Tactivated cellsDifferentially CD8 in Tactivated cellsDifferentially liverCD8 andin Tactivated cells liverCD8 gut: andin Tactivated Liver-activated cells liverCD8 gut: andinT Liver-activated cells liverCD8 gut: andinT Gut-activated CD8cells[liver gut:min OT-I andin Gut-activated CD8liver Tgut: cells OT-I ]and CD8 Naïve (liver)Tgut: OT-I cells CD8 NaïveCD8 ChipT (liver) cells [OT-I OT-I 1medium CD8 (0.121972)(mes)ChipT T cells cells OT-I 2 Chip (0.181083)(mes) (naïve)T cells 1 (0.0993193)Chip (naïve)] Chip 2 (0.0983989) 1 (0.216631)Chip[ 2 (0.282596)max ] CEM 1 Bub1 271.5 4114.7 4302.7 P ( S | Z, I ) = 1.00 Birc5 644.8 10529.1 11186.7 Mean Corr = 0.90545 Sgol1 227.1 1452.5 1718.0 Nuf2 168.4 2821.1 3797.6 Zwilch 174.4 1491.9 2735.1 Bub1b 106.8 1961.0 2568.3 Kntc1 160.9 1306.8 1337.7 Ndc80 264.5 1427.3 1782.3 Cenpk 357.7 2234.3 2961.2 Spc24 323.0 2946.4 3371.4 Cenph 111.7 1089.5 1137.1 Sgol2 137.0 1086.2 1291.9 Ercc6l 251.8 1109.0 1223.1 Spag5 109.8 774.3 977.9 Incenp 452.2 3109.2 4342.5 Nek2 51.6 1256.1 1432.5 Cenpn 338.0 1299.0 1369.6 Cenpu 195.2 456.0 508.5 Cenpw 528.7 2043.1 2427.9 Apitd1 104.5 658.0 763.9 Casc5 119.0 742.5 865.3 Cenpm 116.8 869.2 1100.7 Nup107 1089.6 2182.5 2451.3 Nup85 1022.0 2305.2 2764.7 Nup133 717.7 1482.6 1924.7 Nup43 431.2 680.9 697.2 Nde1 484.3 1210.2 1379.3 Smc1a 4085.3 7270.3 8920.7 Cenpc1 1352.7 1684.2 2751.1 Nudcd2 1714.3 2263.5 2534.3 Cenpt 312.4 502.4 642.4 Cenpo 162.6 255.6 314.9 Ncapg 198.7 2588.9 3117.0 Shcbp1 324.1 3678.6 4170.0 Ccna2 704.6 7106.8 7564.9 Cdk1 291.8 5475.9 7348.8 Aurkb 128.2 1772.9 2297.9 CEM 1 + Kif11 134.2 1696.4 2367.4 Top 10 Genes Melk 55.9 1081.6 1186.7 Kif20a 158.6 2256.8 2318.5 Pbk 583.2 2827.5 4156.3 Tpx2 169.4 2664.4 2780.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE27114" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.478 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

2_ESwt_a2_ESwt_b (0.215305)2_NPwt_a (0.163369)2_NPwt_b (0.0576064)2_TNwt_a (0.0810993)2_TNwt_b (0.220606) (0.262014) [ min ] [ medium ] [ max ] CEM 1 Bub1 79.9 2839.9 5137.6 P ( S | Z, I ) = 1.00 Birc5 191.2 3677.8 4824.1 Mean Corr = 0.90378 Sgol1 99.0 1395.4 1975.6 Nuf2 79.4 1150.3 1244.1 Zwilch 151.4 1008.5 3567.9 Bub1b 181.3 3593.6 6716.0 Kntc1 79.3 1112.9 2157.1 Ndc80 73.5 1068.7 1559.9 Cenpk 52.2 966.7 1257.1 Spc24 151.2 1636.7 2373.2 Cenph 45.5 920.9 1197.5 Sgol2 77.3 1016.6 1845.1 Ercc6l 63.6 1013.2 1313.4 Spag5 67.2 1172.7 1254.5 Incenp 263.0 1515.4 2175.6 Nek2 64.5 213.5 345.4 Cenpn 391.4 2545.6 3507.5 Cenpu 137.6 570.9 1200.3 Cenpw 111.8 1806.7 2839.6 Apitd1 111.0 488.0 742.7 Casc5 101.6 662.5 1141.1 Cenpm 137.8 738.3 1077.9 Nup107 537.1 2918.4 4516.7 Nup85 1040.7 2227.5 3748.5 Nup133 422.3 1736.8 2403.9 Nup43 94.3 424.2 1024.7 Nde1 214.3 1542.5 2018.5 Smc1a 2000.5 3386.7 3796.7 Cenpc1 395.6 972.4 1006.8 Nudcd2 151.2 1169.5 1911.9 Cenpt 1109.6 1443.3 2981.1 Cenpo 61.9 111.2 207.4 Ncapg 76.2 2502.3 3947.5 Shcbp1 87.1 1868.6 2001.0 Ccna2 458.6 4864.0 5144.2 Cdk1 534.6 8130.3 9539.6 Aurkb 76.0 829.6 851.0 CEM 1 + Kif11 106.7 1689.5 2653.3 Top 10 Genes Melk 130.3 2439.8 3798.4 Kif20a 72.8 2396.8 3314.9 Pbk 318.8 2392.0 5641.8 Tpx2 196.4 4084.2 4796.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE6875" 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=GSE6875 Status: Public on Jan 26 2007 Title: Development of Regulatory T cell Precursors in the Absence of a Functional Foxp3 Protein Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17273171 Summary & Design: Summary: To analyze gene expression in in regulatory T cell precursors that develop in the absence of a functional Foxp3 protein as compared to that of normal regulatory T cells

Keywords: Cell type comparison

Overall design: Murine wild-type and mutant (delta) Foxp3 alleles were tagged with EGFP reporters. CD4 positive T cells expressing the respective tagged Foxp3 allele (Foxp3/EGFP and delta Foxp3/EGFP) were isolated from hemizygous male mice by cell sorting using FACS. CD4 positive cells that did not express the EGFP tag were a isolated. Total RNA was prepared and used in the array studies.

Background corr dist: KL-Divergence = 0.0619, L1-Distance = 0.0225, L2-Distance = 0.0006, Normal std = 0.5327

0.758 Kernel fit Pairwise Correlations Normal fit

Density 0.379

0.000 CEM 1

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

Pre-normalization Quantiles

76090_CD4+,76091_CD4+, FoxP3(EGFP-)76092_CD4+, FoxP3(EGFP+)76093_CD4+, mouse(delta)FoxP3(EGFP-)82428_CD4+, cells (delta)FoxP3(EGFP+)mouse82430_CD4+, (0.145377) FoxP3(EGFP+)cells85382_CD4+, (0.121169) mouse (delta)FoxP3(EGFP+)85384_CD4+, cells mouse FoxP3(EGFP+)mouse (0.0649297) cells (delta)FoxP3(EGFP+)cells.txt (0.144052) mouse mouse (0.105082) cells cells[ min(0.108331) (0.107352) mouse ] cells (0.203707)[ medium ] [ max ] CEM 1 Bub1 68.0 785.2 1553.1 P ( S | Z, I ) = 1.00 Birc5 282.3 2560.3 5492.1 Mean Corr = 0.90121 Sgol1 163.2 596.1 1333.6 Nuf2 97.5 886.5 1841.9 Zwilch 103.9 444.4 777.5 Bub1b 107.0 557.0 1062.5 Kntc1 68.3 438.6 847.6 Ndc80 124.5 420.8 786.4 Cenpk 84.9 723.0 1569.3 Spc24 183.6 647.7 1525.7 Cenph 57.0 311.0 675.6 Sgol2 73.6 245.7 522.4 Ercc6l 224.9 685.0 1152.3 Spag5 46.7 218.9 568.3 Incenp 291.5 860.0 1407.2 Nek2 74.1 92.9 235.3 Cenpn 213.7 582.0 1053.9 Cenpu 240.4 571.7 864.4 Cenpw 119.9 503.6 1189.9 Apitd1 144.8 443.5 934.6 Casc5 78.8 373.3 685.4 Cenpm 118.9 278.8 414.7 Nup107 1815.2 2209.9 2719.5 Nup85 928.3 1220.9 1877.5 Nup133 489.7 673.4 937.6 Nup43 176.6 302.2 406.8 Nde1 412.2 784.3 1015.5 Smc1a 2717.5 3269.6 3716.1 Cenpc1 276.6 549.6 909.8 Nudcd2 437.7 871.6 1278.5 Cenpt 455.4 707.4 859.6 Cenpo 192.9 320.5 416.3 Ncapg 102.9 813.2 1737.5 Shcbp1 165.5 1334.8 2813.3 Ccna2 172.5 1878.4 3178.0 Cdk1 210.5 1876.0 4938.6 Aurkb 51.8 317.6 605.2 CEM 1 + Kif11 113.6 632.4 1360.4 Top 10 Genes Melk 88.9 720.3 1637.9 Kif20a 64.0 568.3 1218.7 Pbk 138.6 954.2 2179.6 Tpx2 96.7 791.1 1519.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.126658) suppressorcell null rep2 cellfrom myeloid-derived (0.100234) cell fromnull colon cellfrom myeloid-derived [bone tumor,frommin colon marrow, bone suppressor rep1tumor, ] marrow, (0.0665264)rep1 suppressor rep2 (0.0961383) cell (0.0478196)rep2 from[ (0.0706809) cellmedium colon from tumor, colon rep1tumor, ] (0.25274) rep2 (0.239202)[ max ] CEM 1 Bub1 109.8 2469.4 2663.3 P ( S | Z, I ) = 1.00 Birc5 600.0 4800.5 5538.5 Mean Corr = 0.89821 Sgol1 45.2 1227.5 1415.6 Nuf2 153.6 3811.9 4141.1 Zwilch 49.6 851.3 1098.2 Bub1b 38.8 526.4 692.4 Kntc1 28.4 540.4 803.9 Ndc80 41.4 462.5 651.6 Cenpk 27.8 604.9 833.3 Spc24 59.4 932.3 992.5 Cenph 23.6 208.1 264.1 Sgol2 31.3 630.8 703.3 Ercc6l 34.7 253.8 278.5 Spag5 14.6 438.3 628.3 Incenp 254.1 1517.5 1808.4 Nek2 17.8 78.5 136.5 Cenpn 17.3 58.1 71.7 Cenpu 32.2 276.1 333.3 Cenpw 60.5 472.4 531.3 Apitd1 27.2 80.9 97.0 Casc5 40.5 521.1 553.6 Cenpm 14.6 24.9 28.9 Nup107 210.6 569.3 727.0 Nup85 42.6 75.7 85.6 Nup133 243.2 369.5 425.3 Nup43 14.6 26.5 32.0 Nde1 66.5 358.1 392.7 Smc1a 2259.3 3590.9 4352.3 Cenpc1 575.8 1684.0 1906.2 Nudcd2 262.9 431.9 472.6 Cenpt 50.6 135.7 139.4 Cenpo 39.7 68.7 76.2 Ncapg 66.3 1349.7 1577.5 Shcbp1 318.0 3698.7 3842.8 Ccna2 322.1 3797.9 4391.6 Cdk1 199.9 3340.2 3676.7 Aurkb 113.4 992.8 1118.2 CEM 1 + Kif11 67.6 1254.7 1467.6 Top 10 Genes Melk 53.0 758.0 868.3 Kif20a 34.6 927.4 1235.9 Pbk 100.7 2447.5 2603.0 Tpx2 65.1 1127.4 1376.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE20100" 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=GSE20100 Status: Public on Jul 01 2010 Title: Expression data from primary MEF lacking either HDAC1, HDAC2 or both Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20194438 Summary & Design: Summary: Previously published data suggested some redundant functions between HDAC1 and HDAC2 in mouse. To test this hypothesis, we used microarrays to have a genome wide analysis at the transcription level of primary MEFs lacking HDAC1, HDAC2.

Overall design: MEF HDAC1 F/F were were transduced with two different retroviruses: one virus expresses the Tamoxifen-inducible cre recombinase Cre-ERT2 and the second virus expresses either a small hairpin micro-RNA against HDAC2 or a scrambled version. HDAC1F/F MEFs expressing either a scrambled micro-RNA or a micro-RNA against HDAC2 can be induced by addition of Tamoxifen to delete HDAC1, thereby generating four different genotypes: WT, HDAC1 KO, HDAC2 knockdown (Kd) and HDAC1/2 KO/Kd.

Background corr dist: KL-Divergence = 0.0906, L1-Distance = 0.0823, L2-Distance = 0.0115, Normal std = 0.5232

0.888 Kernel fit Pairwise Correlations Normal fit

Density 0.444

0.000 CEM 1

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

Pre-normalization Quantiles

MEF HDAC1MEF HDAC1+/+MEF + Tamoxien HDAC1+/+MEF + Tamoxien HDAC1+/+ rep1MEF + Tamoxien(0.0293638) HDAC1fl/fl rep2MEF + siRNA(0.038663) HDAC1fl/fl rep3MEF + scrambled siRNA(0.041559) HDAC1fl/flMEF + scrambledsiRNA HDAC1fl/fl +MEF EtOH + scrambledsiRNA HDAC1fl/fl +rep1MEF EtOH + scrambledsiRNA (0.0649275) HDAC1fl/fl +rep2MEF EtOH + scrambledsiRNA (0.0485233) HDAC1fl/fl +rep3MEF Tamoxifen + scrambledsiRNA (0.0633419) HDAC1fl/fl +MEF Tamoxifen + +siRNA rep1EtOH HDAC1fl/fl +MEF Tamoxifen +(0.0369732) +rep1siRNA rep2EtOH HDAC1fl/flMEF (0.0486245) +(0.0294777) +rep2siRNA rep3EtOH HDAC1fl/fl (0.0447193) +(0.0220192) +rep3siRNA Tamoxifen fl/fl (0.0411018) + +siRNA Tamoxifen rep1 + Tamoxifen (0.181852)[ rep2 min (0.131386) rep3 ] (0.177468) [ medium ] [ max ] CEM 1 Bub1 419.4 2592.2 2919.9 P ( S | Z, I ) = 1.00 Birc5 534.9 5086.7 5923.4 Mean Corr = 0.89743 Sgol1 67.2 676.8 1003.9 Nuf2 58.1 630.2 815.0 Zwilch 335.0 1574.6 1878.6 Bub1b 172.2 1372.1 1914.0 Kntc1 92.1 1025.5 1205.5 Ndc80 142.7 1146.5 1469.3 Cenpk 170.5 1053.9 1493.1 Spc24 70.0 833.1 1086.4 Cenph 429.1 1589.4 2063.2 Sgol2 196.2 754.3 952.0 Ercc6l 81.6 983.6 1092.9 Spag5 41.4 565.0 724.6 Incenp 112.8 952.6 1315.7 Nek2 22.1 89.6 119.3 Cenpn 82.1 530.8 898.4 Cenpu 73.2 325.6 508.4 Cenpw 176.6 771.1 1030.0 Apitd1 18.3 93.7 174.7 Casc5 23.3 234.4 330.6 Cenpm 47.5 265.7 528.6 Nup107 515.6 1700.9 2087.4 Nup85 382.5 1271.3 1729.9 Nup133 738.9 1657.1 2243.7 Nup43 92.2 248.3 327.7 Nde1 755.1 1542.8 1796.2 Smc1a 1841.2 3316.9 3860.1 Cenpc1 641.9 945.4 1044.3 Nudcd2 1769.6 2245.2 2922.2 Cenpt 801.3 1004.9 1185.9 Cenpo 44.4 102.3 170.9 Ncapg 96.4 1223.5 1543.3 Shcbp1 657.5 3333.7 4591.9 Ccna2 590.7 3521.7 4910.5 Cdk1 1902.9 6911.0 8340.7 Aurkb 88.3 472.1 642.8 CEM 1 + Kif11 71.5 535.1 710.6 Top 10 Genes Melk 218.1 1104.2 1295.9 Kif20a 486.4 2913.9 3826.9 Pbk 640.4 3776.8 4776.0 Tpx2 577.4 2721.7 3020.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.0435324)66977_ru (0.0610035)70660_lu (0.0352756)74128_wlr (0.0580578)74128_wr (0.101526)74129_wl (0.0948827)C57Bl6_1 (0.0701805)C57Bl6_2 (0.122118)C57Bl6_3 (0.139089)86823-2x (0.120151)82743-lo (0.0453291)77204-10 (0.0679305) (0.040924) [ min ] [ medium ] [ max ] CEM 1 Bub1 50.5 2033.2 4475.7 P ( S | Z, I ) = 1.00 Birc5 126.9 3429.0 5026.4 Mean Corr = 0.89525 Sgol1 104.2 879.4 1698.2 Nuf2 104.7 1363.7 2137.2 Zwilch 95.8 874.1 1826.2 Bub1b 180.3 1157.9 2681.1 Kntc1 89.0 1722.4 2853.3 Ndc80 57.2 510.6 1246.2 Cenpk 133.6 1161.5 1665.0 Spc24 145.4 1484.7 2271.2 Cenph 27.9 625.7 908.2 Sgol2 86.3 1824.9 2391.9 Ercc6l 87.2 517.8 978.5 Spag5 34.1 370.4 898.1 Incenp 176.9 949.5 1600.2 Nek2 66.7 456.6 772.9 Cenpn 308.8 1498.4 2540.5 Cenpu 50.1 504.4 657.2 Cenpw 130.1 1150.0 2103.3 Apitd1 88.3 476.9 807.8 Casc5 44.2 486.3 1202.5 Cenpm 132.4 506.5 871.3 Nup107 420.8 2292.7 3364.4 Nup85 724.2 2335.2 3706.6 Nup133 550.8 1385.4 2578.8 Nup43 144.9 464.1 748.0 Nde1 156.1 376.6 502.7 Smc1a 1656.7 3465.5 4688.5 Cenpc1 603.4 1509.8 2798.2 Nudcd2 464.7 1335.5 2318.4 Cenpt 219.0 828.3 1109.1 Cenpo 65.0 152.0 232.7 Ncapg 20.2 436.1 1052.6 Shcbp1 78.5 1434.5 3205.0 Ccna2 237.9 5467.1 7398.2 Cdk1 188.5 3763.5 4698.6 Aurkb 28.7 630.7 1374.8 CEM 1 + Kif11 49.3 942.5 1459.3 Top 10 Genes Melk 68.0 1734.2 2823.3 Kif20a 75.6 1033.9 2179.2 Pbk 288.6 6546.3 8741.4 Tpx2 87.6 1136.3 2059.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.146105) sh-2LKR13_Wt1 (0.0362302) sh-1LKR13_Control-1 (0.0935101) sh-2LKR13_Control-2 (0.0596926)LKR13_Control-3 (0.0479787)LKR13_Control-4 (0.0750507)LKR13_Kras (0.271059)LKR13_Kras (0.145069) sh-3 (0.0822814) sh-4 (0.0430232) [ min ] [ medium ] [ max ] CEM 1 Bub1 329.4 1319.2 3869.9 P ( S | Z, I ) = 1.00 Birc5 852.4 2733.0 5781.3 Mean Corr = 0.89460 Sgol1 334.2 848.3 1773.1 Nuf2 195.0 477.2 1237.3 Zwilch 452.9 1149.2 2294.7 Bub1b 380.4 1461.8 2868.7 Kntc1 323.5 905.0 1563.0 Ndc80 285.3 540.3 1174.8 Cenpk 304.4 690.1 2038.8 Spc24 268.7 551.9 1367.7 Cenph 231.0 415.0 880.8 Sgol2 428.5 803.2 1998.1 Ercc6l 258.4 750.9 1744.7 Spag5 99.5 419.1 876.5 Incenp 453.1 1349.9 2715.4 Nek2 141.2 477.1 785.5 Cenpn 736.1 1118.9 1830.6 Cenpu 195.7 389.2 872.6 Cenpw 183.8 428.6 1023.6 Apitd1 121.9 336.4 763.6 Casc5 148.4 483.9 1185.5 Cenpm 242.4 560.3 870.0 Nup107 730.6 1081.4 1835.8 Nup85 844.4 1253.8 1989.4 Nup133 827.9 1332.8 1869.9 Nup43 236.4 377.4 915.0 Nde1 492.3 1026.6 1620.6 Smc1a 2509.8 3175.7 4260.7 Cenpc1 423.0 781.4 1397.5 Nudcd2 1246.0 2098.2 3502.3 Cenpt 562.5 980.8 1336.9 Cenpo 79.8 142.3 208.7 Ncapg 169.0 659.8 1759.9 Shcbp1 478.7 998.1 3120.3 Ccna2 635.0 2152.7 4654.8 Cdk1 1940.0 4011.0 7538.6 Aurkb 205.8 1027.7 1908.9 CEM 1 + Kif11 306.5 856.0 2011.1 Top 10 Genes Melk 339.3 1229.4 2194.1 Kif20a 503.4 1571.3 3436.2 Pbk 664.8 2458.7 4855.8 Tpx2 520.5 1977.5 3911.7

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.357964)C2C12-day2 (0.0945971)C2C12-day4 (0.128067)C2C12-control-day0 (0.206311)C2C12-shRp58-day0 (0.103171) (0.10989)[ min ] [ medium ] [ max ] CEM 1 Bub1 111.1 1270.8 1427.8 P ( S | Z, I ) = 1.00 Birc5 404.9 3816.3 5023.7 Mean Corr = 0.89442 Sgol1 261.3 858.4 1263.7 Nuf2 175.5 984.4 1397.5 Zwilch 199.6 763.6 1358.2 Bub1b 325.9 1640.7 2275.7 Kntc1 100.2 557.6 645.2 Ndc80 125.6 460.5 589.4 Cenpk 161.9 698.3 1490.8 Spc24 281.8 1020.1 1985.4 Cenph 39.7 182.4 409.8 Sgol2 189.5 819.8 1146.6 Ercc6l 222.6 601.6 1112.5 Spag5 106.4 510.6 745.2 Incenp 349.7 1512.5 1958.3 Nek2 192.0 387.9 661.4 Cenpn 467.0 1374.8 1700.3 Cenpu 99.2 320.7 559.1 Cenpw 194.8 909.8 1001.9 Apitd1 84.1 303.1 510.1 Casc5 214.9 512.4 947.2 Cenpm 279.4 697.3 900.4 Nup107 1244.7 2102.1 2461.1 Nup85 680.3 1620.5 2272.2 Nup133 471.6 815.2 998.7 Nup43 402.5 761.6 1210.4 Nde1 366.1 766.8 891.4 Smc1a 1786.3 2389.6 2997.3 Cenpc1 498.5 588.1 750.3 Nudcd2 558.4 712.9 1096.1 Cenpt 535.3 1264.4 1345.8 Cenpo 57.8 104.6 201.1 Ncapg 57.8 512.1 653.0 Shcbp1 255.6 1353.6 1997.4 Ccna2 409.6 2279.0 2697.6 Cdk1 814.0 4849.0 6245.7 Aurkb 87.1 401.3 855.2 CEM 1 + Kif11 177.9 794.7 1119.9 Top 10 Genes Melk 82.7 910.6 949.3 Kif20a 187.4 1435.3 1774.5 Pbk 312.4 1708.6 2319.5 Tpx2 185.7 1516.9 1827.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE18135" 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=GSE18135 Status: Public on Jan 15 2010 Title: Gene Expression Profile of Androgen Modulated Genes in the Murine Fetal Developing Lung Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20064212 Summary & Design: Summary: Accumulating evidences suggest that sex affects lung development. During the fetal period, male lung maturation is delayed compared with female and surfactant production appears earlier in female than in male fetal lungs.

We analyzed by microarrays the expression of genes showing a sexual difference and those modulated by endogenous androgens (flutamide).

Overall design: Following flutamide or vehicle administration to pregnant mothers, fetal mouse lungs were studied at gestational day 17 (GD17) and GD18. RNA was extracted and hybridized on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0822, L1-Distance = 0.0567, L2-Distance = 0.0049, Normal std = 0.5081

0.862 Kernel fit Pairwise Correlations Normal fit

Density 0.431

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

FlutamideFlutamide treatedFlutamide treatedmaleVehicule at treatedmaleGD 17,Vehicule at (control) malebiologicalGD 17,Vehicule at (control) biologicalfemaleGD rep1 17,Vehicule (control) at biologicalfemale(0.0345424) GD rep2Vehicule (control)17, at female(0.0547384) biologicalGD rep3Vehicule (control)17, at male(0.0381375) biologicalGDFlutamide rep1 at(control)17, maleGD biological(0.0714177) Flutamide17, rep2at treated malebiologicalGD (0.0576875) Flutamide17, rep3at treated malebiologicalGD (0.0583886)rep1 Vehicule17, at treatedmaleGD biological(0.0786449) rep2 18,Vehicule at (control) malebiologicalGD (0.0519581) rep3 18,Vehicule at (control) biologicalfemaleGD (0.0516896) rep1 18,Vehicule (control) at biologicalfemale(0.0643428) GD rep2Vehicule (control)18, at female(0.0488226) biologicalGD rep3Vehicule (control)18, at male(0.0597029) biologicalGD rep1 at(control)18, maleGD biological(0.0828694) 18, rep2at malebiologicalGD (0.0463167) 18, rep3at biologicalGD (0.0579104)rep1 [18, min biological(0.0243763) rep2 (0.0328656)] rep3 (0.0855887)[ medium ] [ max ] CEM 1 Bub1 589.3 1461.3 1937.4 P ( S | Z, I ) = 1.00 Birc5 1837.6 4164.2 4977.7 Mean Corr = 0.89319 Sgol1 582.2 1285.3 1469.2 Nuf2 857.9 1582.6 1930.5 Zwilch 508.0 1124.9 1391.9 Bub1b 1083.9 2179.3 2389.8 Kntc1 298.1 555.3 683.0 Ndc80 218.3 452.2 582.8 Cenpk 265.4 748.9 1085.4 Spc24 754.7 1404.6 1740.0 Cenph 128.2 308.2 491.0 Sgol2 370.2 797.6 1160.6 Ercc6l 607.2 1349.2 1777.6 Spag5 191.5 398.4 512.8 Incenp 628.9 1093.9 1326.9 Nek2 301.3 363.1 440.0 Cenpn 784.4 1522.0 1740.5 Cenpu 314.2 471.0 530.8 Cenpw 328.9 659.8 853.2 Apitd1 158.2 412.6 555.2 Casc5 164.9 388.6 653.8 Cenpm 463.4 849.0 1016.9 Nup107 922.3 1612.8 1831.6 Nup85 695.0 1147.2 1374.0 Nup133 740.2 1053.1 1224.7 Nup43 154.1 330.5 401.5 Nde1 503.5 851.4 1031.0 Smc1a 1774.5 2133.7 2355.8 Cenpc1 704.2 1069.4 1245.3 Nudcd2 645.4 1142.6 1465.6 Cenpt 572.8 740.0 865.7 Cenpo 155.3 193.6 247.0 Ncapg 288.4 677.5 868.1 Shcbp1 802.9 1829.0 2746.3 Ccna2 1916.0 3420.0 4380.3 Cdk1 2455.1 4678.0 4966.2 Aurkb 385.9 874.9 1040.3 CEM 1 + Kif11 402.3 785.2 1086.6 Top 10 Genes Melk 585.7 1460.6 1638.8 Kif20a 361.6 933.0 1255.8 Pbk 1274.5 2769.4 3140.6 Tpx2 841.2 1678.7 1918.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 Naïve 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 (0.127974)Navie_rep3 (0.112152)Navie_rep4 (0.135203)d14 GC(0.10771) d14B1-8_rep1 GC d14B1-8_rep2 (0.0678338)GC d14B1-8_rep3 (0.0668238)GC d14V23_rep1 (0.0431285)GC d14V23_rep2 (0.0749474) GC V23_rep3 (0.108618) (0.15561) [ min ] [ medium ] [ max ] CEM 1 Bub1 187.9 2176.6 2936.7 P ( S | Z, I ) = 1.00 Birc5 310.1 4721.0 5699.5 Mean Corr = 0.89092 Sgol1 145.5 1437.1 2147.8 Nuf2 219.0 3028.3 3739.3 Zwilch 370.6 1399.2 1751.8 Bub1b 45.0 2429.3 3048.4 Kntc1 176.2 1453.0 1700.7 Ndc80 68.0 412.8 811.3 Cenpk 167.9 1104.3 1335.3 Spc24 239.6 2670.0 3599.3 Cenph 122.0 474.5 663.0 Sgol2 102.4 1349.3 1553.5 Ercc6l 298.1 1243.1 1390.7 Spag5 42.8 581.6 684.7 Incenp 395.1 2516.6 2904.9 Nek2 153.9 1045.4 1952.7 Cenpn 422.5 2429.3 3165.2 Cenpu 232.6 450.1 527.7 Cenpw 332.1 907.7 1583.0 Apitd1 723.8 3736.4 4311.9 Casc5 231.1 1008.5 1193.4 Cenpm 130.1 640.4 1085.8 Nup107 1092.4 2163.7 2695.7 Nup85 1029.8 1951.6 2061.2 Nup133 1205.9 1875.5 2555.4 Nup43 493.4 622.2 756.6 Nde1 348.0 692.3 846.1 Smc1a 3377.0 5830.7 7012.5 Cenpc1 1238.3 1863.5 2766.3 Nudcd2 583.5 1094.0 1681.9 Cenpt 726.8 1004.1 1394.9 Cenpo 212.6 305.7 413.7 Ncapg 165.2 2923.5 3297.5 Shcbp1 303.5 3771.8 5300.2 Ccna2 430.7 4564.9 5583.5 Cdk1 319.5 3890.5 4792.0 Aurkb 205.3 1294.1 1916.4 CEM 1 + Kif11 166.8 1619.1 2254.5 Top 10 Genes Melk 108.7 954.2 1207.2 Kif20a 108.7 1420.7 1826.4 Pbk 219.7 2323.2 2704.4 Tpx2 187.2 2359.0 3519.5

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE6837" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: comparative study

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

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

0.536 Kernel fit Pairwise Correlations Normal fit

Density 0.268

0.000 CEM 1

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

Pre-normalization Quantiles

unstimulatedunstimulated embryonicstimulated embryonicstimulated fibroblasts embryonicstimulated fibroblasts embryonic WT, stimulatedfibroblasts biologicalembryonic KO, stimulatedfibroblasts biologicalembryonicWT, rep1 stimulatedfibroblasts biological embryonicWT,(0.0911133) rep1 fibroblasts biological embryonicrep1WT,(0.0774684) fibroblasts biological(0.0700014) rep2KO, fibroblasts biological (0.0581886) rep3KO,[ biological (0.0665735) min rep1KO, biological(0.286388) rep2] (0.0752322) rep3 (0.275034)[ medium ] [ max ] CEM 1 Bub1 49.1 2906.1 3167.5 P ( S | Z, I ) = 1.00 Birc5 187.3 8632.1 9347.2 Mean Corr = 0.89038 Sgol1 11.9 1208.8 1491.2 Nuf2 18.4 989.4 1153.4 Zwilch 14.8 957.3 1050.3 Bub1b 14.4 2228.1 2777.5 Kntc1 86.6 1090.4 1208.1 Ndc80 40.9 817.8 921.5 Cenpk 95.4 1456.8 2165.3 Spc24 129.1 839.5 1459.6 Cenph 8.4 827.9 1121.6 Sgol2 43.6 856.2 1026.6 Ercc6l 97.3 1669.8 2260.0 Spag5 7.0 735.3 851.5 Incenp 138.2 1733.7 3049.8 Nek2 140.1 518.0 753.9 Cenpn 173.1 907.9 1064.8 Cenpu 120.8 621.8 842.4 Cenpw 101.2 1577.0 2080.9 Apitd1 31.3 361.1 419.9 Casc5 50.1 648.9 856.2 Cenpm 48.7 470.0 570.6 Nup107 299.3 2238.5 2443.4 Nup85 483.8 1857.3 2474.4 Nup133 716.7 2266.4 2636.6 Nup43 100.3 999.4 1064.3 Nde1 570.8 1530.6 1709.8 Smc1a 1909.9 3569.9 3916.1 Cenpc1 339.8 705.2 843.0 Nudcd2 239.4 1843.8 2397.9 Cenpt 214.9 780.9 894.8 Cenpo 20.9 132.8 170.9 Ncapg 78.0 1734.2 2132.1 Shcbp1 46.1 2698.8 2850.5 Ccna2 171.9 3633.6 4723.9 Cdk1 218.2 9389.5 13256.5 Aurkb 10.6 1079.3 1160.0 CEM 1 + Kif11 3.8 1272.5 1581.1 Top 10 Genes Melk 14.3 1316.4 2029.7 Kif20a 11.7 2677.0 4504.1 Pbk 176.2 3428.0 4249.7 Tpx2 128.1 3040.1 3673.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE6689" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keyword(s): timecourse

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

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

0.726 Kernel fit Pairwise Correlations Normal fit

Density 0.363

0.000 CEM 1

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

Pre-normalization Quantiles

Control_ES-LIF(+)_rep1Timepoint1_ES-LIF(-)_rep1Timepoint2_CM_rep1Control_ES-LIF(+)_rep2 (0.0656265)Timepoint1_ES-LIF(-)_rep2 (0.0505049) (0.134681)Timepoint2_CM_rep2Timepoint1b_CP_rep1 (0.0822762)Control_ES-LIF(+)_rep3 (0.0697029) (0.130397)Timepoint1_ES-LIF(-)_rep3 Timepoint2_CM_rep3(0.0487861)Timepoint1b_CP_rep2 (0.111529)Timepoint1b_CP_rep3 (0.0964067) (0.115264) (0.0554668) (0.0393593)[ min ] [ medium ] [ max ] CEM 1 Bub1 1000.7 3449.7 3933.1 P ( S | Z, I ) = 1.00 Birc5 3015.5 6742.0 7689.9 Mean Corr = 0.88601 Sgol1 640.7 1572.3 2058.8 Nuf2 568.4 846.8 1207.1 Zwilch 594.4 1632.1 2148.4 Bub1b 1213.1 3231.1 3673.9 Kntc1 464.3 1164.7 1637.0 Ndc80 403.7 1114.1 1558.7 Cenpk 296.9 1112.0 1254.7 Spc24 667.2 1910.3 3136.3 Cenph 290.2 842.3 1215.2 Sgol2 452.6 1283.6 1606.9 Ercc6l 602.9 1260.7 1505.9 Spag5 300.4 755.8 985.6 Incenp 738.9 1621.4 1803.9 Nek2 248.4 919.4 991.9 Cenpn 1101.7 2151.5 2751.3 Cenpu 450.0 1106.6 1569.9 Cenpw 543.7 1537.1 1887.0 Apitd1 273.1 1195.3 1430.9 Casc5 353.7 463.3 571.8 Cenpm 387.8 787.5 1216.2 Nup107 1198.6 3585.9 4409.1 Nup85 2095.0 5476.0 5951.8 Nup133 1877.0 5350.0 6359.9 Nup43 795.2 2574.8 2835.0 Nde1 953.8 1183.6 1313.5 Smc1a 1444.3 2503.6 3170.4 Cenpc1 496.3 929.3 1445.2 Nudcd2 1671.3 3093.6 4129.1 Cenpt 1248.7 1954.1 2864.9 Cenpo 94.8 221.3 297.2 Ncapg 349.9 1159.3 1565.9 Shcbp1 997.8 2960.2 3496.1 Ccna2 1566.5 3030.7 3487.0 Cdk1 2883.8 6280.4 6973.3 Aurkb 285.5 826.3 1158.9 CEM 1 + Kif11 458.0 1378.7 1563.2 Top 10 Genes Melk 506.1 2245.8 2608.6 Kif20a 843.4 1792.7 1969.3 Pbk 789.5 1303.4 1519.1 Tpx2 749.2 1832.6 2298.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.173202) 1 (0.123285)IFNGIMPGE 2 (0.137903)IFNGstomach 3 (0.105075)stomach uninfectedstomach uninfected 1 (0.0247518)stomach infected 2 (0.0287956)stomach infected gastritisstomach infected gastritis 1 (0.0150771)stomach infected gastritis 2 (0.0184649)stomach infected gastritis 3 (0.0325006)stomach infected metaplasia 4 (0.0114536)stomach infected hyperplasia 1stomach (0.0170137)infected hyperplasia stomach1 infected(0.0122028) hyperplasia stomach2 infected(0.0171998) hyperplasia stomach3 infected(0.0163405) hyperplasia stomach4 infected(0.00981814) metaplasia stomach5 infected(0.00965779) metaplasia 2stomach (0.0231176)infected metaplasia 3stomach (0.0287902)uninfected metaplasia 4stomach (0.018334)uninfected Rg 5stomach (0.0299042) infected1 (0.0179832) Rgstomach infected2 Rg (0.0154617) 1stomach (0.0154024)infected Rg 2stomach (0.0324836)infected Rg 3 (0.0213231)infected Rg 4 (0.017258) Rg 5 (0.0272014)[ min ] [ medium ] [ max ] CEM 1 Bub1 103.7 335.4 3844.4 P ( S | Z, I ) = 1.00 Birc5 590.2 1700.6 4509.6 Mean Corr = 0.88537 Sgol1 285.5 404.7 1678.4 Nuf2 161.1 280.9 1822.9 Zwilch 105.8 242.1 1435.3 Bub1b 274.5 447.2 1814.3 Kntc1 120.0 184.8 908.4 Ndc80 75.0 139.2 655.1 Cenpk 142.7 324.9 1927.8 Spc24 276.6 511.2 1292.6 Cenph 68.3 105.6 1031.1 Sgol2 113.3 227.0 1290.9 Ercc6l 208.2 365.9 2060.5 Spag5 89.1 127.1 893.0 Incenp 385.2 635.1 1394.7 Nek2 102.5 166.4 578.1 Cenpn 207.7 315.0 586.1 Cenpu 190.6 297.3 1242.2 Cenpw 85.0 221.2 1625.6 Apitd1 57.4 126.1 342.5 Casc5 114.7 154.5 798.8 Cenpm 240.5 364.8 519.1 Nup107 424.3 608.8 2032.1 Nup85 355.0 800.1 2349.8 Nup133 245.3 448.0 1840.3 Nup43 129.2 168.7 995.9 Nde1 195.0 275.2 1047.9 Smc1a 1566.7 1956.7 2645.4 Cenpc1 282.4 405.3 1197.9 Nudcd2 197.5 454.6 1714.5 Cenpt 228.6 367.2 791.4 Cenpo 61.1 76.4 184.6 Ncapg 52.7 138.5 785.1 Shcbp1 328.2 661.1 2998.7 Ccna2 801.1 1897.1 5027.2 Cdk1 642.4 1471.8 8807.3 Aurkb 65.0 131.3 990.4 CEM 1 + Kif11 163.8 284.5 965.0 Top 10 Genes Melk 242.5 578.4 2088.5 Kif20a 149.1 313.2 3726.0 Pbk 736.0 1228.0 3580.1 Tpx2 179.8 390.0 4564.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.0360542)C10 formC/EBPa,line an cell with2inducibleof (0.0635756)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(0.035861)an estradiol withinducibleof beta form2C/EBPa, treatedwith(0.0446032)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 (0.184407)hours for beta treatedwith12 2 sampleestradiol (0.155045)hours for beta with24[ sampleestradiol1 hoursmedium for(0.0573936) beta 24 sampleestradiol2 hours for(0.0606553) 48 sample1 hours for(0.0677676) ] 48 sample2 hours (0.079065) sample1 (0.112869)[ max 2 (0.102703) ] CEM 1 Bub1 27.1 1647.8 4482.9 P ( S | Z, I ) = 1.00 Birc5 51.2 2596.6 6815.6 Mean Corr = 0.88191 Sgol1 3.2 754.6 1606.8 Nuf2 2.3 375.9 1157.8 Zwilch 42.0 863.3 2292.4 Bub1b 18.7 1881.5 4510.1 Kntc1 36.5 729.5 1291.0 Ndc80 21.7 862.8 1605.0 Cenpk 71.6 784.3 2459.9 Spc24 12.5 360.8 1197.2 Cenph 19.8 468.6 1696.4 Sgol2 11.1 556.5 2465.5 Ercc6l 46.6 397.0 1872.8 Spag5 1.3 373.5 869.2 Incenp 337.4 1321.6 5922.8 Nek2 62.5 245.7 734.6 Cenpn 82.3 579.6 1420.0 Cenpu 70.5 267.5 722.0 Cenpw 69.8 600.9 2660.2 Apitd1 110.9 761.4 1135.9 Casc5 62.1 197.8 556.2 Cenpm 9.5 301.4 668.1 Nup107 257.2 1074.2 2526.2 Nup85 251.5 827.2 2636.7 Nup133 473.7 1029.0 2057.4 Nup43 80.6 426.4 745.3 Nde1 602.5 1143.4 1699.8 Smc1a 1291.0 3161.7 5794.1 Cenpc1 896.2 1147.4 2554.1 Nudcd2 776.1 2190.1 3749.9 Cenpt 474.9 595.5 831.0 Cenpo 60.6 221.1 386.0 Ncapg 30.4 806.2 2185.9 Shcbp1 5.7 1017.8 4113.0 Ccna2 59.4 2370.2 8322.5 Cdk1 120.1 2010.1 10509.1 Aurkb 80.3 895.9 2111.9 CEM 1 + Kif11 2.1 460.3 2035.6 Top 10 Genes Melk 1.5 317.5 1803.4 Kif20a 14.2 514.4 1454.9 Pbk 50.1 1890.8 6913.9 Tpx2 141.9 1184.9 3696.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE51628" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.843 Kernel fit Pairwise Correlations Normal fit

Density 0.422

0.000 CEM 1

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

Pre-normalization Quantiles

TICNX_48h_rep1TICNX_48h_rep2TICNX_48h_rep3 (0.0737021)TICNX_48h_rep4 (0.0495008)TICNX_96h_rep1 (0.0544367)TICNX_96h_rep2 (0.04924)TICNX_96h_rep3 (0.066551)MTB/TICNX_48h_rep1 (0.034251)MTB/TICNX_48h_rep2 (0.0303357)MTB/TICNX_48h_rep3 MTB/TICNX_48h_rep4(0.0161261) MTB/TICNX_96h_rep1(0.0335334) MTB/TICNX_96h_rep2(0.0337434) MTB/TICNX_96h_rep3(0.0492822) MTB/TICNX_96h_rep4(0.0361177) (0.171826) (0.141696) (0.159659)[ min ] [ medium ] [ max ] CEM 1 Bub1 54.9 435.2 1285.3 P ( S | Z, I ) = 1.00 Birc5 97.0 683.3 1848.7 Mean Corr = 0.87922 Sgol1 107.3 368.0 935.4 Nuf2 71.7 149.0 390.7 Zwilch 52.5 244.0 639.0 Bub1b 82.3 226.0 665.0 Kntc1 90.8 327.7 1218.7 Ndc80 66.6 219.5 662.7 Cenpk 76.2 347.8 1071.5 Spc24 75.2 436.7 1028.9 Cenph 36.2 110.3 499.0 Sgol2 119.2 393.6 1293.8 Ercc6l 139.2 335.2 838.3 Spag5 56.5 106.4 454.9 Incenp 119.2 269.2 664.3 Nek2 47.7 126.1 249.1 Cenpn 233.0 353.1 630.2 Cenpu 70.6 133.2 306.8 Cenpw 112.6 235.5 599.0 Apitd1 77.1 185.8 402.7 Casc5 123.2 207.5 599.9 Cenpm 141.4 222.5 474.1 Nup107 491.5 696.9 1081.3 Nup85 519.3 682.7 1067.4 Nup133 551.8 702.3 1098.3 Nup43 146.5 233.1 468.0 Nde1 265.3 341.9 889.2 Smc1a 1725.4 2042.3 3127.2 Cenpc1 518.5 659.0 945.1 Nudcd2 600.6 826.3 1125.6 Cenpt 171.8 253.3 416.2 Cenpo 59.0 71.7 110.2 Ncapg 23.4 137.7 375.1 Shcbp1 70.4 385.8 955.1 Ccna2 219.6 1448.5 3964.6 Cdk1 184.8 891.9 2444.0 Aurkb 35.1 127.6 415.0 CEM 1 + Kif11 42.9 184.1 521.7 Top 10 Genes Melk 49.7 379.1 1204.4 Kif20a 52.9 238.1 639.4 Pbk 139.2 1422.6 3824.2 Tpx2 76.3 303.0 871.3

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.278866)d17 KGF of mESCsat (Control)differentiation d17treatment of mESCsat withdifferentiation d24 (0.0288522) (0.255202) KGFof mESCsat withdifferentiation d24 treatment DCIof mESCsat withdifferentiation d24 treatment KGF(0.0342048)of at (Control)differentiation d24 and (0.0308748) of DCI withdifferentiation (0.0765023) treatment KGF with treatment DCI[ (0.0321439) withmin treatment KGF(0.0777443) and] (0.0869109) DCI treatment[ medium (0.0986986) ] [ max ] CEM 1 Bub1 400.5 1626.6 4064.9 P ( S | Z, I ) = 1.00 Birc5 456.6 1683.7 4107.4 Mean Corr = 0.87679 Sgol1 199.1 572.5 1312.9 Nuf2 137.2 418.8 926.1 Zwilch 245.7 808.1 1976.4 Bub1b 165.2 591.6 1267.9 Kntc1 147.7 498.2 1507.5 Ndc80 94.1 303.3 820.7 Cenpk 201.4 696.6 1562.7 Spc24 186.1 603.3 1219.9 Cenph 137.0 415.5 993.5 Sgol2 258.7 842.5 1872.2 Ercc6l 134.9 558.0 981.8 Spag5 76.9 232.4 630.9 Incenp 279.3 577.0 1234.0 Nek2 79.6 188.8 345.6 Cenpn 342.1 757.4 1861.9 Cenpu 115.1 258.5 618.7 Cenpw 490.5 880.7 2146.3 Apitd1 80.7 194.3 488.7 Casc5 92.6 257.5 414.0 Cenpm 177.5 376.5 561.2 Nup107 776.1 1274.4 2546.1 Nup85 570.6 1121.0 2016.3 Nup133 548.4 899.0 1755.8 Nup43 207.9 339.5 617.2 Nde1 327.2 447.8 773.1 Smc1a 1333.7 1862.5 3000.5 Cenpc1 605.8 892.1 1351.5 Nudcd2 2127.5 2276.5 2563.7 Cenpt 256.7 601.3 1379.8 Cenpo 75.5 119.8 176.4 Ncapg 102.3 378.8 876.6 Shcbp1 239.1 968.3 2126.3 Ccna2 491.9 1601.8 3245.9 Cdk1 1144.7 3137.0 5440.3 Aurkb 169.1 395.3 1029.2 CEM 1 + Kif11 101.4 412.6 713.8 Top 10 Genes Melk 283.7 745.5 1814.3 Kif20a 245.1 789.3 2017.5 Pbk 673.7 2035.9 2877.1 Tpx2 339.6 892.8 2309.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 (0.079507)C2C12-pMirn0_day (0.0875912)C2C12-pMirn0_day (0.0807288) 3_untreated_rep1C2C12-pMirn0_day 3_untreated_rep2C2C12-pMirn0_day 3_untreated_rep3 C2C12-pMirn0_day(0.0316252) 6_untreated_rep1 C2C12-pMirn0_day(0.0226489) 6_untreated_rep2 C2C12-pMirn0_day(0.0269762) 6_untreated_rep3 C2C12-pMirn0_day(0.0244571) 3_BMP2 C2C12-pMirn0_day(0.0217937) 3_BMP2 treated_rep1 C2C12-pMirn0_day(0.0220796) 3_BMP2 treated_rep2C2C12-pMirn0_day (0.0154821)6_BMP2 treated_rep3C2C12-pMirn378_d0_rep1 (0.022439)6_BMP2 treated_rep1C2C12-pMirn378_d0_rep2 (0.0167761)6_BMP2 treated_rep2C2C12-pMirn378_d0_rep3 (0.0240728) treated_rep3C2C12-pMirn378_day (0.0778128)(0.0242682)C2C12-pMirn378_day (0.0813873)(0.0232737)C2C12-pMirn378_day (0.0809089) 3_untreated_rep1C2C12-pMirn378_day 3_untreated_rep2C2C12-pMirn378_day 3_untreated_rep3C2C12-pMirn378_day (0.0227506) 6_untreated_rep1C2C12-pMirn378_day (0.0175169) 6_untreated_rep2C2C12-pMirn378_day (0.0212361) 6_untreated_rep3C2C12-pMirn378_day (0.0163025) 3_BMP2C2C12-pMirn378_day (0.0160188) 3_BMP2C2C12-pMirn378_day treated_rep1 (0.0155832) 3_BMP2C2C12-pMirn378_day treated_rep2 (0.0240693)6_BMP2 treated_rep3 (0.0238598)6_BMP2 treated_rep1 (0.020331)6_BMP2 treated_rep2 (0.0164241)[ treated_rep3 min (0.0171101) ] (0.0249687)[ medium ] [ max ] CEM 1 Bub1 95.3 345.6 3643.2 P ( S | Z, I ) = 1.00 Birc5 195.0 482.4 6672.6 Mean Corr = 0.87632 Sgol1 51.7 162.4 1427.0 Nuf2 93.1 249.3 1630.7 Zwilch 160.2 288.5 2264.3 Bub1b 41.8 150.3 1526.6 Kntc1 62.3 177.9 1163.8 Ndc80 9.2 96.3 777.3 Cenpk 99.2 250.0 1326.4 Spc24 45.0 207.1 1653.1 Cenph 50.7 102.7 725.7 Sgol2 90.8 165.6 1340.9 Ercc6l 104.6 174.9 1203.8 Spag5 28.1 101.4 628.5 Incenp 151.4 260.7 1639.5 Nek2 62.5 172.2 735.0 Cenpn 169.9 290.6 1321.3 Cenpu 91.1 141.5 683.5 Cenpw 227.1 412.1 1728.8 Apitd1 67.1 144.1 667.5 Casc5 73.1 157.6 921.7 Cenpm 34.6 116.2 492.3 Nup107 604.9 935.2 2134.4 Nup85 567.1 788.3 2262.6 Nup133 560.7 732.1 1446.2 Nup43 250.9 402.8 964.8 Nde1 329.5 503.6 1361.7 Smc1a 1916.0 2506.5 3571.7 Cenpc1 561.6 857.0 1134.4 Nudcd2 1928.5 2575.6 3741.6 Cenpt 193.3 358.8 985.2 Cenpo 51.7 88.5 223.9 Ncapg 51.2 131.6 1339.5 Shcbp1 93.4 290.9 2985.9 Ccna2 239.5 556.8 5259.4 Cdk1 632.3 1170.1 8837.8 Aurkb 49.0 133.6 1229.1 CEM 1 + Kif11 66.9 203.1 1070.4 Top 10 Genes Melk 39.9 174.9 1668.3 Kif20a 104.7 324.9 3579.2 Pbk 295.3 705.2 3864.2 Tpx2 192.9 388.0 2316.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE13693" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13693 Status: Public on Feb 06 2009 Title: Gene expression profiling of normal mouse myeloid cell populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7Rα), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.

Overall design: See summary.

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

0.500 Kernel fit Pairwise Correlations Normal fit

Density 0.250

0.000 CEM 1

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

Pre-normalization Quantiles

NORMALNORMAL BM NEUTROPHILS_2NORMAL BM NEUTROPHILS_1NORMAL BM NEUTROPHILS_3NORMAL (0.176954)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.222968)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.16739)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.0745663) (0.0522509)[ min(0.0431142) (0.0799899)] (0.0749796)[ (0.107787) medium ] [ max ] CEM 1 Bub1 42.5 2427.6 3780.5 P ( S | Z, I ) = 1.00 Birc5 320.0 4381.2 5627.4 Mean Corr = 0.87616 Sgol1 136.1 1741.7 2585.8 Nuf2 73.9 2352.0 4652.5 Zwilch 24.1 1865.6 2347.1 Bub1b 51.4 2540.9 4512.1 Kntc1 26.1 1646.8 2509.9 Ndc80 27.2 574.7 1362.5 Cenpk 34.5 1418.4 1972.5 Spc24 57.3 1422.9 2474.1 Cenph 6.2 601.3 737.3 Sgol2 69.3 2101.4 3578.1 Ercc6l 74.9 1980.3 2539.9 Spag5 8.2 429.4 1334.5 Incenp 180.9 1773.4 3513.4 Nek2 36.4 530.6 722.0 Cenpn 182.1 1899.2 2298.8 Cenpu 160.4 1233.9 1670.6 Cenpw 12.2 915.8 1277.4 Apitd1 35.2 612.2 852.7 Casc5 70.0 360.6 532.1 Cenpm 40.4 530.6 665.6 Nup107 468.7 4154.3 4691.8 Nup85 172.6 2638.3 3593.5 Nup133 59.5 1745.1 2116.8 Nup43 78.4 470.0 775.8 Nde1 136.9 667.8 843.4 Smc1a 1757.1 4665.5 6124.3 Cenpc1 45.1 1148.7 2176.0 Nudcd2 20.5 848.4 1401.0 Cenpt 243.1 1107.6 2465.2 Cenpo 465.6 693.6 1306.0 Ncapg 13.2 1813.6 2913.8 Shcbp1 49.9 3085.0 4736.2 Ccna2 487.4 4284.2 6720.4 Cdk1 467.4 5858.2 9393.7 Aurkb 157.5 3321.3 4394.6 CEM 1 + Kif11 111.0 1149.1 2458.2 Top 10 Genes Melk 191.1 1686.1 2609.5 Kif20a 21.1 884.5 1758.4 Pbk 301.2 4081.5 5837.6 Tpx2 130.7 1702.7 4339.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE38538" 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=GSE38538 Status: Public on Jun 07 2012 Title: Expression data from E12.5 NSP cells, CTL v REST shRNA Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22791895 Summary & Design: Summary: REST is a master regulator of genes that are involved in the acqusition of neuronal fate. The role of REST is not well understood so we attempted to investigate the role of REST in the development of neural cells by analysing the genes that are upregulated when REST is knocked down via shRNA

We used microarrays to assess the genes which were up and down regulated after REST is knocked down

Overall design: E12.5 NSP cells were infected with either control or REST shRNA expressing lentiviruses and collected after 6 days for RNA extraction

Background corr dist: KL-Divergence = 0.0362, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6399

0.634 Kernel fit Pairwise Correlations Normal fit

Density 0.317

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

NSP cellsNSP 6 dayscellsNSP after6 dayscells NSPlentivirus after6 dayscells NSPlentivirus afterinfection6 dayscells NSPlentivirus afterinfection6 daysCTL1cells lentivirus afterinfection6(0.0663413) daysREST lentivirus afterinfection shRNA CTL2 lentivirus infection (0.0612578)1 REST (0.0896696)[ infection minshRNA CTL3 (0.183434) 2 REST] (0.428051) shRNA [3 (0.171246)medium ] [ max ] CEM 1 Bub1 25.8 171.4 426.3 P ( S | Z, I ) = 1.00 Birc5 228.2 1801.4 3601.6 Mean Corr = 0.87525 Sgol1 42.4 174.4 348.9 Nuf2 57.3 344.3 738.6 Zwilch 51.7 434.6 1015.8 Bub1b 50.9 595.5 1427.3 Kntc1 35.5 134.4 312.9 Ndc80 77.9 514.9 1474.2 Cenpk 56.1 344.0 855.2 Spc24 93.9 1052.5 1855.1 Cenph 102.1 375.4 984.3 Sgol2 55.8 261.7 481.9 Ercc6l 66.8 154.5 772.2 Spag5 83.1 302.8 425.2 Incenp 129.2 810.9 1549.0 Nek2 79.4 252.3 442.3 Cenpn 44.4 173.0 422.9 Cenpu 113.7 182.6 375.9 Cenpw 69.0 173.4 486.3 Apitd1 180.8 425.6 1229.9 Casc5 25.0 206.3 437.8 Cenpm 80.0 222.6 412.7 Nup107 1050.2 1327.7 3040.0 Nup85 934.2 1437.7 2880.2 Nup133 803.0 1191.4 1941.1 Nup43 54.1 74.6 109.8 Nde1 421.6 771.4 909.3 Smc1a 556.6 634.9 949.7 Cenpc1 169.8 191.8 210.2 Nudcd2 751.3 906.1 1741.2 Cenpt 420.0 601.6 746.0 Cenpo 155.8 225.6 310.6 Ncapg 154.8 909.0 1711.7 Shcbp1 36.1 141.5 523.2 Ccna2 90.8 1141.3 2360.9 Cdk1 201.1 1506.9 3164.1 Aurkb 73.9 714.1 1551.6 CEM 1 + Kif11 24.4 252.3 492.8 Top 10 Genes Melk 40.4 525.5 1702.2 Kif20a 246.7 1765.8 3419.4 Pbk 163.1 1383.6 3497.5 Tpx2 164.4 1056.5 2260.7

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE9247" 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=GSE9247 Status: Public on Oct 06 2007 Title: Effect of histone deacetylase inhibitors on osteoblast gene expression Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17925016 Summary & Design: Summary: Background:

Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs) accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs), which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin). Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation.

Results:

To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1), sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4) were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1) were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway.

Conclusions: This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that might promote osteoblast maturation following HDI exposure. One gene whose upregulation following HDI treatment is consistent with this notion is Slc9a3r1. Also known as NHERF1, Slc9a3r1 is required for optimal bone density. Similarly, the regulation of Wnt receptor genes indicates that this crucial pathway in osteoblast development is also affected by HDIs. These data support the hypothesis that HDIs regulate the expression of genes that promote osteoblast differentiation and maturation.

Keywords: gene expression

Overall design: To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) or the vehicle control (DMSO) for 18 hours in osteogenic conditions. Gene expression profiles relative to vehicle-treated cells were assessed in triplicate (in some cases quadruplicate) samples by microarray analysis with Affymetrix GeneChip 430 2.0 arrays.

Background corr dist: KL-Divergence = 0.1049, L1-Distance = 0.0636, L2-Distance = 0.0067, Normal std = 0.4730

0.936 Kernel fit Pairwise Correlations Normal fit

Density 0.468

0.000 CEM 1

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

Pre-normalization Quantiles

DMSO TreatedDMSO Treated DMSOControl Treated DMSOControl 1 (0.0439587) Treated MS-275Control 2 (0.0415672) MS-275Control Treated3 (0.0506783) MS-275 Treated 4Rep1 (0.0426401) (0.047395) MS-275Treated Rep2 (0.0333441) TSATreated Rep3 Treated (0.0354811)TSA Rep4 Treated Rep (0.0256972)TSA 1 (0.1718)Treated RepVPA 2 (0.172342)Treated RepVPA 3 (0.163902)Treated RepVPA 1 (0.04241)Treated RepVPA 2 (0.0486014)Treated Rep 3 (0.0460248) Rep 4 (0.0341586)[ min ] [ medium ] [ max ] CEM 1 Bub1 853.1 2576.9 3241.4 P ( S | Z, I ) = 1.00 Birc5 1579.6 7770.2 8691.7 Mean Corr = 0.87488 Sgol1 510.8 2206.2 2528.6 Nuf2 605.7 2749.5 3142.8 Zwilch 291.8 1004.3 1325.2 Bub1b 577.1 2508.7 2795.6 Kntc1 394.5 1896.7 2293.5 Ndc80 367.8 1609.7 1831.4 Cenpk 436.7 2072.4 2194.2 Spc24 436.4 1662.9 1969.0 Cenph 194.6 631.9 743.3 Sgol2 701.7 2558.2 2951.5 Ercc6l 456.5 1466.2 1737.8 Spag5 155.6 870.2 1037.3 Incenp 670.6 3099.1 3411.0 Nek2 156.7 603.8 705.8 Cenpn 691.9 1851.1 2234.6 Cenpu 244.8 578.7 655.8 Cenpw 511.4 1064.6 1266.7 Apitd1 75.8 223.6 283.8 Casc5 174.8 541.1 815.6 Cenpm 473.6 1205.1 1414.1 Nup107 786.2 1885.8 2173.3 Nup85 801.1 2064.7 2342.3 Nup133 705.1 1311.9 1499.8 Nup43 396.0 474.8 502.7 Nde1 654.1 1585.3 1878.8 Smc1a 2179.4 4065.7 4645.2 Cenpc1 833.9 1329.5 1523.2 Nudcd2 613.9 993.8 1232.0 Cenpt 553.7 1008.3 1153.2 Cenpo 50.2 124.6 153.1 Ncapg 343.7 1467.2 1632.2 Shcbp1 725.4 3118.4 3643.9 Ccna2 1395.1 8638.8 9655.0 Cdk1 1283.7 7654.5 8451.6 Aurkb 271.9 1818.8 2152.7 CEM 1 + Kif11 316.7 1256.1 1428.6 Top 10 Genes Melk 843.1 3579.9 4075.8 Kif20a 520.1 2571.3 2900.2 Pbk 857.0 5581.5 6412.4 Tpx2 978.1 3721.1 3918.6

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE46797" 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=GSE46797 Status: Public on May 10 2013 Title: Expression data from c-Myc+ Notch1 T-ALL initiating cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23791182 Summary & Design: Summary: Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity.

Overall design: Three independent Notch1 T-ALL were derived on c-Myc-GFP background and sorted from the spleen of leukemic mice on the basis of GFP expression for RNA extraction and hybridization on Affymetrix microarrays

Background corr dist: KL-Divergence = 0.0376, L1-Distance = 0.0289, L2-Distance = 0.0011, Normal std = 0.6371

0.637 Kernel fit Pairwise Correlations Normal fit

Density 0.318

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

Notch1 Notch1T-ALL MycGFP Notch1T-ALL MycGFP Notch1T-ALL negative MycGFP Notch1T-ALL negative replicate MycGFP Notch1T-ALL negative replicate 1 (0.0956329) MycGFP T-ALL positive replicate 2 (0.193694) MycGFP positive replicate 3 (0.203178) positive replicate 1 (0.305677)[ replicatemin 2 (0.12656) 3] (0.0752574) [ medium ] [ max ] CEM 1 Bub1 191.1 1610.6 3232.7 P ( S | Z, I ) = 1.00 Birc5 2431.9 11433.4 13218.6 Mean Corr = 0.87474 Sgol1 135.4 969.1 1505.8 Nuf2 271.8 1687.7 2622.3 Zwilch 91.5 1023.0 4149.3 Bub1b 133.2 1302.5 1600.9 Kntc1 115.3 670.1 839.2 Ndc80 160.4 587.9 918.4 Cenpk 27.6 736.4 1236.2 Spc24 192.1 2236.8 3824.4 Cenph 86.5 1002.3 1772.5 Sgol2 210.7 2352.1 3963.5 Ercc6l 72.9 501.9 1003.3 Spag5 35.6 149.8 266.1 Incenp 93.0 581.2 859.0 Nek2 70.1 332.0 833.9 Cenpn 47.5 230.9 515.1 Cenpu 80.6 334.8 437.5 Cenpw 238.3 1104.4 1979.5 Apitd1 91.2 649.8 1219.4 Casc5 86.9 651.1 1234.2 Cenpm 125.1 629.6 1102.4 Nup107 877.1 1864.6 2829.2 Nup85 613.6 1711.7 2627.9 Nup133 380.0 1171.4 1705.5 Nup43 81.4 245.8 325.4 Nde1 710.2 1224.8 1679.6 Smc1a 840.9 2051.0 2440.1 Cenpc1 255.1 511.6 723.8 Nudcd2 732.2 2160.3 2970.9 Cenpt 118.4 151.6 334.3 Cenpo 180.2 567.7 829.8 Ncapg 456.4 4796.1 6364.7 Shcbp1 163.3 1748.4 3877.4 Ccna2 482.3 3997.8 5699.1 Cdk1 698.1 5664.8 9993.5 Aurkb 81.8 1520.7 2621.4 CEM 1 + Kif11 59.9 926.5 1219.0 Top 10 Genes Melk 88.7 501.6 980.1 Kif20a 116.6 649.0 1353.2 Pbk 252.3 2728.7 3488.5 Tpx2 198.0 966.6 1282.9

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE48382" 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=GSE48382 Status: Public on Jul 01 2013 Title: ChIp-Chip using RNAP II, CREB C/EBPb and cJun antibody in undifferentiated or differentiated keratinocytes (expression) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24244291 Summary & Design: Summary: Combinatorial recruitment of CREB, C/EBPb and Jun determines activation of promoters upon keratinocyte differentiation

Chromatin immunoprecipitation (ChIP) of RNAP II, CREB C/EBPb and cJun in undifferentiated or differentiated keratinocytes demonstrate recruitment of RNAP II to promoters bound by combination of specific transcription factors. Analysis of mRNA expression data from contrl keratinocytes or keratinovtyes where binding of transcription factors is disrupted demonstrate functional requirements for ceratin class of promoters

Overall design: comparison of undifferentiated and differentated keratinocytes using mRNA expression data

Background corr dist: KL-Divergence = 0.0766, L1-Distance = 0.0223, L2-Distance = 0.0008, Normal std = 0.4867

0.820 Kernel fit Pairwise Correlations Normal fit

Density 0.410

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

DifferentiatedDifferentiated keratinocytesA-C/EBP keratinocytesA-C/EBP expressing treatedDifferentiated expressing treateddifferentiatedwithDifferentiated 5-AZA differentiated withkeratinocytesDifferentiated #1 5-AZA keratinocytes (0.0342995) keratinocytesDifferentiated #2 keratinocytes (0.0823807)#1 keratinocytesUndifferentiated (0.0421247) #1 #2 keratinocytes(0.0576297)Undifferentiated (0.0569217) #2 #3 (0.0970631) (0.0847686)keratinocytes#1 #4 (0.0366603)keratinocytes#2 (0.333072)[ min(0.17508) ] [ medium ] [ max ] CEM 1 Bub1 66.1 280.2 1886.2 P ( S | Z, I ) = 1.00 Birc5 129.9 403.0 2555.5 Mean Corr = 0.87469 Sgol1 118.0 176.9 1073.2 Nuf2 41.6 65.3 198.8 Zwilch 86.0 153.0 924.2 Bub1b 85.6 149.8 920.2 Kntc1 76.6 119.4 408.2 Ndc80 65.1 90.9 460.1 Cenpk 90.2 141.8 607.4 Spc24 85.5 154.0 822.0 Cenph 50.8 82.9 311.0 Sgol2 77.6 154.8 972.2 Ercc6l 118.1 207.1 1020.0 Spag5 35.1 48.6 196.8 Incenp 132.0 230.0 1326.2 Nek2 28.8 43.9 192.8 Cenpn 174.8 260.9 548.5 Cenpu 89.6 128.7 300.9 Cenpw 72.7 127.4 603.3 Apitd1 84.6 116.6 224.5 Casc5 56.0 75.3 210.9 Cenpm 110.3 156.4 238.7 Nup107 448.1 717.7 1814.3 Nup85 555.6 742.0 1934.4 Nup133 357.0 537.1 1511.9 Nup43 305.6 522.9 767.0 Nde1 302.8 564.3 699.3 Smc1a 978.8 1478.4 1868.9 Cenpc1 204.5 270.3 565.9 Nudcd2 969.5 1273.6 1812.5 Cenpt 407.4 549.2 935.8 Cenpo 48.3 63.3 87.0 Ncapg 29.3 72.3 674.2 Shcbp1 159.5 298.0 2138.5 Ccna2 155.8 430.5 3145.4 Cdk1 272.6 873.1 4254.3 Aurkb 50.5 87.3 694.1 CEM 1 + Kif11 44.8 72.4 358.4 Top 10 Genes Melk 96.5 287.0 1493.1 Kif20a 79.6 215.8 1178.1 Pbk 150.9 360.1 2276.2 Tpx2 699.9 1146.7 2946.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE44175" 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=GSE44175 Status: Public on Feb 09 2013 Title: Expression data from mouse embyonic stem cell, neural progenitor and neuron Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23775126 Summary & Design: Summary: The effect of HMGN1 protein on gene expression of mouse ESC, NP and Neurons were investigated by comparing the transcriptome between Hmgn1+/+ and Hmgn1 -/- cells.

Overall design: three cell types, two genotypes, three reps per sample type

Background corr dist: KL-Divergence = 0.0123, L1-Distance = 0.0320, L2-Distance = 0.0019, Normal std = 0.8462

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

EmbyonicEmbyonic stemEmbyonic cell, stem Hmgn1+/+,Neural cell, stem Hmgn1+/+, progenitor,Neural cell, biological Hmgn1+/+, progenitor,Neural biological Hmgn1+/+, rep1 progenitor,Neuron, biological (0.0709264) Hmgn1+/+, rep2Neuron, biological Hmgn1+/+, (0.0640672) Hmgn1+/+, rep3Neuron, biological Hmgn1+/+, (0.0813332)rep1 biologicalEmbyonic biological(0.0202124)Hmgn1+/+, rep2 biologicalEmbyonic rep1(0.0228651) stem rep3 biological(0.071547)Embyonic rep2cell,(0.0211224) stem (0.0735115)Hmgn1-/-,Neural rep3cell, stem (0.0682146)Hmgn1-/-, progenitor,Neural cell, biological Hmgn1-/-, progenitor,Neural biological Hmgn1-/-,rep1 progenitor,Neuron, biological(0.0715404) Hmgn1-/-,rep2 biologicalNeuron, Hmgn1-/-, (0.065519) Hmgn1-/-,rep3 biologicalNeuron, Hmgn1-/-, (0.0755771)rep1 biological biological(0.0212388) Hmgn1-/-, rep2 biological rep1(0.0160698) rep3 biological(0.0758725) rep2(0.0175008) (0.089861) rep3[ min (0.0730209) ] [ medium ] [ max ] CEM 1 Bub1 380.5 3820.2 8355.1 P ( S | Z, I ) = 1.00 Birc5 446.6 3803.6 4652.1 Mean Corr = 0.87455 Sgol1 209.8 1544.7 2892.1 Nuf2 415.4 1552.7 1919.7 Zwilch 224.8 1423.2 4263.9 Bub1b 272.5 1711.8 2900.8 Kntc1 195.3 919.1 2492.8 Ndc80 93.8 728.8 1157.2 Cenpk 163.3 1027.6 1950.0 Spc24 209.2 1533.5 1954.0 Cenph 93.7 1069.2 1689.7 Sgol2 326.7 1558.9 2928.3 Ercc6l 143.0 1291.8 2906.6 Spag5 77.9 502.4 651.9 Incenp 194.0 1004.4 1419.6 Nek2 106.6 590.5 1099.6 Cenpn 324.9 1859.5 2085.9 Cenpu 94.3 661.9 1229.3 Cenpw 276.1 1627.6 2437.3 Apitd1 112.4 567.6 1336.5 Casc5 136.4 715.5 1549.5 Cenpm 175.3 731.4 2041.6 Nup107 790.7 2387.3 3701.2 Nup85 894.5 2400.7 3600.9 Nup133 626.7 1628.5 3839.7 Nup43 137.3 639.1 1625.8 Nde1 254.5 674.6 1129.2 Smc1a 2527.9 3047.0 3488.8 Cenpc1 1331.2 1532.3 2200.7 Nudcd2 817.5 3045.3 5093.0 Cenpt 483.9 1015.1 1548.8 Cenpo 68.4 180.9 346.7 Ncapg 105.1 818.4 1601.7 Shcbp1 302.1 2356.4 3699.9 Ccna2 1029.9 5363.9 5635.3 Cdk1 893.2 4722.4 5388.0 Aurkb 83.0 1039.7 1616.3 CEM 1 + Kif11 109.1 785.1 1366.3 Top 10 Genes Melk 268.5 2200.9 3833.9 Kif20a 269.8 2177.6 3878.2 Pbk 1274.3 3379.6 4745.5 Tpx2 257.9 1727.7 2524.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE51243" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51243 Status: Public on Sep 28 2013 Title: Comparison of the transcriptome of TEL-JAK2- versus activated NOTCH1 (ICN1)-induced T cell acute lymphoblastic leukemias (mouse) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24268771 Summary & Design: Summary: The TEL-JAK2 fusion oncogene and the ICN1 activated allele of NOTCH1 are the result of specific chromosomal translocations in T cell acute lymphoblastic leukemia (T-ALL). Mouse models of these diseases (TEL-JAK2 transgenic mice; Carron C. et al. Blood (2000); a bone marrow transplantation model for ICN1-induced T-ALL) were used to compare the transcriptional program specific to each oncoprotein in mouse models of these leukemias. Tumor load was >50% leukemic cells in all selected organs.

Overall design: Leukemic cells were collected from the thymus of terminally-ill TEL-JAK2 leukemic mice and bone marrow of terminally-ill ICN1 leukemic mice. RNA was extracted from each sample and processed for hybridization to Affymetrix arrays.

Background corr dist: KL-Divergence = 0.0331, L1-Distance = 0.0151, L2-Distance = 0.0003, Normal std = 0.6426

0.621 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

ICN1_1701ICN1_1840 leukemiaICN1_24306 leukemia (0.160453)TJ2_1192 leukemia (0.205442)TJ2_1209 leukemia (0.200843)TJ2_1210 leukemia (0.0946464)TJ2_1261 leukemia (0.109151) leukemia (0.15115) (0.0783143)[ min ] [ medium ] [ max ] CEM 1 Bub1 485.4 1044.7 3644.9 P ( S | Z, I ) = 1.00 Birc5 1257.9 2545.1 10895.4 Mean Corr = 0.87445 Sgol1 355.6 662.4 2352.0 Nuf2 305.5 613.2 2345.5 Zwilch 346.9 742.5 1833.0 Bub1b 766.9 1380.4 3823.2 Kntc1 241.2 791.6 1769.9 Ndc80 225.4 383.3 872.8 Cenpk 314.3 723.6 2818.1 Spc24 385.5 687.3 1752.4 Cenph 146.0 259.0 680.5 Sgol2 185.1 363.7 1039.1 Ercc6l 277.9 511.3 1299.7 Spag5 116.8 270.1 859.7 Incenp 569.4 761.8 2548.2 Nek2 198.8 298.3 1351.1 Cenpn 651.0 1025.5 2384.8 Cenpu 236.9 347.7 1191.4 Cenpw 244.0 530.6 1186.2 Apitd1 171.0 326.3 567.7 Casc5 167.6 308.6 673.7 Cenpm 264.7 385.8 846.2 Nup107 1677.0 1892.6 2500.3 Nup85 1202.1 1887.2 2557.4 Nup133 487.4 737.9 2212.0 Nup43 244.5 305.2 543.6 Nde1 891.7 1230.5 1421.4 Smc1a 4237.8 5533.2 8345.6 Cenpc1 652.7 935.3 1485.8 Nudcd2 677.2 956.3 1581.0 Cenpt 776.2 906.4 1033.0 Cenpo 149.5 242.0 333.0 Ncapg 239.2 593.0 2134.7 Shcbp1 392.5 995.3 2867.8 Ccna2 928.0 2050.9 7761.2 Cdk1 879.5 1921.4 5671.9 Aurkb 229.3 504.1 2110.4 CEM 1 + Kif11 389.0 714.1 2965.1 Top 10 Genes Melk 194.8 357.2 1372.7 Kif20a 267.1 567.5 1997.6 Pbk 613.0 1308.2 5976.7 Tpx2 614.3 1226.6 4243.2

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE34324" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34324 Status: Public on Feb 26 2013 Title: Gene expression by Retinoic Acid in mouse Dendritic Cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23322377 Summary & Design: Summary: The purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.

Overall design:

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

0.890 Kernel fit Pairwise Correlations Normal fit

Density 0.445

0.000 CEM 1

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

Pre-normalization Quantiles

[mDCs]_[control]_[1][mDCs]_[RA]_[1][mDCs]_[Ro]_[1] (0.0522693)[mDCs]_[control+LPS]_[1] (0.0902037)[mDCs]_[RA+LPS]_[1] (0.164403)[mDCs]_[Ro+LPS]_[1][mDCs]_[control]_[2] (0.0831449) [mDCs]_[RA]_[2](0.0950541) [mDCs]_[Ro]_[2](0.0642603) (0.0312767)[mDCs]_[control+LPS]_[2] (0.0436011)[mDCs]_[RA+LPS]_[2] (0.147966)[mDCs]_[Ro+LPS]_[2] (0.100894) (0.0562006) (0.0707267)[ min ] [ medium ] [ max ] CEM 1 Bub1 44.3 364.4 1121.7 P ( S | Z, I ) = 1.00 Birc5 85.5 2064.8 4273.6 Mean Corr = 0.87431 Sgol1 6.4 145.6 634.5 Nuf2 4.9 442.0 1223.7 Zwilch 34.6 162.3 576.2 Bub1b 11.9 404.3 1031.0 Kntc1 12.0 151.9 457.2 Ndc80 19.1 211.2 574.6 Cenpk 55.7 277.4 696.1 Spc24 7.1 453.1 891.2 Cenph 3.4 88.0 269.1 Sgol2 3.8 131.4 287.9 Ercc6l 9.9 231.5 768.1 Spag5 4.3 121.2 304.4 Incenp 198.9 480.5 937.7 Nek2 10.3 115.4 192.2 Cenpn 74.1 480.4 1209.1 Cenpu 65.5 353.1 551.1 Cenpw 124.6 308.0 639.2 Apitd1 64.2 190.3 523.5 Casc5 36.6 214.2 381.4 Cenpm 37.2 286.4 718.4 Nup107 15.9 319.5 745.0 Nup85 203.1 717.2 1289.6 Nup133 178.4 453.7 813.4 Nup43 122.3 203.6 400.4 Nde1 198.1 423.5 771.7 Smc1a 789.4 1581.3 2309.4 Cenpc1 99.7 529.9 737.1 Nudcd2 180.9 460.0 830.4 Cenpt 225.4 585.1 1165.6 Cenpo 3.2 93.1 209.2 Ncapg 12.4 102.5 495.0 Shcbp1 33.7 256.2 1083.4 Ccna2 26.3 793.5 2318.0 Cdk1 497.1 1825.6 3722.8 Aurkb 24.1 154.4 451.5 CEM 1 + Kif11 19.0 152.0 552.7 Top 10 Genes Melk 45.2 302.6 1006.5 Kif20a 10.9 298.8 1118.6 Pbk 37.2 347.7 1410.5 Tpx2 241.2 485.8 1147.0

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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 naïve 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 naïve 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. Naïve 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 (0.0698193) biological replicatebiologicalnaive, 2 (0.0800574) replicatebiological 1 replicate(0.138333) 2 replicate(0.164228) 1 (0.29206) 2 (0.255502)[ min ] [ medium ] [ max ] CEM 1 Bub1 56.8 2543.0 3831.7 P ( S | Z, I ) = 1.00 Birc5 49.8 3485.6 7102.1 Mean Corr = 0.87117 Sgol1 113.1 1521.9 2369.4 Nuf2 54.5 2303.2 4674.1 Zwilch 47.3 992.8 1264.6 Bub1b 135.0 1559.0 2801.4 Kntc1 95.3 1637.6 1918.3 Ndc80 217.1 1015.2 1769.1 Cenpk 66.3 1891.3 2434.9 Spc24 92.0 1296.0 1645.5 Cenph 82.5 879.0 895.3 Sgol2 124.3 1551.3 2443.2 Ercc6l 259.0 1166.4 1385.5 Spag5 56.2 655.6 1168.2 Incenp 162.6 2040.6 2936.2 Nek2 92.3 897.3 2320.5 Cenpn 460.5 1918.5 2743.9 Cenpu 133.6 522.7 552.4 Cenpw 150.3 1253.1 1650.2 Apitd1 304.9 1756.5 2045.6 Casc5 126.0 811.9 1274.2 Cenpm 281.4 1574.5 1763.9 Nup107 946.1 2249.2 2812.0 Nup85 1213.3 2961.3 3475.7 Nup133 551.6 1498.6 1785.5 Nup43 327.4 447.2 568.2 Nde1 373.0 989.0 1469.0 Smc1a 1702.0 4337.5 5077.1 Cenpc1 557.3 1929.3 2066.6 Nudcd2 502.2 1149.2 1460.3 Cenpt 226.7 811.1 1025.7 Cenpo 163.1 213.2 288.0 Ncapg 44.8 2403.0 3560.3 Shcbp1 75.1 2056.1 3643.8 Ccna2 216.1 6329.6 10083.2 Cdk1 97.1 3285.7 5939.8 Aurkb 66.8 1394.9 2299.7 CEM 1 + Kif11 81.1 1574.5 2395.7 Top 10 Genes Melk 66.2 1089.9 1401.8 Kif20a 44.9 1246.7 2971.9 Pbk 97.7 4355.0 4942.2 Tpx2 99.4 1510.7 3574.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 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(0.0953485)liver carcinomahepatocellular - -1 2 normal(0.148209)(0.107399)liver carcinoma - - 3 2 normal(0.0861541) liver(0.138628)carcinoma - - 4 3 (0.0877095) liver(0.123604) - - 5 4 (0.0890303) (0.123918) [ min ] [ medium ] [ max ] CEM 1 Bub1 23.2 830.0 1668.6 P ( S | Z, I ) = 1.00 Birc5 35.9 3983.9 5732.6 Mean Corr = 0.87115 Sgol1 71.1 1171.5 1739.9 Nuf2 56.2 839.0 1220.6 Zwilch 43.6 1458.4 1907.1 Bub1b 89.5 804.0 911.6 Kntc1 47.5 840.8 1289.6 Ndc80 63.5 568.7 711.1 Cenpk 55.8 571.2 1433.0 Spc24 262.9 2242.4 6790.7 Cenph 32.4 281.2 657.7 Sgol2 34.5 640.5 836.4 Ercc6l 83.0 419.9 747.7 Spag5 34.6 227.6 390.6 Incenp 117.6 631.2 1102.0 Nek2 105.1 1017.1 1247.0 Cenpn 1038.4 1293.2 1676.2 Cenpu 71.7 817.1 1082.2 Cenpw 74.1 666.9 956.2 Apitd1 97.2 294.3 407.7 Casc5 47.2 327.8 632.3 Cenpm 244.2 1866.7 3016.6 Nup107 524.8 1280.5 1622.0 Nup85 474.9 1594.4 2086.5 Nup133 322.5 892.4 1371.4 Nup43 189.3 375.0 671.1 Nde1 243.3 618.4 878.5 Smc1a 1916.5 2225.6 3775.0 Cenpc1 142.7 279.1 478.4 Nudcd2 514.2 973.3 1642.1 Cenpt 179.0 575.7 730.2 Cenpo 100.1 129.9 185.5 Ncapg 22.4 623.8 929.7 Shcbp1 60.7 1028.6 1876.7 Ccna2 92.2 3462.1 6910.0 Cdk1 108.8 6408.4 7383.6 Aurkb 40.2 1097.7 1942.9 CEM 1 + Kif11 43.3 812.0 1222.8 Top 10 Genes Melk 71.7 877.8 1582.3 Kif20a 32.2 1890.2 2215.6 Pbk 50.1 4956.2 6584.1 Tpx2 85.7 874.3 1481.7

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25 GEO Series "GSE20696" 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=GSE20696 Status: Public on Sep 30 2010 Title: Expression profiling of 3T3-L1 adipogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20887899 Summary & Design: Summary: 3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogeneic media.

Overall design: Two technical replicates from four time points relative to induction of adipogenesis (day 0)

Background corr dist: KL-Divergence = 0.0408, L1-Distance = 0.0317, L2-Distance = 0.0012, Normal std = 0.6378

0.651 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

3T3-L1_t1_rep13T3-L1_t1_rep23T3-L1_t2_rep1 (0.149452)3T3-L1_t2_rep2 (0.140408)3T3-L1_t3_rep1 (0.103799)3T3-L1_t3_rep2 (0.101197)3T3-L1_t4_rep1 (0.0868902)3T3-L1_t4_rep2 (0.0917471) (0.14907) (0.177437) [ min ] [ medium ] [ max ] CEM 1 Bub1 70.1 1855.5 2805.3 P ( S | Z, I ) = 1.00 Birc5 110.6 2120.3 3663.2 Mean Corr = 0.87081 Sgol1 118.8 800.8 1561.6 Nuf2 70.4 583.4 1178.8 Zwilch 140.0 1410.1 1484.7 Bub1b 102.9 1440.6 2356.0 Kntc1 63.8 441.8 656.8 Ndc80 41.5 233.7 736.7 Cenpk 293.7 1156.8 1442.7 Spc24 49.5 409.3 686.5 Cenph 62.6 757.9 1067.4 Sgol2 60.9 534.6 775.0 Ercc6l 83.3 847.8 1063.6 Spag5 28.8 178.3 312.2 Incenp 260.0 1401.3 1580.0 Nek2 81.8 328.6 505.3 Cenpn 507.4 1500.9 2516.7 Cenpu 115.7 573.6 590.6 Cenpw 202.3 727.3 942.9 Apitd1 79.9 175.6 311.6 Casc5 72.1 637.2 897.9 Cenpm 125.5 456.2 511.9 Nup107 534.6 1649.1 1918.8 Nup85 595.8 1284.4 1660.9 Nup133 403.9 865.2 938.8 Nup43 226.8 537.5 668.8 Nde1 576.9 1049.9 1441.4 Smc1a 1605.4 2465.2 2875.7 Cenpc1 788.0 1041.5 1357.5 Nudcd2 1296.2 2014.3 2699.8 Cenpt 288.8 1098.5 1665.7 Cenpo 69.8 109.0 141.4 Ncapg 77.9 909.9 1567.7 Shcbp1 160.4 1853.2 2757.8 Ccna2 221.0 2746.3 4443.5 Cdk1 1352.3 4009.7 5691.4 Aurkb 49.9 468.0 633.4 CEM 1 + Kif11 42.6 723.2 1097.6 Top 10 Genes Melk 31.2 415.5 869.5 Kif20a 165.6 1219.5 2491.0 Pbk 116.0 1945.5 2137.4 Tpx2 152.5 1591.3 2826.8

Null module Dctn3 Dync1i1 Stra13 Tex14 Seh1l Knstrn Dynlt3 Itgb3bp Sept6 Pinx1 Ndel1 Sept2 Zwint Ahctf1 Dync1li1 Tpr Trp53bp1 Clasp1 Bod1 Csnk1a1 Cenpv Kif2b Clasp2 Zw10 Kif2c Champ1 Ss18l1 Sept7 Hjurp Rangap1 Mad1l1 Bub3 Spc25